[ { "pmid": "11418519", "target": "[\"Span: oncology | Label: Comorbidity\"]", "text": "[Title]: The effect of amiloride on amphotericin B-induced hypokalaemia.\n[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.\n[Drug-Disease]: Amiloride - hypokalaemia" }, { "pmid": "11419566", "target": "[\"Span: 30 to 60 mg by weight or a 50-mg fixed dose once daily | Label: Dosage\"]", "text": "[Title]: Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.\n[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.\n[Drug-Disease]: Metrifonate - AD" }, { "pmid": "11422148", "target": "[\"Span: adults aged 15-85 years | Label: Age\", \"Span: children aged 6-14 years | Label: Age\", \"Span: 10 mg | Label: Dosage\", \"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.\n[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.\n[Drug-Disease]: montelukast - chronic asthma" }, { "pmid": "11422148", "target": "[\"Span: adults aged 15-85 years | Label: Age\", \"Span: children aged 6-14 years | Label: Age\", \"Span: 200 microg twice daily | Label: Dosage\", \"Span: 100 microg or equivalent three times daily | Label: Dosage\"]", "text": "[Title]: Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.\n[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.\n[Drug-Disease]: beclomethasone - chronic asthma" }, { "pmid": "1142528", "target": "[\"Span: 12.5 mg. chlorotrianisene per day | Label: Dosage\"]", "text": "[Title]: Hydroxyurea in stage D carcinoma of the prostate: a pilot study.\n[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.\n[Drug-Disease]: chlorotrianisene - prostatic adenocarcinoma" }, { "pmid": "1142528", "target": "[\"Span: a single oral dose of 80 mg. per kg. hydroxyurea every third day | Label: Dosage\"]", "text": "[Title]: Hydroxyurea in stage D carcinoma of the prostate: a pilot study.\n[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.\n[Drug-Disease]: Hydroxyurea - prostatic adenocarcinoma" }, { "pmid": "11427639", "target": "[\"Span: 250 mg | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps.\n[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.\n[Drug-Disease]: vitamin C - Muscle cramps" }, { "pmid": "11427639", "target": "[\"Span: 400 mg | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps.\n[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.\n[Drug-Disease]: vitamin E - Muscle cramps" }, { "pmid": "11429035", "target": "[\"Span: 500 mg tid on a compassionate-use basis | Label: Dosage\"]", "text": "[Title]: Famciclovir treatment of hepatitis B infection following liver transplantation: a long-term, multi-centre study.\n[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.\n[Drug-Disease]: Famciclovir - hepatitis B infection" }, { "pmid": "11432448", "target": "[\"Span: 0.03 microM | Label: Dosage\"]", "text": "[Title]: Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.\n[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.\n[Drug-Disease]: MK-571 - asthmatic bronchospasms" }, { "pmid": "11432448", "target": "[\"Span: 1 microM | Label: Dosage\"]", "text": "[Title]: Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.\n[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.\n[Drug-Disease]: chlorpheniramine - asthmatic bronchospasms" }, { "pmid": "11432626", "target": "[\"Span: starting from 60 mg/m2 and with stepwise increments of 5 mg/m2 | Label: Dosage\"]", "text": "[Title]: Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.\n[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.\n[Drug-Disease]: L-OHP - colorectal cancer" }, { "pmid": "11432626", "target": "[\"Span: 500 mg/m2 | Label: Dosage\"]", "text": "[Title]: Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.\n[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.\n[Drug-Disease]: LV - colorectal cancer" }, { "pmid": "11432626", "target": "[\"Span: 2600 mg/m2 | Label: Dosage\"]", "text": "[Title]: Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.\n[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.\n[Drug-Disease]: 5-FU - colorectal cancer" }, { "pmid": "11434939", "target": "[\"Span: 0.03% once a day | Label: Dosage\", \"Span: 0.03% twice a day | Label: Dosage\"]", "text": "[Title]: Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.\n[Abstract]: The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.\n[Drug-Disease]: bimatoprost - glaucoma" }, { "pmid": "11434939", "target": "[\"Span: 0.03% once a day | Label: Dosage\", \"Span: 0.03% twice a day | Label: Dosage\"]", "text": "[Title]: Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.\n[Abstract]: The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.\n[Drug-Disease]: bimatoprost - ocular hypertension" }, { "pmid": "11434939", "target": "[\"Span: 0.5% BID | Label: Dosage\"]", "text": "[Title]: Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.\n[Abstract]: The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.\n[Drug-Disease]: timolol - glaucoma" }, { "pmid": "11434939", "target": "[\"Span: 0.5% BID | Label: Dosage\"]", "text": "[Title]: Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.\n[Abstract]: The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.\n[Drug-Disease]: timolol - ocular hypertension" }, { "pmid": "11435324", "target": "[\"Span: 200 mg/d; 200 mg increment every 2 weeks to 800 mg | Label: Dosage\"]", "text": "[Title]: Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients.\n[Abstract]: This report of a phase 2 trial of thalidomide (THAL) (200 mg/d; 200 mg increment every 2 weeks to 800 mg) for 169 patients with advanced myeloma (MM) (abnormal cytogenetics (CG), 67%; prior autotransplant, 76%) extends earlier results in 84 patients. A 25% myeloma protein reduction was obtained in 37% of patients (50% reduction in 30% of patients; near-complete or complete remission in 14%) and was more frequent with low plasma cell labeling index (PCLI) (below 0.5%) and normal CG. Two-year event-free and overall survival rates were 20% +/- 6% and 48% +/- 6%, respectively, and these were superior with normal CG, PCLI of less than 0.5%, and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months (median cumulative dose) (landmark analysis); this supports a THAL dose-response effect in advanced MM.\n[Drug-Disease]: THAL - myeloma protein reduction" }, { "pmid": "11440936", "target": "[]", "text": "[Title]: Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.\n[Abstract]: OBJECTIVE: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. DESIGN: Systematic review. DATA SOURCES: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000. STUDIES: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours. RESULTS: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: \"high\" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11. CONCLUSIONS: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.\n[Drug-Disease]: cannabinoids - nausea" }, { "pmid": "11440936", "target": "[]", "text": "[Title]: Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.\n[Abstract]: OBJECTIVE: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. DESIGN: Systematic review. DATA SOURCES: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000. STUDIES: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours. RESULTS: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: \"high\" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11. CONCLUSIONS: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.\n[Drug-Disease]: cannabinoids - vomiting" }, { "pmid": "11442886", "target": "[\"Span: 9.4 +/- 3.6 mg/day | Label: Dosage\"]", "text": "[Title]: Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia: results of an open-label multicenter study in Japan.\n[Abstract]: This first clinical study of olanzapine in Japanese patients with schizophrenia was conducted to investigate the efficacy and safety of olanzapine. Eighty-one patients were included in the analysis set. Mean modal dose for those patients were 9.4 +/- 3.6 mg/day. For the primary efficacy measure (Final Global Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of patients had moderate improvement or better, and 86.4% of patients had slight improvement or better. Results from the Brief Psychiatric Rating Scale showed improvement from baseline in all clusters including positive psychotic symptoms (thought disturbance) but also against negative symptoms (anergia). The most commonly reported treatment-emergent signs and symptoms with > or =10% incidence, were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms, and events reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The most commonly reported treatment-emergent laboratory changes, with > or = 20% of incidence, were prolactin elevations (24.3%) followed by increases in triglycerides (20.4%). However, mean prolactin values tended to be normalized during the study. This study result suggests that olanzapine is an \"atypical\" antipsychotic.\n[Drug-Disease]: olanzapine - schizophrenia" }, { "pmid": "11443577", "target": "[]", "text": "[Title]: A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.\n[Abstract]: Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "11443583", "target": "[]", "text": "[Title]: Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight.\n[Abstract]: Hypertension and hyperlipidemia are more prevalent after liver transplantation with cyclosporine as the primary immunosuppressive agent compared with tacrolimus. To determine whether blood pressure, serum lipid level, or weight improves when patients switch immunosuppression therapy, we retrospectively studied 26 liver transplant recipients with stable graft function who had been converted from cyclosporine to tacrolimus therapy with a median follow-up of 8 months. One of the 26 patients developed pruritus necessitating withdrawal of tacrolimus. The results therefore concern the remaining 25 patients. With the exception of a small decrease in bilirubin level (P <.05), there was no difference in graft or renal function after conversion. Mean systolic blood pressure decreased from 158 +/- 25 to 148 +/- 22 mm Hg over a mean of 8 +/- 3 months after conversion to tacrolimus (P =.015), whereas mean serum cholesterol level decreased from 5.3 +/- 0.9 to 4.9 +/- 0.9 mmol/L (P =.01). Sixty-eight percent of the patients lost weight, from a mean of 79.4 +/- 22.6 to 76.1 +/- 20.1 kg, in the 11 months after switching to tacrolimus therapy (P =.024). Serum triglyceride and blood glucose levels did not change, and no patient developed diabetes mellitus after conversion. These results indicate that switching from cyclosporine to tacrolimus can reduce blood pressure, serum cholesterol level, and weight after liver transplantation.\n[Drug-Disease]: tacrolimus - Hypertension" }, { "pmid": "11446944", "target": "[]", "text": "[Title]: [Anesthetic management for cesarean delivery in a pregnant patient with congenital antithrombin III deficiency and pulmonary thromboembolism].\n[Abstract]: Antithrombin III (AT III) deficiency is a rare hereditary disease that predisposes a patient to thromboembolic complications. Anticoagulation is essential for preventing recurrence of thrombi. Concentrated AT III replacement is reserved for acute periods of thromboembolism or moments of increased risk. Hemostatic anomalies are generally considered a contraindication for regional anesthesia, due to the potential risk of spinal hematoma. This paper describes a woman with congenital AT III deficiency and heparin-treated pulmonary embolism whose pregnancy of 29 weeks had to be terminated by cesarean section upon signs of fetal distress. We discuss the pathophysiology and treatment in such cases.\n[Drug-Disease]: heparin - congenital AT III deficiency" }, { "pmid": "11448321", "target": "[\"Span: 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week | Label: Dosage\"]", "text": "[Title]: Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.\n[Abstract]: OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN 192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized, investigator-masked, clinical trial involving 100 patients with elevated intraocular pressure (IOP). Study medications were instilled topically. Doses of 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4 weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety parameters included adverse events, hyperemia grading, laser flare meter analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3 concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of 0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or = .02) at every study visit except day 21 (P = .053) and provided better diurnal IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant benefit over once-daily dosing. All treatment regimens were safe and well tolerated, with no clinically significant effects on heart rate or blood pressure and no between-group differences in the incidence of adverse events. The only significant ocular safety finding with AGN 192024 was a dose-related mild increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested, 0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe and well tolerated, and it provided superior ocular hypotensive efficacy and diurnal IOP control compared with timolol in patients with ocular hypertension and glaucoma.\n[Drug-Disease]: AGN 192024 - ocular hypertension" }, { "pmid": "11448321", "target": "[\"Span: 0.5% timolol was given twice daily for 4 weeks | Label: Dosage\"]", "text": "[Title]: Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.\n[Abstract]: OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN 192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized, investigator-masked, clinical trial involving 100 patients with elevated intraocular pressure (IOP). Study medications were instilled topically. Doses of 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4 weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety parameters included adverse events, hyperemia grading, laser flare meter analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3 concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of 0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or = .02) at every study visit except day 21 (P = .053) and provided better diurnal IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant benefit over once-daily dosing. All treatment regimens were safe and well tolerated, with no clinically significant effects on heart rate or blood pressure and no between-group differences in the incidence of adverse events. The only significant ocular safety finding with AGN 192024 was a dose-related mild increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested, 0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe and well tolerated, and it provided superior ocular hypotensive efficacy and diurnal IOP control compared with timolol in patients with ocular hypertension and glaucoma.\n[Drug-Disease]: timolol - ocular hypertension" }, { "pmid": "11452896", "target": "[\"Span: 2 x 25 mg | Label: Dosage\"]", "text": "[Title]: [Does early high dosage dipyridamole in prevention of secondary stroke induce cardiac events?].\n[Abstract]: In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we investigated whether dipyridamole given as antiplatelet drug in patients with TIA or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention trial including 6602 patients with TIA or stroke. Patients were randomized into one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not result in a higher number of cardiac events, e.g., angina pectoris, myocardial infarction or death. The combination of ASA plus DP was superior to either drug alone in the prevention of strokes.\n[Drug-Disease]: ASA - strokes" }, { "pmid": "11452896", "target": "[\"Span: 2 x 200 mg | Label: Dosage\"]", "text": "[Title]: [Does early high dosage dipyridamole in prevention of secondary stroke induce cardiac events?].\n[Abstract]: In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we investigated whether dipyridamole given as antiplatelet drug in patients with TIA or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention trial including 6602 patients with TIA or stroke. Patients were randomized into one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not result in a higher number of cardiac events, e.g., angina pectoris, myocardial infarction or death. The combination of ASA plus DP was superior to either drug alone in the prevention of strokes.\n[Drug-Disease]: DP - strokes" }, { "pmid": "11454181", "target": "[\"Span: five with genotype 1 and one with genotype 4 | Label: Gene\", \"Span: average daily doses of 170-300 mg | Label: Dosage\"]", "text": "[Title]: Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection--a pilot study.\n[Abstract]: Standard treatment for chronic hepatitis C is with interferon (IFN)-alpha and ribavirin for 6-12 months. In dialysis patients only interferon therapy is currently used due to the lack of knowledge concerning ribavirin dosage and side-effects. The aim of this study was to investigate if ribavirin can be added to interferon when treating dialysis patients with hepatitis C. Five patients on haemodialysis and one patient on peritoneal dialysis with chronic hepatitis C, five with genotype 1 and one with genotype 4, were given interferon-alpha2b 3 MU thrice weekly for 4 weeks, whereafter ribavirin 200-400 mg was added, for an intended total treatment period of 28 weeks. Ribavirin plasma concentrations were monitored, using HPLC. Four patients completed the treatment. One patient suffered marked side-effects from interferon and therapy was terminated. One patient developed heart failure and died after 14 weeks of treatment but the death was not considered treatment related. Based on plasma concentrations, ribavirin doses were frequently adjusted initially. The target concentration (10-15 micromol/L) was reached with average daily doses of 170-300 mg ribavirin. Ribavirin induced anaemia was managed with high doses of erytropoietin (20 000-30 000 IU/week). Five of six patients became hepatitis C virus (HCV)-RNA negative during treatment, but four relapsed post-treatment; one is HCV-RNA negative. Hence ribavirin, in combination with IFN-alpha, can be used to treat dialysis patients with HCV. However, this requires reduced ribavirin doses and close monitoring of ribavirin plasma concentrations and haemoglobin. Ribavirin-induced anaemia can be managed with high doses of erythropoeitin.\n[Drug-Disease]: Ribavirin - chronic hepatitis C" }, { "pmid": "11456310", "target": "[\"Span: 47,351 men and 88,565 women | Label: Gender\"]", "text": "[Title]: Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.\n[Abstract]: Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.\n[Drug-Disease]: caffeine - Parkinson's disease" }, { "pmid": "11461176", "target": "[]", "text": "[Title]: Concurrent administration of sustained-release bezafibrate may counteract the increased thrombotic risk associated with oral estrogen therapy.\n[Abstract]: Although hormone replacement therapy (HRT) can have many favorable effects on serum lipids and on vascular endothelium that presumably mediate the decreased risk for heart attack and stroke associated with HRT in observational epidemiology, oral estrogen also has various pro-coagulant effects: increases in serum triglycerides and factor VII activity, decreases in serum antithrombin III and protein S. This may explain the increased risk for venous thromboembolism observed with HRT and oral contraceptives, as well as the temporary increase in coronary risk noted when women with preexisting coronary disease initiate HRT. The well-tolerated hypolipidemic agent bezafibrate has anticoagulant actions that are diametrically opposed to the procoagulant effects of oral estrogen: namely, reductions in serum triglycerides and factor VII activity, and an increase in antithrombin III. However, bezafibrate could be expected to complement the protective effects of oral estrogen on serum lipids and on serum IGF-I activity. Thus, there is reason to believe that concurrent bezafibrate administration would minimize any thrombotic risk associated with HRT or oral contraception, while amplifying the health benefits of oral estrogen, and would make it more feasible to administer these therapies in women at increased vascular risk. These predictions require confirmation in controlled clinical studies. Certain natural hypolipidemic agents may also have potential as adjuvants to oral estrogen, but their effects on hemostasis require further investigation.\n[Drug-Disease]: bezafibrate - thrombotic" }, { "pmid": "11465651", "target": "[\"Span: African American | Label: Body Type\", \"Span: 320 mg/day | Label: Dosage\", \"Span: 160 mg/day | Label: Dosage\"]", "text": "[Title]: Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake.\n[Abstract]: Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks. After this evaluation, while continuing the Na+ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (-6.4/-4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.\n[Drug-Disease]: valsartan - hypertensive" }, { "pmid": "11465651", "target": "[\"Span: African American | Label: Body Type\", \"Span: 12.5 mg/day | Label: Dosage\"]", "text": "[Title]: Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake.\n[Abstract]: Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks. After this evaluation, while continuing the Na+ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (-6.4/-4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.\n[Drug-Disease]: HCTZ - hypertensive" }, { "pmid": "11470055", "target": "[\"Span: 5 to 10 mg/day | Label: Dosage\"]", "text": "[Title]: [Olanzapine efficacy in the treatment of cocaine abuse in methadone maintenance patients. Interaction with plasma levels].\n[Abstract]: INTRODUCTION: The aim of this study was to evaluate the efficacy of the treatment with antipsychotic olanzapine in cocaine abuse methadone patients. The decrease or interruption of cocaine consume as well as the possible pharmacokinetic interaction between olanzapine and methadone were studied. MATERIAL AND METHODS: Patients (n= 21) include in a methadone maintenance program (14 months), with DSM-IV criteria for opioid and cocaine dependence and without schizophrenic diagnostic, were treated with olanzapine 5 to 10 mg/day. The therapeutic outcomes were assessed by personal interviews, cocaine consumption, changes of consumption patrons (via of administration) and secondary effects to olanzapine. Withdrawal symptoms were measured by means of the abbreviate version of the scale of Gossop. Cocaine used was measured by urine analysis (enzymoimmnuoassay). The possible pharmacokinetic interaction between olanzapine and methadone was measured in plasma before and during the treatment in 15 patients. RESULTS: Olanzapine combined with methadone in cocaine abusers was well tolerated in an important proportion of patients. Moreover the consumption of cocaine was decreased or stopped in 53,2% of the patients. In addition, no withdrawal syndrome was observed in any patients. Furthermore the ratios of methadone plasma levels did not change in relation to the dose before and during the treatment, suggesting a lack of pharmacokinetic interaction between methadone and olanzapine. CONCLUSIONS: In conclusion the results of this preliminary study, led us to advance that olanzapine could be a useful treatment for cocaine abuse at least in patients in a Methadone Maintenance Program, with the advantage of not to induce any pharmacokinetic interaction with methadone.\n[Drug-Disease]: olanzapine - cocaine abuse+B40:B41" }, { "pmid": "11470055", "target": "[]", "text": "[Title]: [Olanzapine efficacy in the treatment of cocaine abuse in methadone maintenance patients. Interaction with plasma levels].\n[Abstract]: INTRODUCTION: The aim of this study was to evaluate the efficacy of the treatment with antipsychotic olanzapine in cocaine abuse methadone patients. The decrease or interruption of cocaine consume as well as the possible pharmacokinetic interaction between olanzapine and methadone were studied. MATERIAL AND METHODS: Patients (n= 21) include in a methadone maintenance program (14 months), with DSM-IV criteria for opioid and cocaine dependence and without schizophrenic diagnostic, were treated with olanzapine 5 to 10 mg/day. The therapeutic outcomes were assessed by personal interviews, cocaine consumption, changes of consumption patrons (via of administration) and secondary effects to olanzapine. Withdrawal symptoms were measured by means of the abbreviate version of the scale of Gossop. Cocaine used was measured by urine analysis (enzymoimmnuoassay). The possible pharmacokinetic interaction between olanzapine and methadone was measured in plasma before and during the treatment in 15 patients. RESULTS: Olanzapine combined with methadone in cocaine abusers was well tolerated in an important proportion of patients. Moreover the consumption of cocaine was decreased or stopped in 53,2% of the patients. In addition, no withdrawal syndrome was observed in any patients. Furthermore the ratios of methadone plasma levels did not change in relation to the dose before and during the treatment, suggesting a lack of pharmacokinetic interaction between methadone and olanzapine. CONCLUSIONS: In conclusion the results of this preliminary study, led us to advance that olanzapine could be a useful treatment for cocaine abuse at least in patients in a Methadone Maintenance Program, with the advantage of not to induce any pharmacokinetic interaction with methadone.\n[Drug-Disease]: methadone - cocaine abuse" }, { "pmid": "1147074", "target": "[]", "text": "[Title]: Deanol in the treatment of tardive dyskinesia.\n[Abstract]: A patient who developed severe tardive dyskinesia after the termination of long-term phenothiazine therapy was successfully treated with deanol, a possible precursor of acetylcholine. Physiological measurements were obtained to quantify the clinical course. The authors discuss the practical and heuristic implications of these observations and suggest further consideration of therapy directed toward enhancement of cholinergic activity in the central nervous system.\n[Drug-Disease]: deanol - tardive dyskinesia" }, { "pmid": "11472356", "target": "[\"Span: 0.4 mg/kg/d | Label: Dosage\"]", "text": "[Title]: Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.\n[Abstract]: Patients with chronic immune thrombocytopenic purpura (ITP) who are unresponsive to corticosteroids require splenectomy, but if this fails, treatment is difficult. We tried to induce durable remissions in ITP patients refractory to corticosteroids before or after splenectomy by applying strong immunosuppression with the combination of cyclosporin A (CyA 5 mg/kg/d) and prednisone (0.4 mg/kg/d). Patients were assigned to one of two groups. Group 1, 10 patients refractory to prednisone; and group 2, 10 patients refractory to at least prednisone and splenectomy. Overall response rate was 55% (50% in group 1 and 60% in group 2 patients). Nine of the 10 patients in group 1 finally had a splenectomy because of relapse, insufficient response or toxicity of CyA. Thirty percent of the patients discontinued CyA because of side-effects; hypertension, severe headache and muscle pain being the most frequent encountered. It is concluded that CyA treatment does not avoid, but only postpones, splenectomy in chronic ITP patients who are refractory to corticosteroids. However, CyA can be useful in a subgroup of patients with corticosteroid- and splenectomy-refractory ITP, but treatment toxicity is high.\n[Drug-Disease]: prednisone - chronic immune thrombocytopenic purpura" }, { "pmid": "11472356", "target": "[\"Span: 5 mg/kg/d | Label: Dosage\"]", "text": "[Title]: Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.\n[Abstract]: Patients with chronic immune thrombocytopenic purpura (ITP) who are unresponsive to corticosteroids require splenectomy, but if this fails, treatment is difficult. We tried to induce durable remissions in ITP patients refractory to corticosteroids before or after splenectomy by applying strong immunosuppression with the combination of cyclosporin A (CyA 5 mg/kg/d) and prednisone (0.4 mg/kg/d). Patients were assigned to one of two groups. Group 1, 10 patients refractory to prednisone; and group 2, 10 patients refractory to at least prednisone and splenectomy. Overall response rate was 55% (50% in group 1 and 60% in group 2 patients). Nine of the 10 patients in group 1 finally had a splenectomy because of relapse, insufficient response or toxicity of CyA. Thirty percent of the patients discontinued CyA because of side-effects; hypertension, severe headache and muscle pain being the most frequent encountered. It is concluded that CyA treatment does not avoid, but only postpones, splenectomy in chronic ITP patients who are refractory to corticosteroids. However, CyA can be useful in a subgroup of patients with corticosteroid- and splenectomy-refractory ITP, but treatment toxicity is high.\n[Drug-Disease]: CyA - chronic immune thrombocytopenic purpura" }, { "pmid": "11472706", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.\n[Abstract]: This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia. This was a multicenter, randomized, open-label, parallel-design study of patients with total cholesterol >200 mg/dl, triglycerides between 200 and 800 mg/dl, and apolipoprotein B >110 mg/dl. Patients were randomly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein (VLDL) particles (-31% and -29%, respectively) and small low-density lipoprotein (LDL) particles (-44% and -35%, respectively). Niacin increased the concentration of large LDL (+75%). Atrovastatin reduced the number of LDL particles more than niacin (31% vs 14%). In patients with atherogenic dyslipidemia, both drugs had important effects on lipoprotein subfractions, which contributed to a reduction in coronary heart disease risk. The drugs equally reduced VLDL subclass levels. Niacin shifted the LDL subclass distribution toward the larger particles, more effectively converted patients from LDL phenotype B to phenotype A, and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles. In contrast, atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL, and more effectively, reduced LDL particle numbers. Atorvastatin had a preferred LDL effect, whereas niacin had a preferred high-density lipoprotein effect.\n[Drug-Disease]: Atorvastatin - atherogenic dyslipidemia" }, { "pmid": "11472706", "target": "[\"Span: 3,000 mg daily for 12 weeks | Label: Dosage\"]", "text": "[Title]: Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.\n[Abstract]: This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia. This was a multicenter, randomized, open-label, parallel-design study of patients with total cholesterol >200 mg/dl, triglycerides between 200 and 800 mg/dl, and apolipoprotein B >110 mg/dl. Patients were randomly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein (VLDL) particles (-31% and -29%, respectively) and small low-density lipoprotein (LDL) particles (-44% and -35%, respectively). Niacin increased the concentration of large LDL (+75%). Atrovastatin reduced the number of LDL particles more than niacin (31% vs 14%). In patients with atherogenic dyslipidemia, both drugs had important effects on lipoprotein subfractions, which contributed to a reduction in coronary heart disease risk. The drugs equally reduced VLDL subclass levels. Niacin shifted the LDL subclass distribution toward the larger particles, more effectively converted patients from LDL phenotype B to phenotype A, and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles. In contrast, atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL, and more effectively, reduced LDL particle numbers. Atorvastatin had a preferred LDL effect, whereas niacin had a preferred high-density lipoprotein effect.\n[Drug-Disease]: Niacin - atherogenic dyslipidemia" }, { "pmid": "11473503", "target": "[\"Span: 150-250 mg daily | Label: Dosage\", \"Span: 65 males, 91 females | Label: Gender\", \"Span: aged 18-65 | Label: Age\"]", "text": "[Title]: Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial.\n[Abstract]: OBJECTIVE: To determine the relative efficacy, tolerability and risk of precipitating mania of moclobemide and imipramine in the treatment of bipolar depression. METHOD: A randomized, double-blind, parallel group, multicentre study of moclobemide (MCB) (450-750 mg daily) and imipramine (IMI) (150-250 mg daily) in 21 centres in nine countries; 156 patients (65 males, 91 females) aged 18-65 with bipolar depression (17-item Hamilton Depression Rating Scale (HAMD) score chi16) participated. Clinical status was assessed using standardized rating scales before treatment and at 1,2,3,4,6 and 8 weeks. The data were analysed on an intention to treat basis with the last observation carried forward. RESULTS: In the MCB group, the mean HAMD fell from 23.0 to 13.1, in the IMI group it fell from 22.5 to 9.5; the mean score on the Montgomery-Asberg Depression Rating Scale (MADRS) fell from 29.5 to 16.3 on MCB and from 29.2 to 11.6 on IMI. There were no statistically significant differences between the two groups on any efficacy measures. Anticholinergic side-effects were three times more common with IMI than MCB and weight gain was also greater on IMI. Two patients (3.7%) on MCB and six patients (11%) on IMI were withdrawn because of manic symptoms, with manic symptoms occurring earlier on IMI, although these differences did not reach statistical significance. CONCLUSION: No differences in efficacy were detected between MCB and IMI in the treatment of bipolar depression. The data suggests that MCB is less likely than IMI to precipitate mania.\n[Drug-Disease]: IMI - mania" }, { "pmid": "11473503", "target": "[\"Span: 450-750 mg daily | Label: Dosage\", \"Span: 65 males, 91 females | Label: Gender\", \"Span: aged 18-65 | Label: Age\"]", "text": "[Title]: Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial.\n[Abstract]: OBJECTIVE: To determine the relative efficacy, tolerability and risk of precipitating mania of moclobemide and imipramine in the treatment of bipolar depression. METHOD: A randomized, double-blind, parallel group, multicentre study of moclobemide (MCB) (450-750 mg daily) and imipramine (IMI) (150-250 mg daily) in 21 centres in nine countries; 156 patients (65 males, 91 females) aged 18-65 with bipolar depression (17-item Hamilton Depression Rating Scale (HAMD) score chi16) participated. Clinical status was assessed using standardized rating scales before treatment and at 1,2,3,4,6 and 8 weeks. The data were analysed on an intention to treat basis with the last observation carried forward. RESULTS: In the MCB group, the mean HAMD fell from 23.0 to 13.1, in the IMI group it fell from 22.5 to 9.5; the mean score on the Montgomery-Asberg Depression Rating Scale (MADRS) fell from 29.5 to 16.3 on MCB and from 29.2 to 11.6 on IMI. There were no statistically significant differences between the two groups on any efficacy measures. Anticholinergic side-effects were three times more common with IMI than MCB and weight gain was also greater on IMI. Two patients (3.7%) on MCB and six patients (11%) on IMI were withdrawn because of manic symptoms, with manic symptoms occurring earlier on IMI, although these differences did not reach statistical significance. CONCLUSION: No differences in efficacy were detected between MCB and IMI in the treatment of bipolar depression. The data suggests that MCB is less likely than IMI to precipitate mania.\n[Drug-Disease]: MCB - mania" }, { "pmid": "11476129", "target": "[\"Span: mean age, 16.3 years; range, 10-36 years | Label: Age\", \"Span: mean daily dose, 128.4 mg; range, 100-150 mg | Label: Dosage\"]", "text": "[Title]: Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.\n[Abstract]: Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.\n[Drug-Disease]: Clomipramine - autistic" }, { "pmid": "11476129", "target": "[\"Span: mean age, 16.3 years; range, 10-36 years | Label: Age\", \"Span: mean daily dose, 1.3 mg; range, 1-1.5 mg | Label: Dosage\"]", "text": "[Title]: Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.\n[Abstract]: Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.\n[Drug-Disease]: haloperidol - autistic" }, { "pmid": "11476131", "target": "[\"Span: mean age, 41.6 years; mean duration of illness, 21.7 years | Label: Age\", \"Span: 10 to 40 mg daily | Label: Dosage\"]", "text": "[Title]: Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial.\n[Abstract]: The role of olanzapine in treatment-resistant schizophrenia is still unresolved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder selected for unambiguous resistance to either clozapine or risperidone and to typical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean duration of illness, 21.7 years) were enrolled and treated after cross-titration from their previous antipsychotic treatment with olanzapine 10 to 40 mg daily without any concomitant antipsychotic medication. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score improvement of 3.7 (SD = 15.6; not significant). There was a significant improvement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in patients receiving olanzapine doses higher than 20 mg. A total of 16.7% of patients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04; p < 0.05) and statistically significant, yet modest, weight gain. These results indicate that olanzapine is only modestly effective in these severely treatment-resistant patients with schizophrenia. However, a trial with olanzapine can be recommended in these patients before moving to augmentation strategies, given the lack of proven alternatives and the observation that 16.7% of patients reached the response criteria.\n[Drug-Disease]: olanzapine - schizophrenia" }, { "pmid": "11477829", "target": "[]", "text": "[Title]: [Clinical study on qiangxinling liquid extract in treating congestive heart failure].\n[Abstract]: OBJECTIVE: To find the safe and effective treatment and drugs for congestive heart failure (CHF). METHODS: Ninety CHF patients whose heart function belong to III-IV grade were randomly divided into 3 groups: Group A was treated with Qiangxinling liquid extract (QXLLE); Group B with QXLLE plus small dose of digoxin and Group C with digoxin alone. RESULTS: The total effective rate on heart function of Group A was 86.7%, Group B 93.3% and Group C 83.3%, the effect of Group B was better than that of the other two groups (P < 0.05, P < 0.01). The digoxin withdrawing and reducing rate in Group B was higher than that in Group C (86.7% vs 50.0%, P < 0.05). The left ventricular systolic function, including stroke volume, cardiac output, ejection fraction of the 3 groups were improved after treatment, among them the effect of Group B was the best (P < 0.01). Moreover, improvement in ventricular diastolic function was shown in Group A and B, including the maximum blood flow of the late and the early diastolic stage as well as the ratio of them (P < 0.05, P < 0.01). The plasma renin activity, angiotensin II and atrial natriuretic peptide of Group A and B were also lowered after treatment and were significantly different to those of the Group C (P < 0.01). CONCLUSIONS: QXLLE could improve the heart function, clinical symptoms and neuro-endocrinal indexes of CHF patients and reduce the side effects of digoxin.\n[Drug-Disease]: digoxin - CHF" }, { "pmid": "11479406", "target": "[\"Span: aged between 1 week and 13.5 months | Label: Age\", \"Span: ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg. kg-1. d-1 | Label: Dosage\"]", "text": "[Title]: Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography.\n[Abstract]: BACKGROUND: Reported QTc prolongation associated with cardiac arrhythmia in a small number of children undergoing cisapride therapy and lack of pharmacokinetic correlation provided the impetus for this prospective study. The authors evaluated the relation between cisapride plasma concentrations, the electrocardiographic QT interval, and cardiac rhythm in infants undergoing routine 8-hour polysomnography. METHODS: A total of 211 infants were enrolled: 84 (17 born prematurely) undergoing cisapride therapy for at least 4 days for suspected gastroesophageal reflux and 127 controls (10 born prematurely), aged between 1 week and 13.5 months. Infants underwent continuous bipolar limb lead I recording during routine 8-hour polysomnography. QT intervals and heart rate were measured at hourly intervals. The morning after polysomnography, 12-lead electrocardiography was performed (1 hour after cisapride administration). Cisapride plasma concentrations were determined immediately before and 1 to 2 hours after administration. Serum electrolyte concentrations were measured. RESULTS: The administered cisapride dose ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg. kg-1. d-1. Cisapride plasma concentrations were significantly higher in infants younger than 3 months of age. Cisapride-treated infants younger than 3 months of age had longer QTc intervals compared with age-matched controls. Heart rate was similar for cisapride-treated and control infants. No arrhythmia or atrioventricular conduction abnormalities were observed. CONCLUSIONS: At comparable doses of cisapride and comparable plasma concentrations, the QTc was significantly higher in infants younger than 3 months of age. This confirms age-dependent cisapride pharmacokinetics in the first 10 to 12 weeks strongly correlated with changes in body weight and may also suggest an altered ability of infants younger than 3 months of age to metabolize cisapride. The clinical significance and risk of the increased QTc interval is unclear. Cisapride should be judiciously prescribed in infants younger than the age of 3 months and electrocardiography should be performed before and during therapy.\n[Drug-Disease]: Cisapride - gastroesophageal reflux" }, { "pmid": "11480792", "target": "[\"Span: 150 or 300 mg daily | Label: Dosage\"]", "text": "[Title]: Efficacy and tolerability of long-term therapy using high lamivudine doses for the treatment of chronic hepatitis B.\n[Abstract]: PURPOSE: A long-term follow-up study was carried out to evaluate the tolerability and efficacy of long-term therapy (1 to 3 years) with high doses (150 or 300 mg daily) of lamivudine for chronic hepatitis B. METHODS: Thirty-two patients were studied, including those who were seronegative for hepatitis B e antigen (HBeAg), as well as those with decompensated liver cirrhosis. Viral DNA clearance was monitored by using end-point dilution polymerase chain reaction (PCR), a highly sensitive method. Hepatitis B virus (HBV) polymerase gene mutations associated with resistance were determined by sequencing. RESULTS: Response to lamivudine in the sixth month was observed in 19/32 (59.4%) patients. With one exception, viral DNA results observed at this time were maintained. The YMDD mutation was detected in 12 nonresponder patients (9 YVDD, 2 YIDD, and 1 mixed population Y(V/I)DD), generally associated with the L528M mutation. Re-takeover by the wild type was observed 6 to 18 months after lamivudine withdrawal. Lamivudine response rates in noncirrhotic and cirrhotic patients were 9/18 (50%) and 10/14 (71.4%), respectively. HBeAg to anti-HBe seroconversion was found after different periods in all responder patients. Hepatitis B surface antigen (HBsAg) clearance and anti-HBs seroconversion were occasionally found. CONCLUSIONS: In nonresponder patients, resistant mutants appeared up to the second year of lamivudine therapy. In spite of the presence of resistant mutants, maintenance of therapy was usually associated with a lower viral load. In responder patients, maintenance of therapy was associated with continued absence of detectable HBV DNA in serum, as monitored by highly sensitive methods. No significant side effects caused by lamivudine were observed in our patients, even in those with liver cirrhosis.\n[Drug-Disease]: lamivudine - chronic hepatitis B" }, { "pmid": "11481167", "target": "[\"Span: aged 18-65 years | Label: Dosage\"]", "text": "[Title]: A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.\n[Abstract]: OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.\n[Drug-Disease]: clozapine - schizophrenia" }, { "pmid": "11481696", "target": "[\"Span: 10 mg | Label: Dosage\", \"Span: 20 mg | Label: Dosage\", \"Span: 40 mg | Label: Dosage\"]", "text": "[Title]: Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.\n[Abstract]: Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.\n[Drug-Disease]: idazoxan - dyskinetic" }, { "pmid": "11489769", "target": "[]", "text": "[Title]: Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II).\n[Abstract]: BACKGROUND: Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. METHODS AND RESULTS: Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. CONCLUSIONS: Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.\n[Drug-Disease]: aspirin - myocardial infarction" }, { "pmid": "11489769", "target": "[]", "text": "[Title]: Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II).\n[Abstract]: BACKGROUND: Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. METHODS AND RESULTS: Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. CONCLUSIONS: Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.\n[Drug-Disease]: Enoxaparin - myocardial infarction" }, { "pmid": "11491499", "target": "[\"Span: 20 mg daily | Label: Dosage\"]", "text": "[Title]: Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.\n[Abstract]: OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.\n[Drug-Disease]: Prednisolone - RA" }, { "pmid": "11491499", "target": "[\"Span: 20 mg daily | Label: Dosage\"]", "text": "[Title]: Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.\n[Abstract]: OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.\n[Drug-Disease]: Prednisolone - SLE" }, { "pmid": "11491499", "target": "[\"Span: 20 mg daily | Label: Dosage\"]", "text": "[Title]: Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.\n[Abstract]: OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.\n[Drug-Disease]: Prednisolone - systemic sclerosis" }, { "pmid": "11501851", "target": "[\"Span: 280-360 mg or more | Label: Dosage\"]", "text": "[Title]: From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.\n[Abstract]: BACKGROUND: Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required. PATIENTS AND METHODS: 130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards. RESULTS: The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study. CONCLUSION: Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.\n[Drug-Disease]: codeine - pain" }, { "pmid": "11501851", "target": "[\"Span: 25 microg/hour | Label: Dosage\"]", "text": "[Title]: From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.\n[Abstract]: BACKGROUND: Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required. PATIENTS AND METHODS: 130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards. RESULTS: The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study. CONCLUSION: Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.\n[Drug-Disease]: fentanyl - pain" }, { "pmid": "11501851", "target": "[\"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.\n[Abstract]: BACKGROUND: Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required. PATIENTS AND METHODS: 130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards. RESULTS: The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study. CONCLUSION: Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.\n[Drug-Disease]: morphine - pain" }, { "pmid": "11505079", "target": "[\"Span: children | Label: Age\", \"Span: 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) | Label: Dosage\"]", "text": "[Title]: Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia.\n[Abstract]: Forty-one consecutive children with acute lymphoblastic leukemia (ALL) received prophylaxis therapy with the low molecular weight heparin (LMWH) enoxaparin during L-asparaginase treatment. Enoxaparin was given every 24 h subcutaneously at a median dose of 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) starting at the first dose of L-asparaginase until 1 week after the last dose. Molecular analysis for thrombophilic polymorphisms documented prothrombin G20210A mutation in 3/27 (11%), homozygosity for MTHFR C677T mutation in 5/27 (18.5%, and heterozygosity for factor V Leiden mutation in 5/27 (18.5%) children. There were no thrombotic events during 76 courses of L-asparaginase in 41 patients who had received enoxaparin. One patient suffered brain infarct 7 days after enoxaparin was stopped. There were no bleeding episodes. In a historical control group of 50 ALL children who had not received prophylactic enoxaparin during L-asparaginase treatment, two had thromboembolisms (one deep vein thrombosis and one pulmonary embolism). Enoxaparin is safe and seems to be effective in prevention of thromboembolism in ALL patients during L-asparaginase therapy. This study provides pilot data for a future randomized trial of the use of LMWH during ALL therapy for the prevention of asparaginase-associated thrombotic events.\n[Drug-Disease]: Enoxaparin - acute lymphoblastic leukemia" }, { "pmid": "11510750", "target": "[\"Span: 62+/-4 years old | Label: Dosage\"]", "text": "[Title]: Cilnidipine is as effective as benazepril for control of blood pressure and proteinuria in hypertensive patients with benign nephrosclerosis.\n[Abstract]: To investigate the beneficial effects of cilnidipine, a calcium channel blocker that shows high selectivity for N-type receptors, on the progression of chronic renal insufficiency, we compared the efficacy of cilnidipine to that of benazepril, an angiotensin-converting enzyme (ACE) inhibitor with known renal protective effects, in a one-year trial evaluating hypertensive control, serum creatinine, and albuminuria in a cohort of patients. Given the seeming importance of the etiology of chronic renal insufficiency in determining drug efficacy, we limited our study to 20 patients with a single common condition, benign nephrosclerosis. The average age of the patients was 62+/-4 years old. The changes in systolic and diastolic blood pressure over the course of the study year revealed a similar reduction with cilnidipine and benazepril. Both cilnidipine and benazepril induced similar reductions in systolic and diastolic blood pressure over the course of the study year. The baseline levels of serum creatinine were 1.40+/-0.2 mg/dl and urinary excretion of albumin was 168+/-10 mg daily. The levels of serum creatinine were not significantly changed throughout the study in either group, although the levels of urinary excretion of albumin were significantly decreased in both groups. There were no significant differences in either of these values between the two groups. In conclusion, both cilnidipine and benazepril equally and effectively reduced blood pressure and albuminuria in hypertensive patients with benign nephrosclerosis in a one-year trial.\n[Drug-Disease]: benazepril - albuminuria" }, { "pmid": "11519776", "target": "[\"Span: 40 mg/d | Label: Dosage\"]", "text": "[Title]: Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.\n[Abstract]: BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.\n[Drug-Disease]: pantoprazole - esophagitis" }, { "pmid": "11519776", "target": "[\"Span: 20 mg/d | Label: Dosage\"]", "text": "[Title]: Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.\n[Abstract]: BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.\n[Drug-Disease]: omeprazole - esophagitis" }, { "pmid": "11519776", "target": "[\"Span: 30 mg/d | Label: Dosage\"]", "text": "[Title]: Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.\n[Abstract]: BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.\n[Drug-Disease]: lansoprazole - esophagitis" }, { "pmid": "11519776", "target": "[\"Span: 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07) | Label: Dosage\"]", "text": "[Title]: Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.\n[Abstract]: BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.\n[Drug-Disease]: rabeprazole - esophagitis" }, { "pmid": "11521799", "target": "[\"Span: mean age 53 years | Label: Age\", \"Span: 6000 MBq/m2 | Label: Dosage\"]", "text": "[Title]: The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study.\n[Abstract]: PURPOSE: The aim of this phase II study was to evaluate the tumour response of neuroendocrine tumours to targeted irradiation with the radiolabelled somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90Y-DOTATOC treatment on the malignant carcinoid syndrome and tumour-associated pain was investigated. PATIENTS AND METHODS: Forty-one patients (mean age 53 years) with neuroendocrine gastroenteropancreatic and bronchial tumours were included. Eighty-two percent of the patients had therapy resistant and progressive disease. The treatment consisted of four intravenous injections of a total of 6000 MBq/m2 90Y-DOTATOC, administered at intervals of six weeks. RESULTS: The overall response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of 41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of 41) and progressive disease (PD) in 15% (6 of 41). The median follow up was 15 months (range 1 month to 36 months). The median duration of response has not been reached at 26 months. The two-year survival time was 76 +/- 16%. Eighty-three percent of the patients suffering from the malignant carcinoid syndrome achieved a significant reduction of symptoms. The treatment was well tolerated. A reduction of pain score was observed in all patients (5 of 41) with morphine dependent tumour-associated pain. Side effects included grade III (NCIGC) pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III-IV renal toxicity was observed. CONCLUSION: Targeted radiotherapy with 90Y-DOTATOC is a novel, well-tolerated treatment for neuroendocrine tumours with a remarkable objective response rate, survival time, and symptomatic response.\n[Drug-Disease]: 90Y-DOTATOC - malignant carcinoid syndrome" }, { "pmid": "11521799", "target": "[\"Span: mean age 53 years | Label: Age\", \"Span: 6000 MBq/m2 | Label: Dosage\"]", "text": "[Title]: The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study.\n[Abstract]: PURPOSE: The aim of this phase II study was to evaluate the tumour response of neuroendocrine tumours to targeted irradiation with the radiolabelled somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90Y-DOTATOC treatment on the malignant carcinoid syndrome and tumour-associated pain was investigated. PATIENTS AND METHODS: Forty-one patients (mean age 53 years) with neuroendocrine gastroenteropancreatic and bronchial tumours were included. Eighty-two percent of the patients had therapy resistant and progressive disease. The treatment consisted of four intravenous injections of a total of 6000 MBq/m2 90Y-DOTATOC, administered at intervals of six weeks. RESULTS: The overall response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of 41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of 41) and progressive disease (PD) in 15% (6 of 41). The median follow up was 15 months (range 1 month to 36 months). The median duration of response has not been reached at 26 months. The two-year survival time was 76 +/- 16%. Eighty-three percent of the patients suffering from the malignant carcinoid syndrome achieved a significant reduction of symptoms. The treatment was well tolerated. A reduction of pain score was observed in all patients (5 of 41) with morphine dependent tumour-associated pain. Side effects included grade III (NCIGC) pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III-IV renal toxicity was observed. CONCLUSION: Targeted radiotherapy with 90Y-DOTATOC is a novel, well-tolerated treatment for neuroendocrine tumours with a remarkable objective response rate, survival time, and symptomatic response.\n[Drug-Disease]: 90Y-DOTATOC - neuroendocrine tumours" }, { "pmid": "11521799", "target": "[]", "text": "[Title]: The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study.\n[Abstract]: PURPOSE: The aim of this phase II study was to evaluate the tumour response of neuroendocrine tumours to targeted irradiation with the radiolabelled somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90Y-DOTATOC treatment on the malignant carcinoid syndrome and tumour-associated pain was investigated. PATIENTS AND METHODS: Forty-one patients (mean age 53 years) with neuroendocrine gastroenteropancreatic and bronchial tumours were included. Eighty-two percent of the patients had therapy resistant and progressive disease. The treatment consisted of four intravenous injections of a total of 6000 MBq/m2 90Y-DOTATOC, administered at intervals of six weeks. RESULTS: The overall response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of 41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of 41) and progressive disease (PD) in 15% (6 of 41). The median follow up was 15 months (range 1 month to 36 months). The median duration of response has not been reached at 26 months. The two-year survival time was 76 +/- 16%. Eighty-three percent of the patients suffering from the malignant carcinoid syndrome achieved a significant reduction of symptoms. The treatment was well tolerated. A reduction of pain score was observed in all patients (5 of 41) with morphine dependent tumour-associated pain. Side effects included grade III (NCIGC) pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III-IV renal toxicity was observed. CONCLUSION: Targeted radiotherapy with 90Y-DOTATOC is a novel, well-tolerated treatment for neuroendocrine tumours with a remarkable objective response rate, survival time, and symptomatic response.\n[Drug-Disease]: morphine - pain" }, { "pmid": "11526364", "target": "[]", "text": "[Title]: Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program.\n[Abstract]: BACKGROUND: Atrial fibrillation (AF) is present in a significant number of patients with congestive heart failure (CHF) caused by left ventricular dysfunction and is associated with significant morbidity and increased mortality rates. Thus it is necessary to establish therapy to improve the outcome in this high-risk population. METHODS: We conducted a retrospective analysis of data from the US Carvedilol Heart Failure Trials Program and identified patients with AF at the time of enrollment. In these trials, 1094 patients with at least 3 months of heart failure symptoms and an ejection fraction < or = 0.35 were randomly assigned to receive carvedilol or placebo in a double-blind, stratified program according to performance on an exercise test. RESULTS: One hundred thirty-six patients with concomitant AF and CHF were identified during the screening visit (84 assigned to carvedilol and 52 to placebo). Therapy with carvedilol resulted in a significant improvement in left ventricular ejection fraction (from 23% to 33% with carvedilol and from 24% to 27% with placebo, P =.001). The physician global assessment improved in a greater number of patients treated with carvedilol than in those treated with placebo (71% vs 48%, P =.025). A trend toward a reduction in the combined end point of death or CHF hospitalization was also observed (19% in patients treated with placebo and 7% in patients on carvedilol; relative risk, 0.35; 95% confidence interval, 0.12, 1.02; P =.055). CONCLUSIONS: In patients with AF complicating CHF, carvedilol significantly improves left ventricular ejection fraction and physician global assessment and probably reduces the combined end point of CHF hospitalizations or death.\n[Drug-Disease]: carvedilol - AF" }, { "pmid": "11526364", "target": "[]", "text": "[Title]: Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program.\n[Abstract]: BACKGROUND: Atrial fibrillation (AF) is present in a significant number of patients with congestive heart failure (CHF) caused by left ventricular dysfunction and is associated with significant morbidity and increased mortality rates. Thus it is necessary to establish therapy to improve the outcome in this high-risk population. METHODS: We conducted a retrospective analysis of data from the US Carvedilol Heart Failure Trials Program and identified patients with AF at the time of enrollment. In these trials, 1094 patients with at least 3 months of heart failure symptoms and an ejection fraction < or = 0.35 were randomly assigned to receive carvedilol or placebo in a double-blind, stratified program according to performance on an exercise test. RESULTS: One hundred thirty-six patients with concomitant AF and CHF were identified during the screening visit (84 assigned to carvedilol and 52 to placebo). Therapy with carvedilol resulted in a significant improvement in left ventricular ejection fraction (from 23% to 33% with carvedilol and from 24% to 27% with placebo, P =.001). The physician global assessment improved in a greater number of patients treated with carvedilol than in those treated with placebo (71% vs 48%, P =.025). A trend toward a reduction in the combined end point of death or CHF hospitalization was also observed (19% in patients treated with placebo and 7% in patients on carvedilol; relative risk, 0.35; 95% confidence interval, 0.12, 1.02; P =.055). CONCLUSIONS: In patients with AF complicating CHF, carvedilol significantly improves left ventricular ejection fraction and physician global assessment and probably reduces the combined end point of CHF hospitalizations or death.\n[Drug-Disease]: carvedilol - CHF" }, { "pmid": "11527250", "target": "[\"Span: 450 mg/day | Label: Dosage\"]", "text": "[Title]: Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.\n[Abstract]: BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.\n[Drug-Disease]: Pranlukast - asthma" }, { "pmid": "11527250", "target": "[\"Span: 1,600 microg/day | Label: Dosage\", \"Span: 800 microg/day | Label: Dosage\"]", "text": "[Title]: Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.\n[Abstract]: BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.\n[Drug-Disease]: BDP - asthma" }, { "pmid": "11528156", "target": "[\"Span: 1.0-2.0 g/day | Label: Dosage\"]", "text": "[Title]: Mycophenolate mofetil in the therapy of severe myasthenia gravis.\n[Abstract]: Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.\n[Drug-Disease]: Mycophenolate mofetil - myasthenia gravis" }, { "pmid": "11528249", "target": "[\"Span: 300-400 mg/m(2) | Label: Dosage\"]", "text": "[Title]: A phase I study of raltitrexed (Tomudex) combined with carmofur in metastatic colorectal cancer.\n[Abstract]: OBJECTIVES: The aim of the study was to define the maximum tolerated dose (MTD) of the combination of raltitrexed plus carmofur, and to evaluate the tolerability and efficacy of this combination in metastatic colorectal cancer. METHODS: Twenty-eight patients (23 receiving first-line therapy, 5 receiving second-line therapy) entered the study; 16 were chemonaive. Raltitrexed (Tomudex) 1.5-3.0 mg/m(2) was given as a 15- to 30-min intravenous infusion on day 1 of a 21-day cycle followed by carmofur 300-400 mg/m(2) orally 3 times daily on days 2-14. Therapy was given until disease progression or dose-limiting toxicity (DLT) occurred. RESULTS: A total of 170 cycles of therapy were administered. The MTD was reached at the raltitrexed dose of 3.0 mg/m(2) and the carmofur dose of 400 mg/m(2). DLTs included grade 3-4 diarrhea, fatigue, anorexia, mucositis, anemia, thrombocytopenia, neutropenia, neurological symptoms and febrile neutropenia. Eleven of the 22 evaluable first-line patients achieved a partial response (response rate 50%, 95% confidence interval 29-71%), 8 had stable disease and 3 had disease progression. One of the 5 patients who received second-line therapy responded. CONCLUSIONS: The recommended dose of this combination therapy for further evaluation is raltitrexed 3.0 mg/m(2) plus carmofur 300 mg/m(2). This combination has unique but manageable toxicity and promising efficacy in metastatic colorectal cancer.\n[Drug-Disease]: carmofur - colorectal cancer" }, { "pmid": "11528249", "target": "[\"Span: 1.5-3.0 mg/m(2) | Label: Dosage\"]", "text": "[Title]: A phase I study of raltitrexed (Tomudex) combined with carmofur in metastatic colorectal cancer.\n[Abstract]: OBJECTIVES: The aim of the study was to define the maximum tolerated dose (MTD) of the combination of raltitrexed plus carmofur, and to evaluate the tolerability and efficacy of this combination in metastatic colorectal cancer. METHODS: Twenty-eight patients (23 receiving first-line therapy, 5 receiving second-line therapy) entered the study; 16 were chemonaive. Raltitrexed (Tomudex) 1.5-3.0 mg/m(2) was given as a 15- to 30-min intravenous infusion on day 1 of a 21-day cycle followed by carmofur 300-400 mg/m(2) orally 3 times daily on days 2-14. Therapy was given until disease progression or dose-limiting toxicity (DLT) occurred. RESULTS: A total of 170 cycles of therapy were administered. The MTD was reached at the raltitrexed dose of 3.0 mg/m(2) and the carmofur dose of 400 mg/m(2). DLTs included grade 3-4 diarrhea, fatigue, anorexia, mucositis, anemia, thrombocytopenia, neutropenia, neurological symptoms and febrile neutropenia. Eleven of the 22 evaluable first-line patients achieved a partial response (response rate 50%, 95% confidence interval 29-71%), 8 had stable disease and 3 had disease progression. One of the 5 patients who received second-line therapy responded. CONCLUSIONS: The recommended dose of this combination therapy for further evaluation is raltitrexed 3.0 mg/m(2) plus carmofur 300 mg/m(2). This combination has unique but manageable toxicity and promising efficacy in metastatic colorectal cancer.\n[Drug-Disease]: raltitrexed - colorectal cancer" }, { "pmid": "11529341", "target": "[\"Span: 6 mg | Label: Dosage\"]", "text": "[Title]: Hypotension in spinal anesthesia for cesarean section: a comparison of 0.5% hyperbaric bupivacaine and 5% hyperbaric lidocaine.\n[Abstract]: Hypotension is a common side effect associated with spinal anesthesia. However, there is no previous report comparing the incidence of hypotension between two commonly used local anesthetic agents, bupivacaine and lidocaine. The objective of this study was to compare the incidence of spinal hypotension induced by bupivacaine and lidocaine in parturients undergoing cesarean section. A double blind, randomized controlled trial was conducted in 142 parturients scheduled for cesarean section. The patients were randomized into two groups, 71 each. After receiving 10 ml/kg of normal saline intravenously, patients in the first group were given 2.2 ml of 0.5 per cent hyperbaric bupivacaine plus 0.2 mg of morphine as a spinal anesthetic agent while in the other group, 1.2 ml of 5 per cent hyperbaric lidocaine plus 0.1 mg of epinephrine and 0.2 mg of morphine were administered. Hypotension, defined as 30 per cent less systolic blood pressure than baseline value, was recorded and the patients were treated with 6 mg of ephedrine every 2 minutes until normotension was achieved. There was no statistically significant difference of incidence, onset, duration, and severity of hypotension between the two groups (p > 0.05). The amount of ephedrine used in both groups was also not significantly different. Late onset hypotension occurred after delivery (20-22 minutes after spinal anesthesia was performed) in 17 patients (12%). As such, the rate of hypotension in lidocaine group was comparable to bupivacaine group. Delayed onset hypotension occurring after delivery was noted and these events have never been described. However, the mechanism of late onset hypotension remains unidentified. Thus, bupivacaine and lidocaine can be used interchangeably for spinal anesthesia for elective cesarean section without significant difference in the incidence of hypotension.\n[Drug-Disease]: ephedrine - hypotension" }, { "pmid": "11531681", "target": "[\"Span: 5 ml 1% solution | Label: Dosage\"]", "text": "[Title]: Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine.\n[Abstract]: In a randomised, controlled, double-blinded trial to study the effect of ondansetron pretreatment on the pain produced after intravenous injection of rocuronium and propofol in comparison with lidocaine, 60 patients were randomly assigned to one of three groups. Group 1 received 5 ml of intravenous 0.9% sodium chloride solution pretreatment, group 2 received ondansetron 4 mg (2 mg.ml-1 solution) diluted into a 5-ml solution, and group 3 received 50 mg lidocaine (5 ml 1% solution); this was followed 1 min later by rocuronium and propofol. Pain was reduced significantly in the ondansetron and lidocaine groups (p < 0.0001) compared with placebo, and significantly better with lidocaine than with ondansetron (p = 0.02). We conclude that ondansetron is effective in relieving the pain of rocuronium but is not as effective as lidocaine.\n[Drug-Disease]: lidocaine - pain" }, { "pmid": "11531681", "target": "[\"Span: 4 mg (2 mg.ml-1 solution) | Label: Dosage\"]", "text": "[Title]: Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine.\n[Abstract]: In a randomised, controlled, double-blinded trial to study the effect of ondansetron pretreatment on the pain produced after intravenous injection of rocuronium and propofol in comparison with lidocaine, 60 patients were randomly assigned to one of three groups. Group 1 received 5 ml of intravenous 0.9% sodium chloride solution pretreatment, group 2 received ondansetron 4 mg (2 mg.ml-1 solution) diluted into a 5-ml solution, and group 3 received 50 mg lidocaine (5 ml 1% solution); this was followed 1 min later by rocuronium and propofol. Pain was reduced significantly in the ondansetron and lidocaine groups (p < 0.0001) compared with placebo, and significantly better with lidocaine than with ondansetron (p = 0.02). We conclude that ondansetron is effective in relieving the pain of rocuronium but is not as effective as lidocaine.\n[Drug-Disease]: ondansetron - pain" }, { "pmid": "11532201", "target": "[]", "text": "[Title]: Digitoxin medication and cancer; case control and internal dose-response studies.\n[Abstract]: BACKGROUND: Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. METHODS: Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. RESULTS: The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. CONCLUSION: Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease. These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.\n[Drug-Disease]: digitoxin - cardiac disease" }, { "pmid": "11534318", "target": "[\"Span: 0.65% | Label: Dosage\"]", "text": "[Title]: [Clinical effectiveness and tolerance of climbazole containing dandruff shampoo in patients with seborrheic scalp eczema].\n[Abstract]: Pityrosporum ovale appears to play an important role in the pathogenesis of dandruff as a symptom of seborrheic dermatitis. Climbazole is an antimycotic agent with a high in vitro and in vivo efficacy against P. ovale. In the presented work we investigated the efficacy and safety of a climbazole 0.65% shampoo on seborrheic dermatitis of 30 volunteers. Subjects were diagnosed as having moderate to severe seborrheic dermatitis of the scalp. After a 1-week washout and a 4-week treatment the clinical evaluation showed a successful reduction of dandruff, skin redness and itching in 80% of the volunteers and a mild improvement in 20% of the volunteers. The cosmetic acceptability was very good by the majority. It is concluded that the formulation tested is effective in the treatment of moderate to severe dandruff.\n[Drug-Disease]: climbazole - itching" }, { "pmid": "11534318", "target": "[\"Span: 0.65% | Label: Dosage\"]", "text": "[Title]: [Clinical effectiveness and tolerance of climbazole containing dandruff shampoo in patients with seborrheic scalp eczema].\n[Abstract]: Pityrosporum ovale appears to play an important role in the pathogenesis of dandruff as a symptom of seborrheic dermatitis. Climbazole is an antimycotic agent with a high in vitro and in vivo efficacy against P. ovale. In the presented work we investigated the efficacy and safety of a climbazole 0.65% shampoo on seborrheic dermatitis of 30 volunteers. Subjects were diagnosed as having moderate to severe seborrheic dermatitis of the scalp. After a 1-week washout and a 4-week treatment the clinical evaluation showed a successful reduction of dandruff, skin redness and itching in 80% of the volunteers and a mild improvement in 20% of the volunteers. The cosmetic acceptability was very good by the majority. It is concluded that the formulation tested is effective in the treatment of moderate to severe dandruff.\n[Drug-Disease]: climbazole - seborrheic dermatitis of the scalp" }, { "pmid": "11545549", "target": "[\"Span: 400 mg/day | Label: Dosage\"]", "text": "[Title]: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.\n[Abstract]: OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.\n[Drug-Disease]: Bezafibrate - Hypertriglyceridaemia" }, { "pmid": "11545549", "target": "[]", "text": "[Title]: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.\n[Abstract]: OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.\n[Drug-Disease]: saquinavir - HIV-infected" }, { "pmid": "11545549", "target": "[]", "text": "[Title]: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.\n[Abstract]: OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.\n[Drug-Disease]: ritonavir - HIV-infected" }, { "pmid": "11545549", "target": "[]", "text": "[Title]: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.\n[Abstract]: OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.\n[Drug-Disease]: indinavir - HIV-infected" }, { "pmid": "11549407", "target": "[]", "text": "[Title]: A double-blind placebo-controlled crossover study of phenytoin in individuals with impulsive aggression.\n[Abstract]: The present study examines the behavioral and psychophysiological effects of phenytoin (PHT) in individuals who display impulsive-aggressive outbursts. In a double-blind placebo-controlled crossover design, individuals meeting previously established criteria for impulsive aggression were administered PHT and placebo during separate 6-week conditions. The efficacy measures used were the Overt Aggression Scale (OAS) and the Profile of Mood States (POMS). Psychophysiological measures (evoked potentials) were taken at baseline and at the end of each 6-week condition. Photic stimulation was used to evoke the mid-latency P1-N1-P2 waveform complex. Analysis indicated a significant decrease in the frequency of impulsive-aggressive outbursts during PHT administration compared to baseline and placebo. Analysis of the psychophysiological data showed significantly increased P1 amplitude and significantly longer N1 latency during PHT administration. In addition, a reduction in N1 amplitude during PHT administration was also suggested. These findings indicate reparation of physiological abnormalities previously observed in impulsive-aggressive individuals and imply more efficient sensory processing and effective orienting of attention. Taken together, these results provide insight as to the physiological mechanisms by which PHT serves to ameliorate impulsive-aggressive behavior.\n[Drug-Disease]: PHT - impulsive-aggressive behavior" }, { "pmid": "11551579", "target": "[\"Span: 10 mg once-daily | Label: Dosage\"]", "text": "[Title]: Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.\n[Abstract]: BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.\n[Drug-Disease]: Adefovir dipivoxil - HIV-1/HBV co-infected" }, { "pmid": "11551579", "target": "[\"Span: 150 mg twice daily | Label: Dosage\"]", "text": "[Title]: Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.\n[Abstract]: BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.\n[Drug-Disease]: lamivudine - HIV-1/HBV co-infected" }, { "pmid": "11551579", "target": "[]", "text": "[Title]: Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.\n[Abstract]: BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.\n[Drug-Disease]: lamivudine - HIV-1-infected" }, { "pmid": "11552226", "target": "[]", "text": "[Title]: Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.\n[Abstract]: Investigation of the combination of the taxanes with doxorubicin in the treatment of breast cancer has logically progressed, with the ultimate goal of identifying a safe and effective regimen for use in the adjuvant setting. Initial phase II findings of the concurrent doxorubicin/paclitaxel combination resulted in substantial response rates, but at a high cost. A much higher percentage of patients than expected developed anthracycline-induced cardiomyopathy. Subsequent phase II and phase III trials have determined administration schedules of doxorubicin/paclitaxel that reduce the risk for cardiotoxicity. However, the overall response rate is only modestly improved over sequential single-agent therapy or standard doxorubicin-containing combination therapy. The lack of cardiotoxicity with docetaxel, its high antitumor activity, and its linear pharmacokinetics have made it an attractive taxane for combination with doxorubicin. In addition, it is easily administered in the outpatient setting. Phase I/II trials of the combination of doxorubicin/docetaxel resulted in high response rates with a lack of adverse modification of anthracycline-induced cardiomyopathy. These findings have been confirmed in a large phase III randomized trial where overall response rates and time to disease progression were significantly improved, but the incidence of cardiomyopathy was not different for the doxorubicin/docetaxel versus doxorubicin/cyclophosphamide (AC) regimen. Ongoing studies are underway to assess the role of the doxorubicin/docetaxel combination in the adjuvant setting as primary chemotherapy in the neoadjuvant setting. It is here that the most benefit on survival of breast cancer patients is likely to be shown. At the same time, it is in the adjuvant setting where the absence of potentially late cardiac and other toxicities must be assured.\n[Drug-Disease]: docetaxel - breast cancer" }, { "pmid": "11552226", "target": "[]", "text": "[Title]: Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.\n[Abstract]: Investigation of the combination of the taxanes with doxorubicin in the treatment of breast cancer has logically progressed, with the ultimate goal of identifying a safe and effective regimen for use in the adjuvant setting. Initial phase II findings of the concurrent doxorubicin/paclitaxel combination resulted in substantial response rates, but at a high cost. A much higher percentage of patients than expected developed anthracycline-induced cardiomyopathy. Subsequent phase II and phase III trials have determined administration schedules of doxorubicin/paclitaxel that reduce the risk for cardiotoxicity. However, the overall response rate is only modestly improved over sequential single-agent therapy or standard doxorubicin-containing combination therapy. The lack of cardiotoxicity with docetaxel, its high antitumor activity, and its linear pharmacokinetics have made it an attractive taxane for combination with doxorubicin. In addition, it is easily administered in the outpatient setting. Phase I/II trials of the combination of doxorubicin/docetaxel resulted in high response rates with a lack of adverse modification of anthracycline-induced cardiomyopathy. These findings have been confirmed in a large phase III randomized trial where overall response rates and time to disease progression were significantly improved, but the incidence of cardiomyopathy was not different for the doxorubicin/docetaxel versus doxorubicin/cyclophosphamide (AC) regimen. Ongoing studies are underway to assess the role of the doxorubicin/docetaxel combination in the adjuvant setting as primary chemotherapy in the neoadjuvant setting. It is here that the most benefit on survival of breast cancer patients is likely to be shown. At the same time, it is in the adjuvant setting where the absence of potentially late cardiac and other toxicities must be assured.\n[Drug-Disease]: doxorubicin - breast cancer" }, { "pmid": "11552226", "target": "[]", "text": "[Title]: Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.\n[Abstract]: Investigation of the combination of the taxanes with doxorubicin in the treatment of breast cancer has logically progressed, with the ultimate goal of identifying a safe and effective regimen for use in the adjuvant setting. Initial phase II findings of the concurrent doxorubicin/paclitaxel combination resulted in substantial response rates, but at a high cost. A much higher percentage of patients than expected developed anthracycline-induced cardiomyopathy. Subsequent phase II and phase III trials have determined administration schedules of doxorubicin/paclitaxel that reduce the risk for cardiotoxicity. However, the overall response rate is only modestly improved over sequential single-agent therapy or standard doxorubicin-containing combination therapy. The lack of cardiotoxicity with docetaxel, its high antitumor activity, and its linear pharmacokinetics have made it an attractive taxane for combination with doxorubicin. In addition, it is easily administered in the outpatient setting. Phase I/II trials of the combination of doxorubicin/docetaxel resulted in high response rates with a lack of adverse modification of anthracycline-induced cardiomyopathy. These findings have been confirmed in a large phase III randomized trial where overall response rates and time to disease progression were significantly improved, but the incidence of cardiomyopathy was not different for the doxorubicin/docetaxel versus doxorubicin/cyclophosphamide (AC) regimen. Ongoing studies are underway to assess the role of the doxorubicin/docetaxel combination in the adjuvant setting as primary chemotherapy in the neoadjuvant setting. It is here that the most benefit on survival of breast cancer patients is likely to be shown. At the same time, it is in the adjuvant setting where the absence of potentially late cardiac and other toxicities must be assured.\n[Drug-Disease]: paclitaxel - breast cancer" }, { "pmid": "11555353", "target": "[\"Span: 2 mg/day | Label: Dosage\"]", "text": "[Title]: Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment.\n[Abstract]: We demonstrated the effect of clonazepam (2 mg/day) on Meige syndrome in two schizophrenic patients under continuous treatment with antipsychotic drugs, and changes in the plasma levels of gamma-aminobutyric acid (GABA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in these cases. The plasma levels of HVA and MHPG during treatment with clonazepam were decreased in the responder, while not changed in the non-responder to clonazepam. A difference between the responder and the non-responder was not found in the plasma GABA levels. These results suggest that hyperactivities of the central dopaminergic and noradrenergic neurones are involved in the pathophysiology of Meige syndrome.\n[Drug-Disease]: clonazepam - Meige syndrome" }, { "pmid": "11555383", "target": "[]", "text": "[Title]: Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.\n[Abstract]: OBJECTIVE: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD. METHODOLOGY: Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. RESULTS: It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. CONCLUSIONS: It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.\n[Drug-Disease]: Fluticasone propionate - asthma" }, { "pmid": "11555383", "target": "[]", "text": "[Title]: Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.\n[Abstract]: OBJECTIVE: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD. METHODOLOGY: Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. RESULTS: It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. CONCLUSIONS: It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.\n[Drug-Disease]: BDP - asthma" }, { "pmid": "11555383", "target": "[]", "text": "[Title]: Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.\n[Abstract]: OBJECTIVE: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD. METHODOLOGY: Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. RESULTS: It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. CONCLUSIONS: It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.\n[Drug-Disease]: BUD - asthma" }, { "pmid": "11558979", "target": "[\"Span: 13 females and four males | Label: Gender\", \"Span: age 32-88 years | Label: Age\", \"Span: 0.4 mg/kg | Label: Dosage\", \"Span: 4 mg/kg | Label: Dosage\"]", "text": "[Title]: Interindividual differences in the analgesic response to ketamine in chronic orofacial pain.\n[Abstract]: The analgesic effect of the N-methyl-D-aspartate (NMDA) receptor blocker ketamine in 17 patients (13 females and four males, age 32-88 years) who had suffered neuropathic orofacial pain for time periods ranging from 6 months to 28 years was examined. The patients were given an i.m. test-dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam. Four patients did not experience any analgesic effect of the i.m. test dose. The remaining 13 patients experienced an analgesic effect which lasted for less than 1 h (transient effect) in seven and for several hours (long-term effect) in six. One week later they were given 4 mg/kg ketamine to be taken orally in combination with a hypnotic drug for three consecutive nights. All patients who reported a long-term analgesic effect after i.m. ketamine also reported reduced pain intensity on days after taking ketamine at night. The findings of this open study are in accord with the results from a previous double-blind randomized investigation. In order to evaluate the role of age and pain duration for the analgesic effect of ketamine, we pooled the data from the two studies and performed a correlation analysis of 43 patients. We found a positive correlation between a long pain-history and lack of analgesic effect and also between a short pain-history and a long-term analgesic effect of low-dose ketamine. The apparent relationship between patient age and ketamine response was, however, not statistically significant. Further, patients with pain following a nerve lesion and patients without a known lesion of peripheral nerves were equally distributed between the three response groups. These results indicate that pain mechanisms are subject to alterations with time and that these alterations involve transition from NMDA to non-NMDA receptor mediated transmission in central pain pathways.\n[Drug-Disease]: ketamine - pain" }, { "pmid": "11558979", "target": "[]", "text": "[Title]: Interindividual differences in the analgesic response to ketamine in chronic orofacial pain.\n[Abstract]: The analgesic effect of the N-methyl-D-aspartate (NMDA) receptor blocker ketamine in 17 patients (13 females and four males, age 32-88 years) who had suffered neuropathic orofacial pain for time periods ranging from 6 months to 28 years was examined. The patients were given an i.m. test-dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam. Four patients did not experience any analgesic effect of the i.m. test dose. The remaining 13 patients experienced an analgesic effect which lasted for less than 1 h (transient effect) in seven and for several hours (long-term effect) in six. One week later they were given 4 mg/kg ketamine to be taken orally in combination with a hypnotic drug for three consecutive nights. All patients who reported a long-term analgesic effect after i.m. ketamine also reported reduced pain intensity on days after taking ketamine at night. The findings of this open study are in accord with the results from a previous double-blind randomized investigation. In order to evaluate the role of age and pain duration for the analgesic effect of ketamine, we pooled the data from the two studies and performed a correlation analysis of 43 patients. We found a positive correlation between a long pain-history and lack of analgesic effect and also between a short pain-history and a long-term analgesic effect of low-dose ketamine. The apparent relationship between patient age and ketamine response was, however, not statistically significant. Further, patients with pain following a nerve lesion and patients without a known lesion of peripheral nerves were equally distributed between the three response groups. These results indicate that pain mechanisms are subject to alterations with time and that these alterations involve transition from NMDA to non-NMDA receptor mediated transmission in central pain pathways.\n[Drug-Disease]: midazolam - pain" }, { "pmid": "11559723", "target": "[]", "text": "[Title]: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.\n[Abstract]: PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.\n[Drug-Disease]: ATO - APL" }, { "pmid": "11559723", "target": "[]", "text": "[Title]: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.\n[Abstract]: PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.\n[Drug-Disease]: dexamethasone - APL" }, { "pmid": "11559968", "target": "[\"Span: 4 to 14 years old | Label: Age\"]", "text": "[Title]: A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.\n[Abstract]: Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.\n[Drug-Disease]: fluticasone propionate - asthma" }, { "pmid": "11559968", "target": "[\"Span: 4 to 14 years old | Label: Age\"]", "text": "[Title]: A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.\n[Abstract]: Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.\n[Drug-Disease]: beclomethasone dipropionate - asthma" }, { "pmid": "11560200", "target": "[]", "text": "[Title]: A prospective and retrospective analysis of the nephrotoxicity and efficacy of lipid-based amphotericin B formulations.\n[Abstract]: STUDY OBJECTIVE: To determine the usage patterns of the lipid-based amphotericin B formulations at our institution and to compare the observed nephrotoxicity and efficacy of these formulations. DESIGN: Prospective and retrospective observational study SETTING: Urban 350-bed teaching hospital. PATIENTS: Sixty-seven nonhemodialysis patients who were prescribed greater than 3 days of amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB) from 1996-1999. MEASUREMENTS AND RESULTS: Forty-six patients received ABLC and 21 received L-AmB. Oncology patients accounted for most prescriptions of both formulations. Amphotericin B lipid complex most frequently was prescribed for treatment of documented fungal infections (50%), followed by treatment of neutropenic fever (33%). Liposomal amphotericin B most frequently was prescribed for treatment of neutropenic fever (62%), followed by treatment of documented fungal infections (29%). Seventy-eight percent of patients treated with ABLC and 90% of those who received L-AmB were started on the lipid-based formulation due to being refractory or intolerant to prior antifungal therapy. Two (4.4%) patients receiving ABLC and four (19%) patients receiving L-AmB experienced nephrotoxicity at the end of therapy (NS). Of the patients with a documented fungal infection, 20 out of 23 (87%) of those treated with ABLC and 4 out of 5 (80%) of those treated with L-AmB had a complete or partial response to therapy (NS). One patient with febrile neutropenia had a breakthrough fungal infection while receiving L-AmB. CONCLUSION: No significant differences in nephrotoxicity or efficacy were found between ABLC and L-AmB. Until further studies indicate clinically significant differences in nephrotoxicity between the two liposomal amphotericin B formulations, it is recommended that economics continue to be the major determinant for product selection.\n[Drug-Disease]: L-AmB - fungal infection" }, { "pmid": "11561935", "target": "[\"Span: 4.7+/-2.5 mg/day | Label: Dosage\"]", "text": "[Title]: Efficacy and safety of risperidone in the treatment of schizoaffective disorder: initial results from a large, multicenter surveillance study. Group for the Study of Risperidone in Affective Disorders (GSRAD).\n[Abstract]: BACKGROUND: An adequate therapy for psychotic disorders needs to be effective against mood as well as psychotic symptoms. Analyses of data from clinical trials of risperidone in schizophrenia and small open-label studies in mania suggest that risperidone may have this broad efficacy profile. We present data on a 6-week trial of risperidone for the treatment of schizoaffective disorder that was part of a larger, 6-month surveillance study of patients with affective disorders. METHOD: One hundred two patients suffering from schizoaffective disorder (DSM-IV or ICD-10) entered the trial. Inclusion criteria consisted of a current DSM-IV diagnosis of schizoaffective disorder, bipolar type; DSM-IV manic or mixed psychotic episode; and a Young Mania Rating Scale (YMRS) score > 7 for a mixed episode (> 20 for a manic episode). Assessments included the YMRS, the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), the 4-item Clinical Global Impressions (CGI) scale, and the UKU Side Effect Rating Scale subscale for neurologic side effects. For patients entering the study, open-label risperidone therapy was added to their existing regimens of mood-stabilizing treatments. Other antipsychotic drugs were not allowed. RESULTS: Ninety-five patients completed the 6-week trial. At week 6, the mean +/- SD dose of risperidone was 4.7+/-2.5 mg/day. The mean scores on the assessment scales at baseline and week 6 (unless otherwise stated) were as follows: YMRS, 22.7 and 4.7, an improvement of 18.0 points (p < .0001); PANSS (at baseline and week 4), 74.1 and 54.2, an improvement of 19.9 points (p < .0001); HAM-D, 14.0 and 7.4, an improvement of 6.6 points (p < .0001); CGI (at baseline and week 4), 2.6 and 1.7, an improvement of 0.9 points (p < .0001). At week 4, most patients had shown improvement in symptom severity, and 9.3% were completely symptom-free. There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms as measured by the UKU. Risperidone was well tolerated; side effects were few and generally mild. CONCLUSION: The results to date with risperidone indicate that it may have both antipsychotic and mood-stabilizing properties. Despite the limitations of the open-label design, the results indicate that risperidone is a safe and effective therapy in combination with mood-stabilizers for the treatment of patients with manic, hypomanic, and depressive symptoms of mixed episodes in schizoaffective disorder, bipolar type.\n[Drug-Disease]: risperidone - bipolar type" }, { "pmid": "11570617", "target": "[\"Span: 20 mg twice daily for 1 week | Label: Dosage\"]", "text": "[Title]: Effects of zafirlukast upon clinical, physiologic, and inflammatory responses to natural cat allergen exposure.\n[Abstract]: BACKGROUND: Leukotriene receptor antagonists have been shown to attenuate physiologic changes in the upper and lower airways induced by allergen challenge. However, it is unknown whether these drugs modulate airway inflammation after exposure to allergen in a natural setting. OBJECTIVE: To determine the effects of the oral leukotriene receptor antagonist zafirlukast upon symptoms, changes in pulmonary function, and indices of inflammation in the upper and lower airways induced by natural exposure to cats. METHODS: Zafirlukast, 20 mg twice daily, or placebo was administered to 18 cat-allergic asthmatic patients in this randomized, double-blind, crossover study. Cat room challenges were performed after a 1-week period of each treatment. Upper and lower airway symptoms were measured and spirometry performed before and at regular intervals during each challenge. Nasal lavage and sputum induction were performed 24 hours before and after each challenge. RESULTS: Zafirlukast significantly improved the prechallenge baseline FEV1 (P = 0.001) and attenuated the decrease in FEV1 induced by cat challenge (P = 0.019). Zafirlukast also significantly reduced lower airway symptoms associated with cat challenge (P = 0.005) but had no effects on nasal symptoms. Although zafirlukast did not significantly differ from placebo in its effects on sputum inflammatory cells or eosinophil cationic protein, it significantly reduced the absolute counts of total white cells, lymphocytes, neutrophils, and basophils in nasal lavage fluid. CONCLUSIONS: Zafirlukast, 20 mg twice daily for 1 week, demonstrated a significant protective effect on symptoms of asthma and alterations in pulmonary function induced by natural cat exposure, whereas nasal symptoms and markers of sputum inflammation were not affected by the medication.\n[Drug-Disease]: Zafirlukast - asthma" }, { "pmid": "11573599", "target": "[\"Span: Female | Label: Gender\", \"Span: 5.5 microg kg(-1) | Label: Dosage\"]", "text": "[Title]: Orally administered clonidine significantly reduces pain during injection of propofol.\n[Abstract]: We examined the analgesic effects of orally administered clonidine on pain induced by injection of propofol (Diprivan; 2,6-diisopropyl phenol). Female patients (n=81) were randomly allocated to one of two groups: oral clonidine (5.5 microg kg(-1)) followed by i.v. propofol and a control group given placebo followed by i.v. propofol. The median pain score in the group receiving clonidine, using a four-point scale (0=no pain, 1=minimal pain, 2=moderate pain, 3=severe pain) was 1 (0-2), significantly lower than in the control group [2 (1-3), median (25-75 percentiles), P<0.001].\n[Drug-Disease]: clonidine - pain" }, { "pmid": "11576036", "target": "[]", "text": "[Title]: Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.\n[Abstract]: BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.\n[Drug-Disease]: clozapine - schizophrenia" }, { "pmid": "11576036", "target": "[]", "text": "[Title]: Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.\n[Abstract]: BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.\n[Drug-Disease]: haloperidol - schizophrenia" }, { "pmid": "11576197", "target": "[\"Span: 10-mg | Label: Dosage\"]", "text": "[Title]: Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine.\n[Abstract]: OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.\n[Drug-Disease]: rizatriptan - migraine" }, { "pmid": "11576197", "target": "[\"Span: 50-mg | Label: Dosage\"]", "text": "[Title]: Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine.\n[Abstract]: OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.\n[Drug-Disease]: sumatriptan - migraine" }, { "pmid": "11578682", "target": "[\"Span: 50 microg/day | Label: Dosage\", \"Span: male | Label: Gender\"]", "text": "[Title]: Effect of ethinyl estradiol on the panic response to the panicogenic agent pentagastrin.\n[Abstract]: BACKGROUND: Panic disorder (PD) symptomatology has been reported to be altered by hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch. Gen. Psychiatry, 39 (1982) 701-703; Am. J. Psychiatry, 143 (1986) 508-510] have suggested that the increased cardiovascular risk associated with PD is significantly greater in males, alluding to a potential cardioprotective effect of female hormones in the context of panic attacks. In the present study, we were, therefore, interested in elucidating the role of estrogen in modulating the behavioural and cardiovascular responses induced by the panicogenic agent pentagastrin, a cholecystokinin-B (CCK(B)) receptor agonist. METHODS: A double-blind cross-over placebo-controlled design with randomization of the order of a 3-day pretreatment of ethinyl estradiol (EE) (50 microg/day) or placebo was used to assess the effect of a 30-microg i.v. bolus injection of pentagastrin on panic symptom intensity and on increases in heart rate (DeltaHR), systolic (DeltaSBP) and diastolic (DeltaDBP) blood pressure following each pretreatment. Subjects were 9 male healthy controls and 11 male PD patients. RESULTS: EE pretreatment did not significantly reduce the pentagastrin-induced panic symptom scale (PSS) scores and had no effect on DeltaDBP or DeltaSBP. EE did, however, attenuate the pentagastrin-induced increase in HR in both PD patients and healthy controls. LIMITATIONS: Only male subjects were included in the present study; however, we are currently investigating the influence of female gonadal hormones on the panic response to pentagastrin in female PD patients and healthy controls. CONCLUSION: Our results suggest that estrogens may display cardioprotective effects in the context of panic attacks.\n[Drug-Disease]: ethinyl estradiol - panic attacks" }, { "pmid": "11579891", "target": "[\"Span: children | Label: Age\", \"Span: 10 mg/kg | Label: Dosage\"]", "text": "[Title]: A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.\n[Abstract]: Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.\n[Drug-Disease]: PG - falciparum infection" }, { "pmid": "11579891", "target": "[\"Span: children | Label: Age\", \"Span: 2.5 mg/kg | Label: Dosage\"]", "text": "[Title]: A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.\n[Abstract]: Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.\n[Drug-Disease]: DS - falciparum infection" }, { "pmid": "11579891", "target": "[\"Span: children | Label: Age\", \"Span: 1.25 mg/kg | Label: Dosage\"]", "text": "[Title]: A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.\n[Abstract]: Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.\n[Drug-Disease]: pyrimethamine - falciparum infection" }, { "pmid": "11579891", "target": "[\"Span: children | Label: Age\", \"Span: 25 mg/kg | Label: Dosage\"]", "text": "[Title]: A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.\n[Abstract]: Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.\n[Drug-Disease]: sulfadoxine - falciparum infection" }, { "pmid": "11583721", "target": "[\"Span: 5-10 mg/day | Label: Dosage\"]", "text": "[Title]: Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.\n[Abstract]: Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.\n[Drug-Disease]: simvastatin - hypercholesterolemia" }, { "pmid": "11586115", "target": "[]", "text": "[Title]: Long-term comparative experience with tolcapone and entacapone in advanced Parkinson's disease.\n[Abstract]: The objective of this study was to compare the long-term tolerability and efficacy of tolcapone and entacapone in patients with fluctuating Parkinson's disease (PD). Tolcapone and entacapone are two currently available catechol- O -methyltransferase inhibitors that have demonstrated efficacy in the treatment of advanced PD. There are little published data on long-term experience and no direct comparisons. We compared the results of two separate, simultaneous, long-term open label extensions, one for tolcapone and the other for entacapone. The inclusion/exclusion criteria were similar. Data were collected prospectively at 6, 12, 24, and 36 months. Efficacy measures included the Unified Parkinson's Disease Rating Scale (UPDRS) total score, subscores, items 32 (duration of dyskinesia) and 39 (duration of \"off\" time), and levodopa dose. The two groups were compared using a Mann-Whitney U test for change from baseline and analysis of variance. Tolerability was defined as the ability of patients to maintain therapy and was compared using a Kaplan-Meier analysis. Eleven patients enrolled in the entacapone study and 14 in the tolcapone study. The tolcapone group had more severe disease with significantly higher UPDRS motor score, duration of \"off,\" and levodopa dose requirement. Tolcapone was more effective in lowering UPDRS motor and complication subscores, duration of \"off\" time, and levodopa doses. UPDRS motor scores and change in levodopa dose in the tolcapone group remained below baseline level for 36 months; however, they were above baseline in the entacapone group from 6 months on. Tolerability was the same for both treatments. Tolcapone appears to have greater and longer efficacy with regard to motor symptoms, \"off\" time, and change in levodopa requirements than entacapone. These findings indicate that tolcapone continues to have a place in the treatment of advanced PD. However, the risks associated with this drug, particularly hepatic injury, and the requirement for rigorous blood monitoring, need to be considered when choosing an appropriate treatment for patients with advanced PD.\n[Drug-Disease]: entacapone - PD" }, { "pmid": "11586115", "target": "[]", "text": "[Title]: Long-term comparative experience with tolcapone and entacapone in advanced Parkinson's disease.\n[Abstract]: The objective of this study was to compare the long-term tolerability and efficacy of tolcapone and entacapone in patients with fluctuating Parkinson's disease (PD). Tolcapone and entacapone are two currently available catechol- O -methyltransferase inhibitors that have demonstrated efficacy in the treatment of advanced PD. There are little published data on long-term experience and no direct comparisons. We compared the results of two separate, simultaneous, long-term open label extensions, one for tolcapone and the other for entacapone. The inclusion/exclusion criteria were similar. Data were collected prospectively at 6, 12, 24, and 36 months. Efficacy measures included the Unified Parkinson's Disease Rating Scale (UPDRS) total score, subscores, items 32 (duration of dyskinesia) and 39 (duration of \"off\" time), and levodopa dose. The two groups were compared using a Mann-Whitney U test for change from baseline and analysis of variance. Tolerability was defined as the ability of patients to maintain therapy and was compared using a Kaplan-Meier analysis. Eleven patients enrolled in the entacapone study and 14 in the tolcapone study. The tolcapone group had more severe disease with significantly higher UPDRS motor score, duration of \"off,\" and levodopa dose requirement. Tolcapone was more effective in lowering UPDRS motor and complication subscores, duration of \"off\" time, and levodopa doses. UPDRS motor scores and change in levodopa dose in the tolcapone group remained below baseline level for 36 months; however, they were above baseline in the entacapone group from 6 months on. Tolerability was the same for both treatments. Tolcapone appears to have greater and longer efficacy with regard to motor symptoms, \"off\" time, and change in levodopa requirements than entacapone. These findings indicate that tolcapone continues to have a place in the treatment of advanced PD. However, the risks associated with this drug, particularly hepatic injury, and the requirement for rigorous blood monitoring, need to be considered when choosing an appropriate treatment for patients with advanced PD.\n[Drug-Disease]: tolcapone - PD" }, { "pmid": "11587876", "target": "[]", "text": "[Title]: Neurologic outcomes of pediatric epileptic patients with pentobarbital coma.\n[Abstract]: Status epilepticus is a life-threatening condition requiring emergent medical attention. Although initial therapies with antiepileptic drugs generally terminate seizures within 30 to 60 minutes, patients with refractory status epilepticus require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of refractory status epilepticus in children. The objective of this research was to evaluate the association between the response of pentobarbital coma and neurologic outcomes in refractory status epilepticus. Twenty-three subjects were treated with pentobarbital coma for at least 48 hours. Medical records were reviewed to collect patient demographic information, responses to treatment, and neurologic outcomes. Among the 23 patients reviewed, 12 patients were controlled with pentobarbital (responders), six were unresponsive to pentobarbital (nonresponders), and five patients relapsed after discontinuation or during tapering of pentobarbital (relapser). The mortality rate among the relapser and nonresponder groups combined was 90.9%, but no deaths occurred among the responder group (P < 0.001). The survival rate was greater among toddlers compared with neonates or older children. Failure of seizure control after pentobarbital coma was associated with a poor prognosis. The potential for serious complications of pentobarbital therapy among neonates highlights the need for careful dosing in this age group.\n[Drug-Disease]: pentobarbital - status epilepticus" }, { "pmid": "11593070", "target": "[\"Span: 8.1 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar disorder.\n[Abstract]: The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.\n[Drug-Disease]: olanzapine - bipolar disorder" }, { "pmid": "11593098", "target": "[\"Span: Angiotensin converting enzyme gene | Label: Gene\"]", "text": "[Title]: Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients.\n[Abstract]: OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.\n[Drug-Disease]: irbesartan - hypertension" }, { "pmid": "11593098", "target": "[\"Span: Angiotensin converting enzyme gene | Label: Gene\"]", "text": "[Title]: Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients.\n[Abstract]: OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.\n[Drug-Disease]: atenolol - hypertension" }, { "pmid": "11594440", "target": "[]", "text": "[Title]: Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects.\n[Abstract]: RATIONALE: The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with citicoline decreased self-reported desire to use cocaine in crack cocaine users. OBJECTIVE: The present study was conducted to assess the safety of citicoline in combination with cocaine by investigating whether cocaine-induced cardiovascular and behavioral effects and cocaine plasma levels are altered by citicoline pretreatment. METHODS: Eight healthy male and female volunteers who used cocaine on an occasional basis participated in this randomized, placebo-controlled, three-visit study. During all three visits, subjects received an acute intranasal dose of cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day pretreatment period of either citicoline (1 g/day) or placebo. RESULTS: Citicoline pretreatment did not alter the cardiovascular, physiologic, or subjective effects of acute cocaine. CONCLUSIONS: Although citicoline did not block the acute subjective effects of cocaine in a laboratory environment, the combined use of citicoline and a moderate dose of intranasal cocaine presented no added risk of cardiovascular effects. Further study is necessary to determine whether this medication (which is currently used to treat strokes) will be a useful adjunct to treat cocaine dependence.\n[Drug-Disease]: citicoline - cocaine intoxication" }, { "pmid": "11595064", "target": "[\"Span: 15 men and one woman | Label: Gender\", \"Span: 100 mg daily | Label: Dosage\"]", "text": "[Title]: Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: a 4-year experience.\n[Abstract]: BACKGROUND: Reactivation of hepatitis B after organ transplantation in hepatitis B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our experience of lamivudine treatment in HBsAg carriers who had post-transplant reactivation of hepatitis B. METHODS: The patients were 15 men and one woman. Nine received kidney transplants, six received heart transplants, and one received a lung transplant. They developed a reactivation of hepatitis B 1-101 months (median, 14 months) after transplantation. They received lamivudine 100 mg daily on a compassionate-use basis, and had regular follow ups. The median pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine aminotransferase level was 357 U/L. Four of the 16 patients were positive for HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%) patients. Three were coinfected with hepatitis C virus. RESULTS: The overall survival rate was 75%. All four fatal cases had a pretreatment total serum bilirubin level of > or = 3 mg/dL. Serum HBV-DNA soon became undetectable in 12 survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a lamivudine-resistant strain with variation in the YMDD motif of the HBV polymerase gene developed in three (25%). None had significant adverse reactions to lamivudine treatment. CONCLUSIONS: These results indicated that lamivudine is effective in the treatment of post-transplant hepatitis B reactivation, including patients with dual chronic hepatitis B and C. Early recognition of HBV reactivation and prompt lamivudine treatment are important to prevent mortality.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "1163428", "target": "[]", "text": "[Title]: Minoxidil in severe hypertension: value when conventional drugs have failed.\n[Abstract]: Twenty-six patients were selected for treatment with minoxidil on the basis of hypertension which could not be controlled either because of (1) drug failures and/or (2) side effects of drugs. Sixteen out of the 26 had had one or more previous episodes of malignant hypertension. Reduced renal function was present in the majority; eight patients were on dialysis. Average preminoxidil blood pressure was 202/127 mm. Hg supine and 162/106 upright which fell to 154/87 supine and 143/86 upright after minoxidil. Propranolol or methyldopa was given to control the reflex increase in heart rate. Edema and congestive heart failure refractory to large doses of potent diuretics necessitated discontinuation of the drug in two patients. Minoxidil proved highly efficacious regardless of initial level of blood pressure, etiology, or supine or upright posture.\n[Drug-Disease]: Minoxidil - hypertension" }, { "pmid": "11641310", "target": "[\"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.\n[Abstract]: International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.\n[Drug-Disease]: atenolol - hypertensive" }, { "pmid": "11641310", "target": "[\"Span: 0.625 mg | Label: Dosage\"]", "text": "[Title]: Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.\n[Abstract]: International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.\n[Drug-Disease]: indapamide - hypertensive" }, { "pmid": "11641310", "target": "[\"Span: 2 mg | Label: Dosage\"]", "text": "[Title]: Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.\n[Abstract]: International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.\n[Drug-Disease]: perindopril - hypertensive" }, { "pmid": "11642474", "target": "[\"Span: 2.5-20 mg/day | Label: Dosage\", \"Span: 5-14 years old | Label: Age\"]", "text": "[Title]: A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.\n[Abstract]: OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.\n[Drug-Disease]: olanzapine - bipolar disorder" }, { "pmid": "11675058", "target": "[\"Span: Children younger than 5 years | Label: Age\"]", "text": "[Title]: Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.\n[Abstract]: BACKGROUND: Resistance to the affordable malaria treatments chloroquine and pyrimethamine-sulfadoxine is seriously impeding malaria control through treatment in east Africa. We did an open, alternate drug allocation study to assess the efficacy of chlorproguanil-dapsone in the treatment of falciparum malaria clinically resistant to pyrimethamine-sulfadoxine. METHODS: Children younger than 5 years with non-severe falciparum malaria, attending Muheza district hospital in Tanzania, were treated with the standard regimen of pyrimethamine-sulfadoxine. Patients whose clinical symptoms resolved but who remained parasitaemic 7 days after pyrimethamine-sulfadoxine were followed up for 1 month. Clinical malaria episodes were retreated with either single dose pyrimethamine-sulfadoxine or a 3-day regimen of chlorproguanil-dapsone. Those with parasitaemia after 7 days were treated with chlorproguanil-dapsone. Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps). FINDINGS: 360 children were enrolled and treated with pyrimethamine-sulfadoxine. On day 7, 192 (55%) of 348 had cleared parasitaemia. Of the remaining 156 parasitaemic children, 140 (90%) were followed up to day 28, and 92 (66%) of 140 developed clinical malaria. These 92 patients were alternately retreated with either pyrimethamine-sulfadoxine (46) or chlorproguanil-dapsone (46). 28 (61%) of 46 children retreated with pyrimethamine-sulfadoxine were still parasitaemic at day 7, compared with three (7%) of 44 [corrected] children retreated with chlorproguanil-dapsone. Resistance to pyrimethamine-sulfadoxine increased from 45% (156/348) at the first treatment to 61% (28/46) after retreatment. 83 of 85 parasite isolates collected after the first pyrimethamine-sulfadoxine treatment, and before and after the second treatments with pyrimethamine-sulfadoxine and chlorproguanil-dapsone showed triple-mutant dhfr alleles, associated with a variety of dhps mutations. INTERPRETATION: Most patients treated with pyrimethamine-sulfadoxine, who remain parasitaemic at day 7, develop new malaria symptoms within 1 month. Chlorproguanil-dapsone was a practicable therapy under these circumstances. Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain.\n[Drug-Disease]: chloroquine - malaria symptoms" }, { "pmid": "11677377", "target": "[\"Span: 10 mg/day | Label: Dosage\"]", "text": "[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.\n[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP </= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.\n[Drug-Disease]: benazepril - hypertension" }, { "pmid": "11677377", "target": "[\"Span: 80 mg/day | Label: Dosage\"]", "text": "[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.\n[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP </= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.\n[Drug-Disease]: Valsartan - hypertension" }, { "pmid": "11677377", "target": "[\"Span: 12.5 mg/day | Label: Dosage\"]", "text": "[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.\n[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP </= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.\n[Drug-Disease]: hydrochlorothiazide - hypertension" }, { "pmid": "1167766", "target": "[\"Span: 30 mg./70kg | Label: Dosage\"]", "text": "[Title]: Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.\n[Abstract]: Administration of either gallamine or d-tubocurarine before injecting succinylcholine diminished both the incidence and intensity of muscle fasciculations. Gallamine was more efficient than curare in this respect, 30 mg./70kg. almost entirely preventing fasciculations.\n[Drug-Disease]: Gallamine - fasciculations" }, { "pmid": "1167766", "target": "[]", "text": "[Title]: Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.\n[Abstract]: Administration of either gallamine or d-tubocurarine before injecting succinylcholine diminished both the incidence and intensity of muscle fasciculations. Gallamine was more efficient than curare in this respect, 30 mg./70kg. almost entirely preventing fasciculations.\n[Drug-Disease]: d-tubocurarine - fasciculations" }, { "pmid": "11679185", "target": "[\"Span: 6 mg/ml | Label: Dosage\"]", "text": "[Title]: Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.\n[Abstract]: INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.\n[Drug-Disease]: carboplatin - NSCLC" }, { "pmid": "11679185", "target": "[\"Span: 225 mg/ml | Label: Dosage\"]", "text": "[Title]: Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.\n[Abstract]: INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.\n[Drug-Disease]: paclitaxel - NSCLC" }, { "pmid": "11679186", "target": "[\"Span: 25 mg/m(2) weekly | Label: Dosage\", \"Span: median age of 66 years (range 48-80) | Label: Age\"]", "text": "[Title]: Pilot study of sequential vinorelbine and cisplatin followed by docetaxel for selected IIIB and stage IV non-small cell lung cancer.\n[Abstract]: UNLABELLED: Vinorelbine, cisplatin and docetaxel are known to be efficacious in non-small cell lung cancer (NSCLC). This limited institution pilot study evaluated the novel strategy of sequencing active first line agents prior to progression. The primary objective of this study was to assess the toxicity profile in anticipation of a larger cooperative group standard phase II study. Patients with selected stage IIIB and IV NSCLC, Southwest Oncology Group (SWOG) performance status (PS) of 1 or less and measurable or evaluable disease were eligible. Treatment was cisplatin 100 mg/m(2) day 1 and 29, vinorelbine 25 mg/m(2) weekly for 8 weeks, followed by docetaxel 100 mg/m(2) every 21 days for four cycles if no progression. If grade IV neutropenia developed, G-CSF 5 mcg/kg/day was used in subsequent cycles. Of 18 eligible patients, 17 patients had stage IV disease with a median age of 66 years (range 48-80). Eight patients had a SWOG PS of 1, 10 had a PS of zero. Six of eighteen patients received all 8 weeks of vinorelbine/cisplatin and six of eight patients who went on to receive docetaxel received all four planned cycles; only two patients overall received all planned therapy. One grade III/IV event each of cardiotoxicity (myocardial infarction), renal toxicity (acute renal failure), anemia and thrombocytopenia occurred with vinorelbine and cisplatin, and 2 Grade IV hypersensitivity reactions, manifested by severe back pain with docetaxel occurred. Three deaths occurred during the study, all during treatment with vinorelbine and cisplatin: one due to neutropenic sepsis; one from a pulmonary embolism; and one secondary to severe hypoglycemia in a diabetic patient. Of the 16 patients evaluable for response after vinorelbine/cisplatin, there were two complete responses (12.5%) and three partial responses (19%) for an overall response rate of 31% (95% CI 8-58). One additional patient who received docetaxel experienced a partial response. Two patients remain alive (21+ and 18+ months, respectively). The 1-year survival was 44%. CONCLUSION: This sequence, as defined, was tolerated marginally well in patients with advanced NSCLC. Granulocytopenia was the major toxicity requiring dose adjustments throughout the sequence. Based on response rates and tolerability that were somewhat comparable to other regimens in this disease setting, a modified version of this program, adjusted to decrease the incidence of grade III and IV toxicity, was selected as one arm of a recent randomized phase II trial in the Southwest Oncology Group (SWOG), S9806, evaluating sequential therapy in advanced NSCLC.\n[Drug-Disease]: vinorelbine - NSCLC" }, { "pmid": "11679186", "target": "[\"Span: 100 mg/m(2) day | Label: Dosage\", \"Span: median age of 66 years (range 48-80) | Label: Age\"]", "text": "[Title]: Pilot study of sequential vinorelbine and cisplatin followed by docetaxel for selected IIIB and stage IV non-small cell lung cancer.\n[Abstract]: UNLABELLED: Vinorelbine, cisplatin and docetaxel are known to be efficacious in non-small cell lung cancer (NSCLC). This limited institution pilot study evaluated the novel strategy of sequencing active first line agents prior to progression. The primary objective of this study was to assess the toxicity profile in anticipation of a larger cooperative group standard phase II study. Patients with selected stage IIIB and IV NSCLC, Southwest Oncology Group (SWOG) performance status (PS) of 1 or less and measurable or evaluable disease were eligible. Treatment was cisplatin 100 mg/m(2) day 1 and 29, vinorelbine 25 mg/m(2) weekly for 8 weeks, followed by docetaxel 100 mg/m(2) every 21 days for four cycles if no progression. If grade IV neutropenia developed, G-CSF 5 mcg/kg/day was used in subsequent cycles. Of 18 eligible patients, 17 patients had stage IV disease with a median age of 66 years (range 48-80). Eight patients had a SWOG PS of 1, 10 had a PS of zero. Six of eighteen patients received all 8 weeks of vinorelbine/cisplatin and six of eight patients who went on to receive docetaxel received all four planned cycles; only two patients overall received all planned therapy. One grade III/IV event each of cardiotoxicity (myocardial infarction), renal toxicity (acute renal failure), anemia and thrombocytopenia occurred with vinorelbine and cisplatin, and 2 Grade IV hypersensitivity reactions, manifested by severe back pain with docetaxel occurred. Three deaths occurred during the study, all during treatment with vinorelbine and cisplatin: one due to neutropenic sepsis; one from a pulmonary embolism; and one secondary to severe hypoglycemia in a diabetic patient. Of the 16 patients evaluable for response after vinorelbine/cisplatin, there were two complete responses (12.5%) and three partial responses (19%) for an overall response rate of 31% (95% CI 8-58). One additional patient who received docetaxel experienced a partial response. Two patients remain alive (21+ and 18+ months, respectively). The 1-year survival was 44%. CONCLUSION: This sequence, as defined, was tolerated marginally well in patients with advanced NSCLC. Granulocytopenia was the major toxicity requiring dose adjustments throughout the sequence. Based on response rates and tolerability that were somewhat comparable to other regimens in this disease setting, a modified version of this program, adjusted to decrease the incidence of grade III and IV toxicity, was selected as one arm of a recent randomized phase II trial in the Southwest Oncology Group (SWOG), S9806, evaluating sequential therapy in advanced NSCLC.\n[Drug-Disease]: cisplatin - NSCLC" }, { "pmid": "11682671", "target": "[\"Span: M:F=15:2 | Label: Gender\"]", "text": "[Title]: Outcome of renal transplantation in hepatitis B surface antigen-positive patients after introduction of lamivudine.\n[Abstract]: BACKGROUND: In end-stage renal disease patients with hepatitis B surface antigen (HBsAg), the risk of hepatic dysfunction after immunosuppression represents a large barrier in renal transplantation. Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. We retrospectively investigated the outcome of HBsAg-positive renal transplantation recipients after lamivudine had become available. METHODS: From July 1994 to August 2000, seventeen HBsAg-positive patients (M:F=15:2) received renal allografts (13:4=living:cadaveric donors). Liver function tests at the time of transplantation were normal in all patients. Pre-transplant liver biopsies performed in 15 patients demonstrated minimal inflammatory histology, except in three patients showing pathological and clinical signs of active hepatitis. Lamivudine was started pre-operatively in these three subjects. Another seven patients were treated with lamivudine for post-operative hepatic dysfunction. The remaining seven patients did not develop hepatic dysfunction after transplantation. RESULTS: Lamivudine was initially effective in decreasing serum HBV DNA titres, and in normalizing hepatic enzymes. Lamivudine was well tolerated without significant side effects for 35.5+/-8.9 months after initiation of treatment. HBV DNA became negative in nine patients but remained positive in one patient. Among the nine patients with initial negative conversion of HBV DNA, two developed transient positive conversion of HBV DNA and two demonstrated persistent positive conversion. Among the patients with normal liver histology in the pre-transplant period, 41.6% (5/12) developed liver pathology progression after immunosuppression. All 17 patients had functioning grafts, except for one patient who developed relapsed IgA nephropathy. CONCLUSIONS: Our data showed relatively favourable outcomes in hepatitis B-positive renal transplant recipients receiving lamivudine treatment, even though two patients developed lamivudine resistance.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "11683535", "target": "[\"Span: 13 M | Label: Gender\", \"Span: 15 F | Label: Gender\"]", "text": "[Title]: Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment.\n[Abstract]: Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.\n[Drug-Disease]: pamidronate - multiple myeloma" }, { "pmid": "11684562", "target": "[\"Span: 30 men, 12 women | Label: Gender\", \"Span: 100 or 150 mg | Label: Dosage\"]", "text": "[Title]: Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients.\n[Abstract]: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "11684562", "target": "[\"Span: 30 men, 12 women | Label: Gender\", \"Span: 100 or 150 mg | Label: Dosage\"]", "text": "[Title]: Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients.\n[Abstract]: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.\n[Drug-Disease]: lamivudine - fulminant hepatic failure" }, { "pmid": "11694805", "target": "[\"Span: 40 mg | Label: Dosage\"]", "text": "[Title]: Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease.\n[Abstract]: BACKGROUND: It has been suggested that the effect of a beta2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. OBJECTIVES: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. METHODS: The study was performed using a double-blind, double-dummy, crossover, randomised design, and was conducted on 4 non-consecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 microg of inhaled salmeterol, 50 microg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 microg of inhaled salbutamol and spirometric testing was performed 30 min later. RESULTS: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p < 0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p < 0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 0.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. CONCLUSIONS: Both salmeterol and zafirlukast induced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.\n[Drug-Disease]: zafirlukast - asthma" }, { "pmid": "11694805", "target": "[\"Span: 50 microg | Label: Dosage\"]", "text": "[Title]: Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease.\n[Abstract]: BACKGROUND: It has been suggested that the effect of a beta2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. OBJECTIVES: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. METHODS: The study was performed using a double-blind, double-dummy, crossover, randomised design, and was conducted on 4 non-consecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 microg of inhaled salmeterol, 50 microg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 microg of inhaled salbutamol and spirometric testing was performed 30 min later. RESULTS: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p < 0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p < 0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 0.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. CONCLUSIONS: Both salmeterol and zafirlukast induced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.\n[Drug-Disease]: salmeterol - asthma" }, { "pmid": "11694816", "target": "[]", "text": "[Title]: Comparison of hydrofluoroalkane-beclomethasone dipropionate Autohaler with budesonide Turbuhaler in asthma control.\n[Abstract]: BACKGROUND: Hydrofluoroalkane-beclomethasone dipropionate Autohaler (HFA-BDP AH) is a breath-actuated chlorofluorocarbon (CFC)-free metered dose inhaler in which BDP is in a solution of HFA propellant. Budesonide Turbuhaler (BUD TH) is a breath-dependent dry powder inhaler. OBJECTIVES: To test the hypothesis that half the daily dose of HFA-BDP AH would provide an equivalent control of asthma symptoms to the BUD TH. METHODS: This was an 8-week open study in patients with symptomatic moderate-to-severe asthma, previously on BUD 500-1,000 microg x day(-1), or an equivalent. After 5-14 days' run-in, patients were randomized to HFA-BDP AH 800 microg x day(-1) or BUD TH 1,600 microg x day(-1). The intent-to-treat population consisted of 111 patients on HFA-BDP AH and 98 patients on BUD TH. RESULTS: Mean change from baseline in PEF in the morning (AM PEF) at week 8 was 23.95 liters x min(-1) for HFA-BDP AH and 24.46 liters x min(-1) for BUD TH. A two-sided equivalence test using the 0.51 liter x min(-1) difference gave 95% confidence intervals within a defined equivalence interval of (-infinity, 25 liters x min(-1)) indicating that the mean change in AM PEF was equivalent for the two groups. There were no significant differences in the mean change from baseline in FEV1 or beta-agonist use. Patients using HFA-BDP AH had a significantly greater mean change from baseline in the percentage of days free from shortness of breath (p = 0.05), chest tightness (p = 0.02) and nights without sleep disturbance (p = 0.04) at week 3, and wheeze (p = 0.01), shortness of breath (p = 0.02), chest tightness (p < 0.01) and daily asthma symptoms (p = 0.03) at week 8. The incidence, type and severity of adverse events were similar in each group. At week 8, the mean change from baseline in corrected urine cortisol/creatinine ratio in a subgroup of patients was -0.36 for HFA-BDP and -4.88 for BUD TH (p < 0.01). CONCLUSIONS: HFA-BDP 800 microg x day(-1) provided control of moderate-to-severe asthma with efficacy and safety at least similar to BUD TH 1,600 microg x day(-1).\n[Drug-Disease]: Budesonide - asthma" }, { "pmid": "11696508", "target": "[]", "text": "[Title]: Pre-hospital aspirin for suspected myocardial infarction and acute coronary syndromes: a headache for paramedics?\n[Abstract]: OBJECTIVE: To ascertain the frequency with which paramedics follow protocols for the administration of aspirin to patients to whom an ambulance is called for chest pain associated with suspected ischaemic heart disease. METHODS: Ambulance services in England and Wales who had conducted a recent aspirin administration audit were identified through the National Clinical Effectiveness Programme for the Ambulance Service Association. Data were requested from each of these services with a 100% return rate. RESULTS: Nine services out of a total of 35 had collected appropriate data. The proportion of patients who were given aspirin by a paramedic varied from 11% to 74%. The range of proportions of patients receiving pre-hospital aspirin increased after adding those patients who had already received aspirin from an alternative health provider, to 19% to 78%. It is estimated that at least 15% to 74% of patients who should have been given aspirin by the various ambulance services did not receive it. The proportion of patients for whom aspirin was judged to be inappropriate ranged from 4% to 35%. The reason for these widely varying and generally poor levels of compliance is not known. However, the range of indications and contraindications to the administration of aspirin varied considerably by ambulance service. This also made the comparison of data from different sources difficult. CONCLUSIONS: Aspirin has been shown to be beneficial after a myocardial infarction and for other acute coronary syndromes. However, variances in the proportion of patients with suspected ischaemic heart disease given aspirin in different ambulance services indicates the need for a re-emphasis on the importance of this treatment. A standard protocol for all UK ambulance services should be devised that minimises the number of contraindications to aspirin and otherwise requires its administration to all patients with acute coronary syndromes or suspected myocardial infarction. Regular, standardised audits of compliance should also be conducted and their results widely disseminated.\n[Drug-Disease]: aspirin - myocardial infarction" }, { "pmid": "11698316", "target": "[\"Span: 7.5 mg | Label: Dosage\"]", "text": "[Title]: Postoperative analgesia is not different after local vs systemic administration of meloxicam in patients undergoing inguinal hernia repair.\n[Abstract]: PURPOSE: To distinguish between local and systemic drug effects, we compared pain scores, analgesic consumption and plasma concentrations after local vs i.v. administration of meloxicam 7.5 mg in patients with inguinal hernia repair. METHODS: In a double-blind, randomized study 56 patients received either local or i.v. meloxicam 7.5 mg. Postoperative pain was assessed with a visual analogue scale (VAS) at rest, on mobilization, and on coughing, the need for supplementary analgesics (fentanyl i.v. and/or acetaminophen-codeine tablets) was recorded, and blood samples were drawn during 24 hr after meloxicam administration. RESULTS: No significant differences were found between groups with respect to pain scores, or in the consumption of supplementary analgesics. Following local application of meloxicam, the peak plasma concentration (C(max)) of 0.5 +/- 0.2 mg*L(-1) achieved after 1.8 +/- 0.5 hr was much lower than the C(max) of 2.5 +/- 0.9 mg*L(-1) achieved immediately after i.v. administration (P <0.05). Mean meloxicam plasma concentration after infiltration was significantly lower than after i.v. doses for the first three hours after administration (P <0.05). CONCLUSION: We showed no differences in pain scores and analgesic consumption between local and i.v. administration of meloxicam 7.5 mg during the first 24 hr after herniorrhaphy, while plasma concentration of meloxicam was lower after local administration. These results indicate a lack of difference in pain relief after concentrating meloxicam at the hernia wound or after achieving high blood levels rapidly (i.v.). Local administration of meloxicam may confer an advantage over systemic administration by eliciting lower incidences of systemic adverse effects.\n[Drug-Disease]: meloxicam - Postoperative pain" }, { "pmid": "11704023", "target": "[\"Span: 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) | Label: Dosage\", \"Span: Caucasian patients | Label: Body Type\", \"Span: a mean (+/-SD) age of 63 (+/-8) | Label: Age\"]", "text": "[Title]: Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.\n[Abstract]: PURPOSE: Topical beta-blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24-hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+/-SD) age of 63 (+/-8) years were randomized and crossed over in a double-masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24-hour heart rate compared with placebo (P < or = .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats/min). Timolol gellan showed a numerically but not significantly smaller reduction in 24-hour heart rate, compared with timolol solution. During the night, the mean 12-hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24-hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta-blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences.\n[Drug-Disease]: timolol - open-angle glaucoma" }, { "pmid": "11704797", "target": "[]", "text": "[Title]: Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus.\n[Abstract]: A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.\n[Drug-Disease]: tacrolimus - GVHD" }, { "pmid": "11706781", "target": "[\"Span: 175 mg/m2 | Label: Dosage\"]", "text": "[Title]: 3-hour infusion of single-agent paclitaxel for recurrent ovarian cancer.\n[Abstract]: BACKGROUND: The clinical response, survival, and toxicity of a 3-h infusion of single-agent paclitaxel (175 mg/m2) for Japanese patients with recurrent ovarian cancer were investigated. We also examined whether or not cancer antigen (CA) 125 would be suitable as an indicator of the effects of the paclitaxel on ovarian cancer. METHODS: Twenty-one patients clinically diagnosed as having recurrent ovarian cancer met the entry criteria, agreed to participate in this study, and received the treatment. RESULTS: One hundred and twenty-six courses were administered to the 21 patients. One patient achieved a complete response, and 5 a partial response; the overall response rate was 35.3%. Using CA125 criteria, 42.1% of patients achieved a response. The median progression-free interval was 4.4 months, and the median overall survival time was 14.5 months. While hematological toxicity was not severe, 3 patients experienced severe peripheral neuropathy, and 2 patients experienced grade 4 myalgia/arthralgia. CONCLUSION: The 3-h infusion of single-agent paclitaxel (175 mg/m2) was an effective treatment for patients with recurrent ovarian cancer. CA125 was a useful indicator of the response to the treatment. While peripheral neuropathy and the myalgia/arthralgia were severe, 3-h infusion of single-agent paclitaxel offers a promising treatment for recurrent ovarian cancer.\n[Drug-Disease]: paclitaxel - ovarian cancer" }, { "pmid": "11707788", "target": "[\"Span: 1 microg/kg | Label: Dosage\"]", "text": "[Title]: Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine.\n[Abstract]: BACKGROUND AND OBJECTIVES: Both clonidine and ketamine have been found to prolong the action of local anesthetics through a peripheral mechanism. Our study compares the efficacy of a low dose of clonidine or ketamine separately added to intravenous regional anesthesia (IVRA) with lidocaine to prevent tourniquet pain. METHODS: We conducted a prospective randomized double-blinded study in 45 patients undergoing hand or forearm surgery, with anticipated duration exceeding 1 hour under IVRA. Proximal cuff inflation of a double tourniquet was followed by administration of 40 mL of lidocaine 0.5% and either saline, 1 microg/kg clonidine, or 0.1 mg/kg ketamine. When anesthesia was established, the inflation of the proximal and distal cuff was interchanged. Thereafter, tourniquet pain was rated on a visual analog scale (VAS) every 10 minutes. Intraoperatively, boluses of 25 microg fentanyl were provided for tourniquet pain treatment when required, and total fentanyl consumption was recorded. RESULTS: Patients receiving plain lidocaine persistently reported the highest pain scores among groups (P <.001) 20 minutes after distal cuff inflation. Differences between the groups with additional treatment were noted 50 minutes after distal cuff inflation and until the end of the observation, with significantly lower VAS ratings (P <.001 to P <.01) in ketamine-treated patients. Total fentanyl consumption was significantly decreased by ketamine (70.00 +/- 25.35 microg) or clonidine (136.67 +/- 39.94 microg) compared with the plain lidocaine group (215.33 +/- 52.33 microg) (P <.001 between all groups). CONCLUSIONS: The addition of clonidine 1 microg/kg or ketamine 0.1 mg/kg to lidocaine for IVRA delays the onset of unbearable tourniquet pain and decreases analgesic consumption for tourniquet pain relief, although ketamine has a more potent effect.\n[Drug-Disease]: clonidine - pain" }, { "pmid": "11707788", "target": "[\"Span: 25 microg | Label: Dosage\"]", "text": "[Title]: Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine.\n[Abstract]: BACKGROUND AND OBJECTIVES: Both clonidine and ketamine have been found to prolong the action of local anesthetics through a peripheral mechanism. Our study compares the efficacy of a low dose of clonidine or ketamine separately added to intravenous regional anesthesia (IVRA) with lidocaine to prevent tourniquet pain. METHODS: We conducted a prospective randomized double-blinded study in 45 patients undergoing hand or forearm surgery, with anticipated duration exceeding 1 hour under IVRA. Proximal cuff inflation of a double tourniquet was followed by administration of 40 mL of lidocaine 0.5% and either saline, 1 microg/kg clonidine, or 0.1 mg/kg ketamine. When anesthesia was established, the inflation of the proximal and distal cuff was interchanged. Thereafter, tourniquet pain was rated on a visual analog scale (VAS) every 10 minutes. Intraoperatively, boluses of 25 microg fentanyl were provided for tourniquet pain treatment when required, and total fentanyl consumption was recorded. RESULTS: Patients receiving plain lidocaine persistently reported the highest pain scores among groups (P <.001) 20 minutes after distal cuff inflation. Differences between the groups with additional treatment were noted 50 minutes after distal cuff inflation and until the end of the observation, with significantly lower VAS ratings (P <.001 to P <.01) in ketamine-treated patients. Total fentanyl consumption was significantly decreased by ketamine (70.00 +/- 25.35 microg) or clonidine (136.67 +/- 39.94 microg) compared with the plain lidocaine group (215.33 +/- 52.33 microg) (P <.001 between all groups). CONCLUSIONS: The addition of clonidine 1 microg/kg or ketamine 0.1 mg/kg to lidocaine for IVRA delays the onset of unbearable tourniquet pain and decreases analgesic consumption for tourniquet pain relief, although ketamine has a more potent effect.\n[Drug-Disease]: fentanyl - pain" }, { "pmid": "11707788", "target": "[\"Span: 0.1 mg/kg | Label: Dosage\"]", "text": "[Title]: Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine.\n[Abstract]: BACKGROUND AND OBJECTIVES: Both clonidine and ketamine have been found to prolong the action of local anesthetics through a peripheral mechanism. Our study compares the efficacy of a low dose of clonidine or ketamine separately added to intravenous regional anesthesia (IVRA) with lidocaine to prevent tourniquet pain. METHODS: We conducted a prospective randomized double-blinded study in 45 patients undergoing hand or forearm surgery, with anticipated duration exceeding 1 hour under IVRA. Proximal cuff inflation of a double tourniquet was followed by administration of 40 mL of lidocaine 0.5% and either saline, 1 microg/kg clonidine, or 0.1 mg/kg ketamine. When anesthesia was established, the inflation of the proximal and distal cuff was interchanged. Thereafter, tourniquet pain was rated on a visual analog scale (VAS) every 10 minutes. Intraoperatively, boluses of 25 microg fentanyl were provided for tourniquet pain treatment when required, and total fentanyl consumption was recorded. RESULTS: Patients receiving plain lidocaine persistently reported the highest pain scores among groups (P <.001) 20 minutes after distal cuff inflation. Differences between the groups with additional treatment were noted 50 minutes after distal cuff inflation and until the end of the observation, with significantly lower VAS ratings (P <.001 to P <.01) in ketamine-treated patients. Total fentanyl consumption was significantly decreased by ketamine (70.00 +/- 25.35 microg) or clonidine (136.67 +/- 39.94 microg) compared with the plain lidocaine group (215.33 +/- 52.33 microg) (P <.001 between all groups). CONCLUSIONS: The addition of clonidine 1 microg/kg or ketamine 0.1 mg/kg to lidocaine for IVRA delays the onset of unbearable tourniquet pain and decreases analgesic consumption for tourniquet pain relief, although ketamine has a more potent effect.\n[Drug-Disease]: ketamine - pain" }, { "pmid": "11707788", "target": "[\"Span: 40 mL of lidocaine 0.5% | Label: Dosage\"]", "text": "[Title]: Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine.\n[Abstract]: BACKGROUND AND OBJECTIVES: Both clonidine and ketamine have been found to prolong the action of local anesthetics through a peripheral mechanism. Our study compares the efficacy of a low dose of clonidine or ketamine separately added to intravenous regional anesthesia (IVRA) with lidocaine to prevent tourniquet pain. METHODS: We conducted a prospective randomized double-blinded study in 45 patients undergoing hand or forearm surgery, with anticipated duration exceeding 1 hour under IVRA. Proximal cuff inflation of a double tourniquet was followed by administration of 40 mL of lidocaine 0.5% and either saline, 1 microg/kg clonidine, or 0.1 mg/kg ketamine. When anesthesia was established, the inflation of the proximal and distal cuff was interchanged. Thereafter, tourniquet pain was rated on a visual analog scale (VAS) every 10 minutes. Intraoperatively, boluses of 25 microg fentanyl were provided for tourniquet pain treatment when required, and total fentanyl consumption was recorded. RESULTS: Patients receiving plain lidocaine persistently reported the highest pain scores among groups (P <.001) 20 minutes after distal cuff inflation. Differences between the groups with additional treatment were noted 50 minutes after distal cuff inflation and until the end of the observation, with significantly lower VAS ratings (P <.001 to P <.01) in ketamine-treated patients. Total fentanyl consumption was significantly decreased by ketamine (70.00 +/- 25.35 microg) or clonidine (136.67 +/- 39.94 microg) compared with the plain lidocaine group (215.33 +/- 52.33 microg) (P <.001 between all groups). CONCLUSIONS: The addition of clonidine 1 microg/kg or ketamine 0.1 mg/kg to lidocaine for IVRA delays the onset of unbearable tourniquet pain and decreases analgesic consumption for tourniquet pain relief, although ketamine has a more potent effect.\n[Drug-Disease]: lidocaine - pain" }, { "pmid": "11708572", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.\n[Abstract]: We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.\n[Drug-Disease]: propinox - menstrual pain" }, { "pmid": "11708572", "target": "[\"Span: 125 mg | Label: Dosage\"]", "text": "[Title]: Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.\n[Abstract]: We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.\n[Drug-Disease]: lysine clonixinate - menstrual pain" }, { "pmid": "11708938", "target": "[]", "text": "[Title]: Effects of risperidone on aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures.\n[Abstract]: The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. A double-blind, crossover design was used to compare risperidone with placebo in a 22-week trial with a 6-month follow-up phase. Based on a 50% reduction in mean Aberrant Behavior Checklist--Community total scores, 50% of the participants were identified as responders. Naturalistic observations of a subset of five individuals showed that for 4 out of 5 participants, risperidone was effective in reducing aberrant behavior. Side effects included weight gain (84% of participants) and sedation (40% of participants). The advantages of conducting a comprehensive analysis of the effects of medication on aberrant behavior are discussed.\n[Drug-Disease]: risperidone - aggression" }, { "pmid": "11712796", "target": "[\"Span: 1,000 mg | Label: Dosage\"]", "text": "[Title]: High dose daily amifostine and hypofractionated intensively accelerated radiotherapy for locally advanced breast cancer. A phase I/II study and report on early and late sequellae.\n[Abstract]: Intrinsic radioresistance, tumor hypoxia and ability of cancer cells to undergo rapid repopulation during radiotherapy are associated with failure of radiotherapy. Tumors with low alpha/beta-ratio values or hypoxic tumors unable to undergo re-oxygenation, are unlikely to be eradicated with standard radiotherapy. Although the therapeutic efficacy of accelerated regimens based on low-dose per fraction may be high since they minimize the adverse role of rapid tumor repopulation, the cellular compartment with low alpha/beta-ratio values (i.e. hypoxic cells) remains a limiting factor. Accelerated hypofractionation, which may be more effective in such tumors, cannot be safely applied unless normal tissues are protected. In the present study we assessed the feasibility of hypofractionated and accelerated radiotherapy supported by cytoprotection (HypoARC) with high dose daily amifostine. Fifteen breast cancer patients with locally advanced disease entered radiation-dose escalation protocoL Twelve consecutive fractions of 3.5-4Gy (5 fractions/week) were given to the breast/chest wall, supraclavicular and axillary area, within 17 days. A high dose of amifostine, at 1,000 mg flat dose, was given 20 minutes before each radiotherapy fraction. Amifostine administration was well- tolerated with minor side-effects (vomiting in 6 out of 15 and hypotention in 2 out of 15 patients). Radiation induced acute skin toxicity was negligible (grade 3 in 1 out of 15 patients). Ten out of 15 patients survived more than 12 months and 7 out of 15 more than 18 months following HypoARC. None of these patients showed any signs of late sequellae, such as lung and myoskeletal fibrosis, or brachial plexopathy. Complete and partial responses were obtained in 11 out of 15 (73%) and in 4 out of 15 (27%) patients, respectively. High dose daily amifostine during hypofractionated radiotherapy is feasible. HypoARC regimen is well-tolerated, effective and has minimal acute and late toxicity to normal breast, chest and axillary tissues.\n[Drug-Disease]: amifostine - breast cancer" }, { "pmid": "11712802", "target": "[\"Span: 800 mg/m2 l.V. | Label: Dosage\"]", "text": "[Title]: An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group.\n[Abstract]: Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required.\n[Drug-Disease]: gemcitabine - non-small cell lung cancer" }, { "pmid": "11712802", "target": "[\"Span: 25 mg/m2 intravenous (I.V.) | Label: Dosage\"]", "text": "[Title]: An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group.\n[Abstract]: Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required.\n[Drug-Disease]: vinorelbine - non-small cell lung cancer" }, { "pmid": "11712820", "target": "[]", "text": "[Title]: Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma.\n[Abstract]: Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy. We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival 4+, 10 and 16 months), respectively; 3 patients had a partial response lasting 4, 6 and 8 months (survival 6+, 11+ and 14 months), respectively. Overall response was 27% (95% confidence interval 11-50%). Toxicity was relatively mild and mainly due to nausea. In 3 patients the dose of carboplatin was reduced because of grade 4 haematological toxicity. This described easy outpatient regimen shows comparable results as other polychemotherapeutic regimens in disseminated melanoma, but with a relatively mild toxicity profile.\n[Drug-Disease]: DTIC - melanoma" }, { "pmid": "11712820", "target": "[]", "text": "[Title]: Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma.\n[Abstract]: Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy. We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival 4+, 10 and 16 months), respectively; 3 patients had a partial response lasting 4, 6 and 8 months (survival 6+, 11+ and 14 months), respectively. Overall response was 27% (95% confidence interval 11-50%). Toxicity was relatively mild and mainly due to nausea. In 3 patients the dose of carboplatin was reduced because of grade 4 haematological toxicity. This described easy outpatient regimen shows comparable results as other polychemotherapeutic regimens in disseminated melanoma, but with a relatively mild toxicity profile.\n[Drug-Disease]: carboplatin - melanoma" }, { "pmid": "11713998", "target": "[]", "text": "[Title]: Magnesium sulphate for treatment of eclampsia: the Nigerian experience.\n[Abstract]: The preliminary result of an ongoing study in 4 major hospitals across Nigeria on the use of magnesium sulphate (MgSO4) as an anticonvulsant in the management of eclampsia is presented. All the 21 obstetric patients with eclampsia (recruited so far) were treated with MgSO4 as the only anticonvulsant. All the patients responded well to the treatment regime in terms of control of fit, and remained conscious thereafter. There was no incidence of severe adverse reactions to the drug. The mean number of convulsions in the patients treated was 4. The observed side effects were nausea, vomiting and dizziness in 3 patients and there were 3 perinatal deaths. The findings so far on maternal and fetal outcomes support the routine administration of MgSO4 as the drug of choice for the control of convulsion in women with eclampsia.\n[Drug-Disease]: MgSO4 - eclampsia" }, { "pmid": "11715997", "target": "[]", "text": "[Title]: The use of short-form quality of life questionnaires to measure the impact of imipramine on women with urge incontinence.\n[Abstract]: Short-form questionnaires were used to measure the change in quality of life (QOL) of women with urge-predominant urinary incontinence treated with imipramine hydrochloride. Short forms of the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Index (UDI-6) were integrated into a patient questionnaire, which was given to 25 patients with urge-predominant urinary incontinence before and after treatment with imipramine. Demographic data and self-reports of the number of incontinent episodes were also recorded. Total and subscale QOL scores and number of incontinent episodes were recorded and compared with Wilcoxson's signed ranks test, as well as correlated to the change in number of incontinent episodes with Pearson's correlation coefficient. Treatment with imipramine resulted in a clinical improvement or cure in 16/22 patients (72.7%), with an average reduction in incontinent episodes of 78.7% (P<0.001). The average per cent improvement in QOL scores for total IIQ-7 was 42.1% (P<0.01) and total UDI-6 score was 44.1% (P<0.001). All subscale QOL differences were also significant (P<0.01). The incidence of side effects to imipramine was 41%, which resulted in dose changes. Fourteen per cent eventually discontinued therapy. Neither total nor subscale QOL improvement scores were correlated with improvement in number of incontinent episodes. The short form IIQ-7 and UDI-6 are effective tools to determine change in QOL, as evidenced by the effectiveness of imipramine for the treatment of urge-predominant urinary incontinence. Significant reductions in incontinent episodes and improvements in IIQ-7 and UDI-6 QOL scores were both seen, but were not correlated. Short-form QOL measures can easily be integrated into a patient questionnaire to objectively measure a very subjective topic.\n[Drug-Disease]: imipramine - urinary incontinence" }, { "pmid": "11717605", "target": "[\"Span: 180 to 540 mg | Label: Dosage\"]", "text": "[Title]: Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.\n[Abstract]: BACKGROUND: Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. METHODS: Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. RESULTS: In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. CONCLUSION: These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.\n[Drug-Disease]: verapamil - angina" }, { "pmid": "11717605", "target": "[\"Span: 180 to 540 mg | Label: Dosage\"]", "text": "[Title]: Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.\n[Abstract]: BACKGROUND: Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. METHODS: Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. RESULTS: In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. CONCLUSION: These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.\n[Drug-Disease]: verapamil - hypertension" }, { "pmid": "11718321", "target": "[\"Span: 20 mg/kg/day | Label: Dosage\"]", "text": "[Title]: Divalproex loading in the treatment of cocaine dependence.\n[Abstract]: The current pilot project was designed to evaluate the safety and tolerability of a loading dose of divalproex (DVPX) in subjects with cocaine dependence. Seventeen cocaine-dependent subjects were enrolled in an eight-week, open-label trial of 20 mg/kg/day DVPX. Subjects were seen weekly and urine drug screens were obtained at each visit. Over the eight-week trial, craving intensity and frequency as well as reported time using cocaine decreased significantly. Retention in the current study was 79% at week four and 50% at week eight. The medication and dosing strategy was well tolerated. This pilot study indicates that DVPX loading is well tolerated and may be efficacious in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.\n[Drug-Disease]: DVPX - cocaine dependence" }, { "pmid": "11719720", "target": "[\"Span: women | Label: Gender\", \"Span: mean age 28.6 years | Label: Age\", \"Span: 500 mg | Label: Dosage\"]", "text": "[Title]: Preliminary experience with steroidal ovarian suppression for prevention of severe ovarian hyperstimulation syndrome in IVF patients.\n[Abstract]: The purpose of the study was to evaluate the efficiency of administration of high dose progesterone in combination with oestradiol during the luteal phase for the prevention of ovarian hyperstimulation syndrome in a high-risk population of patients undergoing in vitro fertilization. An observational study was carried out involving 21 women (mean age 28.6 years) undergoing controlled ovarian stimulation for in vitro fertilization. The women were identified as at risk of ovarian hyperstimulation syndrome as they had suffered from the condition when hCG was used for luteal phase support in previous cycles. Steroidal suppression of the stimulated ovary on days 2, 6, 10 and 14 after embryo transfer was achieved by intramuscular injections of 500 mg hydroxyprogesterone caproate and 10 mg oestradiol valerate. The incidence of moderate and severe ovarian hyperstimulation syndrome under steroidal ovarian suppression, serum progesterone concentration and pregnancy rates were compared with those in cycles in which human chorionic gonadotrophin was used for luteal phase support. No cases of moderate or severe ovarian hyperstimulation syndrome occurred under steroidal ovarian suppression. Despite low progesterone concentrations (mean 10.7 nmol l(-1), range 2.6-24.5), indicating almost complete ovarian suppression, the pregnancy rate was not impaired. These preliminary results indicate that steroidal ovarian suppression during the luteal phase is a promising tool for reducing the incidence and severity of ovarian hyperstimulation syndrome in a high-risk population, without compromising the pregnancy rate.\n[Drug-Disease]: hydroxyprogesterone caproate - ovarian hyperstimulation syndrome" }, { "pmid": "11719720", "target": "[\"Span: women | Label: Gender\", \"Span: mean age 28.6 years | Label: Age\", \"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Preliminary experience with steroidal ovarian suppression for prevention of severe ovarian hyperstimulation syndrome in IVF patients.\n[Abstract]: The purpose of the study was to evaluate the efficiency of administration of high dose progesterone in combination with oestradiol during the luteal phase for the prevention of ovarian hyperstimulation syndrome in a high-risk population of patients undergoing in vitro fertilization. An observational study was carried out involving 21 women (mean age 28.6 years) undergoing controlled ovarian stimulation for in vitro fertilization. The women were identified as at risk of ovarian hyperstimulation syndrome as they had suffered from the condition when hCG was used for luteal phase support in previous cycles. Steroidal suppression of the stimulated ovary on days 2, 6, 10 and 14 after embryo transfer was achieved by intramuscular injections of 500 mg hydroxyprogesterone caproate and 10 mg oestradiol valerate. The incidence of moderate and severe ovarian hyperstimulation syndrome under steroidal ovarian suppression, serum progesterone concentration and pregnancy rates were compared with those in cycles in which human chorionic gonadotrophin was used for luteal phase support. No cases of moderate or severe ovarian hyperstimulation syndrome occurred under steroidal ovarian suppression. Despite low progesterone concentrations (mean 10.7 nmol l(-1), range 2.6-24.5), indicating almost complete ovarian suppression, the pregnancy rate was not impaired. These preliminary results indicate that steroidal ovarian suppression during the luteal phase is a promising tool for reducing the incidence and severity of ovarian hyperstimulation syndrome in a high-risk population, without compromising the pregnancy rate.\n[Drug-Disease]: oestradiol valerate - ovarian hyperstimulation syndrome" }, { "pmid": "11721720", "target": "[\"Span: 10 mg bolus + 10 mg/hour for 3 days | Label: Dosage\"]", "text": "[Title]: Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction.\n[Abstract]: BACKGROUND: Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function. METHODS: We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%. RESULTS: Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up). CONCLUSIONS: Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.\n[Drug-Disease]: diltiazem - acute myocardial infarction" }, { "pmid": "11723269", "target": "[\"Span: 2, 6.25, 12.5, or 25 mg | Label: Dosage\"]", "text": "[Title]: Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine.\n[Abstract]: OBJECTIVE: To assess the efficacy and tolerability of oral almotriptan, a selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in the treatment of acute migraine. METHODS: This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomized to a single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset of moderate or severe pain. Patients graded pain intensity on a 4-point verbal scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The primary efficacy variable was headache response at 2 hours. Data were analyzed on an intent-to-treat basis. RESULTS: Nine hundred and three patients were randomized, and 742 were included in the evaluation of the efficacy and tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%, 56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05 for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence of migraine-associated symptoms and the need for escape medication was observed. The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg groups was comparable to that with the placebo group. CONCLUSION: Almotriptan 12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, offering equivalent efficacy and better tolerability compared with the 25 mg dose. The minimum effective dose of almotriptan was 6.25 mg.\n[Drug-Disease]: almotriptan - migraine" }, { "pmid": "11725558", "target": "[\"Span: 2-8 mg/day | Label: Dosage\"]", "text": "[Title]: [Effect of doxazosin on postural changes in blood pressure using a multibiomedical recorder].\n[Abstract]: To investigate the effect of doxazosin on orthostatic blood pressure changes with daily activity, the relationship among blood pressure, physical position and physical activities using an ambulatory multibiomedical monitoring system(TM2425) were studied. The subjects were 22 patients with essential hypertension(EHT group), 23 patients with diabetic mellitus(DM group) and 17 healthy volunteers for the control. Patients were administered doxazosin at 2-8 mg/day for 0.5 month to 12 months. Twenty-four-hour blood pressure, posture and activity were monitored. Systolic blood pressure was higher in the standing position than that in the sitting position in the control group, but there were no differences between these values in the EHT group and DM groups. During the awake, sleep, and standing periods, doxazosin significantly decreased blood pressure in the EHT group; however, it significantly decreased only the standing systolic blood pressure in the DM group. Absolute changes in blood pressure after the administration of doxazosin were not significantly different between the standing and sitting periods in each group. These findings suggest that doxazosin decreases the blood pressure of both patients with essential hypertension and patients with diabetic mellitus without an excessive decrease in standing blood pressure.\n[Drug-Disease]: doxazosin - hypertension" }, { "pmid": "11728832", "target": "[]", "text": "[Title]: Clozapine: its impact on aggressive behavior among patients in a state psychiatric hospital.\n[Abstract]: Clozapine has shown consistent efficacy against positive symptoms of psychoses, and emerging reports indicate improvements in aggression and suicidality. This study evaluated the impact of clozapine aggression in a psychiatric hospital. Over a three year period, 137 subjects with schizophrenia or schizoaffective disorder received clozapine, of whom nearly 50% (n=69) experienced seclusion or restraint. Using a mirror-image study design, seclusion and restraint rates were computed per patient-month pre-clozapine and compared during clozapine treatment to a maximum of 12 months in either direction. The rest of the hospital not receiving clozapine served as a comparator group. Statistically significant reductions occurred in both seclusion (0.44+/-0.46 vs. 0.16+/-0.32, z=-3.91, p=0.0003) and restraint (0.34+/-0.47 vs. 0.08+/-0.23, z=-2.27, p=0.032) during clozapine treatment as compared with the pre-clozapine period. The comparator group experienced a low rate of seclusion and restraint throughout. While there are limitations to a mirror-image design, this study supports the emerging data on the benefits of clozapine for aggressive and violent patients with psychoses. Preliminary data suggests other second generation antipsychotic agents may have similar effects.\n[Drug-Disease]: clozapine - schizophrenia or schizoaffective disorder" }, { "pmid": "11729705", "target": "[]", "text": "[Title]: Evaluation of different nebulized bronchodilators on clinical efficacy and hypokalemia in asthmatic children.\n[Abstract]: Acute asthma attack continues to be a major cause for children admitted to the emergency room. Nebulized beta 2-adrenergic agonists are still the first-line drugs for a rapid bronchodilation effect and an easily administered drug during acute asthma attack. The bronchodilator-induced hypokalemia is thought significant in adult group, but is often ignored in children group. In this study, we conducted a randomized study to compare the laboratory and clinical effects between nebulized salbutamol and terbutaline. We found that both salbutamol and terbutaline nebulization induced a significant hypokalemia (p < 0.05). Terbutaline nebulization also significantly improved the peak expiratory flow rate (PEFR) and respiratory rate (RR), but not venous partial pressure of oxygen (PvO2), venous carbon dioxide tension (PvCO2) and O2 saturation in venous blood (SvO2). In contrast, salbutamol improved not only PEFR and RR, but also PvO2, PvCO2, and SvO2 30 minutes of administration. In conclusion, the nebulized salbutamol, although induced a hypokalemic effect which is similar to terbutaline group, has a better effect on improving O2 saturation than nebulized terbutaline with the same dose 30 minutes after administered for children with acute asthma attack.\n[Drug-Disease]: salbutamol - asthma" }, { "pmid": "11729705", "target": "[]", "text": "[Title]: Evaluation of different nebulized bronchodilators on clinical efficacy and hypokalemia in asthmatic children.\n[Abstract]: Acute asthma attack continues to be a major cause for children admitted to the emergency room. Nebulized beta 2-adrenergic agonists are still the first-line drugs for a rapid bronchodilation effect and an easily administered drug during acute asthma attack. The bronchodilator-induced hypokalemia is thought significant in adult group, but is often ignored in children group. In this study, we conducted a randomized study to compare the laboratory and clinical effects between nebulized salbutamol and terbutaline. We found that both salbutamol and terbutaline nebulization induced a significant hypokalemia (p < 0.05). Terbutaline nebulization also significantly improved the peak expiratory flow rate (PEFR) and respiratory rate (RR), but not venous partial pressure of oxygen (PvO2), venous carbon dioxide tension (PvCO2) and O2 saturation in venous blood (SvO2). In contrast, salbutamol improved not only PEFR and RR, but also PvO2, PvCO2, and SvO2 30 minutes of administration. In conclusion, the nebulized salbutamol, although induced a hypokalemic effect which is similar to terbutaline group, has a better effect on improving O2 saturation than nebulized terbutaline with the same dose 30 minutes after administered for children with acute asthma attack.\n[Drug-Disease]: terbutaline - asthma" }, { "pmid": "11730575", "target": "[\"Span: 4.4 (SD: 2.4 mg/daily; range: 0.5-12 mg/daily) | Label: Dosage\"]", "text": "[Title]: [Risperidone in the treatment of psychotic patients with opiate abuse and dependence].\n[Abstract]: INTRODUCTION: 180 psychotic patients with opiate dependence and abuse (ICD-10) were included in an open label study. The study objectives were to evaluate safety and efficacy of risperidone for a six month follow-up period. The total mean dose was 4.4 (SD: 2.4 mg/daily; range: 0.5-12 mg/daily). METHODS: BPRS, CGI and DDS-SV were used to assess efficacy and UKU subscale for neurological side effects and spontaneous reports for safety. RESULTS: Risperidone treatment improved symptoms, disability of the included patients with a significant reduction in the mean total scores of BPRS, CGI and DDS-SV observed from the first month of treatment onwards. Risperidone also reduced illegal opiate abuse patients from 39% basedate to 18% at month 6. There was a significant reduction (p< 0.0001) in the total UKU subscale for neurological side effects scores from visit 1 onwards for studied sample. Risperidone was well tolerated by the study patients. From 165 elegible patients, just 10 (6.1%) discontinued treatment due to adverse reactions, 94% of the patients did not suffer any adverse event; the most frequent adverse events according spontaneous reports were extrapyramidal effects (3%) and anxiety (1.8%). DISCUSSION: Risperidone improved disability, psychotic symptoms and tolerability of these patients. Those results could mean an outstanding breakthrough in the treatment of these type of disorders and, if it is confirmed that risperidone can lead to abstinence, we would be before a new line of treatment for dual pathology.\n[Drug-Disease]: risperidone - illegal opiate abuse" }, { "pmid": "11730575", "target": "[\"Span: 4.4 (SD: 2.4 mg/daily; range: 0.5-12 mg/daily) | Label: Dosage\"]", "text": "[Title]: [Risperidone in the treatment of psychotic patients with opiate abuse and dependence].\n[Abstract]: INTRODUCTION: 180 psychotic patients with opiate dependence and abuse (ICD-10) were included in an open label study. The study objectives were to evaluate safety and efficacy of risperidone for a six month follow-up period. The total mean dose was 4.4 (SD: 2.4 mg/daily; range: 0.5-12 mg/daily). METHODS: BPRS, CGI and DDS-SV were used to assess efficacy and UKU subscale for neurological side effects and spontaneous reports for safety. RESULTS: Risperidone treatment improved symptoms, disability of the included patients with a significant reduction in the mean total scores of BPRS, CGI and DDS-SV observed from the first month of treatment onwards. Risperidone also reduced illegal opiate abuse patients from 39% basedate to 18% at month 6. There was a significant reduction (p< 0.0001) in the total UKU subscale for neurological side effects scores from visit 1 onwards for studied sample. Risperidone was well tolerated by the study patients. From 165 elegible patients, just 10 (6.1%) discontinued treatment due to adverse reactions, 94% of the patients did not suffer any adverse event; the most frequent adverse events according spontaneous reports were extrapyramidal effects (3%) and anxiety (1.8%). DISCUSSION: Risperidone improved disability, psychotic symptoms and tolerability of these patients. Those results could mean an outstanding breakthrough in the treatment of these type of disorders and, if it is confirmed that risperidone can lead to abstinence, we would be before a new line of treatment for dual pathology.\n[Drug-Disease]: risperidone - psychotic" }, { "pmid": "11731754", "target": "[\"Span: 100 mg i.v. | Label: Dosage\"]", "text": "[Title]: Ketorolac vs tramadol in the treatment of postoperative pain during maxillofacial surgery.\n[Abstract]: BACKGROUND: This study aims to assess the best postoperative analgesia during maxillofacial surgery by using small doses of ketorolac or tramadol or their association and evaluates the presence of adverse effects due to NSAID or opioid use. METHODS: After their informed consent, 51 patients ASA I and II undergoing major maxillofacial surgery, were randomised in three groups and the following protocol was used: group K received ketorolac (30 mg i.v.) at the time of skin closure and repeated after 8 hrs and 16 hrs from the end of the operation. Group T received tramadol (100 mg i.v.) in the same condition; and group KT received first tramadol (100 mg i.v.) during surgery and then ketorolac (30 mg) was given in the administrations that followed. Meperidine 50 mg was used in case of unsatisfactory analgesia. Pain was evaluated using pain intensity scores 2, 4, 6, 12 and 24 hours from the end of the operation. Data was analysed using Anova and c2 test. RESULTS: The groups were comparable with regard to age, weight, duration of surgery. Very good postoperative analgesia was recorded in three groups. There is no difference statistically between K, T and KT groups in the pain scores measured. Only a low number of patients required opioids administration to achieve adequate analgesia. The patients were considered to have achieved excellent analgesia in 64.8% in T group, in 41.2% of the K group and in 58.8% of the KT group. There were no cases of insufficient analgesia. We did not find a significant difference considering BP, HR, respiratory depression in the post-operative period. Vomiting was registered in 41.2% of this T group vs 11.2% of the K group and in 35.5% of the KT group. CONCLUSIONS: Ketorolac and Tramadol produced comparable, effective and low cost postoperative analgesia during maxillofacial surgery. There are only statistically significant differences considering side effects.\n[Drug-Disease]: Tramadol - postoperative pain" }, { "pmid": "11731754", "target": "[\"Span: 30 mg | Label: Dosage\"]", "text": "[Title]: Ketorolac vs tramadol in the treatment of postoperative pain during maxillofacial surgery.\n[Abstract]: BACKGROUND: This study aims to assess the best postoperative analgesia during maxillofacial surgery by using small doses of ketorolac or tramadol or their association and evaluates the presence of adverse effects due to NSAID or opioid use. METHODS: After their informed consent, 51 patients ASA I and II undergoing major maxillofacial surgery, were randomised in three groups and the following protocol was used: group K received ketorolac (30 mg i.v.) at the time of skin closure and repeated after 8 hrs and 16 hrs from the end of the operation. Group T received tramadol (100 mg i.v.) in the same condition; and group KT received first tramadol (100 mg i.v.) during surgery and then ketorolac (30 mg) was given in the administrations that followed. Meperidine 50 mg was used in case of unsatisfactory analgesia. Pain was evaluated using pain intensity scores 2, 4, 6, 12 and 24 hours from the end of the operation. Data was analysed using Anova and c2 test. RESULTS: The groups were comparable with regard to age, weight, duration of surgery. Very good postoperative analgesia was recorded in three groups. There is no difference statistically between K, T and KT groups in the pain scores measured. Only a low number of patients required opioids administration to achieve adequate analgesia. The patients were considered to have achieved excellent analgesia in 64.8% in T group, in 41.2% of the K group and in 58.8% of the KT group. There were no cases of insufficient analgesia. We did not find a significant difference considering BP, HR, respiratory depression in the post-operative period. Vomiting was registered in 41.2% of this T group vs 11.2% of the K group and in 35.5% of the KT group. CONCLUSIONS: Ketorolac and Tramadol produced comparable, effective and low cost postoperative analgesia during maxillofacial surgery. There are only statistically significant differences considering side effects.\n[Drug-Disease]: Ketorolac - postoperative pain" }, { "pmid": "11732515", "target": "[\"Span: children aged 1-9 yr | Label: Age\", \"Span: 0.5 microg kg(-1) | Label: Dosage\"]", "text": "[Title]: Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes.\n[Abstract]: We compared the efficacy of rectally and intravenously administered ketoprofen for pain management after day-case adenoidectomy. Patients (123 children aged 1-9 yr) were allocated randomly to receive on induction of anaesthesia ketoprofen 25 mg rectally with an i.v. placebo, ketoprofen 25 mg i.v. with a rectal placebo, or placebo both i.v. and rectally. The method of anaesthesia and the operative technique were standardized. Postoperative pain was assessed at rest and during swallowing using the Maunuksela pain scale (0=no pain, 10=worst possible pain). Fentanyl 0.5 microg kg(-1) was given as rescue analgesia. There was no significant difference between the two ketoprofen groups in their requirement for rescue analgesics. However, both the proportion of children needing rescue analgesics [55 of 84 children (65%) vs. 33 of 39 children (84%); difference 19%, 95% confidence interval 4-34%, P=0.029] and the number of rescue analgesic doses [mean 1.2 (SD 1.2) vs. 2.2 (1.4); mean difference 0.9, 95% confidence interval 0.4-1.4, P=0.001] were significantly lower among children receiving ketoprofen than in children receiving placebo. Adverse events, duration of operation, perioperative bleeding, pain scores and time of discharge were similar in the three groups.\n[Drug-Disease]: Fentanyl - Postoperative pain" }, { "pmid": "11732515", "target": "[\"Span: children aged 1-9 yr | Label: Age\", \"Span: 25 mg i.v. | Label: Dosage\"]", "text": "[Title]: Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes.\n[Abstract]: We compared the efficacy of rectally and intravenously administered ketoprofen for pain management after day-case adenoidectomy. Patients (123 children aged 1-9 yr) were allocated randomly to receive on induction of anaesthesia ketoprofen 25 mg rectally with an i.v. placebo, ketoprofen 25 mg i.v. with a rectal placebo, or placebo both i.v. and rectally. The method of anaesthesia and the operative technique were standardized. Postoperative pain was assessed at rest and during swallowing using the Maunuksela pain scale (0=no pain, 10=worst possible pain). Fentanyl 0.5 microg kg(-1) was given as rescue analgesia. There was no significant difference between the two ketoprofen groups in their requirement for rescue analgesics. However, both the proportion of children needing rescue analgesics [55 of 84 children (65%) vs. 33 of 39 children (84%); difference 19%, 95% confidence interval 4-34%, P=0.029] and the number of rescue analgesic doses [mean 1.2 (SD 1.2) vs. 2.2 (1.4); mean difference 0.9, 95% confidence interval 0.4-1.4, P=0.001] were significantly lower among children receiving ketoprofen than in children receiving placebo. Adverse events, duration of operation, perioperative bleeding, pain scores and time of discharge were similar in the three groups.\n[Drug-Disease]: ketoprofen - Postoperative pain" }, { "pmid": "11739835", "target": "[]", "text": "[Title]: Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study.\n[Abstract]: The lateral segment of the globus pallidus (GPl) is thought to be overactive in levodopa-induced dyskinesia in PD. Stimulation of cannabinoid receptors in the GPl reduces gamma-aminobutyric acid (GABA) reuptake and enhances GABA transmission and may thus alleviate dyskinesia. In a randomized, double-blind, placebo-controlled, crossover trial (n = 7), the authors demonstrate that the cannabinoid receptor agonist nabilone significantly reduces levodopa-induced dyskinesia in PD.\n[Drug-Disease]: nabilone - dyskinesia" }, { "pmid": "11740135", "target": "[\"Span: elderly patients | Label: Age\", \"Span: 5-10 mg | Label: Dosage\"]", "text": "[Title]: A double-blind, parallel-group study of amlodipine versus long-acting nitrate in the management of elderly patients with stable angina.\n[Abstract]: Ninety-seven elderly patients with stable angina were included in a 28-week, randomized, double-blind, parallel-group comparison of amlodipine 5-10 mg and isosorbide mononitrate 25-50 mg once daily. The total exercise time, as limited by angina, was recorded together with the median incidence per week of angina attacks and glyceryl trinitrate consumption. Safety was assessed by adverse event frequency, measurement of vital signs and laboratory parameters, and quality of life. At the final visit, the total exercise time was significantly greater relative to baseline with amlodipine than isosorbide mononitrate (final/baseline difference: 112.2 vs. 32.2, p = 0.016). There were no statistically significant differences between the groups in relation to the incidence of adverse events. Once daily amlodipine provides significantly better control of stable angina than isosorbide mononitrate in this elderly population.\n[Drug-Disease]: amlodipine - angina" }, { "pmid": "11744130", "target": "[\"Span: 5, 10, 15 or 20 microg/kg/min | Label: Dosage\"]", "text": "[Title]: Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.\n[Abstract]: OBJECTIVE: To compare the efficacy of milrinone and dobutamine in patients chronically treated with carvedilol. BACKGROUND: Milrinone and dobutamine are used to manage decompensated heart failure, but their efficacy in patients on beta-blocker therapy was unknown. METHODS: Twenty patients with decompensated heart failure were prospectively enrolled. Inotropic responses to milrinone (12.5, 25 or 50 microg/kg bolus infusions) or dobutamine (5, 10, 15 or 20 microg/kg/min infusions) were evaluated by right-heart catheterization. RESULTS: Milrinone increased cardiac index (2.0-2.6 l/min/m2, P=0.0001) without significantly altering heart rate (70-75 bpm, P=0.19). Milrinone decreased mean pulmonary artery pressure (36-29 mm Hg, P=0.0001), pulmonary capillary wedge pressure (24-18 mm Hg, P=0.0001) and mean arterial blood pressure (78-75 mm Hg, P=0.0002). Left ventricular stroke volume index increased in the milrinone group (31-35 ml/beat/m2, P=0.0001). Dobutamine produced an increase in cardiac index (2.4-3.3 l/min/m2, P=0.0001) only at doses that are not typically used to treat heart failure (15-20 microg/kg/min). At these doses, dobutamine increased heart rate (68-82 bpm, P=0.008), mean systemic pressure (90-117 mm Hg, P=0.0001) and mean pulmonary artery pressure (21-30 mm Hg, P=0.001). Dobutamine did not alter left ventricular stroke volume index or pulmonary capillary wedge pressure. CONCLUSIONS: Dobutamine and milrinone have different hemodynamic effects in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated heart failure.\n[Drug-Disease]: Dobutamine - heart failure" }, { "pmid": "11744130", "target": "[\"Span: 12.5, 25 or 50 microg/kg | Label: Dosage\"]", "text": "[Title]: Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.\n[Abstract]: OBJECTIVE: To compare the efficacy of milrinone and dobutamine in patients chronically treated with carvedilol. BACKGROUND: Milrinone and dobutamine are used to manage decompensated heart failure, but their efficacy in patients on beta-blocker therapy was unknown. METHODS: Twenty patients with decompensated heart failure were prospectively enrolled. Inotropic responses to milrinone (12.5, 25 or 50 microg/kg bolus infusions) or dobutamine (5, 10, 15 or 20 microg/kg/min infusions) were evaluated by right-heart catheterization. RESULTS: Milrinone increased cardiac index (2.0-2.6 l/min/m2, P=0.0001) without significantly altering heart rate (70-75 bpm, P=0.19). Milrinone decreased mean pulmonary artery pressure (36-29 mm Hg, P=0.0001), pulmonary capillary wedge pressure (24-18 mm Hg, P=0.0001) and mean arterial blood pressure (78-75 mm Hg, P=0.0002). Left ventricular stroke volume index increased in the milrinone group (31-35 ml/beat/m2, P=0.0001). Dobutamine produced an increase in cardiac index (2.4-3.3 l/min/m2, P=0.0001) only at doses that are not typically used to treat heart failure (15-20 microg/kg/min). At these doses, dobutamine increased heart rate (68-82 bpm, P=0.008), mean systemic pressure (90-117 mm Hg, P=0.0001) and mean pulmonary artery pressure (21-30 mm Hg, P=0.001). Dobutamine did not alter left ventricular stroke volume index or pulmonary capillary wedge pressure. CONCLUSIONS: Dobutamine and milrinone have different hemodynamic effects in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated heart failure.\n[Drug-Disease]: milrinone - heart failure" }, { "pmid": "11745184", "target": "[]", "text": "[Title]: A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).\n[Abstract]: BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.\n[Drug-Disease]: cisplatin - breast carcinoma" }, { "pmid": "11745280", "target": "[\"Span: median age of 49 (range, 39-69) | Label: Age\"]", "text": "[Title]: Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma.\n[Abstract]: BACKGROUND: Currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes. A biologic rationale suggests that the mechanism of taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study was to assess the tolerance and efficiency of weekly vinorelbine in metastatic breast carcinoma after failure with taxanes. METHODS: Patients with measurable disease, a World Health Organization performance status of less than 3 and a life expectancy longer than 3 months were eligible. Persistent taxane-induced neuropathy higher than Grade 1 was an exclusion criterion. The initial planned dose was 30 mg/m(2)/week on an outpatient basis without granulocyte colony-stimulating factor (G-CSF). Neutrophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days with a dose reduction of 5 mg/m(2) at the second episode. The dose also was reduced if Grade 3 or 4 toxicity occurred. If the adverse event persisted or if the delay exceeded 14 days between 2 injections given at a dose of 20 mg/m(2), vinorelbine was definitively discontinued. RESULTS: Between November 1997 and March 1999, 40 patients with a median age of 49 (range, 39-69) were enrolled. All of them had previously received anthracyclines and taxanes. Because of the delays in neutrophil recovery, the median dose intensity did not exceed 22.5 mg/m(2)/week (range, 11.25-30), and the initial planned dose of 30 mg/m(2)/week appeared unfeasible without G-CSF. The starting dose therefore was 25 mg/m(2)/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe toxicities were Grade 2-3 neuropathy (n = 5), Grade 2-3 ileus (n = 7), Grade 3 anemia (n = 4), and Grade 3 sepsis (n = 1). Objective responses were observed in 10 of 40 patients (25%), 7 of whom had visceral metastases and 4 who were refractory to taxanes (including 2 patients with liver involvement > 50%). The median time to failure was 6 months (range, 4-12) for responding patients. Disease stabilization was achieved in 9 patients (23%) for a median duration of 5 months (range, 4-6). The median survival duration for the whole population was 6 months (range, 2-18+). CONCLUSIONS: Weekly vinorelbine is an active salvage therapy for metastatic breast carcinoma after failure with anthracyclines and taxanes, even in patients with taxane-refractory metastatic breast carcinoma. This confirms that vinorelbine and taxanes are not cross-resistant.\n[Drug-Disease]: vinorelbine - breast carcinoma" }, { "pmid": "11745287", "target": "[]", "text": "[Title]: Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.\n[Abstract]: BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.\n[Drug-Disease]: doxorubicin - squamous cell cervical carcinoma" }, { "pmid": "11745287", "target": "[]", "text": "[Title]: Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.\n[Abstract]: BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.\n[Drug-Disease]: carboplatin - squamous cell cervical carcinoma" }, { "pmid": "11746615", "target": "[\"Span: 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d. | Label: Dosage\"]", "text": "[Title]: Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations.\n[Abstract]: In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included \"off\" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of fife, was better tolerated, and had a more favorable adverse-event profile than pergolide.\n[Drug-Disease]: Tolcapone - Parkinson's Disease" }, { "pmid": "11746615", "target": "[\"Span: maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day | Label: Dosage\"]", "text": "[Title]: Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations.\n[Abstract]: In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included \"off\" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of fife, was better tolerated, and had a more favorable adverse-event profile than pergolide.\n[Drug-Disease]: pergolide - Parkinson's Disease" }, { "pmid": "11752998", "target": "[\"Span: 0.25-2.0 mg | Label: Dosage\"]", "text": "[Title]: Preliminary efficacy assessment of intrathecal injection of an American formulation of adenosine in humans.\n[Abstract]: BACKGROUND: Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans, and preliminary studies in volunteers and patients with a Swedish formulation of adenosine suggests it may be effective in hypersensitivity states but not with acute noxious stimulation. The purpose of this study was to screen for efficacy of a different formulation of adenosine marketed in the US, using both acute noxious stimulation and capsaicin-evoked mechanical hypersensitivity. METHODS: Following Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg and a double-blind, placebo-controlled trial of adenosine, 2 mg. Cerebrospinal fluid was obtained for pharmacokinetic analysis, and pain ratings in response to acute heat stimuli and areas of mechanical hyperalgesia and allodynia after intradermal capsaicin injection were determined. RESULTS: Adenosine produced no effect on pain report to acute noxious thermal or chemical stimulation but reduced mechanical hyperalgesia and allodynia from intradermal capsaicin injection for at least 24 h. In contrast, residence time of adenosine in cerebrospinal fluid was short (< 4 h). CONCLUSIONS: These results show selective inhibition by intrathecal adenosine of hypersensitivity, presumed to reflect central sensitization in humans after peripheral capsaicin injection. The long-lasting effect is consistent with that observed in preliminary reports of patients with chronic neuropathic pain and is not due to prolonged residence of adenosine in cerebrospinal fluid.\n[Drug-Disease]: adenosine - allodynia" }, { "pmid": "11755835", "target": "[\"Span: 0.2% | Label: Dosage\"]", "text": "[Title]: Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.\n[Abstract]: PURPOSE: To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS: Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS: A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS: Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.\n[Drug-Disease]: brimonidine - ocular hypertension" }, { "pmid": "11755835", "target": "[\"Span: 0.005% | Label: Dosage\"]", "text": "[Title]: Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.\n[Abstract]: PURPOSE: To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS: Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS: A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS: Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.\n[Drug-Disease]: latanoprost - ocular hypertension" }, { "pmid": "11757212", "target": "[\"Span: 70 to 140 mg | Label: Dosage\", \"Span: 300 to 600 mg | Label: Dosage\"]", "text": "[Title]: [Comparison of efficacy, safety and cost-effectiveness of intravenous versus oral propafenone in paroxysmal atrial fibrillation].\n[Abstract]: The purpose of this study was to investigate the efficacy, safety and cost-effectiveness of intravenous and oral propafenone in the conversion of paroxysmal atrial fibrillation propafenone to sinus rhythm. We analysed two groups of 100 consecutive patients (pts) treated because of propafenone with duration < 48 h. The first group was treated with intravenous PFN (bolus of 70 to 140 mg) and the second group was treated with oral PFN (300 to 600 mg). These 2 groups were comparable in age, sex, evidence of CAD, hypertension, mitral valve disease, history of hyperthyroidism and the level of K+ at admittance. Conversion to sinus rhythm was achieved in 64 (64%) pts who received i.v. propafenone and in 77 (77%) who received oral propafenone (p < 0.05). We conclude that oral and intravenous propafenone is safe in the termination of propafenone. Oral route of administration appears to be superior to intravenous because of greater efficacy and cost-effectiveness.\n[Drug-Disease]: propafenone - paroxysmal atrial fibrillation" }, { "pmid": "11757763", "target": "[\"Span: 3.0 g/day | Label: Dosage\"]", "text": "[Title]: Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis.\n[Abstract]: We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take.\n[Drug-Disease]: colestimide - cholestasis" }, { "pmid": "11757763", "target": "[\"Span: 3.0 g/day | Label: Dosage\"]", "text": "[Title]: Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis.\n[Abstract]: We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take.\n[Drug-Disease]: colestimide - hepatitis" }, { "pmid": "11758322", "target": "[]", "text": "[Title]: [Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection].\n[Abstract]: To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P < 0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P < 0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain.\n[Drug-Disease]: lidocaine - pain" }, { "pmid": "11758890", "target": "[]", "text": "[Title]: Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid.\n[Abstract]: We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.\n[Drug-Disease]: beclomethasone dipropionate - asthma" }, { "pmid": "11758890", "target": "[]", "text": "[Title]: Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid.\n[Abstract]: We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.\n[Drug-Disease]: theophylline - asthma" }, { "pmid": "1175893", "target": "[]", "text": "[Title]: Effects of clofibrate in primary biliary cirrhosis hypercholesterolemia and gallstones.\n[Abstract]: A patient with primary biliary cirrhosis is reported in whom the administration of clofibrate in a dose of 1 g per day for 2 months resulted in a marked increase in hypercholesterolemia, and endoscopic retrograde cholangiography showed multiple intrahepatic gallstones. The stones disappeared 3 months after stopping clofibrate and starting chenodeoxycholic acid in a dose of 125 mg daily. These observations are discussed in relation to the known effects of clofibrate on bile composition.\n[Drug-Disease]: chenodeoxycholic acid - intrahepatic gallstones" }, { "pmid": "11762651", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.\n[Abstract]: OBJECTIVE: To assess the maternal, fetal and neonatal safety of enoxaparin in pregnant women who require antithrombotic therapy. DESIGN: Retrospective analysis of case notes of women who received enoxaparin during pregnancy, irrespective of dose, duration and reason for treatment. SETTING: Fifty-five French perinatal centres. SAMPLE: Data from 624 pregnancies in 604 women between 1988 and 1997. The incidence of previous thromboembolism was 29.8%, known thrombophilia 15.2%. METHODS: Indication, regimen of enoxaparin and outcome measures were reported for each pregnancy. Information was obtained from case records, validated by research staff and analysed by an independent scientific committee. MAIN OUTCOME MEASURES: Incidence, seriousness and causality of maternal, fetal and neonatal adverse events, pregnancy outcome, and incidence of venous thromboembolism. RESULTS: Enoxaparin was administered for treatment of an acute episode in 49 cases and for thromboprophylaxis in 574 cases. Serious maternal haemorrhage occurred in 11 cases during pregnancy (1.8%), one being reasonably related to enoxaparin, and in nine cases at delivery (1.4%), all unrelated to enoxaparin. Maternal thrombocytopenia was reported in 10 cases (1.6%). two being serious but unrelated to enoxaparin. Eight pregnancies ended in stillbirth (1.1%). Among the 693 live births, 17 major congenital abnormalities (2.5%) and 10 serious neonatal haemorrhages (1.4%) were reported. None of the fetal or neonatal adverse events was related to enoxaparin. Eight venous thromboembolic events (1.3%) were reported. CONCLUSIONS: The incidence of adverse events reported could be explained by the high risk profile of the study population. Overall, this retrospective study suggests enoxaparin is well tolerated during pregnancy.\n[Drug-Disease]: enoxaparin - thromboembolism" }, { "pmid": "11762651", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.\n[Abstract]: OBJECTIVE: To assess the maternal, fetal and neonatal safety of enoxaparin in pregnant women who require antithrombotic therapy. DESIGN: Retrospective analysis of case notes of women who received enoxaparin during pregnancy, irrespective of dose, duration and reason for treatment. SETTING: Fifty-five French perinatal centres. SAMPLE: Data from 624 pregnancies in 604 women between 1988 and 1997. The incidence of previous thromboembolism was 29.8%, known thrombophilia 15.2%. METHODS: Indication, regimen of enoxaparin and outcome measures were reported for each pregnancy. Information was obtained from case records, validated by research staff and analysed by an independent scientific committee. MAIN OUTCOME MEASURES: Incidence, seriousness and causality of maternal, fetal and neonatal adverse events, pregnancy outcome, and incidence of venous thromboembolism. RESULTS: Enoxaparin was administered for treatment of an acute episode in 49 cases and for thromboprophylaxis in 574 cases. Serious maternal haemorrhage occurred in 11 cases during pregnancy (1.8%), one being reasonably related to enoxaparin, and in nine cases at delivery (1.4%), all unrelated to enoxaparin. Maternal thrombocytopenia was reported in 10 cases (1.6%). two being serious but unrelated to enoxaparin. Eight pregnancies ended in stillbirth (1.1%). Among the 693 live births, 17 major congenital abnormalities (2.5%) and 10 serious neonatal haemorrhages (1.4%) were reported. None of the fetal or neonatal adverse events was related to enoxaparin. Eight venous thromboembolic events (1.3%) were reported. CONCLUSIONS: The incidence of adverse events reported could be explained by the high risk profile of the study population. Overall, this retrospective study suggests enoxaparin is well tolerated during pregnancy.\n[Drug-Disease]: enoxaparin - thrombophilia" }, { "pmid": "11763005", "target": "[\"Span: older than 65 years | Label: Age\", \"Span: mean dose (2.1 +/- SD 1.4 mg/day) | Label: Dosage\"]", "text": "[Title]: The efficacy and safety of risperidone for the treatment of geriatric psychosis.\n[Abstract]: Risperidone is an atypical antipsychotic drug which has been suggested to be beneficial for the treatment of elderly patients with psychotic symptoms. In this study, we assessed the short-term efficacy and the safety of risperidone in geropsychiatric inpatients with psychotic symptoms. The sample population included 110 elderly inpatients with psychotic disorders. Assessment for drug efficacy using the Brief Psychiatric Rating Scale, Sandoz Clinical Assessment-Geriatric scale, and Clinical Global Impression scale was conducted at baseline and also at 4 weeks subsequent to risperidone treatment commencement. Subsequent to commencing risperidone treatment, 80 patients completed a 4-week therapeutic evaluation. Seventy (87.5%) of the 80 patients experienced mild to substantial improvement using the Clinical Global Impression scale. Adverse effects were monitored in all 110 patients. The most commonly detected adverse effects were weakness of legs or walking problems (43/110; 39.1%) and dizziness (32/110; 29.1%). Peripheral edema was noted in 18 (16.4%) patients. Risperidone, in low doses, appeared to have been effective in this sample of patients older than 65 years with psychotic symptoms. The mean dose (2.1 +/- SD 1.4 mg/day) applied was lower then that suggested for young patients and was related to the each specific patient diagnosis. Peripheral edema and walking problems were commonly observed adverse effects for these elderly patients, such problems having not been seen to the same extent in previous studies of young patients.\n[Drug-Disease]: Risperidone - psychotic disorders" }, { "pmid": "11765290", "target": "[\"Span: 5, 10, or 15 mg | Label: Dosage\", \"Span: children | Label: Age\", \"Span: teenagers | Label: Age\"]", "text": "[Title]: Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder.\n[Abstract]: OBJECTIVES: To examine the relationship between age and short-term clinical response to psychostimulant treatment in youths with attention-deficit/hyperactivity disorder (ADHD) and to examine whether weight-corrected doses of optimized psychostimulant therapy varied as a function of patient age. METHOD: One hundred seventy-seven patients were treated with either methylphenidate (MPH) or Adderall (ADL). Sixty-six youths received ADL and 111 patients were treated with MPH. All youths were evaluated at baseline and after receiving a week of treatment at each blinded, randomized dose level (placebo, 5, 10, or 15 mg). A \"best dose\" for each patient was assigned before the medication blind was broken. Behavioral ratings by both teachers and parents were examined for dose and medication effects. RESULTS: The medications had similar efficacy in children and teenagers. Older youths, however, benefited from a smaller weight-adjusted dose of medication than did the younger children. Similar efficacy was observed between the medications. CONCLUSIONS: These data suggest that psychostimulants are equally effective in treating children and adolescents with ADHD. Adolescents with ADHD may not necessarily require more medication than younger children to achieve a similar therapeutic response.\n[Drug-Disease]: ADL - ADHD" }, { "pmid": "11765290", "target": "[\"Span: 5, 10, or 15 mg | Label: Dosage\", \"Span: children | Label: Age\", \"Span: teenagers | Label: Age\"]", "text": "[Title]: Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder.\n[Abstract]: OBJECTIVES: To examine the relationship between age and short-term clinical response to psychostimulant treatment in youths with attention-deficit/hyperactivity disorder (ADHD) and to examine whether weight-corrected doses of optimized psychostimulant therapy varied as a function of patient age. METHOD: One hundred seventy-seven patients were treated with either methylphenidate (MPH) or Adderall (ADL). Sixty-six youths received ADL and 111 patients were treated with MPH. All youths were evaluated at baseline and after receiving a week of treatment at each blinded, randomized dose level (placebo, 5, 10, or 15 mg). A \"best dose\" for each patient was assigned before the medication blind was broken. Behavioral ratings by both teachers and parents were examined for dose and medication effects. RESULTS: The medications had similar efficacy in children and teenagers. Older youths, however, benefited from a smaller weight-adjusted dose of medication than did the younger children. Similar efficacy was observed between the medications. CONCLUSIONS: These data suggest that psychostimulants are equally effective in treating children and adolescents with ADHD. Adolescents with ADHD may not necessarily require more medication than younger children to achieve a similar therapeutic response.\n[Drug-Disease]: methylphenidate - ADHD" }, { "pmid": "11765300", "target": "[\"Span: type 2 diabetes | Label: Comorbidity\", \"Span: mean age 60 yrs | Label: Age\", \"Span: 72% men | Label: Gender\", \"Span: 1000, 1500, or 2000 mg/day (median daily dosage 1000 mg) | Label: Dosage\"]", "text": "[Title]: Cholesterol and glycemic effects of Niaspan in patients with type 2 diabetes.\n[Abstract]: STUDY OBJECTIVE: To determine the effect of Niaspan--a niacin preparation with both immediate- and extended-release characteristics--on lipid and glycemic control in patients with type 2 diabetes. DESIGN: Retrospective study SETTING: Private-practice endocrinology group. PATIENTS: Thirty-two patients (mean age 60 yrs; 72% men) with type 2 diabetes identified by a computerized text search. INTERVENTION: Patients received Niaspan 1000, 1500, or 2000 mg/day (median daily dosage 1000 mg). MEASUREMENTS AND MAIN RESULTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hemoglobin A1c, and transaminase levels were compared for each patient before and 6 months after initiation of Niaspan. Niaspan therapy was associated with a significant 34% increase in HDL (p=0.033), a significant 36% reduction of triglycerides (p=0.049), and no significant change in LDL (p=0.236) or total cholesterol (p=0.122). Mean hemoglobin A1c levels significantly decreased from baseline by 0.5 +/- 0.3% (p=0.032), even though dosages and treatment with antidiabetic agents remained constant. There were no significant changes in transaminase levels. Seven patients (21.9%) discontinued Niaspan; one of them experienced an increase in blood glucose while receiving the agent. CONCLUSION: For most patients with type 2 diabetes, Niaspan is a safe and effective therapy for dyslipidemia and does not exacerbate glycemic control.\n[Drug-Disease]: Niaspan - dyslipidemia" }, { "pmid": "11765585", "target": "[]", "text": "[Title]: [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials].\n[Abstract]: Nephropathy associated with type 2 diabetes mellitus is a rising cause of end-stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy.\n[Drug-Disease]: Losartan - diabetic nephropathy" }, { "pmid": "11765585", "target": "[]", "text": "[Title]: [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials].\n[Abstract]: Nephropathy associated with type 2 diabetes mellitus is a rising cause of end-stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy.\n[Drug-Disease]: Losartan - end-stage renal disease" }, { "pmid": "11768838", "target": "[\"Span: 2, 6, or 10 mg | Label: Dosage\", \"Span: 23 men, 100 women | Label: Gender\"]", "text": "[Title]: Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study.\n[Abstract]: BACKGROUND: The 5-hydroxytryptamine-receptor agonist almotriptan was found to be well tolerated and efficacious when administered orally in clinical trials of migraine treatment. OBJECTIVE: The primary objective of this study was to assess the efficacy and tolerability of 3 different doses of subcutaneous almotriptan in the treatment of acute migraine attacks. METHODS: This was a Phase II multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study conducted over 7 months at 13 practice-oriented centers and 1 larger research-focused center. Patients experiencing moderate to severe migraine with or without aura, as defined by International Headache Society criteria, were randomly assigned to receive a single subcutaneous dose of almotriptan 2, 6, or 10 mg or placebo. The primary end point, pain relief at 2 hours, was self-assessed on a 4-point scale (severe, moderate, mild, or no pain). Patients indicating mild or no pain were considered responders. The analysis was performed on an intent-to-treat basis. RESULTS: A total of 123 patients were enrolled (23 men, 100 women). Overall, almotriptan 6 and 10 mg were significantly more effective than placebo (P < 0.05, Fisher exact test). Response rates for the 6- and 10-mg doses were 96.5% and 90.3%, respectively, compared with 50.0% for placebo (P < 0.05, Fisher exact test). The proportion of patients with pain relief at 2 hours was not significantly different between almotriptan 2 mg and placebo. The response profile for the secondary end points was also better with almotriptan 6 and 10 mg than with placebo. Administration of almotriptan was well tolerated; the most frequently observed drug-associated adverse event was transient local irritation at the injection site. CONCLUSIONS: Almotriptan was well tolerated and significantly more effective than placebo in relieving moderate to severe migraine pain when administered as a single 6- or 10-mg subcutaneous dose.\n[Drug-Disease]: Almotriptan - migraine pain" }, { "pmid": "11770708", "target": "[\"Span: 60 years (73 +/- 6 years) | Label: Age\", \"Span: 5 mg/day | Label: Dosage\", \"Span: 10-20mg | Label: Dosage\"]", "text": "[Title]: A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE).\n[Abstract]: Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11-13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease.\n[Drug-Disease]: pravastatin - cardiovascular disease" }, { "pmid": "11770708", "target": "[\"Span: 60 years (73 +/- 6 years) | Label: Age\", \"Span: 5 mg/day | Label: Dosage\", \"Span: 10-20mg | Label: Dosage\"]", "text": "[Title]: A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE).\n[Abstract]: Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11-13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease.\n[Drug-Disease]: pravastatin - hypercholesterolemia" }, { "pmid": "11773815", "target": "[\"Span: 75 microg | Label: Dosage\"]", "text": "[Title]: Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery.\n[Abstract]: This study evaluates the efficacy and side effects of a low dose of epidural morphine combined with clonidine for postoperative pain relief after lumbar disc surgery. In 36 of 51 patients who accepted the procedure, an epidural catheter was inserted (L1-L2 level). General anesthesia was induced with propofol and sufentanil, and maintained with sevoflurane in O2/N2O. After emergence from anesthesia, epidural analgesia was initiated according to two randomly assigned protocols: 1 mg of morphine with 75 microg of clonidine (Group M) or 12.5 mg of bupivacaine with 75 microg of clonidine (Group B), in 10 mL saline. Piritramide was administered during the first postoperative 24 hours using a patient-controlled analgesia device (PCA). The following parameters were recorded: piritramide consumption during the first 24 hours; pain at rest during the first postoperative hours (D0), during the first night (D1), and during the first mobilization; [visual analogue scale (VAS)]; and the occurrence of drowsiness, motor blockade, respiratory depression, nausea, vomiting, itching, micturition problems, and bladder catheterization during D0 and D1. Epidural administration of morphine-clonidine significantly improved postoperative pain relief and reduced piritramide consumption as compared to epidural bupivacaine-clonidine. Side effects did not differ between groups except for a higher incidence of micturition problems in Group M during D1. The occurrence of bladder catheterization was not significantly higher in that group. We conclude that a low dose of epidural morphine combined with clonidine offers a better postoperative analgesia than does bupivacaine-clonidine. The excellent analgesic conditions were obtained at the expense of a higher incidence of difficulties in initiating micturition.\n[Drug-Disease]: clonidine - postoperative pain" }, { "pmid": "11773815", "target": "[\"Span: 1 mg | Label: Dosage\"]", "text": "[Title]: Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery.\n[Abstract]: This study evaluates the efficacy and side effects of a low dose of epidural morphine combined with clonidine for postoperative pain relief after lumbar disc surgery. In 36 of 51 patients who accepted the procedure, an epidural catheter was inserted (L1-L2 level). General anesthesia was induced with propofol and sufentanil, and maintained with sevoflurane in O2/N2O. After emergence from anesthesia, epidural analgesia was initiated according to two randomly assigned protocols: 1 mg of morphine with 75 microg of clonidine (Group M) or 12.5 mg of bupivacaine with 75 microg of clonidine (Group B), in 10 mL saline. Piritramide was administered during the first postoperative 24 hours using a patient-controlled analgesia device (PCA). The following parameters were recorded: piritramide consumption during the first 24 hours; pain at rest during the first postoperative hours (D0), during the first night (D1), and during the first mobilization; [visual analogue scale (VAS)]; and the occurrence of drowsiness, motor blockade, respiratory depression, nausea, vomiting, itching, micturition problems, and bladder catheterization during D0 and D1. Epidural administration of morphine-clonidine significantly improved postoperative pain relief and reduced piritramide consumption as compared to epidural bupivacaine-clonidine. Side effects did not differ between groups except for a higher incidence of micturition problems in Group M during D1. The occurrence of bladder catheterization was not significantly higher in that group. We conclude that a low dose of epidural morphine combined with clonidine offers a better postoperative analgesia than does bupivacaine-clonidine. The excellent analgesic conditions were obtained at the expense of a higher incidence of difficulties in initiating micturition.\n[Drug-Disease]: morphine - postoperative pain" }, { "pmid": "11773991", "target": "[\"Span: 3 mg | Label: Dosage\", \"Span: 6 mg | Label: Dosage\", \"Span: 60-76 years | Label: Age\"]", "text": "[Title]: ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.\n[Abstract]: The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE-inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation.\n[Drug-Disease]: spirapril - hypertensive" }, { "pmid": "11774936", "target": "[\"Span: 52.4 yr (range = 38-67) | Label: Age\"]", "text": "[Title]: Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome.\n[Abstract]: OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.\n[Drug-Disease]: pantoprazole - Zollinger-Ellison syndrome" }, { "pmid": "11775050", "target": "[\"Span: mean age = 76 years | Label: Age\", \"Span: 0.5-2 mg/day | Label: Dosage\"]", "text": "[Title]: Effect of risperidone on behavioral and psychological symptoms and cognitive function in dementia.\n[Abstract]: AIMS: This open-label study examined the efficacy and tolerability of risperidone in the treatment of aggression, agitation, and psychotic symptoms in dementia. The influence of risperidone on cognitive function was also assessed under conditions reflecting normal, daily clinical care. METHOD: A total of 34 hospital inpatients and outpatients (mean age = 76 years) with DSM-IV dementia disorders were treated with flexible doses of risperidone (0.5-2 mg/day) for 8 weeks. Assessments, conducted at baseline and after weeks 4 and 8, included the Clinical Global Impressions scale (CGI) and Neuropsychiatric Inventory (NPI) ratings. Cognitive function assessments included the Mini-Mental State Examination (MMSE) and specific measures of cognition (Age Concentration Test [AKT] and Brief Syndrome Test [SKT]). Frequency of extrapyramidal symptoms (EPS) was measured according to the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: At the end of the study, 50% of patients (N = 17) were receiving risperidone, 1 mg/day. 18% (N = 6) were receiving 0.5 mg/day, and 32% (N = 11) received > 1 mg/day (mean dose at endpoint = 1.1 mg/day). An improvement in symptoms, as measured by the CGI-Global Impression of Change scale, was reported for 82% of patients (N = 28) (59% [N = 20] much or very much improved). The frequency and severity of delusions, hallucinations, agitation/aggression, and irritability decreased as measured by the NPI. Multiplication of frequency and severity scores revealed a significant decline during the course of treatment (p < .001, end of study vs. baseline). Caregiver responses on the NPI also showed an improvement, with the mean +/- SD total score decreasing from 24.2 +/- 7.3 at baseline to 21.2 +/- 6.3 at study end (p = .002). MMSE, AKT, and SKT results indicated that there was no decrease in cognitive function during the study. Risperidone treatment was well tolerated, and no clinically relevant changes in EPS. vital signs, or weight were detected. CONCLUSION: During treatment with low-dose risperidone, behavioral and psychological symptoms improved overall in 34 patients with dementia, and cognitive function was maintained throughout the treatment period.\n[Drug-Disease]: risperidone - dementia" }, { "pmid": "11785593", "target": "[\"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Comparison of alfentanil and morphine in the prehospital treatment of patients with acute ischaemic-type chest pain.\n[Abstract]: Patients with acute myocardial ischaemic pain would benefit from rapid pain relief. The clinical usefulness of alfentanil, which has a rapid onset of action, was therefore assessed as the initial pain relieving opioid in patients suffering from acute myocardial ischaemic pain. The effects of alfentanil were compared with those of morphine in the prehospital treatment of 40 haemodynamically stable patients suffering from acute ischaemic-type chest pain. After initial assessment, the patients were given either 0.5 mg alfentanil or 5 mg morphine intravenously in a randomized double-blind fashion. The dose was repeated 2 minutes later if severe pain persisted. Arterial pressure, heart rate, respiratory rate and pain expressed on a visual analogue scale was measured before and at 2, 4, 6, 10 and 15 minutes after administration of drugs. After randomization, four patients were excluded. Sixteen patients received alfentanil and 20 patients morphine. Pain relief was faster (p < 0.005) in the alfentanil group than in the morphine group. Alfentanil was found to provide effective analgesia during the follow-up period of 15 minutes. No haemodynamic or respiratory side effects occurred. It is concluded that alfentanil is an effective analgesic in the prehospital treatment of myocardial ischaemic pain.\n[Drug-Disease]: morphine - ischaemic-type chest pain" }, { "pmid": "11785593", "target": "[\"Span: 0.5 mg | Label: Dosage\"]", "text": "[Title]: Comparison of alfentanil and morphine in the prehospital treatment of patients with acute ischaemic-type chest pain.\n[Abstract]: Patients with acute myocardial ischaemic pain would benefit from rapid pain relief. The clinical usefulness of alfentanil, which has a rapid onset of action, was therefore assessed as the initial pain relieving opioid in patients suffering from acute myocardial ischaemic pain. The effects of alfentanil were compared with those of morphine in the prehospital treatment of 40 haemodynamically stable patients suffering from acute ischaemic-type chest pain. After initial assessment, the patients were given either 0.5 mg alfentanil or 5 mg morphine intravenously in a randomized double-blind fashion. The dose was repeated 2 minutes later if severe pain persisted. Arterial pressure, heart rate, respiratory rate and pain expressed on a visual analogue scale was measured before and at 2, 4, 6, 10 and 15 minutes after administration of drugs. After randomization, four patients were excluded. Sixteen patients received alfentanil and 20 patients morphine. Pain relief was faster (p < 0.005) in the alfentanil group than in the morphine group. Alfentanil was found to provide effective analgesia during the follow-up period of 15 minutes. No haemodynamic or respiratory side effects occurred. It is concluded that alfentanil is an effective analgesic in the prehospital treatment of myocardial ischaemic pain.\n[Drug-Disease]: alfentanil - ischaemic-type chest pain" }, { "pmid": "11788559", "target": "[\"Span: 300 mg | Label: Dosage\"]", "text": "[Title]: Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease.\n[Abstract]: BACKGROUND: Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor alpha (TNF-alpha) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. AIM: The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). METHODS: Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-alpha, interleukin (IL)-1 beta, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. RESULTS: Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-alpha and IL-12 decreased during treatment with thalidomide: LPMC (TNF-alpha: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-alpha: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1 beta and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-alpha and IL-12 production. CONCLUSION: The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-alpha and IL-12.\n[Drug-Disease]: thalidomide - Crohn's disease" }, { "pmid": "11791962", "target": "[\"Span: adult | Label: Age\", \"Span: Cameroonian | Label: Body Type\", \"Span: 30 and 35 mg | Label: Dosage\"]", "text": "[Title]: Cardiac effects of amodiaquine and sulfadoxine-pyrimethamine in malaria-infected African patients.\n[Abstract]: The cardiac effect of amodiaquine and sulfadoxine-pyrimethamine was studied in adult Cameroonian patients with acute uncomplicated Plasmodium falciparum malaria by electrocardiographic monitoring over the course of 7 days. Clinical and parasitological responses were monitored until Day 14. Bradycardia was observed in 16 of 20 amodiaquine-treated patients on Day 2, which corresponds to the time when maximal cumulative plasma concentration is reached, and in 12 of 20 patients on Day 7. A bradycardic effect lasting several days was not noted in patients treated with sulfadoxine-pyrimethamine. Significantly prolonged P, PQ, QRS, and QTc intervals were recorded on Day 2 after both 30 and 35 mg of amodiaquine base per kilogram of body weight had been administered, but these intervals were not correlated with the plasma monodesethylamodiaquine (main human active metabolite of amodiaquine) level. Electrocardiographic changes after therapy with sulfadoxine-pyrimethamine were minor and transient. All patients had fever and parasite clearance on or before Day 3 and remained free of fever and parasites until Day 14. None of the patients complained of cardiovascular adverse effects during the follow-up. These results suggest the absence of significant cardiac effects of amodiaquine and sulfadoxine-pyrimethamine at usual therapeutic doses, but they should draw the attention of clinicians treating malaria-infected patients who have taken other antimalarial drugs with cardiovascular side effects or those who are under treatment with cardiovascular drugs.\n[Drug-Disease]: amodiaquine - falciparum malaria" }, { "pmid": "11795014", "target": "[\"Span: 2 mg o.q.d. | Label: Dosage\"]", "text": "[Title]: [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].\n[Abstract]: The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.\n[Drug-Disease]: Trandolapril - albuminuria" }, { "pmid": "11795014", "target": "[\"Span: 2 mg o.q.d. | Label: Dosage\"]", "text": "[Title]: [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].\n[Abstract]: The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.\n[Drug-Disease]: Trandolapril - hypertension" }, { "pmid": "11795014", "target": "[\"Span: 180 mg o.q.d. | Label: Dosage\"]", "text": "[Title]: [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].\n[Abstract]: The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.\n[Drug-Disease]: Verapamil - albuminuria" }, { "pmid": "11795014", "target": "[\"Span: 180 mg o.q.d. | Label: Dosage\"]", "text": "[Title]: [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].\n[Abstract]: The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.\n[Drug-Disease]: Verapamil - hypertension" }, { "pmid": "11798623", "target": "[\"Span: 1 mg/kg | Label: Dosage\", \"Span: 160 mg | Label: Dosage\"]", "text": "[Title]: [Effect of sotalol on systemic hemodynamics and electrophysiology in patients with life-threatening ventricular tachyarrhythmias].\n[Abstract]: OBJECTIVE: To evaluate the systemic hemodynamics and electrophysiology effect of intravenous and oral sotalol and its tolerance of long-term oral therapy in patients with life-threatening ventricular tachyarrhythmias. METHODS: Twenty-three patients, 17 with sustained ventricular tachycardias (VTs), 6 with ventricular fibrillation (VF) were studied. 16 patients were postmyocardial infarction, 4 were right ventricular dysplasia and 3 were dilated cardiomyopathy. RESULTS: Sotalol prevented the induction of arrhythmias in 34.3% with bolus intravenous injection (1 mg/kg body weight) and 60.8% with oral (160 mg twice daily for 10 to 14 days). Both intravenous and oral sotalol led to bradycardia, decreased in cardiac index, increased in left ventricular filling pressure as well as in systemic vascular resistance. The stroke volume increased significantly after sotalol intravenous, but not changed at peak action after oral sotalol. During a follow-up of 3 to 6 months, oral sotalol prevented the recurrent of arrhythmias in 12 of 16 patients who were response to electrophysiology testing. Congestive heart failure associated with a marked bradycardia developed in one patient. This patient was managed with a reduction in the dosage and with a regimen of digoxin and furosemide. CONCLUSION: Sotalol provided effective prophylaxis against life- threatening Ventricular tachyarrhythmias. It exerted significant negative hemodynamics effects but with quite good clinical tolerance, even in patients with compromised heart function.\n[Drug-Disease]: Sotalol - VF" }, { "pmid": "11798623", "target": "[\"Span: 1 mg/kg | Label: Dosage\", \"Span: 160 mg | Label: Dosage\"]", "text": "[Title]: [Effect of sotalol on systemic hemodynamics and electrophysiology in patients with life-threatening ventricular tachyarrhythmias].\n[Abstract]: OBJECTIVE: To evaluate the systemic hemodynamics and electrophysiology effect of intravenous and oral sotalol and its tolerance of long-term oral therapy in patients with life-threatening ventricular tachyarrhythmias. METHODS: Twenty-three patients, 17 with sustained ventricular tachycardias (VTs), 6 with ventricular fibrillation (VF) were studied. 16 patients were postmyocardial infarction, 4 were right ventricular dysplasia and 3 were dilated cardiomyopathy. RESULTS: Sotalol prevented the induction of arrhythmias in 34.3% with bolus intravenous injection (1 mg/kg body weight) and 60.8% with oral (160 mg twice daily for 10 to 14 days). Both intravenous and oral sotalol led to bradycardia, decreased in cardiac index, increased in left ventricular filling pressure as well as in systemic vascular resistance. The stroke volume increased significantly after sotalol intravenous, but not changed at peak action after oral sotalol. During a follow-up of 3 to 6 months, oral sotalol prevented the recurrent of arrhythmias in 12 of 16 patients who were response to electrophysiology testing. Congestive heart failure associated with a marked bradycardia developed in one patient. This patient was managed with a reduction in the dosage and with a regimen of digoxin and furosemide. CONCLUSION: Sotalol provided effective prophylaxis against life- threatening Ventricular tachyarrhythmias. It exerted significant negative hemodynamics effects but with quite good clinical tolerance, even in patients with compromised heart function.\n[Drug-Disease]: Sotalol - Ventricular tachyarrhythmias" }, { "pmid": "11798639", "target": "[]", "text": "[Title]: [An analysis of the therapeutic effects and reactions in treating acute promyelocytic leukemia with intravenous arsenic trioxide or all-trans retinoic acid].\n[Abstract]: OBJECTIVE: To compare the therapeutic effects and reactions of intra venous arsenic trioxide and all-trans retinoic acid in treating patients with acute promyelocytic leukemia (APL). METHODS: 75 cases of APL were randomized either to arsenic trioxide (37) or to all-trans retinoic acid (38). The rates of complete remission (CR), disease free survival (DFS) and side effects were observed. RESULTS: In the two groups of patients with APL, the rate of CR was 86.4% and 84.2%. There was also no significant difference in the rate of DSF phase of CR (P > 0.05). The side effects of these two medications in therapeutic dose were mild and there was no cross resistance between them. CONCLUSION: Arsenic trioxide can lead to apoptosis of leukemic cells and might be a new promising drug to induce differentiation.\n[Drug-Disease]: Arsenic trioxide - APL" }, { "pmid": "11798639", "target": "[]", "text": "[Title]: [An analysis of the therapeutic effects and reactions in treating acute promyelocytic leukemia with intravenous arsenic trioxide or all-trans retinoic acid].\n[Abstract]: OBJECTIVE: To compare the therapeutic effects and reactions of intra venous arsenic trioxide and all-trans retinoic acid in treating patients with acute promyelocytic leukemia (APL). METHODS: 75 cases of APL were randomized either to arsenic trioxide (37) or to all-trans retinoic acid (38). The rates of complete remission (CR), disease free survival (DFS) and side effects were observed. RESULTS: In the two groups of patients with APL, the rate of CR was 86.4% and 84.2%. There was also no significant difference in the rate of DSF phase of CR (P > 0.05). The side effects of these two medications in therapeutic dose were mild and there was no cross resistance between them. CONCLUSION: Arsenic trioxide can lead to apoptosis of leukemic cells and might be a new promising drug to induce differentiation.\n[Drug-Disease]: retinoic acid - APL" }, { "pmid": "11800032", "target": "[\"Span: 61 years (range 43-71 years) | Label: Age\", \"Span: 10 (30%) were women and 23 (70%) were men | Label: Gender\", \"Span: Japanese | Label: Body Type\", \"Span: 80 mg/m2 | Label: Dosage\"]", "text": "[Title]: A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients.\n[Abstract]: We performed a clinical phase II trial of the combination of paclitaxel and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small-cell lung cancer (NSCLC) using a 3-h infusion of paclitaxel followed by a 1 to 2-h infusion of cisplatin, with a short premedication regimen. Treatment was repeated every 21 days for at least two cycles. The patients received paclitaxel 180 mg/m2 followed by cisplatin 80 mg/m2. Enrolled in the trial were 33 chemotherapy-naive patients with stage IIIB (15%) or stage IV (85%) NSCLC. Their median age was 61 years (range 43-71 years). Of the 33 patients, 10 (30%) were women and 23 (70%) were men, and 82% had adenocarcinoma. With 78 courses of chemotherapy administered, 32 patients were evaluable for toxicity and response. Hematologic toxicities were moderate: Japan Clinical Oncology Group (JCOG) grade 3 or 4 neutropenia occurred in 37% of the cycles (53% of patients). Other toxicities consisted mainly of grade 1 or 2 alopecia and nausea/vomiting, but also included grade 1 or 2 neuropathy (47%), hypotension (grade 1 in 6%, grade 3 in 3%) and allergic reactions (grade 1 or 2 in 16%, grade 3 in 3%). Of 32 patients evaluable for response, a partial response was achieved in 10 (31%; 95% confidence interval 16% to 50%), stable disease was seen in 16 (50%), and disease progression was seen in 2 (6%). The median survival time was 14.8 months and the 1-year survival rate was 56%. These results suggest that the combination of paclitaxel and cisplatin is a well-tolerated and active regimen in Japanese patients with advanced NSCLC. In view of the promising survival outcomes, further evaluation in prospective randomized trials with other regimens is warranted.\n[Drug-Disease]: cisplatin - NSCLC" }, { "pmid": "11800032", "target": "[\"Span: 61 years (range 43-71 years) | Label: Age\", \"Span: 10 (30%) were women and 23 (70%) were men | Label: Gender\", \"Span: Japanese | Label: Body Type\", \"Span: 180 mg/m2 | Label: Dosage\"]", "text": "[Title]: A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients.\n[Abstract]: We performed a clinical phase II trial of the combination of paclitaxel and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small-cell lung cancer (NSCLC) using a 3-h infusion of paclitaxel followed by a 1 to 2-h infusion of cisplatin, with a short premedication regimen. Treatment was repeated every 21 days for at least two cycles. The patients received paclitaxel 180 mg/m2 followed by cisplatin 80 mg/m2. Enrolled in the trial were 33 chemotherapy-naive patients with stage IIIB (15%) or stage IV (85%) NSCLC. Their median age was 61 years (range 43-71 years). Of the 33 patients, 10 (30%) were women and 23 (70%) were men, and 82% had adenocarcinoma. With 78 courses of chemotherapy administered, 32 patients were evaluable for toxicity and response. Hematologic toxicities were moderate: Japan Clinical Oncology Group (JCOG) grade 3 or 4 neutropenia occurred in 37% of the cycles (53% of patients). Other toxicities consisted mainly of grade 1 or 2 alopecia and nausea/vomiting, but also included grade 1 or 2 neuropathy (47%), hypotension (grade 1 in 6%, grade 3 in 3%) and allergic reactions (grade 1 or 2 in 16%, grade 3 in 3%). Of 32 patients evaluable for response, a partial response was achieved in 10 (31%; 95% confidence interval 16% to 50%), stable disease was seen in 16 (50%), and disease progression was seen in 2 (6%). The median survival time was 14.8 months and the 1-year survival rate was 56%. These results suggest that the combination of paclitaxel and cisplatin is a well-tolerated and active regimen in Japanese patients with advanced NSCLC. In view of the promising survival outcomes, further evaluation in prospective randomized trials with other regimens is warranted.\n[Drug-Disease]: paclitaxel - NSCLC" }, { "pmid": "11804400", "target": "[\"Span: alpha-calcitonin gene | Label: Gene\"]", "text": "[Title]: Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment.\n[Abstract]: Anethole trithione, a choleretic, has been reported to be effective in the treatment of dry mouth. We have examined the effects of chronic treatment with anethole trithione on salivary secretion, substance P immunoreactive substance (SP-IS) and alpha-calcitonin gene-related peptide immunoreactive substance (alpha-CGRP-IS) concentrations in human saliva. Anethole trithione caused significant increases of saliva SP-IS concentrations from the day 13 (25.3 +/- 1.6 pg mL(-1)) to day 14 (25.8 +/- 1.7 pg mL(-1)) compared with day 1 (19.9 +/- 1.9 pg mL(-1)). Anethole trithione caused significant increase in saliva alpha-CGRP-IS concentration on day 14 (39.9 +/- 4.7 pg mL(-1)) compared with day 1 (27.7 +/- 4.7 pg mL(-1)). Anethole trithione significantly increased the sialosis volumes from day 11 to day 14 (1.6 +/- 0.1-1.7 +/- 0.2 mL) compared with the day 1 (1.2 +/- 0.2 mL). Simple linear regression of the increase in sialosis volume with saliva SP-IS (r = 0.94) and alpha-CGRP-IS (r = 0.97) concentrations was found. These results demonstrated that chronic treatment with anethole trithione affected saliva SP-IS and alpha-CGRP-IS concentration in human saliva and sialosis volume.\n[Drug-Disease]: anethole trithione - dry mouth" }, { "pmid": "11807019", "target": "[\"Span: 1 | Label: Dosage\", \"Span: 1.2 g | Label: Dosage\"]", "text": "[Title]: Sustained suppression of hepatitis C virus by interferon and ribavirin in hemophilic patients not responding to interferon monotherapy.\n[Abstract]: Thirty-nine hemophiliac patients, negative for human immunodeficiency virus, with chronic hepatitis C who failed to respond to interferon (IFN) at 3 million units (MU) given subcutaneously thrice weekly for at least 3 months were retreated with 5 MU IFN for 6 months followed by 3 MU IFN in combination with daily oral doses of 1 or 1.2 g ribavirin. Thirty-four patients (87%) completed the study. In 4 patients treatment was discontinued because of treatment-related symptoms; 1 patient dropped out. Dosage reduction was required in 10 patients (26%) because of ribavirin-related anemia or IFN-related side effects. By intention-to-treat analysis, 14 (37%) had a sustained virologic response with preference for those infected by genotypes other than type 1 (43% versus 12%) and with high transaminases levels (168 U/L versus 116 U/L). Thus, IFN and ribavirin combination therapy led to a sustained suppression of hepatitis in one third of hemophiliac patients resistant to conventional monotherapy.\n[Drug-Disease]: ribavirin - chronic hepatitis C" }, { "pmid": "11808827", "target": "[]", "text": "[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.\n[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.\n[Drug-Disease]: Ketamine - stroking hyperalgesia" }, { "pmid": "11808827", "target": "[]", "text": "[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.\n[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.\n[Drug-Disease]: Ketamine - pain" }, { "pmid": "11808827", "target": "[]", "text": "[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.\n[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.\n[Drug-Disease]: Alfentanil - stroking hyperalgesia" }, { "pmid": "11808827", "target": "[]", "text": "[Title]: Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.\n[Abstract]: The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.\n[Drug-Disease]: Alfentanil - pain" }, { "pmid": "11815957", "target": "[\"Span: 75 mg/m(2) | Label: Dosage\", \"Span: 54 years | Label: Age\"]", "text": "[Title]: Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma.\n[Abstract]: BACKGROUND: The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first-line treatment of metastatic breast carcinoma (MBC). METHODS: Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 (75 mg/m(2)) or doxorubicin (75 mg/m(2)) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS: Median age was 54 years in both treatment groups. All relevant prognostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m(2) for TLC D-99 versus 570 mg/m(2) for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D-99, although the difference was not statistically significant. There was only one report of palmar-plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS: Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity.\n[Drug-Disease]: doxorubicin - MBC" }, { "pmid": "11816545", "target": "[\"Span: 1.2-2.4 g/day | Label: Dosage\"]", "text": "[Title]: Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects.\n[Abstract]: BACKGROUND: Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects. AIM: To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis. METHODS: Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid. RESULTS: Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid. CONCLUSIONS: 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.\n[Drug-Disease]: 5-aminosalicylic acid - ulcerative colitis" }, { "pmid": "11829208", "target": "[\"Span: 100 mg/day | Label: Dosage\"]", "text": "[Title]: Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia.\n[Abstract]: Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6-12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6-12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia.\n[Drug-Disease]: Amisulpride - schizophrenia" }, { "pmid": "11831095", "target": "[]", "text": "[Title]: Divalproex as a calmative adjunct for aggressive schizophrenic patients.\n[Abstract]: BACKGROUND: Selection of appropriate pharmacotherapy for psychotic patients who exhibit dangerousness is an important issue. Divalproex is a fast-acting agent which appears to be safe and effective in such circumstances. The objective of the following inpatient study was to investigate divalproex as a pharmaceutical adjunct in treating agitated and/or violent, psychotic schizophrenic subjects. METHODS: For the purpose of comparison, 147 hospitalized patients were separated into violent (n = 60) and non-violent (n = 87) groups. In addition to antipsychotic drugs given to all subjects, divalproex was preferentially prescribed for the more dangerous patients (n = 40). The clinical status of demographics and parameters related to dangerousness in all participants was assessed to document differences during these admissions and for rehospitalization over one year. RESULTS: Divalproex was well tolerated; however, one individual developed a transient granulocytopenia. Its use in agitated and/or violent psychotic persons appears to have included a calmer, less dangerous hospital course, like that observed among their less disruptive counterparts. CONCLUSIONS: Divalproex seemed to have been helpful in this study at facilitating a more routine hospital course for agitated psychotic patients, similar to that of less overtly disturbed individuals. No significant adverse events were observed. The validity of this study is limited by its retrospective, uncontrolled nature.\n[Drug-Disease]: Divalproex - violent psychotic" }, { "pmid": "11834192", "target": "[\"Span: 2.5 | Label: Dosage\", \"Span: 5.0 mg | Label: Dosage\", \"Span: aged 67 years (range: 50-81) | Label: Age\"]", "text": "[Title]: [Usefulness of olanzapine in the levodopa-induced psychosis in patients with Parkinson's disease].\n[Abstract]: BACKGROUND: To evaluate the antipsychotic efficacy of olanzapine (OLZ) in patients with Parkinson's disease (PD) and drug-induced psychosis (DIP) and its repercussion on the motor function. METHODS: Ten patients (5 women and 5 men) diagnosed of PD and DIP, aged 67 years (range: 50-81), with PD duration of 11.1 years (range: 6-23), treated chronically with levodopa per day, received a dose of 2.5 or 5.0 mg OLZ daily. Data concerning improvement of psychosis and worsening of motor function was based on Positive And Negative Symptoms Scale (PANSS) and Unified Parkinsons Disease Rating Scale (UPDRS) motor. RESULTS: Psychotic symptoms were improved in all patients. In most of them the improvement was almost total. Seven patients increased levodopa dose on OLZ, but significant worsening of motor function was reported just in one patient. None of the patients had agranulocytosis in the blood monitoring. Two patients presented weight gain. Seven patients improved their cognitive status. CONCLUSIONS: We conclude that OLZ at the doses studied may have efficacy for DIP which appears in PD and does not induce worsening of motor function in most of the patients.\n[Drug-Disease]: OLZ - Psychotic symptoms" }, { "pmid": "11835035", "target": "[]", "text": "[Title]: Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study.\n[Abstract]: BACKGROUND: Despite the available evidence from randomized clinical trials, beta-blockers are often not used optimally in patients with congestive heart failure (CHF). This meta-analysis aims at providing a precise and quantitative estimate of the benefit and risks of long-term bisoprolol on major clinical events in patients with CHF, both overall and in selected subgroups. This may help clinicians in their decisions as to whether to prescribe bisoprolol for their individual patients. METHODS: Meta-analysis was performed of results from the 2 randomized, controlled clinical studies in which bisoprolol was compared with placebo (Cardiac Insufficiency Bisoprolol Study [CIBIS and CIBIS II]), which included 3288 patients with proven CHF. The main outcomes were total death, cardiovascular death, sudden death, hospitalization for heart failure, and myocardial infarction. RESULTS: A highly significant 29.3% relative reduction of death (17%, 40%; P =.00003) was observed, as well as significant risk reduction in cardiovascular death and sudden death in favor of bisoprolol. Also, a highly significant relative reduction of 18.4% (25%, 11%; P =.00001) in hospital admission or death was observed. A similar relative reduction of death was consistently observed in selected subgroups of patients. CONCLUSIONS: Bisoprolol prevents major cardiovascular events in patients with CHF with a high benefit-to-risk ratio and can be recommended for these patients.\n[Drug-Disease]: Bisoprolol - CHF" }, { "pmid": "11835461", "target": "[]", "text": "[Title]: Levodopa-induced dyskinesias and continuous subcutaneous infusions of apomorphine: results of a two-year, prospective follow-up.\n[Abstract]: Twelve patients with levodopa-induced dyskinesias were treated with continuous subcutaneous apomorphine. A markedly significant reduction in peak dose dyskinesias occurred over a two-year follow-up.\n[Drug-Disease]: apomorphine - dyskinesias" }, { "pmid": "11835907", "target": "[]", "text": "[Title]: From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis.\n[Abstract]: The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.\n[Drug-Disease]: Ramipril - myocardial infarction" }, { "pmid": "11835907", "target": "[]", "text": "[Title]: From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis.\n[Abstract]: The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.\n[Drug-Disease]: Ramipril - atherosclerosis" }, { "pmid": "11835917", "target": "[]", "text": "[Title]: Tolerability of statin-fibrate and statin-niacin combination therapy in dyslipidemic patients at high risk for cardiovascular events.\n[Abstract]: Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of >1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p <0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.\n[Drug-Disease]: niacin - dyslipidemias" }, { "pmid": "11839425", "target": "[\"Span: Fifteen patients (11 females) | Label: Gender\", \"Span: 1200 +/- 600 mg daily dosage (mean +/- SD) | Label: Dosage\"]", "text": "[Title]: Long-term cohort study comparing medical (oxcarbazepine) and surgical management of intractable trigeminal neuralgia.\n[Abstract]: Trigeminal neuralgia is a recurrent severe shooting neuropathic pain which can be managed both pharmacologically and surgically. However, there are no prospective data that compare these two therapeutic strategies. This study therefore aimed to assess long-term outcome in patients with intractable trigeminal neuralgia treated with oxcarbazepine and later with surgery. Fifteen patients (11 females) with trigeminal neuralgia intractable to available drugs (carbamazepine, phenytoin and baclofen), were prospectively followed for 13 years (1986-1999) with a total follow up time from onset of disease of 16 +/- 6 years (mean +/- SD), range 8-30 years. All patients were contacted in 1999 and 12 replied, two had died and one had last replied in 1996. Patients were first treated with oxcarbazepine 1200 +/- 600 mg daily dosage (mean +/- SD) and subsequently with surgery of their choice. The outcome measures used were: McGill Pain Questionnaire, Hospital Anxiety and Depression Scale, patient satisfaction questionnaire and clinicians' global evaluation. Pain control was initially achieved in all patients and oxcarbazepine was used continuously or intermittently for 4.0 +/- 3 years (mean +/- SD). Thirteen patients experienced some mild side effects and a dose-dependent hyponatraemia was noted. Subsequently, 12 patients required surgery (five microvascular decompressions and seven surgery at the level of the Gasserian ganglion) to control their pain and were followed up for 4.3 +/- 1.7 years post surgery (mean +/- SD). Three patients required repeat surgery to control their pain, which was successful in two. A further two patients continued with low dose medication post initially successful surgery. Three patients reported numbness and one hearing loss after surgery. Kaplan Meier analysis 3 years after oxcarbazepine use and then 3 years after surgery showed that the mean time for recurrence of pain after oxcarbazepine treatment was 10 months whilst for surgery it was 28 months (P<0.0001). Pain free periods and types of complications post surgery varied and depended on the type of surgery performed. Due to the small numbers, it was not possible to analyse the different types of surgical procedures individually. Outcomes after any type of surgery were better on all evaluations and eight patients felt that they should have had surgery earlier. Oxcarbazepine is a potent antineuralgic drug with very good acceptability and tolerability. However, its effectiveness was rather short term necessitating surgical intervention. As surgery was associated with better outcome, patients may therefore benefit from having surgery earlier rather than later in the disease process in order to improve quality of life, freedom from medication and the need for regular follow up. Surgery does not provide pain relief for all patients. This is the first study that has compared outcome in a group of patients who have had both pharmacological and surgical treatments. As these data cannot be extrapolated to other antineuralgic drugs, similar comparative studies would be appropriate.\n[Drug-Disease]: Oxcarbazepine - Trigeminal neuralgia" }, { "pmid": "11840225", "target": "[\"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial.\n[Abstract]: Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.\n[Drug-Disease]: sibutramine - obese" }, { "pmid": "11840256", "target": "[\"Span: 400 mg/day | Label: Dosage\"]", "text": "[Title]: Thalidomide for the treatment of patients with myelodysplastic syndromes.\n[Abstract]: We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA. Patients belonged to the following cytogenetic groups: 15 complex abnormal karyotypes, 12 normal karyotypes, four cases with 5q- as sole anomaly and three single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients). Four patients discontinued the study after less than 5 weeks, because of fatigue (three) or skin rash (one). One patient died of heart failure after 4 weeks. In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria. Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease. Hematological improvement (HI) was observed in 19 patients. Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or =100,000/microl. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence. Six patients (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI-E+HI-N). Hematological improvement occurred after a median of 2 months of thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).\n[Drug-Disease]: thalidomide - MDS" }, { "pmid": "11844897", "target": "[\"Span: 2.5 mg | Label: Dosage\"]", "text": "[Title]: Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.\n[Abstract]: This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.\n[Drug-Disease]: Zolmitriptan - migraine" }, { "pmid": "11844897", "target": "[\"Span: 900 mg | Label: Dosage\"]", "text": "[Title]: Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.\n[Abstract]: This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.\n[Drug-Disease]: acetylsalicylic acid - migraine" }, { "pmid": "11844897", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.\n[Abstract]: This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.\n[Drug-Disease]: metoclopramide - migraine" }, { "pmid": "11846301", "target": "[]", "text": "[Title]: Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.\n[Abstract]: PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.\n[Drug-Disease]: etoposide - rhabdomyosarcoma" }, { "pmid": "11846301", "target": "[]", "text": "[Title]: Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.\n[Abstract]: PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.\n[Drug-Disease]: ifosfamide - rhabdomyosarcoma" }, { "pmid": "11846301", "target": "[]", "text": "[Title]: Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.\n[Abstract]: PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.\n[Drug-Disease]: melphalan - rhabdomyosarcoma" }, { "pmid": "11846301", "target": "[]", "text": "[Title]: Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.\n[Abstract]: PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.\n[Drug-Disease]: vincristine - rhabdomyosarcoma" }, { "pmid": "11893366", "target": "[\"Span: 400 mg | Label: Dosage\"]", "text": "[Title]: Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial.\n[Abstract]: PURPOSE: To determine whether hypertriglyceridemia is associated with systemic inflammation, which may contribute to the increased cardiovascular risk in patients who have hypertriglyceridemia. In addition, we investigated whether fibrates reverse this inflammatory state. PATIENTS AND METHODS: Serum lipid levels, body mass index, insulin resistance, and inflammatory parameters were compared between 18 patients who had severe hypertriglyceridemia without cardiovascular disease and 20 normolipidemic controls. We measured the ex vivo production capacity of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 after whole-blood stimulation with lipopolysaccharide, as well as circulating levels of C-reactive protein and fibrinogen. A randomized controlled trial was conducted to determine whether bezafibrate (400 mg administered daily for 6 weeks) affected these parameters in hypertriglyceridemic patients. RESULTS: When compared with normolipidemic controls, hypertriglyceridemic patients had significantly lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels, body mass index, and insulin resistance. In addition, hypertriglyceridemic patients had a significantly higher production capacity of TNF-alpha (mean difference, 11 700 pg/mL; 95% confidence interval [CI]: 7800 to 15,700 pg/mL]) and IL-6 (mean difference, 20,400 pg/mL; 95% CI: 7800 to 32,900 pg/mL), and higher levels of C-reactive protein (mean difference, 0.8 mg/L; 95% CI: 0.1 to 2.4 mg/L) and fibrinogen (mean difference, 0.8 g/dL; 95% CI: 0.3 to 1.3 g/dL). Bezafibrate therapy significantly increased HDL cholesterol levels, reduced triglyceride and insulin resistance levels, and reduced production capacity of TNF-alpha and IL-6, as well as levels of C-reactive protein and fibrinogen. CONCLUSION: Systemic inflammation is present in patients who have the clinical phenotype that is associated with severe hypertriglyceridemia, and may contribute to the increased risk of cardiovascular disease in these patients. Bezafibrate has anti-inflammatory effects in these patients.\n[Drug-Disease]: bezafibrate - inflammation" }, { "pmid": "11893366", "target": "[\"Span: 400 mg | Label: Dosage\"]", "text": "[Title]: Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial.\n[Abstract]: PURPOSE: To determine whether hypertriglyceridemia is associated with systemic inflammation, which may contribute to the increased cardiovascular risk in patients who have hypertriglyceridemia. In addition, we investigated whether fibrates reverse this inflammatory state. PATIENTS AND METHODS: Serum lipid levels, body mass index, insulin resistance, and inflammatory parameters were compared between 18 patients who had severe hypertriglyceridemia without cardiovascular disease and 20 normolipidemic controls. We measured the ex vivo production capacity of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 after whole-blood stimulation with lipopolysaccharide, as well as circulating levels of C-reactive protein and fibrinogen. A randomized controlled trial was conducted to determine whether bezafibrate (400 mg administered daily for 6 weeks) affected these parameters in hypertriglyceridemic patients. RESULTS: When compared with normolipidemic controls, hypertriglyceridemic patients had significantly lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels, body mass index, and insulin resistance. In addition, hypertriglyceridemic patients had a significantly higher production capacity of TNF-alpha (mean difference, 11 700 pg/mL; 95% confidence interval [CI]: 7800 to 15,700 pg/mL]) and IL-6 (mean difference, 20,400 pg/mL; 95% CI: 7800 to 32,900 pg/mL), and higher levels of C-reactive protein (mean difference, 0.8 mg/L; 95% CI: 0.1 to 2.4 mg/L) and fibrinogen (mean difference, 0.8 g/dL; 95% CI: 0.3 to 1.3 g/dL). Bezafibrate therapy significantly increased HDL cholesterol levels, reduced triglyceride and insulin resistance levels, and reduced production capacity of TNF-alpha and IL-6, as well as levels of C-reactive protein and fibrinogen. CONCLUSION: Systemic inflammation is present in patients who have the clinical phenotype that is associated with severe hypertriglyceridemia, and may contribute to the increased risk of cardiovascular disease in these patients. Bezafibrate has anti-inflammatory effects in these patients.\n[Drug-Disease]: bezafibrate - hypertriglyceridemia" }, { "pmid": "11903116", "target": "[\"Span: adulthood | Label: Dosage\"]", "text": "[Title]: Long-term intrathecal Baclofen infusion in supraspinal spasticity of adulthood.\n[Abstract]: OBJECTIVE: To evaluate long-term results of chronic intrathecal Baclofen infusion on the spasticity, on the spasms and to evaluate the side-effects of the intrathecal Baclofen in patients with supraspinal spasticity. CLINICAL MATERIALS AND METHODS: Fourteen patients with severe progressive refractory to medical therapy spasticity were evaluated after chronic intrathecal Baclofen infusion performed by implantation of subcutaneous pump. The patients had suffered traumatic or anoxic acquired brain injuries. The clinical evaluation was made using Ashworth Scale (AS) and the Spasm Frequency Scale (SFS). RESULTS: The intrathecal therapy showed a statistically significant improvement of the tone and of the spasms. CONCLUSIONS: The intrathecal infusion of Baclofen seems to be an effective treatment in patients with supraspinal spasticity.\n[Drug-Disease]: Baclofen - spasms" }, { "pmid": "11932909", "target": "[]", "text": "[Title]: Trimodality treatment in Stage III nonsmall cell lung carcinoma: prrognostic impact of K-ras mutations after neoadjuvant therapy.\n[Abstract]: BACKGROUND: In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated. METHODS: Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005). CONCLUSIONS: These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches.\n[Drug-Disease]: vindesine - NSCLC" }, { "pmid": "11932909", "target": "[]", "text": "[Title]: Trimodality treatment in Stage III nonsmall cell lung carcinoma: prrognostic impact of K-ras mutations after neoadjuvant therapy.\n[Abstract]: BACKGROUND: In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated. METHODS: Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005). CONCLUSIONS: These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches.\n[Drug-Disease]: carboplatin - NSCLC" }, { "pmid": "11942883", "target": "[\"Span: 5-10 mg | Label: Dosage\"]", "text": "[Title]: Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia.\n[Abstract]: BACKGROUND: Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia. METHODS: One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus. RESULTS: Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus. CONCLUSION: Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered.\n[Drug-Disease]: hydralazine - hypertensive" }, { "pmid": "11942883", "target": "[\"Span: 8 mg | Label: Dosage\"]", "text": "[Title]: Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia.\n[Abstract]: BACKGROUND: Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia. METHODS: One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus. RESULTS: Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus. CONCLUSION: Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered.\n[Drug-Disease]: Nifedipine - hypertensive" }, { "pmid": "12006526", "target": "[\"Span: topo IIalpha gene | Label: Gene\", \"Span: HER-2 | Label: Gene\"]", "text": "[Title]: HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil.\n[Abstract]: PURPOSE: The purpose of this study is to evaluate HER-2 and topoisomerase IIalpha (topo IIalpha) as candidates for predicting the activity of anthracyclines in the adjuvant treatment of breast cancer patients. EXPERIMENTAL DESIGN: In this study, we evaluated HER-2 and topo IIalpha gene aberrations by fluorescence in situ hybridization in a series of 430 primary breast cancer samples. Samples came from node-positive breast cancer patients randomly treated either with one of two anthracycline-based regimens [full-dose epirubicin-cyclophosphamide (HEC) and moderate-dose epirubicin-cyclophosphamide (EC)] or with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in the context of a Phase III adjuvant therapy trial. Event-free survival comparisons were performed between the three study arms in the subgroups of HER-2-amplified and nonamplified tumors. An explorative analysis was also performed to evaluate the predictive value of topo IIalpha in the cohort of HER-2-amplified patients. RESULTS: HER-2 amplification was observed in 73 of the 354 evaluable samples (21%), whereas topo IIalpha amplification was found in 23 of the 61 evaluable HER-2-amplified tumors (38%). The three event-free survival comparisons were CMF versus HEC, CMF versus EC, and EC versus HEC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: (a) CMF versus HEC, HR = 1.42 for HER-2-amplified tumors (95% CI, 0.54-3.76; P = 0.48) and 0.84 for HER-2-nonamplified tumors (95% CI, 0.49-1.44; P = 0.53); (b) CMF versus EC, HR = 1.65 for HER-2-amplified tumors (95% CI, 0.66-4.13; P = 0.29) and 0.66 for HER-2-nonamplified tumors (95% CI, 0.39-1.10; P = 0.11); and (c) EC versus HEC, HR = 0.93 for HER-2-amplified tumors (95% CI, 0.31-2.77, P = 0.90) and 1.33 for HER-2-nonamplified tumors (95% CI, 0.82-2.14; P = 0.25). Observed HRs suggest that the anthracycline-based therapy could be more effective than CMF in the subgroup of HER-2-amplified patients, whereas treatments could be equally active in the HER-2-nonamplified cohort. topo IIalpha evaluation suggests that the superiority of anthracyclines over CMF in HER-2-amplified patients could be confined to the subgroup of topo IIalpha-amplified tumors. CONCLUSIONS: HER-2 could have a predictive value for the activity of anthracycline-based regimens in the adjuvant therapy of breast cancer patients. The predictive value of HER-2 would most likely be related to the concomitant amplification of the topo IIalpha gene.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "12058236", "target": "[]", "text": "[Title]: Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.\n[Abstract]: We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.\n[Drug-Disease]: carmustine - breast cancer" }, { "pmid": "12058236", "target": "[]", "text": "[Title]: Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.\n[Abstract]: We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "12058236", "target": "[]", "text": "[Title]: Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.\n[Abstract]: We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.\n[Drug-Disease]: thiotepa - breast cancer" }, { "pmid": "12072574", "target": "[\"Span: 80 mg/d | Label: Dosage\"]", "text": "[Title]: Valsartan therapy has additive anti-oxidative effect to that of fluvastatin therapy against low-density lipoprotein oxidation: studies in hypercholesterolemic and hypertensive patients.\n[Abstract]: In hypercholesterolemic and hypertensive patients, an increased propensity of their low-density lipoprotein (LDL) to oxidative modification has been observed. Because oxidized LDL (ox-LDL) plays a major role in atherosclerosis, the current study analyzed the anti-oxidative effect of valsartan (an angiotensin II receptor antagonist) therapy in combination with fluvastatin therapy in these patients. Administration of 40 mg/d of fluvastatin for 2 months to seven patients resulted in significant reduction in plasma total and LDL cholesterol (by 24-28%). Valsartan administration (80 mg/d for an additional 2-month period) in combination with fluvastatin did not further affect plasma cholesterol levels. Fluvastatin therapy inhibited the susceptibility of LDL to copper ion-induced oxidation, as shown by prolongation of the lag time by 22% and by a reduction of thiobarbituric acid-reactive substances (TBARS) levels by 14%, as compared with the patient's LDL baseline oxidation. The addition of valsartan to fluvastatin resulted in a further 17% prolongation of the lag time and in an additional reduction of 21% in TBARS levels. In a parallel study, the LDL from eight patients who were first treated with 80 mg/d of valsartan for 2 months demonstrated reduced susceptibility to copper ion-induced oxidation, as observed by prolongation of lag time by 23% and reduction in TBARS levels by 19%, compared with the baseline values. The administration of 40 mg/d of fluvastatin for an additional 2 months in combination with valsartan, however, demonstrated no further inhibitory effect on LDL oxidation. The anti-oxidative properties of fluvastatin and valsartan against LDL oxidation were also demonstrated in vitro and the combination of both drugs was shown to have an additive effect. Valsartan therapy in hypercholesterolemic and hypertensive patients has an additive anti-oxidative effect to that of fluvastatin therapy. This may be related both to the anti-oxidative properties of valsartan and to the blocking of angiotensin II-induced oxidative stress.\n[Drug-Disease]: valsartan - hypertensive" }, { "pmid": "12196335", "target": "[\"Span: men | Label: Gender\", \"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction.\n[Abstract]: BACKGROUND: Erectile dysfunction (ED) is common in patients with congestive heart failure (CHF). ED reduces quality of life, and it may affect compliance, thereby impairing the success of CHF treatment. METHODS AND RESULTS: In the first phase (fixed-dose double-blind, randomized, placebo-controlled, two-way crossover study), we studied in 23 men with CHF the effects of 50 mg sildenafil on exercise and neurohormonal activation. Patients underwent a treadmill 6-minute cardiopulmonary walking (6'WT) test followed by a maximal cardiopulmonary exercise test (ET). In the second phase, patients received sildenafil, taken as required for ED. Sildenafil reduced the heart rate (HR) (bpm) before the 6'WT (from 75+/-15 to 71+/-14, P=0.02) and ET (from 75+/-15 to 71+/-15, P=0.02); the systolic blood pressure (mm Hg) before the 6'WT (from 116+/-18 to 108+/-18, P=0.004) and ET (from 116+/-15 to 108+/-17, P=0.001); the diastolic blood pressure before the 6'WT (from 69+/-9 to 63+/-11, P=0.01) and ET (from 70+/-8 to 65+/-10, P=0.004); and the Ve/VCO2 slope during the 6'WT (from 32+/-7 to 31+/-6, P=0.04) and ET (from 33+/-8 to 31+/-5, P=0.03). Sildenafil attenuated the HR increment during the 6'WT (P=0.003) and ET (P=0.000). Sildenafil increased the peak *O2 from 16.6+/-3.4 to 17.7+/-3.4 mL/kg per min (P=0.025) and the exercise time from 12.3+/-3.4 to 13.7+/-3.2 minutes (P=0.003). Sildenafil improved most scores of International Index of Erectile Function. CONCLUSIONS: Sildenafil was tolerated and effective for ED treatment in CHF, and improved the exercise capacity. The reduction of HR during exercise with sildenafil could theoretically decrease the myocardial oxygen consumption during sexual activity.\n[Drug-Disease]: sildenafil - Erectile dysfunction" }, { "pmid": "12198065", "target": "[\"Span: 1.5 or 3 mg | Label: Dosage\"]", "text": "[Title]: Prophylactic IM small-dose phenylephrine blunts spinal anesthesia-induced hypotensive response during surgical repair of hip fracture in the elderly.\n[Abstract]: UNLABELLED: In a double-blinded, placebo-controlled, randomized study, we evaluated the effect of prophylactic IM phenylephrine at doses of 1.5 and 3 mg on hyperbaric tetracaine spinal anesthesia-induced hypotension in 90 normotensive and hypertensive patients aged >65 yr undergoing surgery for hip fracture. Thirty normotensive patients received 1.5 or 3 mg of phenylephrine IM (N/P-1.5 and N/P-3.0 groups; n = 15 in each), whereas controls received saline (N/C group; n = 15), and 45 hypertensive patients were treated in a similar manner (H/P-1.5, H/P-3.0, and H/C groups; n = 15 in each). All groups had a peak sensory block height of T9, with a range of T8 to T10. The incidence of hypotension (>25% decrease in mean arterial blood pressure [MAP] from baseline) was significantly lower in the patients who received phenylephrine 1.5 or 3 mg than in the controls, both in the normotensive and hypertensive groups (P < 0.01). The N/P-3.0 and N/P-1.5 groups and the H/P-3.0 group had significantly lower percentage reductions in MAP (P < 0.05) and required significantly smaller doses of rescue IV ephedrine (P < 0.05) than did the N/C group or the H/C group. The H/P-1.5 group also required significantly less rescue IV ephedrine (P < 0.05), although it was not sufficient to significantly attenuate the percentage decrease in MAP compared with that in the H/C group. Bradycardia (heart rate <50 bpm) as an adverse effect after IM administration of phenylephrine was not observed in any of the groups. Hypertension (MAP >20% increase from baseline) after medication occurred in the N/P-3.0 and H/P-3.0 groups, but not in the N/P-1.5 and H/P-1.5 groups. We conclude that prophylactic IM injection of 1.5 mg of phenylephrine is a safe (defined as the inhibition of bradycardia and hypertension) and effective means of reducing the incidence of hypotension associated with spinal anesthesia in normotensive and hypertensive elderly patients. IMPLICATIONS: We evaluated the efficacy and safety of small-dose IM phenylephrine for prophylaxis against spinal anesthesia-induced hypotension in normotensive and hypertensive elderly patients. Phenylephrine 1.5 mg IM was effective for reducing the incidence of hypotension and avoided adverse effects.\n[Drug-Disease]: Phenylephrine - hypotension" }, { "pmid": "12233899", "target": "[\"Span: 55-year-old | Label: Age\", \"Span: man | Label: Gender\"]", "text": "[Title]: Treatment of catastrophic antiphospholipid syndrome with defibrotide, a proposed vascular endothelial cell modulator.\n[Abstract]: OBJECTIVE: To define at the molecular level the vascular endothelial cell (VEC) injury characteristics of catastrophic antiphospholipid syndrome (CAPS) and to report successful therapeutic use of a VEC modulator, defibrotide. METHODS: We describe a 55-year-old man with primary APS with an intractable prothrombotic state (CAPS) resistant to combined therapy with heparin, warfarin, aspirin, and dipyridamole. Treatment with defibrotide was conducted in the context of an investigational phase II protocol where the dose was regulated and individualized by disease/patient-specific molecular and clinical markers. RESULTS: The patient entered complete remission with defibrotide treatment. During treatment, dose dependent pharmacological actions of defibrotide and key stress markers for VEC injury were identified. Evidence of defibrotide's polypharmacology included downregulation of cytokines, notably tumor necrosis factor-alpha, as the earliest effect, cellular differentiation of VEC, possibly with direct regulatory effect over cellular genes, and the reversal of platelet consumption and prothrombotic state. Von Willebrand antigen levels were used as the sole marker to guide therapy. CONCLUSION: This case demonstrates effective remission of CAPS with defibrotide treatment. In contrast to theories that CAPS is triggered by ischemic and thrombotic tissue damage, these data present VEC injury as the primary and representative lesion of CAPS. The pathogenesis may involve concurrent impairment of different VEC functions. Achieving remission may require a polypharmacologic approach, represented here by use of defibrotide.\n[Drug-Disease]: defibrotide - catastrophic antiphospholipid syndrome" }, { "pmid": "12359989", "target": "[\"Span: CYP2C9 genotype | Label: Gene\"]", "text": "[Title]: The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial.\n[Abstract]: BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.\n[Drug-Disease]: irbesartan - hypertension" }, { "pmid": "12385445", "target": "[\"Span: five women | Label: Gender\", \"Span: two men | Label: Gender\", \"Span: 2 mg/kg/ day | Label: Dosage\"]", "text": "[Title]: Azathioprine in refractory sprue: results from a prospective, open-label study.\n[Abstract]: OBJECTIVE: Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue. METHODS: We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRgamma gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8-12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/ day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial. RESULTS: After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up. CONCLUSIONS: The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.\n[Drug-Disease]: azathioprine - malabsorptive disorder" }, { "pmid": "12403023", "target": "[]", "text": "[Title]: A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients.\n[Abstract]: Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.\n[Drug-Disease]: Zidovudine - HIV infected" }, { "pmid": "12403023", "target": "[]", "text": "[Title]: A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients.\n[Abstract]: Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.\n[Drug-Disease]: Zalcitabine - HIV infected" }, { "pmid": "12403023", "target": "[]", "text": "[Title]: A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients.\n[Abstract]: Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.\n[Drug-Disease]: Nelfinavir - HIV infected" }, { "pmid": "12501088", "target": "[\"Span: 33-year-old | Label: Age\", \"Span: woman | Label: Gender\", \"Span: primigravida | Label: Body Type\"]", "text": "[Title]: Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during pregnancy.\n[Abstract]: Bipolar disorder in pregnancy was treated with nimodipine, because of lithium-induced nephrogenic diabetes insipidus. A 33-year-old primigravida woman at approximately 22 weeks 6 days of gestation had increasing blood pressure since 16 weeks of gestation, despite methyldopa 500 mg twice daily. She also had hypothyroidism and bipolar disorder, which were treated with levothyroxine and lithium carbonate, respectively. Nephrogenic diabetes insipidus developed, presumably because of chronic lithium exposure in high doses. She did not tolerate carbamazepine (the other agent commonly used for bipolar disorder in pregnancy). Thus, nimodipine was tried and tolerated well; furthermore, it was very effective in controlling her bipolar disorder. Nimodipine successfully controlled the bipolar disorder of a woman during pregnancy, who was intolerant of more commonly used agents.\n[Drug-Disease]: Nimodipine - bipolar disorder" }, { "pmid": "12503839", "target": "[]", "text": "[Title]: The prescription of dexamphetamine to patients with schizophrenia and amphetamine dependence.\n[Abstract]: Patients with a severe mental illness such as schizophrenia have significant rates of concurrent amphetamine use. Such dual diagnosis patients have been shown to have poorer treatment outcomes. Often, they do not comply with treatment plans and have frequent episodes of hospitalization. There is growing evidence for the role of prescribed dexamphetamine in the treatment of amphetamine dependence. The prescription of dexamphetamine to patients with schizophrenia and amphetamine dependence has not been previously reported. Eight schizophrenic patients are described to whom dexamphetamine has been prescribed, with information being extracted retrospectively from case notes. In four out of eight cases, the prescription of dexamphetamine led to apparently good progress both in terms of substance misuse and psychiatric health. In two cases, progress was more equivocal, but appeared to produce some benefit. Two cases could be judged as treatment failures, but the condition and situation of the patients were not worse at the end of treatment than at the beginning. Compliance with neuroleptics increased in most cases. No patients exhibited exacerbation of psychosis as a result of treatment. The rate of outcome success is satisfactory when consideration is given to the difficult nature of this patient group, and their previous failure to respond to intensive treatment. It is argued that benefits may be gained from increased compliance with psychiatric treatment in patients prescribed amphetamine, and that this may outweigh possible risks. However, any conclusions are tentative in view of the nature of this study. A small open-label prospective study is recommended.\n[Drug-Disease]: dexamphetamine - schizophrenic" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: carmustine - breast cancer" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: cisplatin - breast cancer" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: doxorubicin - breast cancer" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: 5-fluorouracil - breast cancer" }, { "pmid": "12523579", "target": "[]", "text": "[Title]: High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.\n[Abstract]: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.\n[Drug-Disease]: tamoxifen - breast cancer" }, { "pmid": "12525732", "target": "[\"Span: Gene mutations within the P/Q type neuronal calcium channel | Label: Gene\"]", "text": "[Title]: Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.\n[Abstract]: Gene mutations within the P/Q type neuronal calcium channel in familial hemiplegic migraine (FHM) suggest a therapeutic role for calcium-channel blockade. The authors have previously reported abortive therapy of FHM with IV verapamil. Here the authors describe four cases of sporadic hemiplegic migraine (SHM) responsive to verapamil, administered either orally or IV. The findings indicate that verapamil is effective therapy for both SHM and FHM.\n[Drug-Disease]: verapamil - familial hemiplegic migraine" }, { "pmid": "12552051", "target": "[\"Span: 0.1 mg | Label: Dosage\", \"Span: 2.75 mg | Label: Dosage\", \"Span: 5.5 mg | Label: Dosage\", \"Span: 8.25 mg | Label: Dosage\", \"Span: adults | Label: Age\"]", "text": "[Title]: Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral \"rescue\" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.\n[Drug-Disease]: droperidol - migraine" }, { "pmid": "12552051", "target": "[\"Span: 0.1 mg | Label: Dosage\", \"Span: 2.75 mg | Label: Dosage\", \"Span: 5.5 mg | Label: Dosage\", \"Span: 8.25 mg | Label: Dosage\", \"Span: adults | Label: Age\"]", "text": "[Title]: Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral \"rescue\" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.\n[Drug-Disease]: droperidol - nausea" }, { "pmid": "12552051", "target": "[\"Span: 0.1 mg | Label: Dosage\", \"Span: 2.75 mg | Label: Dosage\", \"Span: 5.5 mg | Label: Dosage\", \"Span: 8.25 mg | Label: Dosage\", \"Span: adults | Label: Age\"]", "text": "[Title]: Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral \"rescue\" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.\n[Drug-Disease]: droperidol - phonophobia" }, { "pmid": "12552051", "target": "[\"Span: 0.1 mg | Label: Dosage\", \"Span: 2.75 mg | Label: Dosage\", \"Span: 5.5 mg | Label: Dosage\", \"Span: 8.25 mg | Label: Dosage\", \"Span: adults | Label: Age\"]", "text": "[Title]: Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral \"rescue\" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.\n[Drug-Disease]: droperidol - vomiting" }, { "pmid": "12552051", "target": "[\"Span: 0.1 mg | Label: Dosage\", \"Span: 2.75 mg | Label: Dosage\", \"Span: 5.5 mg | Label: Dosage\", \"Span: 8.25 mg | Label: Dosage\", \"Span: adults | Label: Age\"]", "text": "[Title]: Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral \"rescue\" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.\n[Drug-Disease]: droperidol - photophobia" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 10 mg daily | Label: Dosage\", \"Span: 40 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: enalapril - albuminuria" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 10 mg daily | Label: Dosage\", \"Span: 40 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: enalapril - hypertension" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 0.625 mg | Label: Dosage\", \"Span: 2.5 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: indapamide - albuminuria" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 0.625 mg | Label: Dosage\", \"Span: 2.5 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: indapamide - hypertension" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 2 mg | Label: Dosage\", \"Span: maximum of 8 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: perindopril - albuminuria" }, { "pmid": "12654706", "target": "[\"Span: age 59+/-9 | Label: Age\", \"Span: 2 mg | Label: Dosage\", \"Span: maximum of 8 mg | Label: Dosage\"]", "text": "[Title]: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.\n[Abstract]: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.\n[Drug-Disease]: perindopril - hypertension" }, { "pmid": "12661892", "target": "[]", "text": "[Title]: Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane.\n[Abstract]: Oxidative stress has been implicated in a range of disease states, including end-stage renal failure treated with hemodialysis. Hemodialysis with vitamin E-modified membranes reduces lipid peroxidation, but the effect on erythrocyte integrity has not been determined. This study compared antioxidant defense parameters and the resistance of erythrocytes to free radical-mediated hemolysis in patients dialysed with cellulose acetate membranes at baseline and with a vitamin E-modified membrane (Excebrane Clirans; Terumo Corporation) for 13 wk. Resistance of erythrocytes to free radical attack was assessed in vitro using the peroxyl hemolysis test. The time to 50% hemolysis (T50%) increased significantly during the first 6 wk of Excebrane use (p < 0.05), but this parameter returned to baseline by 13 wk. Glutathione concentration and erythrocyte superoxide dismutase activity were unchanged during the study, but glutathione peroxidase activity increased from low levels at baseline and became significantly higher at 6 and 13 wk (p < 0.001). Total erythrocyte polyunsaturated fatty acid content and C18:2 level increased (p < 0.001) and saturated fatty acids (total, C16:0, C18:0, C22:0 and C24:0) decreased (p < 0.03). Total monounsaturated fatty acid content was unchanged. The increased resistance of erythrocytes to hemolysis, the increased glutathione peroxidase activity, and the increased degree of unsaturation of fatty acids in the erythrocyte membrane are compatible with a reduction of oxidative stress during hemodialysis with vitamin E-modified membranes.\n[Drug-Disease]: vitamin E - hemolysis" }, { "pmid": "12662204", "target": "[]", "text": "[Title]: The effect of vitamin E-bonded dialyzer membrane on red blood cell survival in hemodialyzed patients.\n[Abstract]: Reduced red blood cell (RBC) survival due to oxidative damage is one of the causes of anemia in patients under long-term hemodialysis. Recently, it has been shown that vitamin E-bonded dialyzer membrane is able to reduce the oxidative stress during hemodialysis. In humans, creatine content in RBC is used to measure RBC life span and erythropoietic capacity, since it rapidly declines as the RBCs become old. Therefore this study aimed to elucidate the effect of vitamin E-bonded dialyzer membrane on RBC life span by measuring creatine content in RBC.\n[Drug-Disease]: vitamin E - anemia" }, { "pmid": "12675867", "target": "[]", "text": "[Title]: Vitamin E-bonded hemodialyzer improves atherosclerosis associated with a rheological improvement of circulating red blood cells.\n[Abstract]: BACKGROUND: Vitamin E-bonded hemodialyzer is known to improve oxidative stress in patients with hemodialysis. However, there is little information available as to whether or not this membrane clinically improves atherosclerosis. Furthermore, it remains unknown whether there is any effect of the membrane on rheology of circulating red blood cells. METHOD: We conducted a randomized, open-labeled, prospective control study (N = 34) for 1 year to investigate the effect of vitamin E-bonded cellulose membrane dialyzer (EE) (N = 17) on carotid atherosclerotic changes [intima-media thickness (IMT) of carotid arteries] and the viscosity, percentage of dysmorphism (%DMR) of red blood cells (RBCs) and their distribution width-standard deviation (RDW-SD), in comparison with cellulose membrane (SU) (N = 17) identical to EE without vitamin E-bonded membrane. Erythropoietin (EPO) dose used for the treatment of uremic anemia was also calculated. RESULTS: The IMT significantly decreased in the EE group, while in the SU group the IMT significantly increased. The viscosity of RBCs in hemodialysis patients (4.70 +/- 0.45 cP) was greater than that in healthy individuals (3.73 +/- 0.15 cP). EE significantly improved the viscosity (from 4.84 +/- 0.41 cP to 4.51 +/- 0.54 cP, P < 0.01), %DMR (from 2.29 +/- 2.17% to 1.90 +/- 1.49%, P < 0.01), and RDW-SD (from 54.4 +/- 7.6 fL to 49.3 +/- 5.9 fL, P < 0.01). On the contrary, these parameters all worsened in the SU group. EPO dose needed for the treatment of anemia was significantly (P < 0.05) reduced from 5383 +/- 2655 U/week to 4235 +/- 3103 U/week in the EE group. During these period, mean blood pressure, Kt/V urea, and serum beta2-microglobulin were not changed between the two groups. CONCLUSION: These findings suggest that vitamin E-bonded hemodialyzer is very useful for improving atherosclerosis from a clinical point of view. As one of the underlying mechanisms, as well as antioxidant effects, we want to address an important role of the improvement of rheology of circulating RBCs, which may also help to reduce the requirement of EPO dose in the treatment of anemia of ESRD patients.\n[Drug-Disease]: vitamin E - atherosclerosis" }, { "pmid": "12679006", "target": "[\"Span: 15 were males | Label: Gender\", \"Span: 16 females | Label: Gender\", \"Span: median age 35.4 years | Label: Age\", \"Span: 0.16 mg x kg(-1) x d(-1) | Label: Dosage\"]", "text": "[Title]: [Clinical observation of the short-term efficacy of the treatment with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) in newly diagnosed acute promyelocytic leukemia (APL)].\n[Abstract]: OBJECTIVE: To study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate. METHOD: Thirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed. RESULT: Two patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1. CONCLUSION: ATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.\n[Drug-Disease]: As(2)O(3) - APL" }, { "pmid": "12679006", "target": "[\"Span: 15 were males | Label: Gender\", \"Span: 16 females | Label: Gender\", \"Span: median age 35.4 years | Label: Age\", \"Span: 25 mg x m(-2) x d(-1) | Label: Dosage\"]", "text": "[Title]: [Clinical observation of the short-term efficacy of the treatment with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) in newly diagnosed acute promyelocytic leukemia (APL)].\n[Abstract]: OBJECTIVE: To study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate. METHOD: Thirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed. RESULT: Two patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1. CONCLUSION: ATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.\n[Drug-Disease]: ATRA - APL" }, { "pmid": "12680319", "target": "[\"Span: 67-year-old | Label: Age\", \"Span: man | Label: Gender\"]", "text": "[Title]: [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].\n[Abstract]: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.\n[Drug-Disease]: fosfomycin - glomerulonephritis" }, { "pmid": "12680319", "target": "[\"Span: 67-year-old | Label: Age\", \"Span: man | Label: Gender\"]", "text": "[Title]: [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].\n[Abstract]: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.\n[Drug-Disease]: fosfomycin - proteinuria" }, { "pmid": "12680319", "target": "[\"Span: 67-year-old | Label: Age\", \"Span: man | Label: Gender\"]", "text": "[Title]: [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].\n[Abstract]: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.\n[Drug-Disease]: Vancomycin - glomerulonephritis" }, { "pmid": "12680319", "target": "[\"Span: 67-year-old | Label: Age\", \"Span: man | Label: Gender\"]", "text": "[Title]: [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].\n[Abstract]: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.\n[Drug-Disease]: Vancomycin - proteinuria" }, { "pmid": "12680486", "target": "[]", "text": "[Title]: [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].\n[Abstract]: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.\n[Drug-Disease]: amiloride - diabetes insipidus" }, { "pmid": "12698877", "target": "[]", "text": "[Title]: Treatment of inoperable pancreatic carcinoma using a cell-based local chemotherapy: results of a phase I/II clinical trial.\n[Abstract]: BACKGROUND: The use of ifosfamide for conventional chemotherapy of pancreatic tumors is limited by systemic toxicity caused, in part, by its activation by liver-specific cytochrome enzymes and the subsequent systemic distribution of metabolites. Activation at the tumor site, on the other hand, should reduce systemic toxicity and provide more effective local therapeutic concentrations. The results of a phase I/II open, single-arm clinical trial of local intratumor activation of ifosfamide are presented. METHODS: Treatment involved angiographic implantation of encapsulated allogeneic cells, genetically modified to overexpress the enzyme cytochrome P-450 2B1, into the vasculature leading to the tumor. The cells are protected from immune rejection and locally activate systemically administered ifosfamide to antitumor metabolites. RESULTS: Of the 14 patients treated, 4 showed tumor regression and the other 10 patients showed stable disease, i.e., no further tumor growth. The median survival of the patient cohort was twice that of the control group. The 1-year survival was 36%, i.e., threefold that of the control group (twice that reported for gemcitabine). As far as clinical benefit was concerned, 4 of the 13 evaluable patients reported improvements in pain assessment at the last observation, with 6 remaining unchanged (4 of these experienced no pain) and 3 patients experiencing slightly greater pain. Using a worst case scenario, 50% experienced a clinical benefit, which rose to 71% of patients if a best case scenario was applied. The best predictor of clinical benefit was lack of pain, whereas significant weight loss possibly predicts a poor clinical benefit. CONCLUSIONS: The data obtained from this phase I/II clinical trial are promising and suggest that further clinical trials are warranted.\n[Drug-Disease]: ifosfamide - pancreatic tumors" }, { "pmid": "12712474", "target": "[\"Span: 0.15 mg/kg per day | Label: Dosage\", \"Span: median age was 44 years (range, 26-72 years) | Label: Age\"]", "text": "[Title]: Use of arsenic trioxide (As2O3) in the treatment of patients with acute promyelocytic leukemia: the M. D. Anderson experience.\n[Abstract]: BACKGROUND: Approximately 20-30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) and an anthracycline develop recurrent disease. It has been reported that arsenic trioxide (As(2)O(3)) is effective in this setting. The authors report the experience of The M. D. Anderson Cancer Center with As(2)O(3) in the treatment of patients with recurrent APL. METHODS: Twelve patients who developed recurrent APL after treatment with ATRA were included. Patients received intravenous As(2)O(3) 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days. Their median age was 44 years (range, 26-72 years), and the median duration of first remission was 52 weeks (range, 23-292 weeks). RESULTS: All 12 patients achieved a CR. The median time to achieve CR was 52 days (range, 27-75 days). Seven of 10 evaluable patients achieved a molecular remission (i.e., polymerase chain reaction [PCR] analysis was negative for the gene encoding fusion of the nuclear receptor for retinoic acid to the PML gene at the time of CR; 70% of patients; 95% confidence interval, 0.35-0.93), and all other patients had negative PCR results after they received post-remission therapy. All patients received subsequent therapy: Four patients received As(2)O(3) alone, six patients received As(2)O(3) with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As(2)O(3). Eight patients continued in CR after a median follow-up of 24 months (range, 9-45 months). Side effects were mild, except for two patients who developed Grade 2 and 3 peripheral neuropathy, respectively; one of those patients required discontinuation of therapy. CONCLUSIONS: As(2)O(3) is effective and well tolerated therapy for patients with recurrent APL. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable.\n[Drug-Disease]: As(2)O(3) - acute promyelocytic leukemia" }, { "pmid": "12717482", "target": "[\"Span: age (less than 65 years versus at least 65 years) | Label: Age\", \"Span: history of diabetes mellitus or hypertension | Label: Comorbidity\"]", "text": "[Title]: Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT).\n[Abstract]: This study examined the effects of long term cholesterol lowering therapy with simvastatin on progression and regression of coronary atherosclerosis, as determined by quantitative angiographic end points, in subgroups of patients with known coronary risk factors. In this randomized, placebo controlled clinical trial, the effect of simvastatin on coronary atherosclerosis was compared with that of placebo in 394 patients who had paired coronary angiograms taken an average of four years apart. The effects of treatment on the following prespecified subgroups were examined: sex, age (less than 65 years versus at least 65 years), smoking status (current or previous/never), history of diabetes mellitus or hypertension, and severity of coronary artery lesions (diameter at least 50% versus less than 50%). There were significantly smaller decreases in the average minimum diameters, between closeout and baseline angiograms, in all simvastatin-treated subgroups, compared with placebo. Trends toward or significantly smaller decreases in the average of the mean diameters, and similar smaller increases in percentage diameter stenosis were also seen in all subgroups. The slowing of angiographically demonstrable coronary atherosclerotic narrowing supports the contention that this treatment effect is causally related to the reduction of coronary events repeatedly seen in large outcome clinical trials of lipid lowering therapy. Also, this treatment effect occurs in the presence or absence of the traditional coronary risk factors.\n[Drug-Disease]: simvastatin - coronary atherosclerotic" }, { "pmid": "12728089", "target": "[\"Span: 6- to 72-month-old children | Label: Age\", \"Span: 45 mg/kg/d | Label: Dosage\"]", "text": "[Title]: Antibiotic treatment of acute otorrhea through tympanostomy tube: randomized double-blind placebo-controlled study with daily follow-up.\n[Abstract]: OBJECTIVE: The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled study in outpatient setting. PATIENTS: Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study. INTERVENTIONS: Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube. MAIN OUTCOME MEASURES: Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid. RESULTS: The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days). CONCLUSIONS: Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.\n[Drug-Disease]: amoxicillin-clavulanate - acute otitis media" }, { "pmid": "12759298", "target": "[\"Span: 300 mg once daily | Label: Dosage\"]", "text": "[Title]: Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.\n[Abstract]: OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.\n[Drug-Disease]: fenofibrate - gout" }, { "pmid": "12759298", "target": "[\"Span: 300 mg once daily | Label: Dosage\"]", "text": "[Title]: Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.\n[Abstract]: OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.\n[Drug-Disease]: fenofibrate - hypertriglyceridaemia" }, { "pmid": "12759298", "target": "[\"Span: 50 mg once daily | Label: Dosage\"]", "text": "[Title]: Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.\n[Abstract]: OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.\n[Drug-Disease]: losartan - gout" }, { "pmid": "12759298", "target": "[\"Span: 50 mg once daily | Label: Dosage\"]", "text": "[Title]: Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.\n[Abstract]: OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.\n[Drug-Disease]: losartan - hypertension" }, { "pmid": "12763375", "target": "[]", "text": "[Title]: A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation.\n[Abstract]: BACKGROUND/AIMS: To compare the efficacy in preventing hepatitis B virus (HBV) recurrence of lamivudine vs. lamivudine plus hepatitis B immune globulin (HBIg) after a short course of HBIg and lamivudine in liver transplanted chronic hepatitis B patients. METHODS: Forty-six patients with HBV cirrhosis received lamivudine before liver transplantation and were then randomized to receive lamivudine plus HBIg for 1 month followed by lamivudine or both drugs for 17 months. RESULTS: Thirty-two patients were transplanted and 29 were randomized to receive combination therapy (15 cases) or lamivudine monotherapy (14 cases). HBV DNA was undetectable in all cases (17 induced by lamivudine therapy) at the time of liver transplantation. After 18 months of follow-up, all patients survived without HBV recurrence: hepatitis Bs antigen and HBV DNA were negative; however, HBV DNA was detected by polymerase chain reaction in four cases (three with HBIg plus lamivudine and one with lamivudine). Alanine aminotransferase levels were normal except in six cases (one HCV and two HDV coinfections). There were no drug-related adverse events. CONCLUSIONS: Lamivudine monotherapy after a short course of lamivudine and HBIg is equally as efficacious in preventing HBV recurrence as HBIg plus lamivudine during the first 18 months after liver transplantation. This strategy is more economic and convenient to administer than long-term HBIg plus lamivudine.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "12771277", "target": "[\"Span: 5 microM/L | Label: Dosage\", \"Span: 10 microM/L | Label: Dosage\", \"Span: 80 to 120 mg | Label: Dosage\", \"Span: allergic to quinidine | Label: Comorbidity\"]", "text": "[Title]: Treatment of slow-channel congenital myasthenic syndrome with fluoxetine.\n[Abstract]: The authors found that fluoxetine significantly shortens at 5 microM/L and nearly normalizes at 10 microM/L the prolonged opening bursts of slow-channel congenital myasthenic syndrome (SCCMS) acetylcholine receptors (AChR) expressed in fibroblasts. Prompted by this observation, they treated two SCCMS patients allergic to quinidine with up to 80 to 120 mg of fluoxetine per day over 3 years (serum fluoxetine + norfluoxetine levels 8 to 11 microM/L). Both patients showed marked subjective and objective improvement by quantitative muscle strength testing and electromyography.\n[Drug-Disease]: fluoxetine - congenital myasthenic syndrome" }, { "pmid": "12811213", "target": "[\"Span: 1 woman | Label: Gender\", \"Span: breast cancer | Label: Comorbidity\", \"Span: 3 men | Label: Gender\", \"Span: non-Hodgkin lymphoma | Label: Comorbidity\", \"Span: 41 to 63 years | Label: Age\", \"Span: 100 mg/d | Label: Dosage\", \"Span: 150 mg/d | Label: Dosage\"]", "text": "[Title]: Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine.\n[Abstract]: The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "1281807", "target": "[]", "text": "[Title]: Efficacy and safety of sotalol in patients with complex ventricular arrhythmias.\n[Abstract]: Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)\n[Drug-Disease]: sotalol - ventricular tachycardia" }, { "pmid": "1281807", "target": "[]", "text": "[Title]: Efficacy and safety of sotalol in patients with complex ventricular arrhythmias.\n[Abstract]: Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)\n[Drug-Disease]: sotalol - ventricular premature beats" }, { "pmid": "12818978", "target": "[\"Span: 8 mg | Label: Dosage\", \"Span: 4 mg | Label: Dosage\"]", "text": "[Title]: A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery.\n[Abstract]: UNLABELLED: In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus. IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.\n[Drug-Disease]: ondansetron - Postoperative nausea and vomiting" }, { "pmid": "12835612", "target": "[\"Span: beta2AR genotype | Label: Gene\"]", "text": "[Title]: Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure.\n[Abstract]: Although the widespread introduction of beta-adrenoceptor antagonists into the management of congestive heart failure (CHF) has led to significant improvements in morbidity and mortality, it is also apparent that clinical responses to this therapy vary substantially. With the recognition that functionally significant genetic polymorphisms of the beta2-adrenoceptor exist with clinically relevant allelic frequency, we hypothesized that beta2-adrenoceptor genotype may affect the response to carvedilol. The clinical response, influence on left ventricular function and beta2-adrenoceptor (beta2AR) genotype was determined in 80 patients treated with carvedilol. A clinically significant improvement in left ventricular function (good responder) was defined as an absolute improvement of 10% in the left ventricular ejection fraction or 5% in the fractional shortening. Consistent with studies performed in vitro on the influence of beta2AR genotype and receptor desensitization, subjects who were homozygous for the allele encoding the Gln27 polymorphism displayed a significantly lower proportion of good responders than patients who were homozygous or heterozygous for the Glu27 polymorphism (26% versus 63%, P=0.003). These data demonstrate a significant influence of beta2AR genotype in the response to carvedilol in CHF patients. Accordingly, determination of beta2AR status may be of value in the tailoring of individual therapy in patients with CHF.\n[Drug-Disease]: carvedilol - CHF" }, { "pmid": "1286497", "target": "[\"Span: mean dose: 0.73 mg [7.3 ml] | Label: Dosage\"]", "text": "[Title]: Reversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I.\n[Abstract]: Flumazenil is a competitive benzodiazepine antagonist that rapidly reverses the residual effects of benzodiazepines following intravenous conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous diazepam were randomly allocated to receive intravenous doses of flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5-minute assessment, and memory was assessed at the 180-minute assessment. Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation, psychomotor impairment, and amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102 flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93 flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of amnesia at the 5-minute assessment was achieved in 75% of 101 flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%) flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the flumazenil group was dizziness (6%). There were no serious adverse experiences related to the test drug. Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous conscious sedation induced by diazepam. For most (70%) of these flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment.\n[Drug-Disease]: flumazenil - amnesia" }, { "pmid": "1287915", "target": "[]", "text": "[Title]: Aminosidine (paromomycin) in the treatment of leishmaniasis imported into the United Kingdom.\n[Abstract]: We report 11 patients with leishmaniasis from different endemic areas, treated in the UK with intravenous aminosidine alone or in combination with other drugs. Clinical and parasitological cures were achieved in all 7 patients from the Mediterranean zone who had visceral disease, with one relapse. Two of 4 patients with cutaneous or mucosal disease were cured; the other 2, from Iraq and Iran, did not respond. Toxic effects were high-tone deafness in 2 patients, one of whom had pre-existing renal impairment, and transient, mild elevation of serum creatinine in 3. Aminosidine is an effective, tolerable and relatively non-toxic alternative to existing antileishmanial drugs for the treatment of visceral leishmaniasis. Further studies will be needed to assess its place in cutaneous and mucosal disease.\n[Drug-Disease]: Aminosidine - visceral leishmaniasis" }, { "pmid": "12897636", "target": "[]", "text": "[Title]: Mirtazapine in L-dopa-induced dyskinesias.\n[Abstract]: Mirtazapine is a novel antidepressant with a pharmacologic profile (alpha-2 antagonist, 5HT-(1A) agonist, and 5HT-(2) antagonist) that renders it potentially useful for l-dopa-induced dyskinesias. Drugs with 5HT-(1A) agonistic activity, such as buspirone and tandospirone, have been reported to be effective in reducing l-dopa-induced dyskinesias. Furthermore, 5HT-(2) antagonism may, by reducing substantia nigra pars reticulata hyperactivity, play a role in the improvement of Parkinsonian symptoms and l-dopa-induced dyskinesias, as has been observed with ritanserin, a 5HT-(2) antagonist. Alpha-2 antagonists, such as idazoxan, have recently also been reported to improve l-dopa-induced dyskinesias. The authors investigated the antidyskinetic properties of mirtazapine by designing an open-label study of 20 Parkinsonian patients with l-dopa-induced dyskinesias. Mirtazapine proved to be moderately effective in reducing l-dopa-induced dyskinesias, either alone or in association with amantadine. Mirtazapine may be of use in patients who do not respond or are intolerant to amantadine.\n[Drug-Disease]: Mirtazapine - dyskinesias" }, { "pmid": "12897636", "target": "[]", "text": "[Title]: Mirtazapine in L-dopa-induced dyskinesias.\n[Abstract]: Mirtazapine is a novel antidepressant with a pharmacologic profile (alpha-2 antagonist, 5HT-(1A) agonist, and 5HT-(2) antagonist) that renders it potentially useful for l-dopa-induced dyskinesias. Drugs with 5HT-(1A) agonistic activity, such as buspirone and tandospirone, have been reported to be effective in reducing l-dopa-induced dyskinesias. Furthermore, 5HT-(2) antagonism may, by reducing substantia nigra pars reticulata hyperactivity, play a role in the improvement of Parkinsonian symptoms and l-dopa-induced dyskinesias, as has been observed with ritanserin, a 5HT-(2) antagonist. Alpha-2 antagonists, such as idazoxan, have recently also been reported to improve l-dopa-induced dyskinesias. The authors investigated the antidyskinetic properties of mirtazapine by designing an open-label study of 20 Parkinsonian patients with l-dopa-induced dyskinesias. Mirtazapine proved to be moderately effective in reducing l-dopa-induced dyskinesias, either alone or in association with amantadine. Mirtazapine may be of use in patients who do not respond or are intolerant to amantadine.\n[Drug-Disease]: amantadine - dyskinesias" }, { "pmid": "1403792", "target": "[\"Span: 2 x 30 mg/kg, p.o. | Label: Dosage\"]", "text": "[Title]: Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem.\n[Abstract]: Zolpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]. The present study investigated whether tolerance and physical dependence develop after repeated treatment with zolpidem as is observed with benzodiazepines. Mice were given zolpidem or the benzodiazepine midazolam (2 x 30 mg/kg, p.o.) for 10 consecutive days. Tolerance to central depressant effects (evaluated by recording spontaneous locomotor activity) and to anticonvulsant effects (measured against pentylenetetrazole-, electroshock- and isoniazid-induced convulsions) was assessed 42 hr after the last administration. A decrease in the latency to isoniazid-induced convulsions was taken as an index of physical dependence and was evaluated 3, 6, 14, 24, 42 and 67 hr after the end of chronic drug treatment. Repeated treatment with midazolam produced tolerance to its sedative and anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3 to 5. Fourteen hr after discontinuation of treatment, spontaneous withdrawal was observed and lasted 3 days. When flumazenil was given 3 or 6 hr after the final midazolam injection, precipitated withdrawal was observed. In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects. Moreover, neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice.\n[Drug-Disease]: zolpidem - convulsions" }, { "pmid": "1403792", "target": "[\"Span: 2 x 30 mg/kg, p.o. | Label: Dosage\"]", "text": "[Title]: Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem.\n[Abstract]: Zolpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]. The present study investigated whether tolerance and physical dependence develop after repeated treatment with zolpidem as is observed with benzodiazepines. Mice were given zolpidem or the benzodiazepine midazolam (2 x 30 mg/kg, p.o.) for 10 consecutive days. Tolerance to central depressant effects (evaluated by recording spontaneous locomotor activity) and to anticonvulsant effects (measured against pentylenetetrazole-, electroshock- and isoniazid-induced convulsions) was assessed 42 hr after the last administration. A decrease in the latency to isoniazid-induced convulsions was taken as an index of physical dependence and was evaluated 3, 6, 14, 24, 42 and 67 hr after the end of chronic drug treatment. Repeated treatment with midazolam produced tolerance to its sedative and anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3 to 5. Fourteen hr after discontinuation of treatment, spontaneous withdrawal was observed and lasted 3 days. When flumazenil was given 3 or 6 hr after the final midazolam injection, precipitated withdrawal was observed. In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects. Moreover, neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice.\n[Drug-Disease]: midazolam - convulsions" }, { "pmid": "1411317", "target": "[\"Span: 89 older adults | Label: Age\", \"Span: pre-existing renal impairment | Label: Comorbidity\"]", "text": "[Title]: A comparison of netilmicin and tobramycin therapy in patients with renal impairment.\n[Abstract]: We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.\n[Drug-Disease]: netilmicin - bacterial infections" }, { "pmid": "1411317", "target": "[\"Span: 89 older adults | Label: Age\", \"Span: pre-existing renal impairment | Label: Comorbidity\"]", "text": "[Title]: A comparison of netilmicin and tobramycin therapy in patients with renal impairment.\n[Abstract]: We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.\n[Drug-Disease]: tobramycin - bacterial infections" }, { "pmid": "14502318", "target": "[\"Span: 9 women | Label: Gender\", \"Span: 4 men | Label: Gender\", \"Span: 42.5 years | Label: Age\", \"Span: 37.3 kg/m2 | Label: Body Type\"]", "text": "[Title]: The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis.\n[Abstract]: OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH. SUBJECTS: There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively. METHOD: The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months. RESULTS: Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively). CONCLUSION: The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.\n[Drug-Disease]: sibutramine - steatosis" }, { "pmid": "14502318", "target": "[\"Span: 9 women | Label: Gender\", \"Span: 4 men | Label: Gender\", \"Span: 42.5 years | Label: Age\", \"Span: 37.3 kg/m2 | Label: Body Type\"]", "text": "[Title]: The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis.\n[Abstract]: OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH. SUBJECTS: There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively. METHOD: The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months. RESULTS: Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively). CONCLUSION: The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.\n[Drug-Disease]: sibutramine - obese" }, { "pmid": "14502318", "target": "[\"Span: 8 women | Label: Gender\", \"Span: 4 men | Label: Gender\", \"Span: 43.2 years | Label: Age\", \"Span: 36.1 kg/m2 | Label: Body Type\"]", "text": "[Title]: The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis.\n[Abstract]: OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH. SUBJECTS: There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively. METHOD: The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months. RESULTS: Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively). CONCLUSION: The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.\n[Drug-Disease]: orlistat - steatosis" }, { "pmid": "14502318", "target": "[\"Span: 8 women | Label: Gender\", \"Span: 4 men | Label: Gender\", \"Span: 43.2 years | Label: Age\", \"Span: 36.1 kg/m2 | Label: Body Type\"]", "text": "[Title]: The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis.\n[Abstract]: OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH. SUBJECTS: There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively. METHOD: The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months. RESULTS: Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively). CONCLUSION: The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.\n[Drug-Disease]: orlistat - obese" }, { "pmid": "14604312", "target": "[\"Span: 12.5 mg | Label: Dosage\", \"Span: 25 mg | Label: Dosage\", \"Span: 50 mg | Label: Dosage\", \"Span: 100 mg | Label: Dosage\"]", "text": "[Title]: Long-term efficacy and safety of sildenafil for patients with erectile dysfunction.\n[Abstract]: BACKGROUND: To investigate the long-term efficacy and safety of sildenafil for patients with erectile dysfunction (ED). METHODS: Between March 1999 and February 2001, a total of 3168 patients visited Taipei Veterans General Hospital for prescription of sildenafil. The follow-up period was 1-3 years. A questionnaire was designed for evaluation of efficacy and safety of sildenafil via telephone survey. RESULTS: Of the 3168 patients, 1414 were interviewed by telephone. Data from telephone questionnaires were successfully obtained in 1074 cases. Achievement of the first penile erection after sildenafil was reported in 58.8% of our patients. The distribution of the first doses was 0.6%, 8.5%, 81.9% and 90% for 12.5 mg, 25 mg, 50 mg and 100 mg, respectively. After administration of sildenafil, 72.1% men had successful intercourses \"sometimes\" or \"always achieving vaginal penetration\", and 72.3% had \"slight difficulty\" or \"no difficulty\" in maintaining of sexual intercourses. The \"sometimes/most times/always\" satisfaction accounted 63.9% and 62.8%, respectively for patients and partners. The global assessment of penile erection was improved in 58.6% of the patients. The sexual confidence of the patients was moderate, high and very high in 72.4% of the patients. Of the 434 patients who failed first penile erections, 400 (92.2%) were related to improper administration of sildenafil. Discontinuation of sildenafil in the last 3 months before telephone survey was found in 852 patients (80.2%). The causes of discontinuation were loss of efficacy in 51.6% of patients, lack of sexual desire in 8.8%, and chronic diseases in 8.2%. Spontaneous erection without sildenafil was claimed in 21.5% of the patients (most times in 9.5% and always in 12.0%). The rate of adverse events after taking sildenafil were 16.6%, and the most common adverse event was facial flushing (9.2%). CONCLUSIONS: The results of this study demonstrated that the efficacy of sildenafil was similar to the previous clinical trials. The adverse events after sildenafil were mild and tolerable. Recovery of complete or partial spontaneous erection was noted in some patients (21.5% in our study) after long-term usage of sildenafil.\n[Drug-Disease]: sildenafil - erectile dysfunction" }, { "pmid": "14658977", "target": "[\"Span: mean age of 42.7 years (range, 18-55 years) | Label: Age\", \"Span: 9.1 mg/day (range, 2.5-22.5 mg/day) | Label: Dosage\"]", "text": "[Title]: Olanzapine for self-injurious, aggressive, and disruptive behaviors in intellectually disabled adults: a retrospective, open-label, naturalistic trial.\n[Abstract]: BACKGROUND: The effectiveness of olanzapine in treating challenging behaviors in the intellectually disabled and its ability to substitute for conventional antipsychotic drugs were evaluated. METHOD: A total of 20 institutionalized adults with a mean age of 42.7 years (range, 18-55 years) with intellectual disability and aggression, self-injurious behavior, destructive/disruptive behavior, or combinations of these behaviors were studied. These individuals were receiving multiple psychotropic medications at baseline and were given additional treatment with the atypical antipsychotic agent olanzapine. The mean dose of olanzapine was 9.1 mg/day (range, 2.5-22.5 mg/day). Effectiveness was determined by retrospective review of the summaries of quarterly neuropsychiatric behavioral reviews and retrospective review of longitudinal behavioral graphs of target symptoms. Data were collected from 1995 to 2000. RESULTS: A significant decrease in global challenging behaviors and specific target behaviors (i.e., aggression, self-injurious behaviors, destructive/disruptive behaviors) occurred (p <.05). A numerical decrease in the dosage of concurrent conventional antipsychotic medications occurred over the course of the first 6 months of olanzapine therapy, and a statistically significant (p <.005) decrease from the start of olanzapine therapy occurred in those subjects who received olanzapine for longer than 6 months (mean = 20.3 months). A significant increase in weight occurred in the subject group during the first 6 months of olanzapine treatment (p <.006), and sedation and constipation were the other common side effects noted. CONCLUSIONS: Olanzapine was found to be effective in the treatment of challenging behaviors in the intellectually disabled and in part could be substituted for administration of conventional antipsychotic drugs.\n[Drug-Disease]: Olanzapine - aggression" }, { "pmid": "14695733", "target": "[\"Span: Ten men | Label: Gender\", \"Span: 10 women | Label: Gender\", \"Span: 0.3 mg/kg intravenous | Label: Dosage\"]", "text": "[Title]: Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences.\n[Abstract]: BACKGROUND: Morphine-6-glucuronide (M6G) is a metabolite of morphine and a micro-opioid agonist. To quantify the potency and speed of onset-offset of M6G and explore putative sex dependency, the authors studied the pharmacokinetics and pharmacodynamics of M6G in volunteers using a placebo-controlled, randomized, double-blind study design. METHODS: Ten men and 10 women received 0.3 mg/kg intravenous M6G and placebo (two thirds of the dose as bolus, one third as a continuous infusion over 1 h) on separate occasions. For 7 h, pain tolerance was measured using gradually increasing transcutaneous electrical stimulation, and blood samples were obtained. A population pharmacokinetic (inhibitory sigmoid Emax)-pharmacodynamic analysis was used to analyze M6G-induced changes in tolerated stimulus intensity. The improvement in model fits by inclusion of covariate sex was tested for significance. P values less than 0.01 were considered significant. Taking into account previous morphine data, a predictive pharmacokinetic-pharmacodynamic model was constructed to determine the contribution of M6G to morphine analgesia. RESULTS: M6G concentrations did not differ between men and women. M6G caused analgesia significantly greater than that observed with placebo (P < 0.01). The M6G analgesia data were well described by the pharmacokinetic-pharmacodynamic model. The M6G effect site concentration causing a 25% increase in current (C25) was 275 +/- 135 nm (population estimate +/- SE), the blood effect site equilibration half-life was 6.2 +/- 3.3 h, and the steepness parameter was 0.71 +/- 0.18. Intersubject variability was 167% for C25 and 218% for the effect half-life. None of the model parameters showed sex dependency. CONCLUSIONS: A cumulative dose of 0.3 mg/kg M6G, given over 1 h, produces long-term analgesia greater than that observed with placebo, with equal dynamics (potency and speed of onset-offset) in men and women. Possible causes for the great intersubject response variability, such as genetic polymorphism of the micro-opioid receptor and placebo-related phenomena, are discussed. The predictive pharmacokinetic-pharmacodynamic model was applied successfully and was used to estimate M6G analgesia after morphine in patients with normal and impaired renal function.\n[Drug-Disease]: M6G - pain" }, { "pmid": "14744177", "target": "[\"Span: male | Label: Gender\", \"Span: 25 mg | Label: Dosage\", \"Span: 75 mg | Label: Dosage\"]", "text": "[Title]: An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction.\n[Abstract]: BACKGROUND: Sexual dysfunction frequently occurs in treated and untreated patients with schizophrenia. Sildenafil is used for treatment of erectile dysfunction caused by diverse factors. The aim of our study was to evaluate its potential value, safety, and effect on compliance with anti-psychotic medications in risperidone-treated male schizophrenia patients suffering from erectile dysfunction. METHOD: In a 6-week open-label trial, sildenafil was administered to 12 male schizophrenia (DSM-IV) patients, treated with risperidone and reporting erectile dysfunction. The starting dose was 25 mg with the possibility to increase the dose to 75 mg. Three patients who did not respond stopped sildenafil treatment after 3 weeks. The effect on sexual function was assessed by the International Index of Erectile Function and the Valevski-Weizman Male Sexual Function scale. RESULTS: Nine (75%) of the 12 patients completed the 6-week trial, and 3 patients (25%) stopped taking sildenafil after 3 weeks due to lack of response. We observed statistically significant improvements in all sexual function domains (desire, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction) in the 9 patients who completed the trial and in most of the domains for all 12 study participants. More than half (8/12; 67%) of the patients exhibited partial or much improvement. CONCLUSION: Sildenafil is a useful agent for the treatment of erectile dysfunction in risperidone-treated male schizophrenia patients.\n[Drug-Disease]: Sildenafil - erectile dysfunction" }, { "pmid": "14747671", "target": "[\"Span: (500 mg) every 3 mo | Label: Dosage\", \"Span: 6-71 mo | Label: Age\"]", "text": "[Title]: Low dose daily iron supplementation improves iron status and appetite but not anemia, whereas quarterly anthelminthic treatment improves growth, appetite and anemia in Zanzibari preschool children.\n[Abstract]: Iron deficiency and helminth infections are two common conditions of children in developing countries. The consequences of helminth infection in young children are not well described, and the efficacy of low dose iron supplementation is not well documented in malaria-endemic settings. A 12-mo randomized, placebo controlled, double-blind trial of 10 mg daily iron and/or mebendazole (500 mg) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6-71 mo with hemoglobin > 70 g/L at baseline. The trial was designed to examine treatment effects on growth, anemia and appetite in two age subgroups. Iron did not affect growth retardation, hemoglobin concentration or mild or moderate anemia (hemoglobin < 110 g/L or < 90 g/L, respectively), but iron significantly improved serum ferritin and erythrocyte protoporphyrin. Mebendazole significantly reduced wasting malnutrition. but only in children <30 mo old. The adjusted odds ratios (AORs) for mebendazole in this age group were 0.38 (95% CI: 0.16, 0.90) for weight-for-height less than -1 Z-score and 0.29 (0.09, 0.91) for small arm circumference. In children <24 mo old, mebendazole also reduced moderate anemia (AOR: 0.41, 0.18, 0.94). Both iron and mebendazole improved children's appetite, according to mothers' report. In this study, iron's effect on anemia was limited, likely constrained by infection, inflammation and perhaps other nutrient deficiencies. Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections. We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children, with deleterious effects on protein metabolism and erythropoiesis.\n[Drug-Disease]: Mebendazole - anemia" }, { "pmid": "14751650", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.\n[Abstract]: BACKGROUND: Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS: Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS: Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.\n[Drug-Disease]: omapatrilat - hypertension" }, { "pmid": "14751650", "target": "[\"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.\n[Abstract]: BACKGROUND: Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS: Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS: Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.\n[Drug-Disease]: enalapril - hypertension" }, { "pmid": "14767549", "target": "[]", "text": "[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.\n[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P<0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.\n[Drug-Disease]: cis-platinum - osteosarcoma" }, { "pmid": "14767549", "target": "[]", "text": "[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.\n[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P<0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.\n[Drug-Disease]: doxorubicin - osteosarcoma" }, { "pmid": "14767549", "target": "[]", "text": "[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.\n[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P<0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.\n[Drug-Disease]: ifosfamide - osteosarcoma" }, { "pmid": "1479049", "target": "[\"Span: 8.1 +/- 2.8 years | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Clonidine treatment of hyperactive and impulsive children with autistic disorder.\n[Abstract]: Many autistic children have associated problems of inattention, impulsivity, and hyperactivity that limit the effectiveness of educational and behavioral interventions. Few controlled psychopharmacologic trials have been conducted in autistic children to determine which agents may be effective for these associated features. Eight male children (8.1 +/- 2.8 years) with autistic disorder, diagnosed by DSM-III-R criteria, completed a placebo-controlled, double-blind crossover trial of clonidine. Subjects were included in the study if they had inattention, impulsivity, and hyperactivity that was excessive for their developmental level. Subjects had not tolerated or responded to other psychopharmacologic treatments (neuroleptics, methylphenidate, or desipramine). Teacher ratings on the Aberrant Behavior Checklist irritability, stereotypy, hyperactivity, and inappropriate speech factors were lower during treatment with clonidine than during treatment with placebo. Attention deficit disorder with hyperactivity: Comprehensive Teacher's Rating Scale ratings were not significantly improved during the study, except for oppositional behavior. Parent Conners Abbreviated Parent-Teacher Questionnaire ratings significantly improved during clonidine treatment. Clonidine led to increased ratings of the side effects of drowsiness and decreased activity. Clinician ratings (Children's Psychiatric Rating Scale Autism, Hyperactivity, Anger and Speech Deviance factors; Children's Global Assessment Scale; Clinical Global Impressions efficacy) of videotaped sessions were not significantly different between clonidine and placebo. Clonidine was modestly effective in the short-term treatment of irritability and hyperactivity in some children with autistic disorder.\n[Drug-Disease]: Clonidine - Attention deficit disorder" }, { "pmid": "1479049", "target": "[\"Span: 8.1 +/- 2.8 years | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Clonidine treatment of hyperactive and impulsive children with autistic disorder.\n[Abstract]: Many autistic children have associated problems of inattention, impulsivity, and hyperactivity that limit the effectiveness of educational and behavioral interventions. Few controlled psychopharmacologic trials have been conducted in autistic children to determine which agents may be effective for these associated features. Eight male children (8.1 +/- 2.8 years) with autistic disorder, diagnosed by DSM-III-R criteria, completed a placebo-controlled, double-blind crossover trial of clonidine. Subjects were included in the study if they had inattention, impulsivity, and hyperactivity that was excessive for their developmental level. Subjects had not tolerated or responded to other psychopharmacologic treatments (neuroleptics, methylphenidate, or desipramine). Teacher ratings on the Aberrant Behavior Checklist irritability, stereotypy, hyperactivity, and inappropriate speech factors were lower during treatment with clonidine than during treatment with placebo. Attention deficit disorder with hyperactivity: Comprehensive Teacher's Rating Scale ratings were not significantly improved during the study, except for oppositional behavior. Parent Conners Abbreviated Parent-Teacher Questionnaire ratings significantly improved during clonidine treatment. Clonidine led to increased ratings of the side effects of drowsiness and decreased activity. Clinician ratings (Children's Psychiatric Rating Scale Autism, Hyperactivity, Anger and Speech Deviance factors; Children's Global Assessment Scale; Clinical Global Impressions efficacy) of videotaped sessions were not significantly different between clonidine and placebo. Clonidine was modestly effective in the short-term treatment of irritability and hyperactivity in some children with autistic disorder.\n[Drug-Disease]: Clonidine - autistic disorder" }, { "pmid": "14974368", "target": "[]", "text": "[Title]: [The influence of lamivudine therapy on the course of chronic hepatitis B in renal allograft recipients].\n[Abstract]: The aim of this study was to evaluate efficacy and safety of lamivudine therapy in renal allograft recipients with chronic hepatitis B infection. Twenty-four patients with chronic hepatitis B after renal transplantation were observed. We obtained HBV replication blockage in 95% of patients, in half of them also ALT normalisation was observed. Delayed HBV replication blockage was observed in patients with prolonged duration of haemodialysotherapy or HBV infection and HCV coinfection, although listed parameters did not influence overall treatment efficacy. After lamivudine discontinuation HBV replication relapsed, in part of patients with ALT activity elevation. We did not observed any serious adverse reactions under lamivudine therapy.\n[Drug-Disease]: lamivudine - chronic hepatitis B" }, { "pmid": "14979511", "target": "[\"Span: HIV | Label: Comorbidity\"]", "text": "[Title]: Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension.\n[Abstract]: As antiretroviral therapy has improved life expectancy in human immunodeficiency virus (HIV) infection, the life-limiting complication of HIV-related pulmonary hypertension has come into focus. Inhalation of the stable prostacyclin analogue iloprost is an effective treatment for various forms of precapillary pulmonary hypertension. The main objective of the present study was to evaluate the safety and efficacy of inhaled iloprost in HIV-related pulmonary hypertension. In eight patients with severe pulmonary hypertension related to HIV infection, right heart and femoral artery catheterisation were performed. The acute effect of oxygen, inhaled nitric oxide and aerosolised iloprost was investigated. Four patients underwent long-term treatment with inhaled iloprost. The rank order of pulmonary vasodilatory potency was iloprost>NO>O2, with a maximum reduction (mean +/- SEM) in pulmonary vascular resistance of 30.6 +/- 3.1% (p < 0.001), 5.9 +/- 3.9% and -0.6 +/- 3.9%, respectively. Concomitantly, inhaled iloprost significantly increased the cardiac index and central venous oxygen saturation. Chronic treatment with inhaled iloprost tended to improve the 6 min walking distance and decreased pulmonary vascular resistance in all patients (although not significantly). No serious adverse events and no major interactions with the ongoing antiretroviral therapy were noted. In conclusion, inhaled iloprost is a potent pulmonary vasodilator in human immune deficiency virus-related pulmonary hypertension. Future studies are warranted to confirm the encouraging long-term beneficial results observed in the present limited number of patients.\n[Drug-Disease]: iloprost - pulmonary hypertension" }, { "pmid": "15087989", "target": "[]", "text": "[Title]: Propofol reduces cognitive impairment after electroconvulsive therapy.\n[Abstract]: BACKGROUND: Cognitive impairments are the main complication after electroconvulsive therapy (ECT). Modification of treatment parameters has been shown to affect the magnitude of these impairments, but the role of anesthetic type remains unclear. This study tested whether there is a difference in cognitive impairments immediately after ECT with propofol compared to thiopental anesthesia. METHODS: This randomized, double-blind, crossover study included 15 patients receiving right unilateral ECT for depression. Patients received propofol or thiopental on alternating ECTs up to 6 treatments. Immediate and delayed verbal memory, motor speed, reaction speed, visuospatial, and executive functions were assessed 45 minutes after each ECT. Differences were assessed with repeated measures analysis of variance. RESULTS: Cognitive impairments were reduced after ECT with propofol compared to thiopental. Time to emergence was quicker and EEG seizure duration was shorter after propofol treatments. There was no significant correlation between seizure duration and neuropsychological test performance. CONCLUSIONS: Our results indicate that cognitive impairments in the early recovery period after ECT are reduced with propofol compared to thiopental anesthesia. We suggest that, in addition to ECT parameters, the type of anesthetic agent should be considered to reduce cognitive impairments after ECT.\n[Drug-Disease]: propofol - cognitive impairments" }, { "pmid": "1514343", "target": "[\"Span: mean age of 4.3 +/- 0.6 years | Label: Age\", \"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Injection pain, cardiovascular changes and recovery following induction of anaesthesia with propofol in combination with alfentanil or lignocaine in children.\n[Abstract]: The effect of pretreatment with alfentanil 10 (Alf10), 15 (Alf15) or 20 (Alf20) micrograms.kg-1 on reducing injection pain caused by propofol was compared with lignocaine 10 mg mixed with propofol (Lign). This double-blind, double-dummy and randomized study included 100 children with a mean age of 4.3 +/- 0.6 years, 25 children in each group, undergoing minor otolaryngological surgery. The children were premedicated orally with midazolam 0.5 mg.kg-1 and atropine 0.03 mg.kg-1. Injection pain occurred in 4% in the Lign group. The corresponding figures were 40, 16 and 20% in the Alf10, Alf15 and Alf20 groups, respectively. Both 1% lignocaine 10 mg and alfentanil 15 micrograms.kg-1 reduced injection pain significantly compared with alfentanil 10 micrograms.kg-1. Pretreatment with alfentanil significantly diminished haemodynamic responses to tracheal intubation. Furthermore, the concomitant use of alfentanil and propofol caused transient severe bradycardia and a significant decrease in heart rate after laryngoscopy.\n[Drug-Disease]: lignocaine - pain" }, { "pmid": "1514343", "target": "[\"Span: mean age of 4.3 +/- 0.6 years | Label: Age\", \"Span: 15 micrograms.kg-1 | Label: Dosage\", \"Span: 10 micrograms.kg-1 | Label: Dosage\"]", "text": "[Title]: Injection pain, cardiovascular changes and recovery following induction of anaesthesia with propofol in combination with alfentanil or lignocaine in children.\n[Abstract]: The effect of pretreatment with alfentanil 10 (Alf10), 15 (Alf15) or 20 (Alf20) micrograms.kg-1 on reducing injection pain caused by propofol was compared with lignocaine 10 mg mixed with propofol (Lign). This double-blind, double-dummy and randomized study included 100 children with a mean age of 4.3 +/- 0.6 years, 25 children in each group, undergoing minor otolaryngological surgery. The children were premedicated orally with midazolam 0.5 mg.kg-1 and atropine 0.03 mg.kg-1. Injection pain occurred in 4% in the Lign group. The corresponding figures were 40, 16 and 20% in the Alf10, Alf15 and Alf20 groups, respectively. Both 1% lignocaine 10 mg and alfentanil 15 micrograms.kg-1 reduced injection pain significantly compared with alfentanil 10 micrograms.kg-1. Pretreatment with alfentanil significantly diminished haemodynamic responses to tracheal intubation. Furthermore, the concomitant use of alfentanil and propofol caused transient severe bradycardia and a significant decrease in heart rate after laryngoscopy.\n[Drug-Disease]: alfentanil - pain" }, { "pmid": "15150204", "target": "[\"Span: 154-mEq/L | Label: Dosage\"]", "text": "[Title]: Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.\n[Abstract]: CONTEXT: Contrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy. OBJECTIVE: To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast. DESIGN, SETTING, AND PATIENTS: A prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast. INTERVENTIONS: Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure. MAIN OUTCOME MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast. RESULTS: There were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate; P =.09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%). CONCLUSION: Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.\n[Drug-Disease]: sodium bicarbonate - renal failure" }, { "pmid": "15188945", "target": "[\"Span: preproendothelin-1 genotype | Label: Gene\", \"Span: men | Label: Gender\", \"Span: women | Label: Gender\"]", "text": "[Title]: Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).\n[Abstract]: BACKGROUND: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment. HYPOTHESIS: This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol. METHODS: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg 13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women. CONCLUSIONS: Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.\n[Drug-Disease]: irbesartan - hypertensive" }, { "pmid": "15188945", "target": "[\"Span: preproendothelin-1 genotype | Label: Gene\", \"Span: men | Label: Gender\", \"Span: women | Label: Gender\"]", "text": "[Title]: Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).\n[Abstract]: BACKGROUND: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment. HYPOTHESIS: This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol. METHODS: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg 13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women. CONCLUSIONS: Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.\n[Drug-Disease]: atenolol - hypertensive" }, { "pmid": "1521438", "target": "[\"Span: 2 to 12 months old | Label: Age\", \"Span: 5 ng/kg/min | Label: Dosage\", \"Span: 10 ng/kg/min | Label: Dosage\", \"Span: 15 ng/kg/min | Label: Dosage\"]", "text": "[Title]: Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery.\n[Abstract]: OBJECTIVE: To evaluate the hemodynamic effects of tolazoline and prostacyclin in infants with pulmonary vasospasm after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Pediatric ICU. PATIENTS: The cohort consisted of 42 infants and children with congenital heart disease and pulmonary hypertension who underwent corrective surgery and were monitored postoperatively using pulmonary artery catheters. Fourteen infants (2 to 12 months old) in this group required postoperative treatment with tolazoline or prostacyclin. INTERVENTIONS: Tolazoline was administered as a bolus of 0.5 mg/kg for treatment of persistent pulmonary hypertension or acute pulmonary hypertensive crisis. If its effectiveness was proved after 30 mins by hemodynamic measurements, a continuous iv infusion of 0.5 mg/kg/hr was established. Higher doses of tolazoline were avoided. If tolazoline treatment did not fulfill the criteria for pulmonary vasodilation, prostacyclin was given by continuous iv infusion at a starting rate of 5 ng/kg/min, followed by 10 ng/kg/min. In three patients, the infusion rate was increased to 15 ng/kg/min. RESULTS: Bolus administration of tolazoline resulted in a distinct pulmonary vasodilation in seven infants: mean pulmonary artery pressure and pulmonary vascular resistance decreased by an average of 35% and 45%, respectively. In these patients, tolazoline was infused over the following 12 to 72 hrs. One infant who received tolazoline for 72 hrs developed a clinically important gastrointestinal hemorrhage. In seven nonresponders to tolazoline, prostacyclin (PGI2) at an infusion rate of 5 ng/kg/min led to pulmonary vasodilation in five patients, at an iv infusion rate of 10 ng/kg/min in all seven infants studied. The latter dose of PGI2 reduced the mean pulmonary artery pressure by an average of 37%, and pulmonary vascular resistance by 43%. Transient withdrawal of prostacyclin in five infants demonstrated its short half-life and clinical effectiveness. Apart from a facial flush, no side-effects were encountered using PGI2 as an infusion over durations ranging from 12 to 504 hrs. CONCLUSIONS: These data suggest that, if tolazoline in a relatively low dose proves to be inefficient, prostacyclin can still be used as a safe and effective drug for treatment of pulmonary vasospasm. Prostacyclin offers more than a pharmacologic alternative to increased tolazoline dosages.\n[Drug-Disease]: Prostacyclin - acute pulmonary hypertensive" }, { "pmid": "1521438", "target": "[\"Span: 2 to 12 months old | Label: Age\", \"Span: bolus of 0.5 mg/kg | Label: Dosage\"]", "text": "[Title]: Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery.\n[Abstract]: OBJECTIVE: To evaluate the hemodynamic effects of tolazoline and prostacyclin in infants with pulmonary vasospasm after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Pediatric ICU. PATIENTS: The cohort consisted of 42 infants and children with congenital heart disease and pulmonary hypertension who underwent corrective surgery and were monitored postoperatively using pulmonary artery catheters. Fourteen infants (2 to 12 months old) in this group required postoperative treatment with tolazoline or prostacyclin. INTERVENTIONS: Tolazoline was administered as a bolus of 0.5 mg/kg for treatment of persistent pulmonary hypertension or acute pulmonary hypertensive crisis. If its effectiveness was proved after 30 mins by hemodynamic measurements, a continuous iv infusion of 0.5 mg/kg/hr was established. Higher doses of tolazoline were avoided. If tolazoline treatment did not fulfill the criteria for pulmonary vasodilation, prostacyclin was given by continuous iv infusion at a starting rate of 5 ng/kg/min, followed by 10 ng/kg/min. In three patients, the infusion rate was increased to 15 ng/kg/min. RESULTS: Bolus administration of tolazoline resulted in a distinct pulmonary vasodilation in seven infants: mean pulmonary artery pressure and pulmonary vascular resistance decreased by an average of 35% and 45%, respectively. In these patients, tolazoline was infused over the following 12 to 72 hrs. One infant who received tolazoline for 72 hrs developed a clinically important gastrointestinal hemorrhage. In seven nonresponders to tolazoline, prostacyclin (PGI2) at an infusion rate of 5 ng/kg/min led to pulmonary vasodilation in five patients, at an iv infusion rate of 10 ng/kg/min in all seven infants studied. The latter dose of PGI2 reduced the mean pulmonary artery pressure by an average of 37%, and pulmonary vascular resistance by 43%. Transient withdrawal of prostacyclin in five infants demonstrated its short half-life and clinical effectiveness. Apart from a facial flush, no side-effects were encountered using PGI2 as an infusion over durations ranging from 12 to 504 hrs. CONCLUSIONS: These data suggest that, if tolazoline in a relatively low dose proves to be inefficient, prostacyclin can still be used as a safe and effective drug for treatment of pulmonary vasospasm. Prostacyclin offers more than a pharmacologic alternative to increased tolazoline dosages.\n[Drug-Disease]: tolazoline - acute pulmonary hypertensive" }, { "pmid": "15360003", "target": "[\"Span: 71 years | Label: Age\"]", "text": "[Title]: Evaluation of temozolomide in patients with myelodysplastic syndrome.\n[Abstract]: In our previous phase I study of temozolomide in patients with acute leukemia, temozolomide was well tolerated and demonstrated significant anti-leukemic activity. The maximum tolerated dose was 200 mg/m2/d for 7 days, repeated approximately every 5-6 weeks. In the current study, we evaluated the same dose of temozolomide in patients with myelodysplastic syndrome. Fourteen patients received 19 courses of temozolomide. The median age was 71 years. In this study, treatment was poorly tolerated with patients requiring admission in 9 of 19 courses. Toxicity included worsening cytopenias, neutropenic fever, and exacerbation of cardiac disease, the latter due to worsening anemia. An unusual finding was the development of leukocytoclastic vasculitis in 4 patients. There were no formal responses to therapy. The current schedule of temozolomide is not efficacious in patients with myelodysplastic syndrome.\n[Drug-Disease]: temozolomide - leukemic" }, { "pmid": "15374793", "target": "[\"Span: 10 mg/day | Label: Dosage\"]", "text": "[Title]: Effectiveness and tolerability of ezetimibe add-on therapy to a bile acid resin-based regimen for hypercholesterolemia.\n[Abstract]: Combination lipid-reducing therapy is increasingly used, particularly for the management of severe or combined dyslipidemia in patients at high risk for coronary heart disease. To assess the potential additive effects of combining the cholesterol absorption inhibitor ezetimibe with a bile acid resin (BAR), a prospective chart review was performed of 40 patients in whom ezetimibe 10 mg/day was added to a stable regimen that included a BAR. At an average follow-up of 107 +/- 57 days, ezetimibe coadministration significantly reduced total cholesterol by 18%, triglycerides by 14%, and low-density lipoprotein cholesterol by 19% (all p < or =0.03), without significantly changing high-density lipoprotein cholesterol, and the combination was well tolerated.\n[Drug-Disease]: ezetimibe - hypercholesterolemia" }, { "pmid": "15378354", "target": "[\"Span: adolescents | Label: Age\", \"Span: 120 mg tid | Label: Dosage\"]", "text": "[Title]: Addition of orlistat to conventional treatment in adolescents with severe obesity.\n[Abstract]: UNLABELLED: To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5-15 months (average duration of treatment 11.7 +/- 3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2 +/- 3.7 months, range 6-17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost -6.27 +/- 5.4 kg, whereas those in the control group gained 4.16 +/- 6.45 kg (P < 0.001) during the study period. Patients in the orlistat group lost -7.65% +/- 6.5% of their initial body weight, whereas, those of the control group gained 5.7% +/- 8.3% (P < 0.001). The body mass index decreased in the orlistat group by -4.09 +/- 2.9 kg/m2 while it increased by + 0.11 +/- 2.49 kg/m2 in the control group (P < 0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group. CONCLUSION: Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents.\n[Drug-Disease]: orlistat - obesity" }, { "pmid": "15389992", "target": "[\"Span: heterozygous GCH1 mutations | Label: Gene\"]", "text": "[Title]: Amantadine for levodopa-induced choreic dyskinesia in compound heterozygotes for GCH1 mutations.\n[Abstract]: Amantadine suppressed severe levodopa-induced choreic dyskinesia, which developed at initiation of levodopa therapy, in two siblings manifesting dystonia with motor delay phenotype of GTP cyclohydrolase I deficiency caused by compound heterozygous GCH1 mutations. Our finding suggests a beneficial effect of amantadine on this type of dyskinesia frequently observed in relatively severe dopamine-deficient metabolic disorders.\n[Drug-Disease]: amantadine - dyskinesia" }, { "pmid": "15491244", "target": "[\"Span: 15-30 mg/day | Label: Dosage\"]", "text": "[Title]: Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study.\n[Abstract]: BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone. METHOD: Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003. RESULTS: The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a \"much improved\" or \"very much improved\" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment. CONCLUSIONS: We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.\n[Drug-Disease]: mirtazapine - OCD" }, { "pmid": "15491244", "target": "[\"Span: 20-80 mg/day | Label: Dosage\"]", "text": "[Title]: Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study.\n[Abstract]: BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone. METHOD: Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003. RESULTS: The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a \"much improved\" or \"very much improved\" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment. CONCLUSIONS: We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.\n[Drug-Disease]: citalopram - OCD" }, { "pmid": "15520061", "target": "[\"Span: 30 mg/m2 | Label: Dosage\"]", "text": "[Title]: Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.\n[Abstract]: BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.\n[Drug-Disease]: VRL - prostate cancer" }, { "pmid": "15520061", "target": "[\"Span: 40 mg/day | Label: Dosage\"]", "text": "[Title]: Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.\n[Abstract]: BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.\n[Drug-Disease]: hydrocortisone - prostate cancer" }, { "pmid": "1552034", "target": "[\"Span: 57 +/- 7 mg/day | Label: Dosage\"]", "text": "[Title]: A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.\n[Abstract]: In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.\n[Drug-Disease]: buspirone - OCD" }, { "pmid": "1552034", "target": "[]", "text": "[Title]: A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.\n[Abstract]: In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.\n[Drug-Disease]: clomipramine - OCD" }, { "pmid": "1552034", "target": "[]", "text": "[Title]: A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.\n[Abstract]: In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.\n[Drug-Disease]: fluoxetine - OCD" }, { "pmid": "15562083", "target": "[\"Span: 5 mg/mL (1.5 mg/kg) | Label: Dosage\"]", "text": "[Title]: Single-injection paravertebral block before general anesthesia enhances analgesia after breast cancer surgery with and without associated lymph node biopsy.\n[Abstract]: Paravertebral block (PVB) seems to decrease postoperative pain and postoperative nausea and vomiting (PONV) after breast surgery, but the studies have not been placebo controlled. We studied 60 patients scheduled for breast cancer surgery randomly given single-injection PVB at T3 with bupivacaine 5 mg/mL (1.5 mg/kg) or saline before general anesthesia. The patient and attending investigators were blinded; the PVB or the sham block was performed behind a curtain by an anesthesiologist not involved in the study. The patients given PVB with bupivacaine needed 40% less IV opioid medication (primary outcome variable) in the postanesthesia care unit, had a longer latency to the first opioid dose, and had less pain at rest after 24 h than the control patients (P < 0.01). They also had less PONV in the postanesthesia care unit (P < 0.05), were less sedated until 90 min (P < 0.05), and performed better in the digit symbol substitution test at 90 min and the ocular coordination test 60-120 min after surgery (P < 0.05). The average peak bupivacaine plasma concentration was 750 ng/mL. One patient had bilateral convulsions immediately after bupivacaine injection. We conclude that PVB before general anesthesia for breast cancer surgery reduced postoperative pain, opioid consumption, and occurrence of PONV and improved recovery from anesthesia.\n[Drug-Disease]: bupivacaine - postoperative pain" }, { "pmid": "15562083", "target": "[\"Span: 5 mg/mL (1.5 mg/kg) | Label: Dosage\"]", "text": "[Title]: Single-injection paravertebral block before general anesthesia enhances analgesia after breast cancer surgery with and without associated lymph node biopsy.\n[Abstract]: Paravertebral block (PVB) seems to decrease postoperative pain and postoperative nausea and vomiting (PONV) after breast surgery, but the studies have not been placebo controlled. We studied 60 patients scheduled for breast cancer surgery randomly given single-injection PVB at T3 with bupivacaine 5 mg/mL (1.5 mg/kg) or saline before general anesthesia. The patient and attending investigators were blinded; the PVB or the sham block was performed behind a curtain by an anesthesiologist not involved in the study. The patients given PVB with bupivacaine needed 40% less IV opioid medication (primary outcome variable) in the postanesthesia care unit, had a longer latency to the first opioid dose, and had less pain at rest after 24 h than the control patients (P < 0.01). They also had less PONV in the postanesthesia care unit (P < 0.05), were less sedated until 90 min (P < 0.05), and performed better in the digit symbol substitution test at 90 min and the ocular coordination test 60-120 min after surgery (P < 0.05). The average peak bupivacaine plasma concentration was 750 ng/mL. One patient had bilateral convulsions immediately after bupivacaine injection. We conclude that PVB before general anesthesia for breast cancer surgery reduced postoperative pain, opioid consumption, and occurrence of PONV and improved recovery from anesthesia.\n[Drug-Disease]: bupivacaine - postoperative nausea and vomiting" }, { "pmid": "15577136", "target": "[]", "text": "[Title]: [Effects of SERM on breast cancer and cardiovascular disease: making a comparison between raloxifene use and hormone replacement therapy on the risks of the diseases].\n[Abstract]: According to the report of MORE trial, raloxifene (RLX) compensate for the faults of hormone replacement therapy with the reasons following below; 1) RLX inhibits onset of breast cancer with estrogen receptor remarkably, 2) RLX inhibits onset of cardiovascular disease in its high risk group. However, because RLX has a elevated risk of venous thrombosis as same as hormone replacement therapy, we should give attention to this disease at the use of RLX.\n[Drug-Disease]: RLX - breast cancer" }, { "pmid": "15610953", "target": "[]", "text": "[Title]: Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study.\n[Abstract]: Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.\n[Drug-Disease]: topiramate - mania" }, { "pmid": "15610953", "target": "[]", "text": "[Title]: Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study.\n[Abstract]: Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.\n[Drug-Disease]: divalproex - mania" }, { "pmid": "15610953", "target": "[]", "text": "[Title]: Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study.\n[Abstract]: Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.\n[Drug-Disease]: risperidone - mania" }, { "pmid": "15625544", "target": "[]", "text": "[Title]: Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease.\n[Abstract]: We conducted a phase II trial in 19 chronic graft-versus-host disease (cGVHD) patients with rapamycin, calcineurin inhibitors, and prednisone with the goals of controlling cGVHD, reducing prednisone use, and defining the safety of this regimen. Rapamycin was begun as second-line (n = 9) or more than second-line (n = 10) therapy. With a median follow-up of 42 months, 16 patients were evaluable for response. Nine patients discontinued rapamycin because of poor compliance/patient request (n = 2) or an adverse event (n = 7), 3 of whom were not evaluable because of withdrawal at < or =1 month or noncompliance. The adverse events included serum creatinine > or =2.4 mg/dL (n = 4), hemolytic uremic syndrome (n = 2), and relapse of malignancy (n = 1). Fifteen of 16 evaluable patients had a clinical response. Five of the 16 discontinued the drug, and 1 died of relapsed leukemia. Of the 10 patients who continued rapamycin, 2 discontinued and 1 successfully tapered all systemic immunosuppression. Three of the 10 developed progressive cGVHD with tapering immunosuppression; all responded to resumption of prior medications. Four of the 10 patients required alternate therapy for persistent or progressive cGVHD while receiving rapamycin; prednisone was discontinued (n = 2) or tapered at the time of progressive disease (n = 2). Seventeen of 19 original patients were alive. One death was due to relapsed malignancy, and 1 was due to congestive heart failure. In this report of rapamycin as cGVHD therapy, there is evidence of rapamycin's efficacy. Given the significant toxicities described, investigation of altered administration of rapamycin and calcineurin inhibitors should be pursued in future cGVHD trials.\n[Drug-Disease]: prednisone - graft-versus-host disease" }, { "pmid": "15625544", "target": "[]", "text": "[Title]: Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease.\n[Abstract]: We conducted a phase II trial in 19 chronic graft-versus-host disease (cGVHD) patients with rapamycin, calcineurin inhibitors, and prednisone with the goals of controlling cGVHD, reducing prednisone use, and defining the safety of this regimen. Rapamycin was begun as second-line (n = 9) or more than second-line (n = 10) therapy. With a median follow-up of 42 months, 16 patients were evaluable for response. Nine patients discontinued rapamycin because of poor compliance/patient request (n = 2) or an adverse event (n = 7), 3 of whom were not evaluable because of withdrawal at < or =1 month or noncompliance. The adverse events included serum creatinine > or =2.4 mg/dL (n = 4), hemolytic uremic syndrome (n = 2), and relapse of malignancy (n = 1). Fifteen of 16 evaluable patients had a clinical response. Five of the 16 discontinued the drug, and 1 died of relapsed leukemia. Of the 10 patients who continued rapamycin, 2 discontinued and 1 successfully tapered all systemic immunosuppression. Three of the 10 developed progressive cGVHD with tapering immunosuppression; all responded to resumption of prior medications. Four of the 10 patients required alternate therapy for persistent or progressive cGVHD while receiving rapamycin; prednisone was discontinued (n = 2) or tapered at the time of progressive disease (n = 2). Seventeen of 19 original patients were alive. One death was due to relapsed malignancy, and 1 was due to congestive heart failure. In this report of rapamycin as cGVHD therapy, there is evidence of rapamycin's efficacy. Given the significant toxicities described, investigation of altered administration of rapamycin and calcineurin inhibitors should be pursued in future cGVHD trials.\n[Drug-Disease]: rapamycin - graft-versus-host disease" }, { "pmid": "15629415", "target": "[\"Span: 79.4 mg/day | Label: Dosage\", \"Span: 155 mg/day | Label: Dosage\", \"Span: 18 to 75 years | Label: Age\"]", "text": "[Title]: Efficacy and safety of oxymorphone extended release in chronic low back pain: results of a randomized, double-blind, placebo- and active-controlled phase III study.\n[Abstract]: UNLABELLED: This multicenter, randomized, double-blind, placebo- and active-controlled trial was conducted to compare the analgesic efficacy and safety of oxymorphone extended release (ER) with placebo and oxycodone controlled release (CR) in ambulatory patients with moderate to severe chronic low back pain requiring opioid therapy. Patients (N = 213) aged 18 to 75 years were randomized to receive oxymorphone ER (10 to 110 mg) or oxycodone CR (20 to 220 mg) every 12 hours during a 7- to 14-day dose-titration phase. Patients achieving effective analgesia at a stable opioid dose entered an 18-day double-blind treatment phase and either continued opioid therapy or received placebo. With stable dosing throughout the treatment phase, oxymorphone ER (79.4 mg/day) and oxycodone CR (155 mg/day) were superior to placebo for change from baseline in pain intensity as measured on a visual analog scale; the LS mean differences were -18.21 and 18.55 (95% CI, -25.83 to -10.58 and -26.12 to -10.98, respectively; P = .0001). Use of rescue medication was 20 mg per day. Adverse events for the active drugs were similar; the most frequent were constipation and sedation. Oxymorphone ER and oxycodone CR were generally safe and effective for controlling low back pain. Oxymorphone ER was equianalgesic to oxycodone CR at half the milligram daily dosage, with comparable safety. PERSPECTIVE: Definitive studies of long-acting opioids in patients with chronic low back pain are lacking. We report the results of a multicenter, randomized, placebo-controlled, double-blind study evaluating the analgesic efficacy and safety of oxymorphone ER and oxycodone CR in opioid-experienced patients with chronic low back pain.\n[Drug-Disease]: oxycodone - constipation" }, { "pmid": "15629415", "target": "[\"Span: 79.4 mg/day | Label: Dosage\", \"Span: 155 mg/day | Label: Dosage\", \"Span: 18 to 75 years | Label: Age\"]", "text": "[Title]: Efficacy and safety of oxymorphone extended release in chronic low back pain: results of a randomized, double-blind, placebo- and active-controlled phase III study.\n[Abstract]: UNLABELLED: This multicenter, randomized, double-blind, placebo- and active-controlled trial was conducted to compare the analgesic efficacy and safety of oxymorphone extended release (ER) with placebo and oxycodone controlled release (CR) in ambulatory patients with moderate to severe chronic low back pain requiring opioid therapy. Patients (N = 213) aged 18 to 75 years were randomized to receive oxymorphone ER (10 to 110 mg) or oxycodone CR (20 to 220 mg) every 12 hours during a 7- to 14-day dose-titration phase. Patients achieving effective analgesia at a stable opioid dose entered an 18-day double-blind treatment phase and either continued opioid therapy or received placebo. With stable dosing throughout the treatment phase, oxymorphone ER (79.4 mg/day) and oxycodone CR (155 mg/day) were superior to placebo for change from baseline in pain intensity as measured on a visual analog scale; the LS mean differences were -18.21 and 18.55 (95% CI, -25.83 to -10.58 and -26.12 to -10.98, respectively; P = .0001). Use of rescue medication was 20 mg per day. Adverse events for the active drugs were similar; the most frequent were constipation and sedation. Oxymorphone ER and oxycodone CR were generally safe and effective for controlling low back pain. Oxymorphone ER was equianalgesic to oxycodone CR at half the milligram daily dosage, with comparable safety. PERSPECTIVE: Definitive studies of long-acting opioids in patients with chronic low back pain are lacking. We report the results of a multicenter, randomized, placebo-controlled, double-blind study evaluating the analgesic efficacy and safety of oxymorphone ER and oxycodone CR in opioid-experienced patients with chronic low back pain.\n[Drug-Disease]: oxycodone - low back pain" }, { "pmid": "15629415", "target": "[\"Span: 79.4 mg/day | Label: Dosage\", \"Span: 155 mg/day | Label: Dosage\", \"Span: 18 to 75 years | Label: Age\"]", "text": "[Title]: Efficacy and safety of oxymorphone extended release in chronic low back pain: results of a randomized, double-blind, placebo- and active-controlled phase III study.\n[Abstract]: UNLABELLED: This multicenter, randomized, double-blind, placebo- and active-controlled trial was conducted to compare the analgesic efficacy and safety of oxymorphone extended release (ER) with placebo and oxycodone controlled release (CR) in ambulatory patients with moderate to severe chronic low back pain requiring opioid therapy. Patients (N = 213) aged 18 to 75 years were randomized to receive oxymorphone ER (10 to 110 mg) or oxycodone CR (20 to 220 mg) every 12 hours during a 7- to 14-day dose-titration phase. Patients achieving effective analgesia at a stable opioid dose entered an 18-day double-blind treatment phase and either continued opioid therapy or received placebo. With stable dosing throughout the treatment phase, oxymorphone ER (79.4 mg/day) and oxycodone CR (155 mg/day) were superior to placebo for change from baseline in pain intensity as measured on a visual analog scale; the LS mean differences were -18.21 and 18.55 (95% CI, -25.83 to -10.58 and -26.12 to -10.98, respectively; P = .0001). Use of rescue medication was 20 mg per day. Adverse events for the active drugs were similar; the most frequent were constipation and sedation. Oxymorphone ER and oxycodone CR were generally safe and effective for controlling low back pain. Oxymorphone ER was equianalgesic to oxycodone CR at half the milligram daily dosage, with comparable safety. PERSPECTIVE: Definitive studies of long-acting opioids in patients with chronic low back pain are lacking. We report the results of a multicenter, randomized, placebo-controlled, double-blind study evaluating the analgesic efficacy and safety of oxymorphone ER and oxycodone CR in opioid-experienced patients with chronic low back pain.\n[Drug-Disease]: oxymorphone - low back pain" }, { "pmid": "15694876", "target": "[\"Span: 5% | Label: Dosage\"]", "text": "[Title]: Assessment of pain quality in chronic neuropathic and nociceptive pain clinical trials with the Neuropathic Pain Scale.\n[Abstract]: UNLABELLED: Although a number of measures of pain qualities exist, little research has examined the potential for these measures to identify the unique effects of pain treatments on different pain qualities. We examined the utility of the Neuropathic Pain Scale (NPS) for assessing changes in pain qualities after open label lidocaine patch 5% in 3 samples of patients: patients with peripheral neuropathic pain, low back pain, and osteoarthritis. With one exception (\"cold\" pain in subjects with low back pain), each of the NPS items showed significant change after open label lidocaine patch. In addition, significantly larger changes were observed for the NPS items reflecting global pain intensity and pain unpleasantness and for items assessing sharp and deep pain than for items assessing cold, sensitive, and itchy pain. The pattern of changes in pain qualities did not differ across the 3 diagnostic groups, but it did differ from the patterns of changes in pain qualities associated with other analgesic treatments. The results support the potential utility of the NPS for assessing the patterns of changes in pain qualities that can be observed after pain treatment. PERSPECTIVE: Pain clinical trials that include measures of pain qualities, such as the NPS, might identify distinct patterns of treatment effects on those pain qualities. This research might be used to help clinicians target analgesics to match the specific qualities associated with a patient's pain and to better understand the mechanisms of analgesic effects in drug development programs.\n[Drug-Disease]: lidocaine - peripheral neuropathic pain" }, { "pmid": "15705083", "target": "[\"Span: young | Label: Age\", \"Span: older | Label: Age\", \"Span: men | Label: Gender\"]", "text": "[Title]: The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.\n[Abstract]: The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.\n[Drug-Disease]: doxazosin - hypertension" }, { "pmid": "15705083", "target": "[\"Span: young | Label: Age\", \"Span: older | Label: Age\", \"Span: men | Label: Gender\"]", "text": "[Title]: The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.\n[Abstract]: The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.\n[Drug-Disease]: doxazosin - benign prostatic hyperplasia" }, { "pmid": "15705083", "target": "[\"Span: young | Label: Age\", \"Span: older | Label: Age\", \"Span: men | Label: Gender\"]", "text": "[Title]: The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.\n[Abstract]: The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.\n[Drug-Disease]: doxazosin - sexual dysfunction" }, { "pmid": "15705083", "target": "[\"Span: young | Label: Age\", \"Span: older | Label: Age\", \"Span: men | Label: Gender\"]", "text": "[Title]: The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.\n[Abstract]: The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.\n[Drug-Disease]: finasteride - benign prostatic hyperplasia" }, { "pmid": "15730347", "target": "[\"Span: depressive symptoms | Label: Comorbidity\", \"Span: 200 mg twice daily | Label: Dosage\"]", "text": "[Title]: Nefazodone treatment of cocaine dependence with comorbid depressive symptoms.\n[Abstract]: AIMS: In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT(2A) receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use. DESIGN: An 8-week, double blind, placebo-controlled design was used. SETTING: The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center. PARTICIPANTS: Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher. INTERVENTION: Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received individual counseling. MEASUREMENTS: Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning. FINDINGS: Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use. CONCLUSIONS: These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels.\n[Drug-Disease]: nefazodone - cocaine dependence" }, { "pmid": "15775269", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: [Rationale for the treatment of postmenopausal women by SERM].\n[Abstract]: Raloxifene has been developed as a selective estrogen receptor modulator (SERM) that binds to estrogen receptor (ER) and acts as an estrogen agonist in some tissues while acting as an estrogen antagonist in certain tissues. Raloxifene exerts anti-estrogenic actions in the uterus and the mammary gland, whereas it has estrogenic effects on bone and serum lipids. As a result, raloxifene increases bone volume and reduces vertebral fractures without increasing the incidence of uterine cancer. In addition, raloxifene reduces the incidence of breast cancer to nearly a third of those without raloxifene treatment by markedly reducing the development of ER-positive breast cancer. Raloxifene also reduces the risk of cardiovascular events among postmenopausal women with increased cardiovascular risk. From these observations, postmenopausal osteoporotic women without multiple or severe fractures who have risk factors for breast cancer or cardiovascular disorders can be excellent candidates for raloxifene treatment.\n[Drug-Disease]: raloxifene - breast cancer" }, { "pmid": "15775269", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: [Rationale for the treatment of postmenopausal women by SERM].\n[Abstract]: Raloxifene has been developed as a selective estrogen receptor modulator (SERM) that binds to estrogen receptor (ER) and acts as an estrogen agonist in some tissues while acting as an estrogen antagonist in certain tissues. Raloxifene exerts anti-estrogenic actions in the uterus and the mammary gland, whereas it has estrogenic effects on bone and serum lipids. As a result, raloxifene increases bone volume and reduces vertebral fractures without increasing the incidence of uterine cancer. In addition, raloxifene reduces the incidence of breast cancer to nearly a third of those without raloxifene treatment by markedly reducing the development of ER-positive breast cancer. Raloxifene also reduces the risk of cardiovascular events among postmenopausal women with increased cardiovascular risk. From these observations, postmenopausal osteoporotic women without multiple or severe fractures who have risk factors for breast cancer or cardiovascular disorders can be excellent candidates for raloxifene treatment.\n[Drug-Disease]: raloxifene - cardiovascular disorders" }, { "pmid": "15791634", "target": "[\"Span: 2 and 5 mg twice daily | Label: Dosage\"]", "text": "[Title]: Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.\n[Abstract]: Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P < or = 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD.\n[Drug-Disease]: sarizotan - dyskinesias" }, { "pmid": "15866657", "target": "[\"Span: adult | Label: Age\"]", "text": "[Title]: Adefovir dipivoxil therapy in liver transplant recipients with lamivudine-resistant hepatitis B virus.\n[Abstract]: Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide. One effective strategy to prevent recurrence or transmission of HBV infection after liver transplantation exists is prescription of Lamivudine, although it is associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide analogue of adenosine that has achieved significant results in virologic, biochemical, and clinical parameters in lamivudine-resistant HBV-infected patients. Between 1990 and 2003 7 adult recipients of orthotopic liver transplants who experienced lamivudine-resistant HBV infection (pretransplantation or posttransplantation) were enrolled in a prospective study to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2 x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD, 1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end of the follow-up. HBe antigen seroconversion was observed in 1 patient. No significant adverse effects were recorded, except for renal functional impairment in 1 patient who had previous renal insufficiency. In our study, adefovir was an effective drug to suppression HBV replication in liver transplant recipients with lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of the drug was excellent. None of the patients developed resistance to adefovir. Therapy with AD in liver transplant recipients is effective and safe, although renal function should be monitored closely.\n[Drug-Disease]: AD - HBV infection" }, { "pmid": "15877736", "target": "[\"Span: FAS mutations | Label: Gene\", \"Span: aged 9 months to 17 years | Label: Age\"]", "text": "[Title]: Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome.\n[Abstract]: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias.\n[Drug-Disease]: MMF - cytopenias" }, { "pmid": "15877736", "target": "[\"Span: FAS mutations | Label: Gene\", \"Span: aged 9 months to 17 years | Label: Age\"]", "text": "[Title]: Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome.\n[Abstract]: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias.\n[Drug-Disease]: MMF - ALPS" }, { "pmid": "15921073", "target": "[\"Span: type-2 diabetes | Label: Comorbidity\", \"Span: mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day) | Label: Dosage\"]", "text": "[Title]: The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements.\n[Abstract]: The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.\n[Drug-Disease]: doxazosin - albuminuria" }, { "pmid": "15921073", "target": "[\"Span: type-2 diabetes | Label: Comorbidity\", \"Span: mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day) | Label: Dosage\"]", "text": "[Title]: The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements.\n[Abstract]: The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.\n[Drug-Disease]: doxazosin - hypertension" }, { "pmid": "15932730", "target": "[\"Span: 11 males | Label: Gender\", \"Span: 9 females | Label: Gender\", \"Span: aged 58 +/- 13 | Label: Age\"]", "text": "[Title]: [The effect of carvedilol on apoptosis gene PDCD5 expression in chronic heart failure patients].\n[Abstract]: OBJECTIVE: To observe the changes of serum PDCD5 antibody in chronic ischemic heart failure patients and the effect of carvedilol treatment. METHODS: Twenty chronic ischemic heart failure patients, 11 males and 9 females, aged 58 +/- 13, with the left ventricular ejection fraction (LVEF) < 45% by echocardiography and New York Heart Association (NYHA) cardiac function classification II-III, were treated with carvedilol for 6 months with a target dosage of 50 mg/d. The serum PDCD5 antibody was tested by ELISA before and after carvedilol treatment and compared with those of 20 healthy persons. RESULTS: The A value of PDCD5 antibody in the heart failure patients was 3.5 +/- 1.4, significantly higher that in than healthy persons (1.9 +/- 1.0, P < 0.01). After treatment of carvedilol, the A value of PDCD5 antibody in the heart failure patients decreased to 2.5 +/- 1.2 (P < 0.05). In 6 months maintenance treatment, 14 (70%) patients reached the dosage 50 mg/d, 4 (20%) reached 25 mg/d, and 2 (10%) reached 12.5 mg/d. Five patients (25%) had side effect such as dizziness, nausea and cough, one patient (5%) was hospitalized for 3 weeks because of heart failure, no patient died. After treatment of carvedilol, the NYHA degree increased by 0.3 (P < 0.05), LVEF increased from 35.5% +/- 7.8% to 42.7% +/- 9.6% (P < 0.05), left ventricular end-diastolic diameter decreased 5.3 mm (P < 0.05), and left ventricular end-systolic diameter decreased by 8.1 mm (P < 0.01). CONCLUSION: The titer of apoptosis gene PDCD5 antibody in the serum of chronic ischemic heart failure patients are higher, which shows apoptosis and treatment of carvedilol significantly decreases its titer.\n[Drug-Disease]: carvedilol - ischemic heart failure" }, { "pmid": "15941081", "target": "[\"Span: chronic hepatitis C | Label: Comorbidity\", \"Span: female | Label: Gender\"]", "text": "[Title]: No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and Hodgkin's disease.\n[Abstract]: There is insufficient information on the effects of chemotherapy protocols for Hodgkin's disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HD who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HD is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD.\n[Drug-Disease]: ABVD - Hodgkin's disease" }, { "pmid": "16081343", "target": "[\"Span: MTHFR C677T polymorphism | Label: Gene\", \"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients--a family-based association study.\n[Abstract]: Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.\n[Drug-Disease]: benazepril - hypertensive" }, { "pmid": "16115903", "target": "[]", "text": "[Title]: Breast cancer molecular subtypes respond differently to preoperative chemotherapy.\n[Abstract]: PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported \"breast intrinsic\" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.\n[Drug-Disease]: doxorubicin - breast cancer" }, { "pmid": "16115903", "target": "[]", "text": "[Title]: Breast cancer molecular subtypes respond differently to preoperative chemotherapy.\n[Abstract]: PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported \"breast intrinsic\" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.\n[Drug-Disease]: paclitaxel - breast cancer" }, { "pmid": "1615846", "target": "[\"Span: 68% of whom had atherosclerotic vascular disease | Label: Comorbidity\"]", "text": "[Title]: Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.\n[Abstract]: The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)\n[Drug-Disease]: lovastatin - hyperlipidemia" }, { "pmid": "1615846", "target": "[\"Span: 68% of whom had atherosclerotic vascular disease | Label: Comorbidity\"]", "text": "[Title]: Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.\n[Abstract]: The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)\n[Drug-Disease]: gemfibrozil - hyperlipidemia" }, { "pmid": "16159073", "target": "[]", "text": "[Title]: Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage.\n[Abstract]: INTRODUCTION: Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy. METHODS: This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period. RESULTS: All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p = 0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema. CONCLUSION: FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit.\n[Drug-Disease]: vitamin K - intracranial hemorrhage" }, { "pmid": "1616115", "target": "[\"Span: 3 to 10 years | Label: Age\", \"Span: 0.075 mg/kg | Label: Dosage\"]", "text": "[Title]: [Droperidol versus metoclopramide. Prevention of emesis following strabismus surgery in children].\n[Abstract]: Vomiting after strabismus surgery is a major problem that remains as yet unsolved, especially in children. Droperidol and metoclopramide, both known as powerful antiemetic drugs, were compared in this study. METHODS. One hundred ASA class I and II children ranging from 3 to 10 years of age were studied in a double-blind, randomised fashion. They were assigned to three groups: group D (n = 33) received 0.075 mg/kg droperidol, group M (n = 33) 0.15 mg/kg metoclopramide, and group N (n = 34) 0.1 ml/kg NaCl i.v. upon arrival in the post-anaesthesia recovery room (PARR). After oral premedication with 0.4 mg/kg midazolam, anaesthesia was induced via a face mask by inhalation of halothane, nitrous oxide, and oxygen. Barbiturates, atropine, and succinylcholine were not used; 0.05 mg/kg vecuronium was given to facilitate intubation. Gastric contents were aspirated by a gastric tube at the end of the operation. Vomiting and retching were recorded for 24 h; recovery from anaesthesia was assessed by a modified Steward score. RESULTS. The three groups were comparable regarding age, body weight, duration of anaesthesia, number of repaired eye muscles, and occurrence of the oculocardiac reflex (OCR). During the first 24 h postoperatively 21/33 (64%) patients of group D vomited, 24/33 (73%) of group M, and 33/34 (97%) of group N. The differences between groups D and N and between M and N were significant (P less than 0.01); comparison of groups D and M showed no statistical significance. Droperidol was more effective in reducing severe vomiting. Of the group N children, 47% vomited more than 6 times in 24 h compared to 18% of group M and 0% of group D. Age, sex, duration of anaesthesia, number of repaired eye muscles, and occurrence of the OCR had no influence on postoperative vomiting. Despite being administered at the end of the operation, droperidol did not prolong the patients' stay in the PARR. The post-anaesthetic scores for group D children were only slightly lower compared to groups M and N. CONCLUSIONS. Droperidol (0.075 mg/kg) and metoclopramide (0.15 mg/kg) both reduce postoperative vomiting after strabismus surgery. Droperidol seems to be more effective in reducing severe vomiting. Postoperative sedation after droperidol was not a major problem in our experience.\n[Drug-Disease]: droperidol - vomiting" }, { "pmid": "1616115", "target": "[\"Span: 3 to 10 years | Label: Age\", \"Span: 0.15 mg/kg | Label: Dosage\"]", "text": "[Title]: [Droperidol versus metoclopramide. Prevention of emesis following strabismus surgery in children].\n[Abstract]: Vomiting after strabismus surgery is a major problem that remains as yet unsolved, especially in children. Droperidol and metoclopramide, both known as powerful antiemetic drugs, were compared in this study. METHODS. One hundred ASA class I and II children ranging from 3 to 10 years of age were studied in a double-blind, randomised fashion. They were assigned to three groups: group D (n = 33) received 0.075 mg/kg droperidol, group M (n = 33) 0.15 mg/kg metoclopramide, and group N (n = 34) 0.1 ml/kg NaCl i.v. upon arrival in the post-anaesthesia recovery room (PARR). After oral premedication with 0.4 mg/kg midazolam, anaesthesia was induced via a face mask by inhalation of halothane, nitrous oxide, and oxygen. Barbiturates, atropine, and succinylcholine were not used; 0.05 mg/kg vecuronium was given to facilitate intubation. Gastric contents were aspirated by a gastric tube at the end of the operation. Vomiting and retching were recorded for 24 h; recovery from anaesthesia was assessed by a modified Steward score. RESULTS. The three groups were comparable regarding age, body weight, duration of anaesthesia, number of repaired eye muscles, and occurrence of the oculocardiac reflex (OCR). During the first 24 h postoperatively 21/33 (64%) patients of group D vomited, 24/33 (73%) of group M, and 33/34 (97%) of group N. The differences between groups D and N and between M and N were significant (P less than 0.01); comparison of groups D and M showed no statistical significance. Droperidol was more effective in reducing severe vomiting. Of the group N children, 47% vomited more than 6 times in 24 h compared to 18% of group M and 0% of group D. Age, sex, duration of anaesthesia, number of repaired eye muscles, and occurrence of the OCR had no influence on postoperative vomiting. Despite being administered at the end of the operation, droperidol did not prolong the patients' stay in the PARR. The post-anaesthetic scores for group D children were only slightly lower compared to groups M and N. CONCLUSIONS. Droperidol (0.075 mg/kg) and metoclopramide (0.15 mg/kg) both reduce postoperative vomiting after strabismus surgery. Droperidol seems to be more effective in reducing severe vomiting. Postoperative sedation after droperidol was not a major problem in our experience.\n[Drug-Disease]: metoclopramide - vomiting" }, { "pmid": "16226812", "target": "[]", "text": "[Title]: A three-year follow-up study of patients with the respiratory subtype of panic disorder after treatment with clonazepam.\n[Abstract]: The demographic, clinical and therapeutic features of the respiratory subtype of panic disorder (PD) versus the non-respiratory subtype were studied in a prospective design. Sixty-seven PD outpatients (DSM-IV), who had previously been categorized into respiratory (n=35) and non-respiratory (n=32) subgroups, were openly treated with clonazepam for a 3-year period. The principal measure of efficacy was the number of panic attacks, obtained from the Sheehan Panic and Anticipatory Anxiety Scale. In the first 8 weeks of treatment (acute phase), the respiratory subtype group had a significantly faster response to clonazepam. During the follow-up (weeks 12-156), the two subgroups did not differ significantly in the number of panic attacks experienced from baseline to end point. Patients in the respiratory subtype were characterized by a later onset of disorder and a family history of PD. Patients in the non-respiratory subgroup had a significantly higher number of past depressive episodes than those in the respiratory subgroup. The respiratory subgroup had a faster response after 8 weeks of treatment and an equivalent response in the 3-year follow-up period. Clonazepam had a sustained therapeutic effect over the entire treatment period.\n[Drug-Disease]: Clonazepam - panic attacks" }, { "pmid": "16239842", "target": "[]", "text": "[Title]: 5-Aminosalicylates and effects on renal function in patients with Crohn's disease.\n[Abstract]: BACKGROUND: Case reports concerning irreversible renal failure caused by 5-aminosalicylates (5-ASA) have been published. The aim of this study was to investigate the effect of long-term use of 5-ASA on renal function in patients with Crohn's disease (CD). METHODS: This was a retrospective survey in 200 consecutive outpatients with CD. Endogenous creatinine clearance (ECC) was estimated from serum creatinine with the Cockroft and Gault formula. The first ECC was chosen close to the start of 5-ASA and the second was the most recent ECC available. RESULTS: In 153 patients (59 men and 94 women), sufficient data were available for analysis. The interval between ECCs was 11 years, with a mean exposure to 5-ASA of 8.6 years. The cumulative dose of 5-ASA amounted to 9 kg. The ECC declined 0.3 +/- 5 mL/min/yr (from 100 +/- 25 to 92 +/- 28 mL/min; P < 0.01). In a multiple linear regression model, duration of the interval was a significant predictor for change in ECC (P < 0.0001), but cumulative dose of 5-ASA was not predictive (P = 0.30). No interstitial nephritis was reported, and in the 8 patients with the largest decline in ECC, comorbidity causing renal function impairment was present. CONCLUSIONS: The mean decline in ECC of 0.3 mL/min/yr in patients with CD does not exceed the decline expected from physiologic aging. Furthermore, the cumulative dose of 5-ASA was not a predictor for change in renal function. However, as interstitial nephritis caused by 5-ASA may rarely occur, we still advocate measurements of serum creatinine before and during treatment.\n[Drug-Disease]: 5-ASA - Crohn's disease" }, { "pmid": "16275125", "target": "[]", "text": "[Title]: Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke Prevention Study.\n[Abstract]: According to recent epidemiological data in Japan, stroke affects roughly 5.3 males and 3.9 females per 1000 person-years and is the third leading cause of mortality. At present, management strategies for secondary prevention of stroke include aggressive treatment of cardiovascular risk factors (i.e., hypertension, smoking cessation, etc.). Antiplatelet drugs in Japan, namely aspirin and cilostazol, are utilized regularly for the prevention of secondary stroke. While aspirin is beneficial for a wide range of cardiovascular endpoints, including total and ischemic strokes, it is also associated with significantly increased risks for hemorrhagic infarction. Cilostazol, by contrast, has been shown to significantly reduce the risk of recurrent strokes without affecting the occurrence of intracranial hemorrhage. In the Cilostazol Stroke Prevention Study, a randomized double-blind, placebo-controlled trial involving more than 1000 Japanese patients, cilostazol was found to reduce the risk of secondary stroke by 41.7% compared with placebo, a statistically significant reduction (P = 0.015). The greatest risk reduction (43.4% in cilostazol versus placebo, P = 0.0373) was found in patients who initially had a lacunar infarction, suggesting that cilostazol has a specific effect against small-vessel disease. In addition, cilostazol achieved significant risk reductions on a number of combined endpoints (e.g., cerebral infarction, intracranial hemorrhage, myocardial infarction, or vascular death), and was associated with benefits in intent-to-treat analyses. These findings indicate that cilostazol may have a role as a vascular neuroprotectant, but the clinical implications are limited by the fact that patients were randomized to placebo instead of aspirin, which is the standard of care.\n[Drug-Disease]: cilostazol - cerebral infarction" }, { "pmid": "16275125", "target": "[]", "text": "[Title]: Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke Prevention Study.\n[Abstract]: According to recent epidemiological data in Japan, stroke affects roughly 5.3 males and 3.9 females per 1000 person-years and is the third leading cause of mortality. At present, management strategies for secondary prevention of stroke include aggressive treatment of cardiovascular risk factors (i.e., hypertension, smoking cessation, etc.). Antiplatelet drugs in Japan, namely aspirin and cilostazol, are utilized regularly for the prevention of secondary stroke. While aspirin is beneficial for a wide range of cardiovascular endpoints, including total and ischemic strokes, it is also associated with significantly increased risks for hemorrhagic infarction. Cilostazol, by contrast, has been shown to significantly reduce the risk of recurrent strokes without affecting the occurrence of intracranial hemorrhage. In the Cilostazol Stroke Prevention Study, a randomized double-blind, placebo-controlled trial involving more than 1000 Japanese patients, cilostazol was found to reduce the risk of secondary stroke by 41.7% compared with placebo, a statistically significant reduction (P = 0.015). The greatest risk reduction (43.4% in cilostazol versus placebo, P = 0.0373) was found in patients who initially had a lacunar infarction, suggesting that cilostazol has a specific effect against small-vessel disease. In addition, cilostazol achieved significant risk reductions on a number of combined endpoints (e.g., cerebral infarction, intracranial hemorrhage, myocardial infarction, or vascular death), and was associated with benefits in intent-to-treat analyses. These findings indicate that cilostazol may have a role as a vascular neuroprotectant, but the clinical implications are limited by the fact that patients were randomized to placebo instead of aspirin, which is the standard of care.\n[Drug-Disease]: cilostazol - myocardial infarction" }, { "pmid": "16275125", "target": "[]", "text": "[Title]: Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke Prevention Study.\n[Abstract]: According to recent epidemiological data in Japan, stroke affects roughly 5.3 males and 3.9 females per 1000 person-years and is the third leading cause of mortality. At present, management strategies for secondary prevention of stroke include aggressive treatment of cardiovascular risk factors (i.e., hypertension, smoking cessation, etc.). Antiplatelet drugs in Japan, namely aspirin and cilostazol, are utilized regularly for the prevention of secondary stroke. While aspirin is beneficial for a wide range of cardiovascular endpoints, including total and ischemic strokes, it is also associated with significantly increased risks for hemorrhagic infarction. Cilostazol, by contrast, has been shown to significantly reduce the risk of recurrent strokes without affecting the occurrence of intracranial hemorrhage. In the Cilostazol Stroke Prevention Study, a randomized double-blind, placebo-controlled trial involving more than 1000 Japanese patients, cilostazol was found to reduce the risk of secondary stroke by 41.7% compared with placebo, a statistically significant reduction (P = 0.015). The greatest risk reduction (43.4% in cilostazol versus placebo, P = 0.0373) was found in patients who initially had a lacunar infarction, suggesting that cilostazol has a specific effect against small-vessel disease. In addition, cilostazol achieved significant risk reductions on a number of combined endpoints (e.g., cerebral infarction, intracranial hemorrhage, myocardial infarction, or vascular death), and was associated with benefits in intent-to-treat analyses. These findings indicate that cilostazol may have a role as a vascular neuroprotectant, but the clinical implications are limited by the fact that patients were randomized to placebo instead of aspirin, which is the standard of care.\n[Drug-Disease]: cilostazol - intracranial hemorrhage" }, { "pmid": "11910301", "target": "[\"Span: gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) | Label: Gene\", \"Span: angiotensinogen T174M | Label: Gene\", \"Span: M235T | Label: Gene\", \"Span: angiotensin-converting enzyme I/D | Label: Gene\", \"Span: AT1-receptor A1166C | Label: Gene\", \"Span: aldosterone synthase (CYP11B2) -344 C/T | Label: Gene\"]", "text": "[Title]: Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.\n[Abstract]: BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.\n[Drug-Disease]: irbesartan - hypertension" }, { "pmid": "11910301", "target": "[\"Span: gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) | Label: Gene\", \"Span: angiotensinogen T174M | Label: Gene\", \"Span: M235T | Label: Gene\", \"Span: angiotensin-converting enzyme I/D | Label: Gene\", \"Span: AT1-receptor A1166C | Label: Gene\", \"Span: aldosterone synthase (CYP11B2) -344 C/T | Label: Gene\"]", "text": "[Title]: Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.\n[Abstract]: BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.\n[Drug-Disease]: atenolol - hypertension" }, { "pmid": "11915580", "target": "[\"Span: up to 3 doses/day of 50 mg | Label: Dosage\"]", "text": "[Title]: A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.\n[Abstract]: Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.\n[Drug-Disease]: DCF - primary dysmenorrhea" }, { "pmid": "11915580", "target": "[\"Span: up to 3 doses/day of 50 mg | Label: Dosage\"]", "text": "[Title]: A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.\n[Abstract]: Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.\n[Drug-Disease]: DCF - Low back pain" }, { "pmid": "11915580", "target": "[\"Span: 2.5 mg/24 h | Label: Dosage\"]", "text": "[Title]: A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.\n[Abstract]: Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.\n[Drug-Disease]: GTN - primary dysmenorrhea" }, { "pmid": "11915580", "target": "[\"Span: 2.5 mg/24 h | Label: Dosage\"]", "text": "[Title]: A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.\n[Abstract]: Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.\n[Drug-Disease]: GTN - Low back pain" }, { "pmid": "11937179", "target": "[\"Span: diabetes | Label: Comorbidity\", \"Span: 67 years (SD 7) | Label: Age\"]", "text": "[Title]: Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.\n[Abstract]: BACKGROUND: The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients. METHODS: As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction). FINDINGS: Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002. INTERPRETATION: Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.\n[Drug-Disease]: atenolol - hypertension" }, { "pmid": "11937179", "target": "[\"Span: diabetes | Label: Comorbidity\", \"Span: 67 years (SD 7) | Label: Age\"]", "text": "[Title]: Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.\n[Abstract]: BACKGROUND: The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients. METHODS: As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction). FINDINGS: Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002. INTERPRETATION: Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.\n[Drug-Disease]: Losartan - hypertension" }, { "pmid": "11948390", "target": "[\"Span: neonate | Label: Age\"]", "text": "[Title]: Efficacy of phenytoin against hyponatremic seizures due to SIADH after administration of anticancer drugs in a neonate.\n[Abstract]: A neonate with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) developed refractory hyponatremic seizures following administration of anticancer drugs. The seizures did not respond to diazepam, phenobarbital, or lidocaine, but resolved immediately with administration of phenytoin. The low water-excretion capacity in neonates should be taken into consideration when fluid loading is attempted, to avoid renal damage upon administration of drugs such as cisplatin that have a potential damaging effect on the kidney. Phenytoin could be the therapy of choice for SIADH and resulting seizures in the neonatal period.\n[Drug-Disease]: Phenytoin - SIADH" }, { "pmid": "11948390", "target": "[\"Span: neonate | Label: Age\"]", "text": "[Title]: Efficacy of phenytoin against hyponatremic seizures due to SIADH after administration of anticancer drugs in a neonate.\n[Abstract]: A neonate with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) developed refractory hyponatremic seizures following administration of anticancer drugs. The seizures did not respond to diazepam, phenobarbital, or lidocaine, but resolved immediately with administration of phenytoin. The low water-excretion capacity in neonates should be taken into consideration when fluid loading is attempted, to avoid renal damage upon administration of drugs such as cisplatin that have a potential damaging effect on the kidney. Phenytoin could be the therapy of choice for SIADH and resulting seizures in the neonatal period.\n[Drug-Disease]: Phenytoin - seizures" }, { "pmid": "11963264", "target": "[\"Span: adults | Label: Age\"]", "text": "[Title]: [Possibilities and limits of treatment of aggressive behavior in patients with mental retardation with risperidone].\n[Abstract]: Despite definite indication for psychopharmacologic intervention, severe and persistent symptoms of aggressive and self-injurious behaviour still remain a therapeutic challenge. As recent research has demonstrated, not only the dopaminergic and serotonergic but also the endogenous opiate system plays a role in the pathogenesis of self-injurious behaviour. Nevertheless, the efficacy of classical neuroleptics as well as opiate antagonists is questioned. In open and controlled studies, the administration of the atypical neuroleptic risperidone (a serotonin 2A-dopamine D2 antagonist) was associated with a long-term effect in reducing self-injuries. In our clinical trial, 20 mentally retarded adults presenting with severe self-injurious and aggressive behaviour were administered risperidone over a follow-up period of 35 months. Clinical efficacy was measured with the Disability Assessment Schedule (DAS), conducted in a home for people with mental retardation. In 17 patients, a significant reduction in self-injurious behaviour is shown. Besides, there was a significant overall clinical improvement in behaviour.\n[Drug-Disease]: risperidone - aggressive behavior" }, { "pmid": "11974943", "target": "[\"Span: Japanese | Label: Body Type\", \"Span: aged 65 and over (75.5 +/- 5.6 y.o.) | Label: Age\", \"Span: 10-20 mg daily | Label: Dosage\"]", "text": "[Title]: [Effects of carvedilol on the hemodynamics and its tolerance in elderly patients].\n[Abstract]: Clinical trials have shown that beta-blockers can produce symptomatic improvement and decrease the risk of death in chronic heart failure patients. However, the side effects of beta-blockers including worsening heart failure, AV-block, contracting peripheral vessels and unfavorable effects on glucose and cholesterol metabolism tend to make physicians hesitate to prescribe beta-blockers for elderly patients. Carvedilol is a novel non-selective beta-blocker without intrinsic sympathomimetic activity (ISA) and has vasodilating effect through blocking alpha 1 receptor. We examined the effects of carvedilol on cardiac parameters in order to clarify whether beta-blocker may affect left ventricular function in elderly Japanese patients with hypertension, angina pectoris, or both. We examined the hemodynamic effect of carvedilol in 16 patients with hypertension, angina patients or both, aged 65 and over (75.5 +/- 5.6 y.o.). After 12 weeks treatment with 10-20 mg daily oral administration, echocardiography was performed and hemodynamic parameters were calculated to evaluate their cardiac functions. Blood pressure was significantly decreased, especially in systolic pressure (163.8/87.6 +/- 15.6/11.2 mmHg to 141.6/76.9 +/- 16.6/11.7 mmHg, p < 0.001/p < 0.01, respectively). Ejection fraction increase (65.8 +/- 11.8% to 71.2 +/- 11.4%, p < 0.05) accompanied heart rate decrease (72.0 +/- 16.1 bpm to 63.9 +/- 11.4 bpm, p < 0.05). Carvedilol increased ejection fraction and decreased blood pressure safely in elderly patients with hypertension, angina pectoris, or both. Taking the condition of each patient into consideration, alpha-beta-blocker can be beneficial in elder patients.\n[Drug-Disease]: Carvedilol - hypertension" }, { "pmid": "12023789", "target": "[\"Span: ERCC1 | Label: Gene\", \"Span: beta-tubulin mutations | Label: Gene\", \"Span: loss of heterozygosity in the region of the enzyme ribonucleotide reductase | Label: Gene\"]", "text": "[Title]: Pemetrexed combination therapy in the treatment of non-small cell lung cancer.\n[Abstract]: Until recently, the treatment of non-small cell lung cancer (NSCLC) was limited to the cisplatin combinations, including a small number of cytotoxic drugs. More recently, combinations with taxanes and gemcitabine have slightly improved outcome. However, when the literature is revisited, it can be realized that older drugs such as nitrogen mustard have some degree of activity in NSCLC, traditionally considered a chemoresistant tumor. However, drugs that are mostly ineffective when used as single agents, such as 5-fluorouracil (5-FU), have significant activity when combined with cisplatin in the treatment of patients with NSCLC. 5-FU constitutes the backbone of chemotherapy for colorectal cancer patients. 5-FU is equally interesting because it permits investigation of thymidylate synthase (TS) levels as a genetic target for predicting response and survival. The assessment of TS levels and ERCC1 as a marker of cisplatin resistance is leading to customized chemotherapy. The possibility of discriminating cisplatin resistance is particularly attractive in choosing between cisplatin and non-cisplatin combinations in the treatment of NSCLC. We have reviewed phase I and II studies of pemetrexed in NSCLC. The response rate is approximately 20% with single-agent pemetrexed and approximately 40% in combination with cisplatin. This combination has mild to moderate toxicity. Other synergistic combinations that should be explored include pemetrexed with gemcitabine, CPT-11, docetaxel, carboplatin, or oxaliplatin. In the future, pharmacogenomically oriented chemotherapy trials should be undertaken based on the accumulated evidence that several genetic markers, such as ERCC1, beta-tubulin mutations, and loss of heterozygosity in the region of the enzyme ribonucleotide reductase, can predict resistance to cisplatin, taxanes, or gemcitabine, respectively. Mechanisms of resistance to pemetrexed need to be investigated, including the potential role of TS messenger RNA. In summary, pemetrexed has emerged as a promising new cytotoxic drug in the arsenal of chemotherapy treatments for NSCLC.\n[Drug-Disease]: pemetrexed - NSCLC" }, { "pmid": "12023789", "target": "[\"Span: ERCC1 | Label: Gene\", \"Span: beta-tubulin mutations | Label: Gene\", \"Span: loss of heterozygosity in the region of the enzyme ribonucleotide reductase | Label: Gene\"]", "text": "[Title]: Pemetrexed combination therapy in the treatment of non-small cell lung cancer.\n[Abstract]: Until recently, the treatment of non-small cell lung cancer (NSCLC) was limited to the cisplatin combinations, including a small number of cytotoxic drugs. More recently, combinations with taxanes and gemcitabine have slightly improved outcome. However, when the literature is revisited, it can be realized that older drugs such as nitrogen mustard have some degree of activity in NSCLC, traditionally considered a chemoresistant tumor. However, drugs that are mostly ineffective when used as single agents, such as 5-fluorouracil (5-FU), have significant activity when combined with cisplatin in the treatment of patients with NSCLC. 5-FU constitutes the backbone of chemotherapy for colorectal cancer patients. 5-FU is equally interesting because it permits investigation of thymidylate synthase (TS) levels as a genetic target for predicting response and survival. The assessment of TS levels and ERCC1 as a marker of cisplatin resistance is leading to customized chemotherapy. The possibility of discriminating cisplatin resistance is particularly attractive in choosing between cisplatin and non-cisplatin combinations in the treatment of NSCLC. We have reviewed phase I and II studies of pemetrexed in NSCLC. The response rate is approximately 20% with single-agent pemetrexed and approximately 40% in combination with cisplatin. This combination has mild to moderate toxicity. Other synergistic combinations that should be explored include pemetrexed with gemcitabine, CPT-11, docetaxel, carboplatin, or oxaliplatin. In the future, pharmacogenomically oriented chemotherapy trials should be undertaken based on the accumulated evidence that several genetic markers, such as ERCC1, beta-tubulin mutations, and loss of heterozygosity in the region of the enzyme ribonucleotide reductase, can predict resistance to cisplatin, taxanes, or gemcitabine, respectively. Mechanisms of resistance to pemetrexed need to be investigated, including the potential role of TS messenger RNA. In summary, pemetrexed has emerged as a promising new cytotoxic drug in the arsenal of chemotherapy treatments for NSCLC.\n[Drug-Disease]: cisplatin - NSCLC" }, { "pmid": "12093990", "target": "[\"Span: 5 children | Label: Age\", \"Span: immunocompromised | Label: Comorbidity\", \"Span: 2 were neonates | Label: Age\", \"Span: partial DiGeorge syndrome | Label: Comorbidity\", \"Span: progressive disseminated disease | Label: Comorbidity\"]", "text": "[Title]: Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.\n[Abstract]: BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/METHODS: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.\n[Drug-Disease]: ribavirin - adenovirus disease" }, { "pmid": "12093990", "target": "[\"Span: 5 children | Label: Age\", \"Span: immunocompromised | Label: Comorbidity\", \"Span: 2 were neonates | Label: Age\", \"Span: partial DiGeorge syndrome | Label: Comorbidity\", \"Span: progressive disseminated disease | Label: Comorbidity\"]", "text": "[Title]: Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.\n[Abstract]: BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/METHODS: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.\n[Drug-Disease]: ribavirin - adenovirus hemorrhagic cystitis" }, { "pmid": "12113327", "target": "[\"Span: gestational age of 26 (23-30) wk | Label: Body Type\", \"Span: birthweight 690 (390-1310) g | Label: Body Type\", \"Span: 0.05 and 2.6 microg kg(-1) per minute | Label: Body Type\"]", "text": "[Title]: Epinephrine treatment of hypotension in very low birthweight infants.\n[Abstract]: UNLABELLED: The aim of this study was to examine the influence of a continuous infusion of epinephrine (adrenaline) on mean arterial blood pressure (MABP), heart rate, urine output and base deficit in very low birthweight infants (VLBWI) with systemic hypotension. In VLBWI who received an infusion of epinephrine for at least 12 h the mean urine output, administered fluid volume, base deficit and administered buffer 12 h before and 12 h during the infusion were recorded. If the infusion was shorter, but given for at least 2 h, the mean heart rate and MABP 2 h before and 2 h during the infusion were recorded. Thirty-one infants with a gestational age of 26 (23-30) wk [median (minimum-maximum)] and birthweight 690 (390-1310) g were included in this retrospective chart review. The patients received an infusion of epinephrine at a postnatal age of 3 (1-21) d. The doses ranged between 0.05 and 2.6 microg kg(-1) per minute within the first 24 h of administration. Three of 31 infants received epinephrine on 2 different occasions. The MABP [+7 (-1 to 13) mmHg, p=0.000001] and the heart rate [+10 (-10 to 42) bpm, p=0.000036] increased significantly (n = 34), whereas total volume administration and urine output remained the same between the 2 periods (Wilcoxon matched pairs test). The base deficit increased significantly [-3 (-10.2 to 2.6), p = 0.0014, n = 19] without a change in the administration of buffer. CONCLUSION: The infusion of epinephrine increased the MABP and the heart rate without decreasing urine output in VLBWI with hypotension not responding to a dopamine infusion up to 15 microg kg(-1) per minute. A potential adverse effect was an increase in metabolic acidosis.\n[Drug-Disease]: epinephrine - hypotension" }, { "pmid": "12145722", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.\n[Abstract]: Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.\n[Drug-Disease]: azithromycin - blindness" }, { "pmid": "12145722", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.\n[Abstract]: Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.\n[Drug-Disease]: azithromycin - diarrhea" }, { "pmid": "12167115", "target": "[\"Span: 20 mg once daily | Label: Dosage\"]", "text": "[Title]: Randomized comparative study of omeprazole and famotidine in reflux esophagitis.\n[Abstract]: BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.\n[Drug-Disease]: Omeprazole - esophagitis" }, { "pmid": "12167115", "target": "[\"Span: 20 mg once daily | Label: Dosage\"]", "text": "[Title]: Randomized comparative study of omeprazole and famotidine in reflux esophagitis.\n[Abstract]: BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.\n[Drug-Disease]: Omeprazole - reflux esophagitis" }, { "pmid": "12167115", "target": "[\"Span: 20 mg twice daily | Label: Dosage\"]", "text": "[Title]: Randomized comparative study of omeprazole and famotidine in reflux esophagitis.\n[Abstract]: BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.\n[Drug-Disease]: famotidine - esophagitis" }, { "pmid": "12167115", "target": "[\"Span: 20 mg twice daily | Label: Dosage\"]", "text": "[Title]: Randomized comparative study of omeprazole and famotidine in reflux esophagitis.\n[Abstract]: BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.\n[Drug-Disease]: famotidine - reflux esophagitis" }, { "pmid": "12167389", "target": "[\"Span: 25 mg twice daily | Label: Dosage\"]", "text": "[Title]: Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials.\n[Abstract]: BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. It is uncertain, however, if beta-blockade provides a similar degree of clinical benefit for heart failure patients with atrial fibrillation (AF) as those in sinus rhythm (SR). AIMS: To compare the effectiveness of beta blockade in patients with heart failure and AF. METHODS: Patients with chronic heart failure were randomized to treatment (double blind) with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy. Response was assessed after 12 weeks by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LVEF, 2-D echocardiography measurement of left ventricular (LV) dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate changes. RESULTS: Both beta-blockers produced significant improvements in LVEF in both the SR group: (+6+/-10% at 12-week, P<0.001) and the AF group: (+11+/-9% at 12-week, P<0.05). However, significant improvement in symptoms (P<0.001) and exercise capacity (P<0.001) were observed only in the SR group but not in the AF group despite a significant improvement in LVEF. CONCLUSION: Beta-blockers were effective in improving LV ejection fraction in chronic heart failure patients in either SR or AF but had less effect on symptoms and exercise capacity in those with AF.\n[Drug-Disease]: carvedilol - heart failure" }, { "pmid": "12167389", "target": "[\"Span: 50 mg twice daily | Label: Dosage\"]", "text": "[Title]: Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials.\n[Abstract]: BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. It is uncertain, however, if beta-blockade provides a similar degree of clinical benefit for heart failure patients with atrial fibrillation (AF) as those in sinus rhythm (SR). AIMS: To compare the effectiveness of beta blockade in patients with heart failure and AF. METHODS: Patients with chronic heart failure were randomized to treatment (double blind) with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy. Response was assessed after 12 weeks by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LVEF, 2-D echocardiography measurement of left ventricular (LV) dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate changes. RESULTS: Both beta-blockers produced significant improvements in LVEF in both the SR group: (+6+/-10% at 12-week, P<0.001) and the AF group: (+11+/-9% at 12-week, P<0.05). However, significant improvement in symptoms (P<0.001) and exercise capacity (P<0.001) were observed only in the SR group but not in the AF group despite a significant improvement in LVEF. CONCLUSION: Beta-blockers were effective in improving LV ejection fraction in chronic heart failure patients in either SR or AF but had less effect on symptoms and exercise capacity in those with AF.\n[Drug-Disease]: metoprolol - heart failure" }, { "pmid": "12174927", "target": "[\"Span: 1000 mg/mq | Label: Dosage\"]", "text": "[Title]: A phase II study of gemcitabine and tamoxifen in advanced pancreatic cancer.\n[Abstract]: BACKGROUND: Advanced pancreatic cancer (APC) constitutes a poor-prognosis disease with few and disappointing therapeutic options. In recent years chemotherapy has demonstrated a positive effect on disease-related symptoms with the introduction of a novel pyrimidine analogue, gemcitabine. Moreover there is experimental and clinical evidence that endocrine therapy may play a small but unexplored role in the management of APC. Therefore we performed a phase II study to assess whether the combination of gemcitabine and tamoxifen could be an active and safe schedule for the treatment of APC in terms of response rate and clinical benefits. MATERIALS AND METHODS: Twenty-seven evaluable consecutive patients with locally advanced, unresectable or metastatic adenocarcinoma of the pancreas were treated with gemcitabine (1000 mg/mq given as a short infusion once weekly for 3 consecutive weeks out of every 4 weeks) and tamoxifen (20 mg daily starting the second day after gemcitabine). The treatment was continued until progression or unacceptable toxicity. Evaluation of efficacy included response rate, time to progression, survival and clinical benefit, an integrated measurement of pain parameters, weight and performance status. RESULTS: A partial response was achieved in 11% of patients while 48% experienced stable disease, lasting at least 8 weeks; disease progression was documented in 41% of patients. The median time of progression was 4.5 months; the median survival-time was 8 months and one-year survival was 31%. Clinical benefit was documented in 59% of patients with a median duration of 13 weeks. No gastrointestinal or haematological grade 4 toxicity was observed. In general the treatment showed a satisfactory safety profile and tamoxifen-related toxicity was not documented. CONCLUSION: The combination of gemcitabine and tamoxifen appears to be an innovative therapeutic approach in the management of APC with interesting clinical activity and a good profile of toxicity. This novel schedule of treatment deserves further investigation in large randomized trials to assess if the addition of tamoxifen could improve the therapeutic results of gemcitabine in APC, mostly in term of quality of lfe.\n[Drug-Disease]: gemcitabine - adenocarcinoma of the pancreas" }, { "pmid": "12174927", "target": "[\"Span: 20 mg daily | Label: Dosage\"]", "text": "[Title]: A phase II study of gemcitabine and tamoxifen in advanced pancreatic cancer.\n[Abstract]: BACKGROUND: Advanced pancreatic cancer (APC) constitutes a poor-prognosis disease with few and disappointing therapeutic options. In recent years chemotherapy has demonstrated a positive effect on disease-related symptoms with the introduction of a novel pyrimidine analogue, gemcitabine. Moreover there is experimental and clinical evidence that endocrine therapy may play a small but unexplored role in the management of APC. Therefore we performed a phase II study to assess whether the combination of gemcitabine and tamoxifen could be an active and safe schedule for the treatment of APC in terms of response rate and clinical benefits. MATERIALS AND METHODS: Twenty-seven evaluable consecutive patients with locally advanced, unresectable or metastatic adenocarcinoma of the pancreas were treated with gemcitabine (1000 mg/mq given as a short infusion once weekly for 3 consecutive weeks out of every 4 weeks) and tamoxifen (20 mg daily starting the second day after gemcitabine). The treatment was continued until progression or unacceptable toxicity. Evaluation of efficacy included response rate, time to progression, survival and clinical benefit, an integrated measurement of pain parameters, weight and performance status. RESULTS: A partial response was achieved in 11% of patients while 48% experienced stable disease, lasting at least 8 weeks; disease progression was documented in 41% of patients. The median time of progression was 4.5 months; the median survival-time was 8 months and one-year survival was 31%. Clinical benefit was documented in 59% of patients with a median duration of 13 weeks. No gastrointestinal or haematological grade 4 toxicity was observed. In general the treatment showed a satisfactory safety profile and tamoxifen-related toxicity was not documented. CONCLUSION: The combination of gemcitabine and tamoxifen appears to be an innovative therapeutic approach in the management of APC with interesting clinical activity and a good profile of toxicity. This novel schedule of treatment deserves further investigation in large randomized trials to assess if the addition of tamoxifen could improve the therapeutic results of gemcitabine in APC, mostly in term of quality of lfe.\n[Drug-Disease]: tamoxifen - adenocarcinoma of the pancreas" }, { "pmid": "12355680", "target": "[]", "text": "[Title]: Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence.\n[Abstract]: OBJECTIVE: To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapses during protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence. METHOD: We conducted a 6-week, open-label pilot study comparing risperidone with typical neuroleptics in a sample of withdrawn cocaine-dependent schizophrenia patients. RESULTS: Preliminary results suggest that individuals treated with risperidone had significantly less cue-elicited craving and substance abuse relapses at study completion. Further, they showed a trend toward a greater reduction in negative and global symptoms of schizophrenia. CONCLUSION: Atypical neuroleptics may help reduce craving and relapses in this population. Future research should include more rigorous double-blind placebo-controlled studies with this class of medications.\n[Drug-Disease]: risperidone - schizophrenia" }, { "pmid": "12368962", "target": "[]", "text": "[Title]: Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.\n[Abstract]: The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.\n[Drug-Disease]: melphalan - myeloma" }, { "pmid": "12392612", "target": "[\"Span: average of 50 years old | Label: Age\", \"Span: female | Label: Gender\"]", "text": "[Title]: [Clinical analysis of 22 patients with primary biliary cirrhosis].\n[Abstract]: OBJECTIVE: To improve the diagnosis and management of primary biliary cirrhosis (PBC). METHODS: Clinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy. RESULTS: There were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15). CONCLUSIONS: PBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients\n[Drug-Disease]: Ursodeoxycholic acid - fatigue" }, { "pmid": "12392612", "target": "[\"Span: average of 50 years old | Label: Age\", \"Span: female | Label: Gender\"]", "text": "[Title]: [Clinical analysis of 22 patients with primary biliary cirrhosis].\n[Abstract]: OBJECTIVE: To improve the diagnosis and management of primary biliary cirrhosis (PBC). METHODS: Clinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy. RESULTS: There were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15). CONCLUSIONS: PBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients\n[Drug-Disease]: Ursodeoxycholic acid - primary biliary cirrhosis" }, { "pmid": "12392612", "target": "[\"Span: average of 50 years old | Label: Age\", \"Span: female | Label: Gender\"]", "text": "[Title]: [Clinical analysis of 22 patients with primary biliary cirrhosis].\n[Abstract]: OBJECTIVE: To improve the diagnosis and management of primary biliary cirrhosis (PBC). METHODS: Clinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy. RESULTS: There were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15). CONCLUSIONS: PBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients\n[Drug-Disease]: Ursodeoxycholic acid - pruritus" }, { "pmid": "12401614", "target": "[\"Span: aged 20-70 yr old | Label: Age\", \"Span: 2 mL of metoclopramide (10 mg) | Label: Dosage\"]", "text": "[Title]: A comparison of metoclopramide and lidocaine for preventing pain on injection of diazepam.\n[Abstract]: UNLABELLED: We compared the ability of metoclopramide with IV lidocaine pretreatment to abolish pain from a diazepam injection. In a randomized, prospective, double-blinded, placebo-controlled clinical trial, 159 patients (ASA physical status I and II), aged 20-70 yr old, were allocated to one of three groups. Placebo and study drugs were injected IV immediately before 0.1 mg/kg of diazepam into a dorsal hand vein. Patients in Groups 1, 2, and 3 received 2 mL of placebo, 2 mL of lidocaine 1%, and 2 mL of metoclopramide (10 mg), respectively. The patient's response was graded using a 4-point scale. Any score other than 0 represented pain on injection. We observed that the incidence of pain on diazepam injection was 83% in the placebo group, which was decreased to 70% and 39% in patients pretreated with metoclopramide and lidocaine, respectively. Although there was no significant difference in the incidence of pain in Groups 1 and 3 (P > 0.05), Group 3 showed significantly less patients with severe pain scores than Group 1 as diazepam was injected (P < 0.000). Group 2 showed a significantly less frequent incidence of pain than the saline (P < 0.000) and the metoclopramide (P < 0.002) groups as diazepam was injected. The intensity of pain in Group 2 was significantly less than Group 3 (P = 0.012). The intensity of diazepam injection pain was intense with placebo as compared with other groups (P < 0.000). Metoclopramide, rather than lidocaine pretreatment, may be a reasonable analgesic alternative for painful injections. IMPLICATIONS: Metoclopramide, rather than lidocaine pretreatment, may be a reasonable analgesic alternative to decrease pain from a diazepam injection, especially when there is a medical condition in which lidocaine should be used very cautiously.\n[Drug-Disease]: Metoclopramide - pain" }, { "pmid": "12421483", "target": "[\"Span: CYP2D6*10 genotype | Label: Gene\", \"Span: Chinese | Label: Body Type\", \"Span: 450-600 mg per day in three divided doses | Label: Dosage\"]", "text": "[Title]: Effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia.\n[Abstract]: AIM: To determine the effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia. METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC> or =1000/d) were recruited. They were normal in routine laboratory testing and administered propafenone hydrochloride 450-600 mg per day in three divided doses. Twelve lead cardiogram and 24 h Holter monitoring were performed before and after 7 d treatment of propafenone. Steady-state peak and trough concentrations of propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular arrhythmia after propafenone treatment. PR interval prolongation was increased from 0.146 s+/-0.018 s to 0.161 s+/-0.022 s (P<0.05). CYP2D6 genotypes played an important role in plasma levels and effects of propafenone. In 450 mg/d group, patients with homozygous mutant of CYP2D6*10 not only had a Cmax of propafenone two times as high as those of wild-type genotype, but also showed a two fold higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1 (P<0.05). CONCLUSION: CYP2D6*10 genotype is relevant to decreased activity of CYP2D6 enzyme in Chinese patients. Elevated plasma concentration is consistent with better efficacy of propafenone in patients with ventricular arrhythmia.\n[Drug-Disease]: propafenone - ventricular premature contractions" }, { "pmid": "12434673", "target": "[\"Span: 7 male and 8 female | Label: Gender\", \"Span: aged 53.24 +/- 6.60 years | Label: Age\", \"Span: BMI 26.97 +/- 1.24 kg/m2 | Label: Body Type\"]", "text": "[Title]: Effects of ramipril therapy on some components of insulin resistance syndrome in patients with essential hypertension.\n[Abstract]: Essential hypertension presents a component of insulin resistance syndrome. Insulin resistance exists whenever normal concentration of hormone produces less than normal biologic response. This prospective clinical study included 15 patients (7 male and 8 female), with normal glucose tolerance, aged 53.24 +/- 6.60 years, BMI 26.97 +/- 1.24 kg/m2, with mild-to-moderate essential hypertension before and after ramipril treatment lasting 12 weeks. For assessment of peripheral insulin sensitivity and glucose effectiveness we used a reduced samples Bergman's Minimal Model method. At week 12, we noted a 50% elevation of mean insulin sensitivity index, but without achieving normal reference values (Si = 1.22 +/- 0.66 vs 1.78 +/- 0.8 x 10(-4) min/microU/ml). Glucose effectiveness, plasma lipids and electrolytes were relatively unchanged. Haemoglobin and platelet count were significantly decreased. Being metabolically neutral, with antithrombotic activity, ramipril can be recommended for treatment of patients with hypertension and insulin resistance, especially for patients with accompanied diabetes mellitus.\n[Drug-Disease]: ramipril - hypertension" }, { "pmid": "12461832", "target": "[\"Span: elderly | Label: Age\"]", "text": "[Title]: Acute toxicity of local anesthetic ropivacaine and mepivacaine during a combined lumbar plexus and sciatic block for hip surgery.\n[Abstract]: Hip fracture is a common pathology in elderly patients. Intercurrent diseases, mainly cardiac and respiratory, often result in significant morbidity and mortality. Anesthesia for hip fracture can be provided by general or regional techniques. The combination of a lumbar plexus and posterior sciatic nerve block represents an alternative to neuraxial technique of anaesthesia such as spinal anesthesia (4, 6). We report a case of acute toxicity resulting in the injection of local anesthetics Ropivacaine and Mepivacaine in elderly patient. An elderly woman was scheduled for surgical repair of a fractured femur neck by dynamic hip screw synthesis. Anesthesia was realized by peripheral nerve bi-block (lumbar plexus and posterior sciatic block) (7). The patient experienced seizures and dysrhythmias twenty minutes after block completion and injection of the anesthetic solution [Ropivacaine 0.75%, administered for lumbar plexus block performed via the posterior approach (WINNIE) and Mepivacaine 1.5%, administered for posterior sciatic nerve block (LABAT)]. Cardiopulmonary resuscitation was successful. All signs of toxicity disappeared after injection of midazolam and atropine, intubation and 100% oxygen ventilation. We decided to proceed with surgery. The postoperative course was uncomplicated and made a full recovery.\n[Drug-Disease]: atropine - toxicity" }, { "pmid": "12461832", "target": "[\"Span: elderly | Label: Age\"]", "text": "[Title]: Acute toxicity of local anesthetic ropivacaine and mepivacaine during a combined lumbar plexus and sciatic block for hip surgery.\n[Abstract]: Hip fracture is a common pathology in elderly patients. Intercurrent diseases, mainly cardiac and respiratory, often result in significant morbidity and mortality. Anesthesia for hip fracture can be provided by general or regional techniques. The combination of a lumbar plexus and posterior sciatic nerve block represents an alternative to neuraxial technique of anaesthesia such as spinal anesthesia (4, 6). We report a case of acute toxicity resulting in the injection of local anesthetics Ropivacaine and Mepivacaine in elderly patient. An elderly woman was scheduled for surgical repair of a fractured femur neck by dynamic hip screw synthesis. Anesthesia was realized by peripheral nerve bi-block (lumbar plexus and posterior sciatic block) (7). The patient experienced seizures and dysrhythmias twenty minutes after block completion and injection of the anesthetic solution [Ropivacaine 0.75%, administered for lumbar plexus block performed via the posterior approach (WINNIE) and Mepivacaine 1.5%, administered for posterior sciatic nerve block (LABAT)]. Cardiopulmonary resuscitation was successful. All signs of toxicity disappeared after injection of midazolam and atropine, intubation and 100% oxygen ventilation. We decided to proceed with surgery. The postoperative course was uncomplicated and made a full recovery.\n[Drug-Disease]: midazolam - toxicity" }, { "pmid": "12566371", "target": "[\"Span: 30 [10 to 40] mg/d | Label: Dosage\"]", "text": "[Title]: Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.\n[Abstract]: BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.\n[Drug-Disease]: Lisinopril - hypercholesterolemia" }, { "pmid": "12566371", "target": "[\"Span: 30 [10 to 40] mg/d | Label: Dosage\"]", "text": "[Title]: Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.\n[Abstract]: BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.\n[Drug-Disease]: Lisinopril - nephropathies" }, { "pmid": "12566371", "target": "[\"Span: 30 [10 to 40] mg/d | Label: Dosage\"]", "text": "[Title]: Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.\n[Abstract]: BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.\n[Drug-Disease]: Lisinopril - hypertriglyceridemia" }, { "pmid": "12593465", "target": "[\"Span: 2 months to 14 years of age | Label: Age\", \"Span: 0.15 mg/kg/minute initially as bolus in 1 minute | Label: Dosage\", \"Span: 1 to 7 microg/kg/minute as continuous infusion | Label: Dosage\"]", "text": "[Title]: Eight-year study of childhood status epilepticus: midazolam infusion in management and outcome.\n[Abstract]: Sixty-eight children 2 months to 14 years of age were admitted with status epilepticus to Sultan Qaboos University Hospital from November 1993 to December 2001. Thirty-eight children (55.9%) had refractory status epilepticus and 30 (44.1%) had established status epilepticus. The children with refractory status epilepticus had received intravenous or per rectal diazepam and intravenous phenytoin/phenobarbital (either or both) before continuous infusion of midazolam was given. Fifty-one children received continuous midazolam infusion. In 38 children with refractory status epilepticus, the midazolam infusion was given in addition to the long-acting antiepilepsy drug, whereas 13 (18.8%) children needed only midazolam to control the established status epilepticus. Seventeen (25%) children were controlled with phenytoin sodium alone. Midazolam was given 0.15 mg/kg/minute initially as bolus in 1 minute, followed by 1 to 7 microg/kg/minute as continuous infusion. The status could not be controlled in one child (1.5%) suffering from neurodegenerative disease. Two children needed mechanical ventilation following prolonged apnea after diazepam administration in one and diazepam plus phenobarbital in the other. No metabolic derangements or compromise of vital functions was noted on midazolam infusion. All children made a complete recovery. There was one death related to meningoencephalitis.\n[Drug-Disease]: midazolam - status epilepticus" }, { "pmid": "12616591", "target": "[]", "text": "[Title]: Olanzapine treatment of anorexia nervosa: a retrospective study.\n[Abstract]: BACKGROUND: Recent reports raise the possibility that olanzapine, which commonly causes weight gain in non-eating-disordered subjects, assisted weight gain and mood during refeeding in anorexia nervosa (AN) patients. METHODS: Eighteen AN subjects who engaged in open treatment with olanzapine were retrospectively questioned about their response. RESULTS: Subjects reported a significant reduction in anxiety, difficulty eating, and core eating disorder symptoms after taking olanzapine. DISCUSSION: These data lend support to the possibility that olanzapine may be useful in AN patients. CONCLUSION: A controlled trial is necessary to prove that olanzapine is efficacious.\n[Drug-Disease]: olanzapine - anorexia nervosa" }, { "pmid": "12633129", "target": "[\"Span: DSM-IV bipolar disorder | Label: Comorbidity\", \"Span: dose of 25 mg/day | Label: Dosage\", \"Span: 12.5 mg/day | Label: Dosage\", \"Span: maximum dose of 300 mg/day | Label: Dosage\", \"Span: 13 men | Label: Gender\", \"Span: 17 women | Label: Gender\", \"Span: bipolar I disorder (N = 22) | Label: Comorbidity\", \"Span: bipolar II disorder (N = 7) | Label: Comorbidity\", \"Span: bipolar disorder not otherwise specified (N = 1) | Label: Comorbidity\", \"Span: mean +/- SD age of 35.4 +/- 7.2 years | Label: Age\"]", "text": "[Title]: Lamotrigine in patients with bipolar disorder and cocaine dependence.\n[Abstract]: BACKGROUND: Bipolar disorder is associated with the highest substance abuse rates of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Open-label lamotrigine was examined in 30 outpatients with DSM-IV bipolar disorder and cocaine dependence. Lamotrigine was either added to existing medication regimens or used as monotherapy. METHOD: Lamotrigine was started at a dose of 25 mg/day (12.5 mg/day in those taking valproic acid) and titrated to a maximum dose of 300 mg/day. Subjects received a baseline evaluation including a structured clinical interview and weekly assessments for 12 weeks with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Cocaine Craving Questionnaire (CCQ). At each appointment, a urine sample was obtained, and participants reported drug use during the previous week. The subjects consisted of 13 men and 17 women with cocaine dependence and bipolar I disorder (N = 22), bipolar II disorder (N = 7), or bipolar disorder not otherwise specified (N = 1), with a mean +/- SD age of 35.4 +/- 7.2 years. Data were analyzed using the last observation carried forward on all subjects who completed the baseline evaluation and at least 1 postbaseline assessment. RESULTS: Significant improvement was observed in HAM-D, YMRS, and BPRS scores (p < or =.02). Cravings also significantly decreased as measured by the CCQ (p <.001). Dollar amount spent on drugs decreased nonsignificantly. Lamotrigine was well tolerated, with no subjects discontinuing due to side effects. CONCLUSION: Lamotrigine treatment was well tolerated in this sample and associated with statistically significant improvement in mood and drug cravings but not drug use. The findings suggest that larger controlled trials of lamotrigine are needed in this population.\n[Drug-Disease]: lamotrigine - cocaine dependence" }, { "pmid": "12640257", "target": "[\"Span: B2 bradykinin receptor (B2BKR) polymorphism | Label: Gene\", \"Span: B2BKR +9/+9 genotypes | Label: Gene\"]", "text": "[Title]: B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.\n[Abstract]: OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.\n[Drug-Disease]: irbesartan - left ventricular (LV) hypertrophy" }, { "pmid": "12640257", "target": "[\"Span: B2 bradykinin receptor (B2BKR) polymorphism | Label: Gene\", \"Span: B2BKR +9/+9 genotypes | Label: Gene\"]", "text": "[Title]: B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.\n[Abstract]: OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.\n[Drug-Disease]: atenolol - left ventricular (LV) hypertrophy" }, { "pmid": "12681025", "target": "[\"Span: 120 mg t.i.d. | Label: Dosage\", \"Span: aged 18-70 years old | Label: Age\", \"Span: BMI > 27 kg/m2 | Label: Body Type\", \"Span: Latin-American | Label: Body Type\"]", "text": "[Title]: Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.\n[Abstract]: AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.\n[Drug-Disease]: orlistat - obese non-insulin-dependent diabetic" }, { "pmid": "12681025", "target": "[\"Span: 120 mg t.i.d. | Label: Dosage\", \"Span: aged 18-70 years old | Label: Age\", \"Span: BMI > 27 kg/m2 | Label: Body Type\", \"Span: Latin-American | Label: Body Type\"]", "text": "[Title]: Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.\n[Abstract]: AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.\n[Drug-Disease]: orlistat - obese diabetic" }, { "pmid": "12682082", "target": "[\"Span: > or =50 years of age | Label: Age\", \"Span: 50 to 200 mg daily | Label: Dosage\"]", "text": "[Title]: Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.\n[Abstract]: Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.\n[Drug-Disease]: eplerenone - hypertension" }, { "pmid": "12682082", "target": "[\"Span: > or =50 years of age | Label: Age\", \"Span: 2.5 to 10 mg daily | Label: Dosage\"]", "text": "[Title]: Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.\n[Abstract]: Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.\n[Drug-Disease]: amlodipine - hypertension" }, { "pmid": "12688316", "target": "[\"Span: elderly patients | Label: Age\", \"Span: 50 mg | Label: Dosage\", \"Span: 50 mg/m2 | Label: Dosage\"]", "text": "[Title]: Efficacy and toxicity of liposomal daunorubicin included in PVABEC regimen for aggressive NHL of the elderly.\n[Abstract]: Liposomes used for delivering antineoplastic drugs to sites of disease are able to minimize side effects and enhance therapeutic efficacy. Liposomal Daunorubicin (Daunoxome; DNX) has a selective and higher accumulation in neoplastic tissues and seems to be able to escape Multi-Drug Resistance (MDR). We treated 35 elderly patients with aggressive non-Hodgkin's lymphoma (NHL) with PVBECDNX, a regimen analogue to P-VABEC in which doxorubicin is replaced with DNX at a dose of 50 mg (first 13 patients) and thereafter 50 mg/m2. Twenty-six out of 35 patients were evaluable for response; 15 obtained a CR, 5 a PR (overall response rate of 77%). After a median follow-up of 13 months the 2-years actuarial overall survival was 75% and the failure-free survival was 71%. Two patients out of six no responders died because of progression of disease, and one died in CR because of pre-existing cardiovascular disorders. Eight patients did not tolerate DNX infusion (back pain). Non-haematological toxicity was mild. This study confirms that PVABEC-like regimens are able to induce a high overall response rate in a percentage of patients affected by aggressive lymphoma and shows that DNX is as effective as Daunorubicin in these disorders, but its acute toxicity is reduced.\n[Drug-Disease]: P-VABEC - aggressive non-Hodgkin's lymphoma" }, { "pmid": "12708602", "target": "[\"Span: CYP2A6 | Label: Gene\", \"Span: CYP2A6*2 | Label: Gene\", \"Span: CYP2A6*3 | Label: Gene\", \"Span: CYP2A6*4A | Label: Gene\", \"Span: 90 mg | Label: Dosage\", \"Span: German | Label: Body Type\"]", "text": "[Title]: Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin.\n[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.\n[Drug-Disease]: coumarin - venous insufficiency" }, { "pmid": "12723015", "target": "[\"Span: Nigerian | Label: Body Type\", \"Span: 53 +/- 6 years | Label: Age\", \"Span: 14 men | Label: Gender\", \"Span: 14 women | Label: Gender\", \"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity.\n[Abstract]: OBJECTIVES: Congestive heart failure (CHF) is characterized by an initial compensatory, but subsequently deleterious, activation of both the renin-angiotensin (RAS) and the sympathetic nervous system (SNS). Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF. Carvedilol, a mixed alpha and beta-blocker with antioxidant properties, and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF. However, beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma. The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings. The aims of the present study were to examine and compare the cardiovascular, autonomic, and clinical effects of additional alpha-1, or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF. METHODS: Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics, were randomized to 3 groups of similar demographics according to a single blind, parallel group design. The patients were aged 53 +/- 6 years, and comprised 14 men and 14 women, with a mean cardiothoracic ratio of 0.66 +/- 0.03, and ejection fraction of 0.38 +/- 0.10, 60% hypertensive etiology. Group 1 patients received 5 mg enalapril alone, group 2 received 5 mg enalapril + 1 mg prazosin, and group 3 received 5 mg enalapril + 50 mg atenolol. All medication was taken daily for 4 weeks. Blood pressure, heart rate, pressure rate product, 6-minute walk test, NYHA class, and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment. Two-way repeated measures ANOVA, and a one-way ANOVA were used in data analysis. RESULTS: The 3 treatments caused significant (P<.001 ANOVA) and similar improvements for the NYHA class (-1.0 to -1.6), and increased the 6-minute distance covered (+130 m to +205 m). Although no treatment differences were observed, a trend suggesting a greater improvement with enalapril + atenolol became apparent. By the fourth week, the sympathoplegic treatments, enalapril + atenolol, and enalapril + prazosin, caused significant reductions in the pressure rate product (-3726 +/- 1885 mm Hg x beats/min; -3498 +/- 396 mm Hg beats/min, respectively), (compared to enalapril alone (-1349 +/- 894 mm Hg x beats/min) (P<.001 ANOVA). During the Valsalva maneuver, the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol (944 +/- 66 msec) or with enalapril + prazosin (825 +/- 48 msec), compared to enalapril alone (760 +/- 45 msec) (P<.001 ANOVA). The phase II Valsalva tachycardia were similar between treatments. The respiratory sinus arrhythmia ratio increased significantly (P<.005 ANOVA) and equally on all treatments. However, the pressor and chronotropic responses to forearm isometric handgrip increased significantly on the enalapril + prazosin combination (P<.02), compared to the other treatments. CONCLUSIONS: Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF, but also the resultant improvement in exercise tolerance and NYHA class. Compared to using ACE inhibition alone, the combined therapies caused a marked reduction in the pressure rate product, an index of myocardial oxygen consumption, and a greater enhancement of cardiac parasympathetic activity. Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade. Conversely, the pressor and chronotropic abnormalities during forearm isometric handgrip in CHF, were normalized by alpha-1, but not beta-1, blockade. Thus, the combined reflex cardiac vagal augmentation following selective beta-1 blockade, and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition, may be of major therapeutic and prognostic benefit in Blacks with non-ischemic (hypertensive) CHF stabilized on digoxin and diuretics.\n[Drug-Disease]: atenolol - CHF" }, { "pmid": "12723015", "target": "[\"Span: Nigerian | Label: Body Type\", \"Span: 53 +/- 6 years | Label: Age\", \"Span: 14 men | Label: Gender\", \"Span: 14 women | Label: Gender\", \"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity.\n[Abstract]: OBJECTIVES: Congestive heart failure (CHF) is characterized by an initial compensatory, but subsequently deleterious, activation of both the renin-angiotensin (RAS) and the sympathetic nervous system (SNS). Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF. Carvedilol, a mixed alpha and beta-blocker with antioxidant properties, and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF. However, beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma. The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings. The aims of the present study were to examine and compare the cardiovascular, autonomic, and clinical effects of additional alpha-1, or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF. METHODS: Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics, were randomized to 3 groups of similar demographics according to a single blind, parallel group design. The patients were aged 53 +/- 6 years, and comprised 14 men and 14 women, with a mean cardiothoracic ratio of 0.66 +/- 0.03, and ejection fraction of 0.38 +/- 0.10, 60% hypertensive etiology. Group 1 patients received 5 mg enalapril alone, group 2 received 5 mg enalapril + 1 mg prazosin, and group 3 received 5 mg enalapril + 50 mg atenolol. All medication was taken daily for 4 weeks. Blood pressure, heart rate, pressure rate product, 6-minute walk test, NYHA class, and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment. Two-way repeated measures ANOVA, and a one-way ANOVA were used in data analysis. RESULTS: The 3 treatments caused significant (P<.001 ANOVA) and similar improvements for the NYHA class (-1.0 to -1.6), and increased the 6-minute distance covered (+130 m to +205 m). Although no treatment differences were observed, a trend suggesting a greater improvement with enalapril + atenolol became apparent. By the fourth week, the sympathoplegic treatments, enalapril + atenolol, and enalapril + prazosin, caused significant reductions in the pressure rate product (-3726 +/- 1885 mm Hg x beats/min; -3498 +/- 396 mm Hg beats/min, respectively), (compared to enalapril alone (-1349 +/- 894 mm Hg x beats/min) (P<.001 ANOVA). During the Valsalva maneuver, the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol (944 +/- 66 msec) or with enalapril + prazosin (825 +/- 48 msec), compared to enalapril alone (760 +/- 45 msec) (P<.001 ANOVA). The phase II Valsalva tachycardia were similar between treatments. The respiratory sinus arrhythmia ratio increased significantly (P<.005 ANOVA) and equally on all treatments. However, the pressor and chronotropic responses to forearm isometric handgrip increased significantly on the enalapril + prazosin combination (P<.02), compared to the other treatments. CONCLUSIONS: Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF, but also the resultant improvement in exercise tolerance and NYHA class. Compared to using ACE inhibition alone, the combined therapies caused a marked reduction in the pressure rate product, an index of myocardial oxygen consumption, and a greater enhancement of cardiac parasympathetic activity. Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade. Conversely, the pressor and chronotropic abnormalities during forearm isometric handgrip in CHF, were normalized by alpha-1, but not beta-1, blockade. Thus, the combined reflex cardiac vagal augmentation following selective beta-1 blockade, and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition, may be of major therapeutic and prognostic benefit in Blacks with non-ischemic (hypertensive) CHF stabilized on digoxin and diuretics.\n[Drug-Disease]: enalapril - CHF" }, { "pmid": "12723015", "target": "[\"Span: Nigerian | Label: Body Type\", \"Span: 53 +/- 6 years | Label: Age\", \"Span: 14 men | Label: Gender\", \"Span: 14 women | Label: Gender\", \"Span: 1 mg | Label: Dosage\"]", "text": "[Title]: Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity.\n[Abstract]: OBJECTIVES: Congestive heart failure (CHF) is characterized by an initial compensatory, but subsequently deleterious, activation of both the renin-angiotensin (RAS) and the sympathetic nervous system (SNS). Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF. Carvedilol, a mixed alpha and beta-blocker with antioxidant properties, and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF. However, beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma. The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings. The aims of the present study were to examine and compare the cardiovascular, autonomic, and clinical effects of additional alpha-1, or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF. METHODS: Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics, were randomized to 3 groups of similar demographics according to a single blind, parallel group design. The patients were aged 53 +/- 6 years, and comprised 14 men and 14 women, with a mean cardiothoracic ratio of 0.66 +/- 0.03, and ejection fraction of 0.38 +/- 0.10, 60% hypertensive etiology. Group 1 patients received 5 mg enalapril alone, group 2 received 5 mg enalapril + 1 mg prazosin, and group 3 received 5 mg enalapril + 50 mg atenolol. All medication was taken daily for 4 weeks. Blood pressure, heart rate, pressure rate product, 6-minute walk test, NYHA class, and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment. Two-way repeated measures ANOVA, and a one-way ANOVA were used in data analysis. RESULTS: The 3 treatments caused significant (P<.001 ANOVA) and similar improvements for the NYHA class (-1.0 to -1.6), and increased the 6-minute distance covered (+130 m to +205 m). Although no treatment differences were observed, a trend suggesting a greater improvement with enalapril + atenolol became apparent. By the fourth week, the sympathoplegic treatments, enalapril + atenolol, and enalapril + prazosin, caused significant reductions in the pressure rate product (-3726 +/- 1885 mm Hg x beats/min; -3498 +/- 396 mm Hg beats/min, respectively), (compared to enalapril alone (-1349 +/- 894 mm Hg x beats/min) (P<.001 ANOVA). During the Valsalva maneuver, the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol (944 +/- 66 msec) or with enalapril + prazosin (825 +/- 48 msec), compared to enalapril alone (760 +/- 45 msec) (P<.001 ANOVA). The phase II Valsalva tachycardia were similar between treatments. The respiratory sinus arrhythmia ratio increased significantly (P<.005 ANOVA) and equally on all treatments. However, the pressor and chronotropic responses to forearm isometric handgrip increased significantly on the enalapril + prazosin combination (P<.02), compared to the other treatments. CONCLUSIONS: Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF, but also the resultant improvement in exercise tolerance and NYHA class. Compared to using ACE inhibition alone, the combined therapies caused a marked reduction in the pressure rate product, an index of myocardial oxygen consumption, and a greater enhancement of cardiac parasympathetic activity. Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade. Conversely, the pressor and chronotropic abnormalities during forearm isometric handgrip in CHF, were normalized by alpha-1, but not beta-1, blockade. Thus, the combined reflex cardiac vagal augmentation following selective beta-1 blockade, and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition, may be of major therapeutic and prognostic benefit in Blacks with non-ischemic (hypertensive) CHF stabilized on digoxin and diuretics.\n[Drug-Disease]: prazosin - CHF" }, { "pmid": "12742009", "target": "[\"Span: allergic rhinitis | Label: Comorbidity\", \"Span: 20mg | Label: Dosage\"]", "text": "[Title]: Effects of zafirlukast on bronchial asthma and allergic rhinitis.\n[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< 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.\n[Drug-Disease]: zafirlukast - bronchial asthma" }, { "pmid": "12757969", "target": "[]", "text": "[Title]: Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.\n[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.\n[Drug-Disease]: buprenorphine - cocaine abuse" }, { "pmid": "12757969", "target": "[\"Span: 150 mg/day | Label: Dosage\"]", "text": "[Title]: Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.\n[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.\n[Drug-Disease]: DMI - cocaine abuse" }, { "pmid": "12791117", "target": "[\"Span: aged between 6 and 15 years | Label: Age\", \"Span: 0.3 mg.kg-1 | Label: Dosage\", \"Span: ASA class I or II | Label: Body Type\"]", "text": "[Title]: Comparison of patient-controlled analgesia with and without a background infusion after appendicectomy in children.\n[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.\n[Drug-Disease]: pethidine - postoperative pain" }, { "pmid": "12804728", "target": "[\"Span: 66% of patients had coronary heart disease (CHD) or equivalent risk | Label: Comorbidity\"]", "text": "[Title]: Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model.\n[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.\n[Drug-Disease]: niacin - dyslipidemia" }, { "pmid": "12884821", "target": "[\"Span: 20-year-old | Label: Age\", \"Span: Japanese | Label: Body Type\", \"Span: woman | Label: Gender\"]", "text": "[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].\n[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.\n[Drug-Disease]: ara-C - acute myeloid leukemia" }, { "pmid": "12884821", "target": "[\"Span: 20-year-old | Label: Age\", \"Span: Japanese | Label: Body Type\", \"Span: woman | Label: Gender\"]", "text": "[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].\n[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.\n[Drug-Disease]: etoposide - acute myeloid leukemia" }, { "pmid": "12884821", "target": "[\"Span: 20-year-old | Label: Age\", \"Span: Japanese | Label: Body Type\", \"Span: woman | Label: Gender\"]", "text": "[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].\n[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.\n[Drug-Disease]: idarubicin - acute myeloid leukemia" }, { "pmid": "1292206", "target": "[]", "text": "[Title]: [The results of a clinical trial of the new drug agent carbabenzpyride].\n[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.\n[Drug-Disease]: carbabenzpyride - fever" }, { "pmid": "1292206", "target": "[]", "text": "[Title]: [The results of a clinical trial of the new drug agent carbabenzpyride].\n[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.\n[Drug-Disease]: carbabenzpyride - pain" }, { "pmid": "1406482", "target": "[\"Span: 300 mg | Label: Dosage\", \"Span: 163 men | Label: Gender\", \"Span: 47 women | Label: Gender\"]", "text": "[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].\n[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.\n[Drug-Disease]: allopurinol - gout and hyperuricaemia" }, { "pmid": "1406482", "target": "[\"Span: 300 mg | Label: Dosage\", \"Span: 163 men | Label: Gender\", \"Span: 47 women | Label: Gender\"]", "text": "[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].\n[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.\n[Drug-Disease]: allopurinol - hyperuricemia" }, { "pmid": "1406482", "target": "[\"Span: 60 mg | Label: Dosage\", \"Span: 163 men | Label: Gender\", \"Span: 47 women | Label: Gender\"]", "text": "[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].\n[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.\n[Drug-Disease]: benzbromarone - gout and hyperuricaemia" }, { "pmid": "1406482", "target": "[\"Span: 60 mg | Label: Dosage\", \"Span: 163 men | Label: Gender\", \"Span: 47 women | Label: Gender\"]", "text": "[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].\n[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.\n[Drug-Disease]: benzbromarone - hyperuricemia" }, { "pmid": "14505127", "target": "[\"Span: thiopurine methyltransferase ( TPMT) mutation | Label: Gene\", \"Span: Japanese | Label: Body Type\", \"Span: 50 mg/day | Label: Dosage\"]", "text": "[Title]: Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.\n[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.\n[Drug-Disease]: AZA - ulcerative colitis" }, { "pmid": "14505127", "target": "[\"Span: thiopurine methyltransferase ( TPMT) mutation | Label: Gene\", \"Span: Japanese | Label: Body Type\", \"Span: 50 mg/day | Label: Dosage\"]", "text": "[Title]: Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.\n[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.\n[Drug-Disease]: AZA - Crohn's disease" }, { "pmid": "14623919", "target": "[\"Span: human epidermal growth factor receptor 2 (HER2) | Label: Gene\", \"Span: 25 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Combination of trastuzumab and vinorelbine in metastatic breast cancer.\n[Abstract]: BACKGROUND: Since the clinical introduction of trastuzumab (Herceptin) for metastatic breast cancers that overexpress human epidermal growth factor receptor 2 (HER2), this anticancer agent has played an important role in breast cancer treatment. We examined the effects of trastuzumab and vinorelbine (Navelbine) as a second- or third-line therapy in 24 patients whose HER2-positive tumors did not respond to or relapsed after administration of trastuzumab alone or in combination with taxane. METHODS: Trastuzumab was administered at 2 mg/kg (loading dose 4 mg/kg) once weekly and vinorelbine at 25 mg/m(2) once weekly. The median treatment duration was 118.5 days (range, 22-351 days). RESULTS: The response rate was 42% (95% confidence interval (CI): 22%-63%). The adverse events of NCI-CTC grade 3 or above consisted of neutropenia in three patients; other adverse events, including vasculitis, generalized fatigue, anemia and thrombocytopenia, were grade 1 or 2. All adverse events were reversible after treatment withdrawal and were easily manageable. CONCLUSION: A combination of trastuzumab and vinorelbine can be safely administered on an outpatient basis, and is useful in the treatment of patients with HER2-overexpressing metastatic breast cancer.\n[Drug-Disease]: vinorelbine - breast cancer" }, { "pmid": "14693982", "target": "[\"Span: 120 mg | Label: Dosage\", \"Span: BMI >=30 kg/m2 | Label: Body Type\", \"Span: normal (79%) or impaired (21%) glucose tolerance (IGT) | Label: Body Type\"]", "text": "[Title]: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.\n[Abstract]: OBJECTIVE: It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS: In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS: Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].\n[Drug-Disease]: orlistat - obese" }, { "pmid": "14740310", "target": "[\"Span: ASA I - III | Label: Body Type\", \"Span: 2 % | Label: Dosage\"]", "text": "[Title]: [Propofol-LCT versus propofol-MCT/LCT with or without lidocaine - a comparison on pain on injection].\n[Abstract]: OBJECTIVE: A disadvantage of Propofol (commercial preparation containing long-chain triglycerides; Propofol-LCT) is pain on injection, which is reported by 54 - 100 % of the patients. Many different approaches have been used in an attempt to decrease the pain on injection of propofol. The currently most efficacious treatment is lidocaine given intravenously with a tourniquet prior to Propofol injection. In previous studies, larger concentrations of free propofol in the aqueous phase of an emulsion were associated with more pain on injection. A new formulation of propofol (a mixture of long-chain and medium-chain triglycerides in the carrier emulsion; Propofol-MCT/LCT) reduces the incidence of pain on bolus injection. This study was designed to investigate, whether the use of Propofol-MCT/LCT alleviates pain on injection to a similar degree as pretreatment with lidocaine. METHODS: Eighty patients (ASA I - III) were randomly assigned to four groups according to a double-blinded protocol, to receive either lidocaine 2 % or normal saline given iv. with a 60 seconds tourniquet time before the injection of Propofol-LCT or Propofol-MCT/LCT. (group 1: 2 ml NaCl 0,9 %, Propofol-LCT; group 2: 2 ml NaCl 0,9 %, Propofol-MCT/LCT; group 3: 2 ml lidocaine 2 %, Propofol-LCT; group 4: 2 ml lidocaine 2 %, Propofol-MCT/LCT). Assessment of pain on injection was performed after 30 % of the induction dose was given. RESULTS: Pain on injection caused by Propofol-LCT with pre-treatment of lidocaine and Propofol-MCT/LCT alone is shown to be equivalent. Comparison of Propofol-MCT/LCT with pre-treatment of lidocaine and Propofol-LCT alone shows a statistical noticeable p-value of 0.035. Propofol-MCT/LCT with pre-treatment of lidocaine suggests a tendency of causing less pain compared to Propofol-MCT/LCT. Analysis of the postoperative questionnaire supplies no significant difference. CONCLUSION: The results suggest that pain on injection is reduced equivalent using either Propofol-MCT/LCT alone or Propofol-LCT with pre-treatment of lidocaine. Pre-treatment with lidocaine before Propofol-MCT/LCT seems to have an additional effect.\n[Drug-Disease]: lidocaine - pain" }, { "pmid": "14747881", "target": "[\"Span: aged 61-80 years | Label: Age\", \"Span: 160 mg | Label: Dosage\"]", "text": "[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.\n[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P<0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P<0.05 vs baseline and P<0.01 vs enalapril) and the word list recall score (+18.7%; P<0.05 vs baseline and P<0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.\n[Drug-Disease]: valsartan - hypertensive" }, { "pmid": "14747881", "target": "[\"Span: aged 61-80 years | Label: Age\", \"Span: 160 mg | Label: Dosage\"]", "text": "[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.\n[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P<0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P<0.05 vs baseline and P<0.01 vs enalapril) and the word list recall score (+18.7%; P<0.05 vs baseline and P<0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.\n[Drug-Disease]: valsartan - episodic memory" }, { "pmid": "14747881", "target": "[\"Span: aged 61-80 years | Label: Age\", \"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.\n[Abstract]: OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P<0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P<0.05 vs baseline and P<0.01 vs enalapril) and the word list recall score (+18.7%; P<0.05 vs baseline and P<0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.\n[Drug-Disease]: enalapril - hypertensive" }, { "pmid": "14871278", "target": "[\"Span: aged 11-79 years | Label: Age\", \"Span: median cumulative dose of 3206 mg | Label: Dosage\"]", "text": "[Title]: Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?\n[Abstract]: BACKGROUND: Reports that up to 26% of subjects with psoriasis develop cirrhosis have led to a recommendation of serial liver biopsies after each cumulative dose of 1500 mg of methotrexate. AIM: To evaluate the progression of liver injury in patients with psoriasis and the impact of monitoring by liver biopsy on their management. METHODS: One hundred and twenty-one liver biopsies from 66 subjects (aged 11-79 years) with psoriasis, receiving a median cumulative dose of 3206 mg of methotrexate over a period of 280.5 weeks, were evaluated. RESULTS: The assessment of advanced fibrosis according to the Ishak system (>or= 4) correlated perfectly with that of the Scheuer system (>or= 3) and poorly with that of the Roenigk scale (>or= 3b) (r2 = 1.0 and 0.31, respectively). Two of 24 pre-treatment biopsies showed advanced fibrosis and both subjects were heavy drinkers. The cumulative probabilities of advanced fibrosis (Ishak >or= 4) were 0%, 2.6%, 2.6%, 8.2% and 8.2% at cumulative doses of 1500, 3000, 4500, 5000 and 6000 mg, respectively. None of the subjects developed cirrhosis during follow-up or discontinued therapy on the basis of liver biopsy findings. CONCLUSIONS: Advanced hepatic fibrosis with low-dose methotrexate therapy is much less frequent than previously reported. Pre-treatment or monitoring liver biopsies in accordance with the current guidelines have little impact on patient management.\n[Drug-Disease]: methotrexate - psoriasis" }, { "pmid": "14964956", "target": "[\"Span: 4% | Label: Dosage\"]", "text": "[Title]: Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into the tympanic cavity.\n[Abstract]: Tinnitus is an otological symptom that is encountered often, yet its treatment is difficult. If tinnitus is of cochlear origin, a reasonable assumption is that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic infusion of a local anesthetic (4% lidocaine) to anesthetize the inner ear was conducted in a patient suffering from tinnitus. Transtympanic infusion of 4% lidocaine was performed as a treatment for cochlear tinnitus, and its efficacy was investigated. The overall efficacy rate for the 292 patients with 369 affected ears was 81%. In the investigation of the treatment results in cases of different underlying ear diseases, the efficacy rate was high for tinnitus accompanying sudden deafness and labyrinthine vertigo. However, vestibular symptoms, such as vertigo and nausea, developed after lidocaine infusion. No permanent side effects were noted. Lidocaine infusion is thought to be a useful treatment option for tinnitus and should be considered before surgical treatment. Inner ear anesthesia into the tympanic cavity has been carried out in patients who had cochlear tinnitus and in whom conservative methods of therapy, such as oral medication, had proved unsuccessful. This treatment method is useful as a local therapy for cochlear tinnitus.\n[Drug-Disease]: Lidocaine - tinnitus" }, { "pmid": "14972420", "target": "[\"Span: 600mg orally twice daily | Label: Dosage\", \"Span: 1200mg orally twice daily | Label: Dosage\"]", "text": "[Title]: Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity.\n[Abstract]: AIMS: Prophylactic administration of N-acetylcysteine (NAC) (600mg orally twice daily), along with hydration, prevents contrast agent-associated nephrotoxicity (CAN) induced by a low dose of non-ionic, low-osmolality contrast dye. We tested whether a double dose of NAC is more effective to prevent CAN. METHODS AND RESULTS: Two-hundred-twenty-four consecutive patients with chronic renal insufficiency (creatinine level > or =1.5mg/dl and/or creatinine clearance <60ml/min), referred to our institution for coronary and/or peripheral procedures, were randomly assigned to receive 0.45% saline intravenously and NAC at the standard dose (600mg orally twice daily; SD Group; n=110) or at a double dose (1200mg orally twice daily; DD Group; n=114) before and after a non-ionic, low-osmolality contrast dye administration. Increase of at least 0.5mg/dl of the creatinine concentration 48h after the procedure occurred in 12/109 patients (11%) in the SD Group and 4/114 patients (3.5%) in the DD Group (P=0.038; OR=0.29; 95% CI=0.09-0.94). In the subgroup with low (<140ml, or contrast ratio <=1) contrast dose, no significant difference in renal function deterioration occurred between the 2 groups. In the subgroup with high (> or =140ml, or contrast ratio >1) contrast dose, the event was significantly more frequent in the SD Group. Conclusions Double dose of NAC seems to be more effective than the standard dose in preventing CAN, especially with high volumes of non-ionic, low-osmolality contrast agent.\n[Drug-Disease]: NAC - nephrotoxicity" }, { "pmid": "14977831", "target": "[\"Span: Ribonucleotide reductase subunit M1 (RRM1) | Label: Gene\", \"Span: excision repair cross-complementing group 1 (ERCC1) gene | Label: Gene\"]", "text": "[Title]: Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.\n[Abstract]: PURPOSE: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. RESULTS: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P < 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016). CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.\n[Drug-Disease]: gemcitabine - NSCLC" }, { "pmid": "14977831", "target": "[\"Span: Ribonucleotide reductase subunit M1 (RRM1) | Label: Gene\", \"Span: excision repair cross-complementing group 1 (ERCC1) gene | Label: Gene\"]", "text": "[Title]: Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.\n[Abstract]: PURPOSE: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. RESULTS: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P < 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016). CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.\n[Drug-Disease]: cisplatin - NSCLC" }, { "pmid": "14985565", "target": "[]", "text": "[Title]: Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.\n[Abstract]: BACKGROUND: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.\n[Drug-Disease]: ribavirin - SARS" }, { "pmid": "15039761", "target": "[\"Span: escalating 15-30 or 30-60 mg | Label: Dosage\"]", "text": "[Title]: Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.\n[Abstract]: Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.\n[Drug-Disease]: d-amphetamine - cocaine dependence" }, { "pmid": "15039761", "target": "[\"Span: 1.1 mg/kg | Label: Dosage\"]", "text": "[Title]: Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.\n[Abstract]: Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.\n[Drug-Disease]: methadone - opioid dependence" }, { "pmid": "15064916", "target": "[\"Span: male | Label: Gender\", \"Span: 5-10 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine versus fluphenazine in an open trial in patients with psychotic combat-related post-traumatic stress disorder.\n[Abstract]: RATIONALE: Combat-related post-traumatic stress disorder (PTSD) is often complicated with other psychiatric comorbidities, and is refractory to treatment. OBJECTIVE: The aim of an open, comparative 6-week study was to compare olanzapine and fluphenazine, as a monotherapy, for treating psychotic combat-related PTSD. METHOD: Fifty-five male war veterans with psychotic PTSD (DSM-IV criteria) were treated for 6 weeks with olanzapine (n=28) or fluphenazine (n=27) in a 5-10 mg/day dose range, once or twice daily. Patients were evaluated at baseline, and after 3 and 6 weeks of treatment, using Watson's PTSD scale, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression Improvement Scale (CGI-I), Patient Global Impression Improvement Scale (PGI-I) and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS). RESULTS: At baseline, patient's data (age, duration of combat experience and scores in all measurement instruments) did not differ. After 3 and 6 weeks of treatment, olanzapine was significantly more efficacious than fluphenazine in reducing symptoms in PANSS (negative, general psychopathology subscale, supplementary items), Watson's PTSD (avoidance, increased arousal) subscales, CGI-S, CGI-I, and PGI-I scale. Both treatments affected similarly the symptoms listed in PANSS positive and Watson's trauma re-experiencing subscales. Fluphenazine induced more extrapyramidal symptoms. Prolongation of the treatment for 3 additional weeks did not affect the efficacy of either drug. CONCLUSIONS: Our data indicate that both fluphenazine and olanzapine were effective for particular symptom profile in psychotic combat-related PTSD. Olanzapine was better than fluphenazine in reducing most of the psychotic and PTSD symptoms, and was better tolerated in psychotic PTSD patients.\n[Drug-Disease]: Olanzapine - psychotic PTSD" }, { "pmid": "15064916", "target": "[\"Span: male | Label: Gender\", \"Span: 5-10 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine versus fluphenazine in an open trial in patients with psychotic combat-related post-traumatic stress disorder.\n[Abstract]: RATIONALE: Combat-related post-traumatic stress disorder (PTSD) is often complicated with other psychiatric comorbidities, and is refractory to treatment. OBJECTIVE: The aim of an open, comparative 6-week study was to compare olanzapine and fluphenazine, as a monotherapy, for treating psychotic combat-related PTSD. METHOD: Fifty-five male war veterans with psychotic PTSD (DSM-IV criteria) were treated for 6 weeks with olanzapine (n=28) or fluphenazine (n=27) in a 5-10 mg/day dose range, once or twice daily. Patients were evaluated at baseline, and after 3 and 6 weeks of treatment, using Watson's PTSD scale, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression Improvement Scale (CGI-I), Patient Global Impression Improvement Scale (PGI-I) and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS). RESULTS: At baseline, patient's data (age, duration of combat experience and scores in all measurement instruments) did not differ. After 3 and 6 weeks of treatment, olanzapine was significantly more efficacious than fluphenazine in reducing symptoms in PANSS (negative, general psychopathology subscale, supplementary items), Watson's PTSD (avoidance, increased arousal) subscales, CGI-S, CGI-I, and PGI-I scale. Both treatments affected similarly the symptoms listed in PANSS positive and Watson's trauma re-experiencing subscales. Fluphenazine induced more extrapyramidal symptoms. Prolongation of the treatment for 3 additional weeks did not affect the efficacy of either drug. CONCLUSIONS: Our data indicate that both fluphenazine and olanzapine were effective for particular symptom profile in psychotic combat-related PTSD. Olanzapine was better than fluphenazine in reducing most of the psychotic and PTSD symptoms, and was better tolerated in psychotic PTSD patients.\n[Drug-Disease]: fluphenazine - psychotic PTSD" }, { "pmid": "15073451", "target": "[\"Span: 5-40 mg | Label: Dosage\"]", "text": "[Title]: Rosuvastatin-induced arrest in progression of renal disease.\n[Abstract]: Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5-40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (> or =96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR > or =60 vs. <60 ml/min/1.73 m(2)) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.\n[Drug-Disease]: rosuvastatin - renal disease" }, { "pmid": "15077842", "target": "[\"Span: 60 mg (20 mg TID) | Label: Dosage\"]", "text": "[Title]: An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.\n[Abstract]: A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.\n[Drug-Disease]: methylphenidate - attention deficit/hyperactivity disorder" }, { "pmid": "15077842", "target": "[\"Span: 60 mg (20 mg TID) | Label: Dosage\"]", "text": "[Title]: An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.\n[Abstract]: A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.\n[Drug-Disease]: methylphenidate - cocaine dependence" }, { "pmid": "15136595", "target": "[]", "text": "[Title]: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.\n[Abstract]: PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "15136595", "target": "[]", "text": "[Title]: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.\n[Abstract]: PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.\n[Drug-Disease]: doxorubicin - breast cancer" }, { "pmid": "15136595", "target": "[]", "text": "[Title]: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.\n[Abstract]: PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.\n[Drug-Disease]: fluorouracil - breast cancer" }, { "pmid": "15136595", "target": "[]", "text": "[Title]: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.\n[Abstract]: PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.\n[Drug-Disease]: paclitaxel - breast cancer" }, { "pmid": "15148588", "target": "[\"Span: Chinese | Label: Body Type\", \"Span: 10 mg | Label: Dosage\", \"Span: D919G polymorphism of methionine synthase (MTR) gene | Label: Gene\"]", "text": "[Title]: D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.\n[Abstract]: Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene and the antihypertensive effect of this angiotensin-converting enzyme inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and family-based association tests (additive model P=0.018, dominant model P=0.025) demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. Our finding suggests that the D919G polymorphism of the MTR gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril therapy in hypertensive patients of Anhui Province, China.\n[Drug-Disease]: benazepril - hypertensive" }, { "pmid": "15148649", "target": "[\"Span: colorectal cancer (DCC) gene | Label: Gene\"]", "text": "[Title]: Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients.\n[Abstract]: PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy. METHODS: The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated. RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC-; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO-) only 54 percent are alive ( P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- survival rate was 75 percent and disease-free survival rate 62 percent ( P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- both dropped to zero ( P = 0.0002). On the other hand, in the DCC- tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC-/CHEMO- had 57 percent survival; DCC-/CHEMO+ had 52 percent survival). CONCLUSIONS: DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC- tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC- patients.\n[Drug-Disease]: 5-fluorouracil - colorectal cancer" }, { "pmid": "15148649", "target": "[\"Span: colorectal cancer (DCC) gene | Label: Gene\"]", "text": "[Title]: Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients.\n[Abstract]: PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy. METHODS: The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated. RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC-; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO-) only 54 percent are alive ( P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- survival rate was 75 percent and disease-free survival rate 62 percent ( P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- both dropped to zero ( P = 0.0002). On the other hand, in the DCC- tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC-/CHEMO- had 57 percent survival; DCC-/CHEMO+ had 52 percent survival). CONCLUSIONS: DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC- tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC- patients.\n[Drug-Disease]: levamisole - colorectal cancer" }, { "pmid": "15156430", "target": "[\"Span: cocaine use | Label: Comorbidity\", \"Span: hepatitis C virus | Label: Comorbidity\"]", "text": "[Title]: Directly observed therapy for the management of HIV-infected patients in a methadone program.\n[Abstract]: The objective of this prospective, observational clinical study was to evaluate the safety and efficacy of once-daily and twice-daily directly observed therapy (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing methadone treatment. Methadone and highly active antiretroviral therapy (HAART) were dispensed daily as DOT, with patients in the twice-daily HAART group self-administering the second dose. Clinical and laboratory end points were monitored, along with the impact of ongoing cocaine use. We studied 54 patients coinfected with HIV and hepatitis C virus. At baseline, the median virus load was 111,000 copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24 months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice-daily HAART group had virus loads of <400 copies/mL, regardless of ongoing cocaine use. Thirty-two patients required methadone dose adjustment, which was managed without modification of HAART. Treatment-limiting hepatic toxicity was rare. A DOT program of coadministered methadone and HAART can be implemented with good results, even for patients who continue to use cocaine.\n[Drug-Disease]: methadone - immunodeficiency virus (HIV)-infected" }, { "pmid": "15160669", "target": "[\"Span: 79-year-old | Label: Age\", \"Span: woman | Label: Gender\", \"Span: three vessel disease | Label: Comorbidity\", \"Span: mitral | Label: Comorbidity\", \"Span: tricuspid regurgitation | Label: Comorbidity\"]", "text": "[Title]: [Clinical experience of landiolol for the treatment of intraoperative rapid atrial fibrillation].\n[Abstract]: A 79-year-old woman with three vessel disease and mitral as well as tricuspid regurgitation underwent operation twice. Preoperatively she had atrial fibrillation and heart failure. The first operation was coronary artery bypass grafting (CABG), and the second was mediastinal dissection for mediastinitis one month after the CABG. In both operations she developed rapid atrial fibrillation and ventricular fibrillation, showing her cardiac irritablility. Both operations were performed under cardiopulmonary bypass and support. In the first operation digoxin and verapamil partly reduced heart rate of rapid atrial fibrillation from 140-170 to 110-140 beats x min-1, which made us use another drug, a short acting selective beta 1 blocker landiolol in the second operation. Landiolol successfully reduced the heart rate of rapid atrial fibrillation from 140-160 to 80-90 beats x min-1. This case demonstrates that landiolol can be safely used in a patient with heart failure due to rapid atrial fibrillation resistant to digoxin and verapamil.\n[Drug-Disease]: landiolol - atrial fibrillation" }, { "pmid": "15160669", "target": "[\"Span: 79-year-old | Label: Age\", \"Span: woman | Label: Gender\", \"Span: three vessel disease | Label: Comorbidity\", \"Span: mitral | Label: Comorbidity\", \"Span: tricuspid regurgitation | Label: Comorbidity\"]", "text": "[Title]: [Clinical experience of landiolol for the treatment of intraoperative rapid atrial fibrillation].\n[Abstract]: A 79-year-old woman with three vessel disease and mitral as well as tricuspid regurgitation underwent operation twice. Preoperatively she had atrial fibrillation and heart failure. The first operation was coronary artery bypass grafting (CABG), and the second was mediastinal dissection for mediastinitis one month after the CABG. In both operations she developed rapid atrial fibrillation and ventricular fibrillation, showing her cardiac irritablility. Both operations were performed under cardiopulmonary bypass and support. In the first operation digoxin and verapamil partly reduced heart rate of rapid atrial fibrillation from 140-170 to 110-140 beats x min-1, which made us use another drug, a short acting selective beta 1 blocker landiolol in the second operation. Landiolol successfully reduced the heart rate of rapid atrial fibrillation from 140-160 to 80-90 beats x min-1. This case demonstrates that landiolol can be safely used in a patient with heart failure due to rapid atrial fibrillation resistant to digoxin and verapamil.\n[Drug-Disease]: digoxin - atrial fibrillation" }, { "pmid": "15160669", "target": "[\"Span: 79-year-old | Label: Age\", \"Span: woman | Label: Gender\", \"Span: three vessel disease | Label: Comorbidity\", \"Span: mitral | Label: Comorbidity\", \"Span: tricuspid regurgitation | Label: Comorbidity\"]", "text": "[Title]: [Clinical experience of landiolol for the treatment of intraoperative rapid atrial fibrillation].\n[Abstract]: A 79-year-old woman with three vessel disease and mitral as well as tricuspid regurgitation underwent operation twice. Preoperatively she had atrial fibrillation and heart failure. The first operation was coronary artery bypass grafting (CABG), and the second was mediastinal dissection for mediastinitis one month after the CABG. In both operations she developed rapid atrial fibrillation and ventricular fibrillation, showing her cardiac irritablility. Both operations were performed under cardiopulmonary bypass and support. In the first operation digoxin and verapamil partly reduced heart rate of rapid atrial fibrillation from 140-170 to 110-140 beats x min-1, which made us use another drug, a short acting selective beta 1 blocker landiolol in the second operation. Landiolol successfully reduced the heart rate of rapid atrial fibrillation from 140-160 to 80-90 beats x min-1. This case demonstrates that landiolol can be safely used in a patient with heart failure due to rapid atrial fibrillation resistant to digoxin and verapamil.\n[Drug-Disease]: verapamil - atrial fibrillation" }, { "pmid": "15170009", "target": "[\"Span: women | Label: Gender\", \"Span: atopy | Label: Comorbidity\", \"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Zafirlukast for severe recurrent vulvovaginal candidiasis: an open label pilot study.\n[Abstract]: BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) has been linked to allergic disease, particularly allergic rhinitis. OBJECTIVE: A pilot study to assess the possible use of the leukotriene receptor antagonist zafirlukast as a treatment for recurrent VVC. METHODS: 20 women with six or more symptomatic attacks of VVC in the past year (at least four proved microbiologically). Clinical atopy determined by the International Study for Asthma and Allergies in Childhood (ISAAC) questionnaire assessed blindly. Monitoring by daily symptom diary and self taken vaginal swabs. Treatment with zafirlukast 20 mg twice daily for 24 weeks or until three microbiologically confirmed episodes of VVC. Response assessed by daily symptom diary and self taken vaginal swabs. Subjective response scales for improvement, side effects, and change in other allergic disease completed when stopping treatment. Semistructured telephone interview 1 year after stopping medication. RESULTS: 14 patients (70%) reported a subjective response on the improvement response scale. Six (30%) showed a complete response with no further symptomatic attacks of VVC or negative swabs when symptomatic. Seven (37%) remained symptom free 18 months after entering the study-that is, 12 months after stopping therapy. 11 (58%) remained symptom free for at least 3 months after stopping therapy. This does not include one patient who remained symptom free but continued on zafirlukast because of an improvement in her asthma. There was no clear relation between response and atopic status. Six of nine atopic subjective responders reported improvements in other allergic symptoms. Side effects were minimal; one seemed clearly attributable to the drug. CONCLUSION: Zafirlukast offers a potential new treatment for recurrent VVC that requires confirmation in controlled studies.\n[Drug-Disease]: Zafirlukast - vulvovaginal candidiasis" }, { "pmid": "15191617", "target": "[]", "text": "[Title]: Three year naturalistic outcome study of panic disorder patients treated with paroxetine.\n[Abstract]: BACKGROUND: This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment, 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia, 3) To observe paroxetine's tolerability over a 24 month period. METHODS: 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. RESULTS: Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. CONCLUSIONS: The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.\n[Drug-Disease]: paroxetine - panic disorder" }, { "pmid": "1519856", "target": "[\"Span: AIDS | Label: Comorbidity\", \"Span: 4 mg/kg/d | Label: Dosage\"]", "text": "[Title]: Higher pentamidine levels in AIDS patients with hypoglycemia and azotemia during treatment of Pneumocystis carinii pneumonia.\n[Abstract]: Trimethoprim-sulfamethoxazole (TMP-SMZ) and pentamidine are both licensed for the treatment of Pneumocystis carinii pneumonia (PCP). However, their use is associated with various adverse side effects. In this prospective study, 26 AIDS patients with 32 episodes of PCP were treated with pentamidine (4 mg/kg/d). Each patient was treated for 12 to 21 days, depending on the rapidity of onset of the clinical response. During the 32 PCP episodes, hypoglycemia occurred in 16 instances, azotemia in 12, liver toxicity in 10, and leukopenia in 8. The occurrence of thrombopenia, leukopenia, and liver toxicity was not related to age, pentamidine levels, or other complications. However, patients who had hypoglycemia during pentamidine treatment had higher serum pentamidine levels than patients who did not have hypoglycemia (107 +/- 40 versus 70 +/- 26 ng/ml, p less than 0.004). In addition, we observed that patients with azotemia showed higher pentamidine levels during treatment (120 +/- 35 versus 64 +/- 22 ng/ml, p less than 0.001). In fact, 100% (11/11) of patients with serum pentamidine concentration greater than 100 ng/ml had fasting hypoglycemia and/or azotemia, while 33% (7/21) of those with pentamidine levels less than 100 ng/ml had these side effects (p less than 0.001). The relative risk of these complications with pentamidine levels greater than 100 ng/ml was 3 (95% confidence interval, 1.6 to 5.5). Fine-tuning the dose of pentamidine may eventually prove useful to avoid toxicity and optimize therapy.\n[Drug-Disease]: pentamidine - Pneumocystis carinii pneumonia" }, { "pmid": "15201012", "target": "[]", "text": "[Title]: Treatment of acute heart failure in an infant after cardiac surgery using levosimendan.\n[Abstract]: An infant, 2 months old, underwent cardiac surgery because of congenital heart defects and pulmonary hypertension. Surgery was performed in hypothermia and cardiac standstill. On the second day after surgery the infant had to be resuscitated due to a combination of acute left-ventricular failure, pulmonary vascular hypertension and a slight right-to-left-shunt. A breakthrough in the treatment was achieved by using levosimendan to improve left-ventricular function and to decrease vascular resistance.\n[Drug-Disease]: levosimendan - acute heart failure" }, { "pmid": "15203277", "target": "[]", "text": "[Title]: Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression.\n[Abstract]: Twenty-eight myelodysplastic syndromes (MDS) patients were treated with arsenic trioxide (ATO) and thalidomide. Seven patients responded including one complete hematologic and cytogenetic response and one with regression in spleen size. Two trilineage responses were seen in patients with inv(3)(q21q26.2). Three of five patients who had high pre-therapy EVI1 levels showed unexpectedly good responses while two died early in the first cycle. In vitro studies using 32Dcl3 cells forced to express EVI1 confirmed increased sensitivity of these cells to ATO. Both low/high risk MDS may benefit significantly from therapy with ATO/thalidomide, and those with high pre-therapy EVI1 expression may be uniquely sensitive.\n[Drug-Disease]: ATO - MDS" }, { "pmid": "15203277", "target": "[]", "text": "[Title]: Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression.\n[Abstract]: Twenty-eight myelodysplastic syndromes (MDS) patients were treated with arsenic trioxide (ATO) and thalidomide. Seven patients responded including one complete hematologic and cytogenetic response and one with regression in spleen size. Two trilineage responses were seen in patients with inv(3)(q21q26.2). Three of five patients who had high pre-therapy EVI1 levels showed unexpectedly good responses while two died early in the first cycle. In vitro studies using 32Dcl3 cells forced to express EVI1 confirmed increased sensitivity of these cells to ATO. Both low/high risk MDS may benefit significantly from therapy with ATO/thalidomide, and those with high pre-therapy EVI1 expression may be uniquely sensitive.\n[Drug-Disease]: thalidomide - MDS" }, { "pmid": "15236812", "target": "[\"Span: 36% female | Label: Gender\"]", "text": "[Title]: Sex differences in cocaine-dependent individuals' response to disulfiram treatment.\n[Abstract]: The objective of this study is to evaluate differential response to disulfiram treatment of cocaine dependence by sex. Sex by treatment interactions from two pooled randomized clinical trials involving 191 cocaine-dependent subjects (36% female) were evaluated. Primary outcomes were days of abstinence and percentage of drug-free urine specimens. Significant sex by treatment interactions were found, where men treated with disulfiram had better outcomes than those who were not. Women had an intermediate outcome regardless of whether they received disulfiram. Sex differences in response to disulfiram treatment have important clinical and theoretical implications. Reasons for this apparent sex-based response are not clear, but possible mechanisms worthy of greater study include differences in alcohol use by sex as well as differences in dopamine-mediated responses to cocaine and disulfiram.\n[Drug-Disease]: disulfiram - cocaine dependence" }, { "pmid": "15257186", "target": "[\"Span: type 2 diabetes | Label: Comorbidity\", \"Span: ages 60.0 +/- 9.9 years | Label: Age\", \"Span: 64% men | Label: Gender\", \"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study.\n[Abstract]: OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.\n[Drug-Disease]: enalapril - hypertension" }, { "pmid": "15257186", "target": "[\"Span: type 2 diabetes | Label: Comorbidity\", \"Span: ages 60.0 +/- 9.9 years | Label: Age\", \"Span: 64% men | Label: Gender\", \"Span: 1.5 mg | Label: Dosage\"]", "text": "[Title]: Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study.\n[Abstract]: OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.\n[Drug-Disease]: Indapamide - hypertension" }, { "pmid": "15331141", "target": "[\"Span: CLOCK gene polymorphism (3111 T/C substitution) | Label: Gene\"]", "text": "[Title]: Genetic dissection of drug effects in clinical practice: CLOCK gene and clozapine-induced diurnal sleepiness.\n[Abstract]: Psychotic patients treated with clozapine often experience persistent daytime sleepiness. This is a frequent side effect of clozapine that may reduce patient compliance. We hypothesized that clozapine might interfere with the circadian rhythms regulated by the biological clock. In 171 patients with major psychosis, we investigated the association between hypersomnolence during clozapine therapy and a CLOCK gene polymorphism (3111 T/C substitution). Forty-six patients showed persistent daytime sleepiness and were classified as \"sleepy\". \"Sleepy\" patients were significantly more likely to have a mutated allele compared to both \"non sleepy\" patients and healthy subjects (chi2 = 20.36, d.f. = 1, P = 0.000007, and chi2 = 13.91, d.f. = 1, P = 0.0002, respectively). We conclude that an interaction between clozapine and the CLOCK gene polymorphism 3111 T/C substitution could explain persistent daytime sleepiness in a significant proportion of patients treated with clozapine.\n[Drug-Disease]: clozapine - Psychotic" }, { "pmid": "15383198", "target": "[\"Span: aged 60-80 | Label: Age\", \"Span: median dosage, 200 mg/day | Label: Dosage\"]", "text": "[Title]: A comparison of extrapyramidal symptoms in older outpatients treated with quetiapine or risperidone.\n[Abstract]: OBJECTIVE: To compare the tolerability of quetiapine with risperidone in older outpatients. RESEARCH DESIGN AND METHODS: Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn). MAIN OUTCOME MEASURES: The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy. RESULTS: Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P < 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores. CONCLUSIONS: Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.\n[Drug-Disease]: quetiapine - psychotic disorders" }, { "pmid": "15383198", "target": "[\"Span: aged 60-80 | Label: Age\", \"Span: median dosage, 3 mg/day | Label: Dosage\"]", "text": "[Title]: A comparison of extrapyramidal symptoms in older outpatients treated with quetiapine or risperidone.\n[Abstract]: OBJECTIVE: To compare the tolerability of quetiapine with risperidone in older outpatients. RESEARCH DESIGN AND METHODS: Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn). MAIN OUTCOME MEASURES: The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy. RESULTS: Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P < 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores. CONCLUSIONS: Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.\n[Drug-Disease]: risperidone - psychotic disorders" }, { "pmid": "15385353", "target": "[\"Span: 20 mg of lidocaine (2 mL of lidocaine 1%) | Label: Dosage\"]", "text": "[Title]: Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine.\n[Abstract]: Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.\n[Drug-Disease]: lidocaine - pain" }, { "pmid": "15385353", "target": "[\"Span: 200 mg | Label: Dosage\"]", "text": "[Title]: Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine.\n[Abstract]: Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.\n[Drug-Disease]: triglycerides - pain" }, { "pmid": "15519660", "target": "[\"Span: a total daily dose ranging from 2.5 to 20mg in single or divided doses | Label: Dosage\"]", "text": "[Title]: Safety and efficacy of alamifovir in patients with chronic hepatitis B virus infection.\n[Abstract]: BACKGROUND/AIMS: Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. METHODS: A randomised, placebo controlled, dose escalation study of oral alamifovir was conducted in 66 chronic hepatitis B infected patients who were selected based on stable HBV DNA (>10(5)copies/ml), with no significant liver pathology. They received either placebo or alamifovir at a total daily dose ranging from 2.5 to 20mg in single or divided doses for 28 days and were followed up for approximately 12 weeks after cessation of treatment. RESULTS: All doses showed significant antiviral activity, with mean plasma viral load reductions ranging from 1.5 to 2.6 log(10) after 28 days of dosing. Once and twice daily regimen for the same daily dose (5mg BID vs 10mg QD, 10mg BID vs 20mg QD) showed no apparent difference in the rate and extent of viral decline, or viral reduction at day 28. Post-treatment viral suppression was dose dependent. There were no serious adverse events attributable to study drug, nor were significant dose related events identified. CONCLUSIONS: Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety profile.\n[Drug-Disease]: Alamifovir - chronic hepatitis B virus infection" }, { "pmid": "15565615", "target": "[]", "text": "[Title]: Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection.\n[Abstract]: Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 10(5) copies/mL in contrast to 100% of the tenofovir-treated patients (P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection.\n[Drug-Disease]: tenofovir - HBV infection" }, { "pmid": "15567936", "target": "[\"Span: HER-2/neu | Label: Gene\"]", "text": "[Title]: HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.\n[Abstract]: PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.\n[Drug-Disease]: docetaxel - breast cancer" }, { "pmid": "15567936", "target": "[\"Span: HER-2/neu | Label: Gene\"]", "text": "[Title]: HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.\n[Abstract]: PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.\n[Drug-Disease]: doxorubicin - breast cancer" }, { "pmid": "15591903", "target": "[\"Span: 47-year-old | Label: Age\", \"Span: man | Label: Gender\", \"Span: germline alteration in intron 1 of WT1: IVS1-6 C-->A | Label: Gene\"]", "text": "[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.\n[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.\n[Drug-Disease]: etoposide - nephroblastoma" }, { "pmid": "15591903", "target": "[\"Span: 47-year-old | Label: Age\", \"Span: man | Label: Gender\", \"Span: germline alteration in intron 1 of WT1: IVS1-6 C-->A | Label: Gene\"]", "text": "[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.\n[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.\n[Drug-Disease]: melphalan - nephroblastoma" }, { "pmid": "15591903", "target": "[\"Span: 47-year-old | Label: Age\", \"Span: man | Label: Gender\", \"Span: germline alteration in intron 1 of WT1: IVS1-6 C-->A | Label: Gene\"]", "text": "[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.\n[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.\n[Drug-Disease]: carboplatin - nephroblastoma" }, { "pmid": "15592662", "target": "[\"Span: PPAR-gamma2 (Pro12Ala) | Label: Gene\", \"Span: PGC-1alpha (Gly482Ser) | Label: Gene\", \"Span: women | Label: Gender\"]", "text": "[Title]: Common polymorphisms of the PPAR-gamma2 (Pro12Ala) and PGC-1alpha (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.\n[Abstract]: AIM/HYPOTHESIS: We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2; Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. METHODS: Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1alpha gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined by the polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: The Pro12Pro genotype of the PPAR-gamma2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1alpha gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-gamma2 gene, but only the carriers of the 482Ser allele of the PGC-1alpha gene were responsive to acarbose treatment. CONCLUSION/INTERPRETATION: We conclude that the Pro12Pro genotype of the PPAR-gamma2 gene and the 482Ser allele of the PGC-1alpha gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.\n[Drug-Disease]: acarbose - type 2 diabetes" }, { "pmid": "15592807", "target": "[\"Span: 3.7+/-1.1 x 2.9+/-0.8 mg | Label: Dosage\"]", "text": "[Title]: [Apomorphine in the treatment of Parkinson's Disease].\n[Abstract]: Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine's action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists. The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson's disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittent subutaneous apomorphine applications (intermittent apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8+/-8.7%. For this an average of 3.7+/-1.1 x 2.9+/-0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8+/-13.5% and the additional levodopa dose by 30.3+/-31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5+/-19.1% and the additional levodopa dose by 65.5+/-21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson's disease which should be used before more invasive approaches are considered.\n[Drug-Disease]: apomorphine - dyskinesias" }, { "pmid": "15592807", "target": "[\"Span: 3.7+/-1.1 x 2.9+/-0.8 mg | Label: Dosage\"]", "text": "[Title]: [Apomorphine in the treatment of Parkinson's Disease].\n[Abstract]: Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine's action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists. The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson's disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittent subutaneous apomorphine applications (intermittent apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8+/-8.7%. For this an average of 3.7+/-1.1 x 2.9+/-0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8+/-13.5% and the additional levodopa dose by 30.3+/-31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5+/-19.1% and the additional levodopa dose by 65.5+/-21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson's disease which should be used before more invasive approaches are considered.\n[Drug-Disease]: apomorphine - idiopathic Parkinson's disease" }, { "pmid": "15592807", "target": "[]", "text": "[Title]: [Apomorphine in the treatment of Parkinson's Disease].\n[Abstract]: Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine's action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists. The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson's disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittent subutaneous apomorphine applications (intermittent apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8+/-8.7%. For this an average of 3.7+/-1.1 x 2.9+/-0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8+/-13.5% and the additional levodopa dose by 30.3+/-31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5+/-19.1% and the additional levodopa dose by 65.5+/-21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson's disease which should be used before more invasive approaches are considered.\n[Drug-Disease]: domperidone - orthostatic hypotension" }, { "pmid": "15592807", "target": "[]", "text": "[Title]: [Apomorphine in the treatment of Parkinson's Disease].\n[Abstract]: Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine's action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists. The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson's disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittent subutaneous apomorphine applications (intermittent apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8+/-8.7%. For this an average of 3.7+/-1.1 x 2.9+/-0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8+/-13.5% and the additional levodopa dose by 30.3+/-31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5+/-19.1% and the additional levodopa dose by 65.5+/-21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson's disease which should be used before more invasive approaches are considered.\n[Drug-Disease]: domperidone - nausea" }, { "pmid": "15592807", "target": "[]", "text": "[Title]: [Apomorphine in the treatment of Parkinson's Disease].\n[Abstract]: Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine's action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists. The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson's disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittent subutaneous apomorphine applications (intermittent apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8+/-8.7%. For this an average of 3.7+/-1.1 x 2.9+/-0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8+/-13.5% and the additional levodopa dose by 30.3+/-31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5+/-19.1% and the additional levodopa dose by 65.5+/-21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson's disease which should be used before more invasive approaches are considered.\n[Drug-Disease]: levodopa - idiopathic Parkinson's disease" }, { "pmid": "15623613", "target": "[\"Span: flavin monooxygenase 3 (FMO3), a hepatic microsomal enzyme | Label: Gene\", \"Span: M66I | Label: Gene\", \"Span: P153L | Label: Gene\", \"Span: E158K | Label: Gene\", \"Span: V257M | Label: Gene\", \"Span: E305X | Label: Gene\", \"Span: E308G | Label: Gene\", \"Span: R492W | Label: Gene\"]", "text": "[Title]: Genetic polymorphisms of human flavin monooxygenase 3 in sulindac-mediated primary chemoprevention of familial adenomatous polyposis.\n[Abstract]: PURPOSE: Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) effective in regressing adenomas in patients with familial adenomatous polyposis (FAP). However, a recent randomized trial showed that sulindac, when compared with placebo, failed to prevent the development of adenomatous polyps in genotypically positive but phenotypically negative FAP patients. The present study determined whether polymorphisms in the gene encoding flavin monooxygenase 3 (FMO3), a hepatic microsomal enzyme that inactivates sulindac, played a role in determining the efficacy of sulindac in preventing polyposis in this cohort of FAP patients. EXPERIMENTAL DESIGN: Genotyping was performed on seven established FMO3 polymorphisms previously shown to have functional relevance-M66I, P153L, E158K, V257M, E305X, E308G, and R492W-in 21 and 20 FAP patients, who received sulindac and placebo, respectively. RESULTS: None of the 41 patients exhibited heterozygous or homozygous M66I and R492W variant alleles, or homozygous P153L, V257M, and E305X variant alleles. Among sulindac-treated patients who did not develop adenomas (\"responders\"), 4 (33%) were homozygous for E158K and 2 (17%) were homozygous for E308G variant alleles. In contrast, none of the patients on sulindac who developed adenomas (\"nonresponders\") exhibited homozygosity for either of the two variant alleles. In addition, polymorphisms in the E158K or E308G allele were associated with a significant reduction in mucosal prostanoid levels in patients treated with sulindac. CONCLUSIONS: Polymorphisms in FMO3, particularly at the E158K and E308G loci, may reduce activity in catabolizing sulindac and result in an increased efficacy to prevent polyposis in FAP.\n[Drug-Disease]: sulindac - polyposis" }, { "pmid": "15655050", "target": "[]", "text": "[Title]: Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients.\n[Abstract]: One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or > or =1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of adefovir dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with adefovir dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.\n[Drug-Disease]: adefovir dipivoxil - chronic hepatitis B" }, { "pmid": "15669887", "target": "[]", "text": "[Title]: Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction.\n[Abstract]: BACKGROUND: Interferon-alpha (IFN-alpha) plus ribavirin is used to treat hepatitis C virus (HCV) infection and is associated with a high rate of depression. Newer, pegylated preparations of IFN-alpha have a longer half-life, require once-per-week dosing, and may be associated with reduced neuropsychiatric burden. Limited data exist on depression during pegylated IFN-alpha therapy. METHOD: Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) in 162 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of treatment with pegylated IFN alpha-2b (PEG IFN) plus weight-based (N = 86) versus standard dose (N = 76) ribavirin. Data were collected from March 2001 to April 2003. RESULTS: Compared with baseline, mean SDS index scores were significantly increased by week 4 and remained elevated throughout the study. Thirty-nine percent of the sample experienced moderate to severe depressive symptoms (SDS index score > or = 60) at some point during PEG IFN/ribavirin therapy. Baseline depression scores significantly predicted severity of depressive symptoms during PEG IFN/ribavirin treatment (simple regression analysis: Y = 0.55X + 32.7, p < .0001). In addition, assignment to weight-based ribavirin treatment and history of depression were associated with increased likelihood of developing moderate to severe depressive symptoms (odds ratio [OR] = 2.7, 95% CI = 1.3 to 5.6, p < .01, and OR = 3.3, 95% CI = 1.3 to 8.1, p < .01, respectively). CONCLUSIONS: Development of moderate to severe depressive symptoms occurred frequently during PEG IFN/ribavirin treatment and was predicted by baseline depression scores and higher doses of ribavirin. History of major depressive disorder was also a significant predictive factor, but only through association with elevated baseline depression status. All of these factors can be evaluated and addressed to limit neuropsychiatric morbidity during HCV treatment.\n[Drug-Disease]: ribavirin - HCV-infected" }, { "pmid": "15695147", "target": "[\"Span: men | Label: Gender\", \"Span: women | Label: Gender\"]", "text": "[Title]: Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial).\n[Abstract]: The comparison of treatment effect and co-morbidity between the genders in the Valsartan Heart Failure Trial showed equal benefit of treatment in men and women. Co-morbidities, such as diabetes and coronary artery disease, increased nonfatal cardiac morbidity more in women than in men.\n[Drug-Disease]: Valsartan - heart failure" }, { "pmid": "1575137", "target": "[\"Span: 160 to 480 mg/day | Label: Dosage\"]", "text": "[Title]: Short- and long-term antiarrhythmic and hemodynamic effects of d,l-sotalol in patients with symptomatic ventricular arrhythmias.\n[Abstract]: The antiarrhythmic and hemodynamic effects of sotalol (160 to 480 mg/day), a beta-blocking agent that prolongs ventricular repolarization, were examined in 38 patients with complex symptomatic ventricular ectopic activity. During ambulatory monitoring, 24 patients (63%) exhibited a reduction of greater than 75% in single ventricular premature beats (VPBs) and greater than 90% reduction in repetitive arrhythmia. In contrast to the effects of other agents, left ventricular ejection fraction as determined by radionuclide angiography was not impaired, increasing slightly from 45 +/- 14% to 47 +/- 14% during therapy (p less than 0.05). Antiarrhythmic drug efficacy did not correlate with baseline ejection fraction or sotalol-induced changes in ventricular function. Late follow-up studies disclosed that antiarrhythmic efficacy and tolerance were maintained in the majority of patients. Repeat radionuclide angiography at 6 months revealed no late drug-induced depression of left ventricular function. Sotalol appears to be an effective and well tolerated agent for treatment of complex ventricular ectopic activity, even in the setting of compromised cardiac function.\n[Drug-Disease]: Sotalol - arrhythmia" }, { "pmid": "15751770", "target": "[\"Span: chronic hepatitis | Label: Comorbidity\", \"Span: B | Label: Comorbidity\"]", "text": "[Title]: Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy.\n[Abstract]: BACKGROUND/AIMS: We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-alpha) and ribavirin combination therapy for patients with chronic hepatitis C and B virus (HCV/HBV) coinfection and to elucidate the interaction of these two viruses. METHODS: Forty-two chronic HCV/HBV-coinfected patients (29 IFN-naive, 13 IFN-relapsed) and 84 HCV-monoinfected controls, matched for age, sex and previous history of IFN-alpha therapy, were enrolled. All patients were treated with IFN-alpha-2b 6 MU three-times weekly plus ribavirin 1000-1200 mg daily for 24 weeks. Serum HCV RNA and HBV DNA were determined every 24 weeks for 72 weeks. RESULTS: The rate of HCV sustained virological response (SVR) was comparable among IFN-naive and IFN-relapsed HCV/HBV-coinfected patients and IFN-naive and IFN-relapsed HCV-monoinfected patients (69.0%, 69.2%, 67.2% and 57.7%, respectively; intention-to-treat analysis). HCV genotype 1b, high pretreatment HCV RNA levels and liver fibrosis were significantly associated with a lower HCV SVR. Of 16 baseline HBV viraemic patients, five (31.3%) achieved HBV SVR, which correlated negatively to HCV genotype non-1b and HCV SVR. Only one (6.3%) had simultaneous seroclearance of HCV and HBV. Antibodies to HBV surface antigen seroconversion developed in five (11.9%) patients during long-term follow-up. HCV responders had significantly higher rates of HBV DNA resurgence than HCV non-responders during and after treatment. Reciprocal viral interference was noted between HCV and HBV after IFN-alpha/ribavirin therapy. CONCLUSIONS: IFN-alpha/ribavirin combination therapy is effective for HCV/HBV-coinfected patients in eradicating HCV infection and might promote HBV seroclearance, and there is a mutual viral response and reciprocal viral interaction between HBV and HCV.\n[Drug-Disease]: ribavirin - chronic hepatitis C" }, { "pmid": "1576068", "target": "[\"Span: 500 mg | Label: Dosage\", \"Span: 1000 mg | Label: Dosage\"]", "text": "[Title]: An evaluation of buffered aspirin and aspirin tablets in postoperative pain after third molar surgery.\n[Abstract]: 1. Single doses (500 and 1000 mg) of both buffered aspirin and aspirin tablets were compared with placebo in a randomised double-blind trial of parallel design in patients with postoperative pain after third molar surgery. 2. Only buffered aspirin 500 mg provided significant pain relief (P = 0.016) during the 5 h investigation period. 3. A significant correlation (P = 0.004) was observed between overall pain scores after the various aspirin treatments and aspirin esterase activity. 4. Buffered aspirin preparations afforded a slight advantage over aspirin tablets in the control of postoperative pain after third molar surgery. However, the duration of analgesia was short (approximately 2 h). 5. Aspirin esterase activity appears to be an important determinant of the drug's efficacy in postoperative dental pain.\n[Drug-Disease]: aspirin - postoperative pain" }, { "pmid": "15788353", "target": "[\"Span: insertion/deletion (I/D) polymorphism of ACE gene | Label: Gene\"]", "text": "[Title]: A study of the relationships between angiotensin- converting enzyme gene, chymase gene polymorphisms, pharmacological treatment with ACE inhibitor and regression of left ventricular hypertrophy in essential hypertension patients treated with benazepril.\n[Abstract]: BACKGROUND: About 15-37% of the adult population worldwide suffers from hypertension. Hypertension is responsible for one-third of all global deaths. Left ventricular hypertrophy (LVH) is one of the most important characteristics of hypertension target organ damage and is also an independent risk factor for cardiovascular events. Therefore, effective regression of LVH is a main aim of hypertension treatment and also an important public health concern. However, few studies of the regression of LVH have been reported. In particular, little is known about the relationship between the genotypes of angiotensin-converting enzyme (ACE) and chymase (CMA) genes, and the effectiveness of antihypertensive drugs in regression of LVH. AIM: The study investigated whether the insertion/deletion (I/D) polymorphism of ACE gene and the A/B polymorphism of the CMA gene are related to the regression of LVH in essential hypertension patients who were participants in a long-term trial of therapy with benazepril. SUBJECTS AND METHODS: Data from 157 patients was collected and used in the analysis. The genotypes of ACE and CMA genes were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Left ventricular mass (LVM) was measured by echocardiography, and left ventricular mass index (LVMI) was calculated. RESULTS: Blood pressure was markedly reduced and heart rate was unchanged by long-term treatment with benazepril. Regression of LVH was observed. The mean reduction in LVMI was 41.50+/-28.48 g m-2. Reduction of LVM, LVMI and percentage reduction of LVMI were more in the DD group than in the II and ID groups (P<0.05). No significant difference in other indices was found in the different genotype groups of ACE (P>0.05). No significant difference in all indices was found among the different genotype groups of CMA (P>0.05). No interaction was found between the genotypes of ACE and CMA. CONCLUSION: Hypertension patients with the DD genotype are more likely to have regression of LVH when treated with benazepril than patients with other genotypes of ACE. No evidence was found to support an association between CMA genotype and regression of LVH in patients or to support the interaction between the two genes in regression of LVH.\n[Drug-Disease]: benazepril - Hypertension" }, { "pmid": "15788353", "target": "[\"Span: insertion/deletion (I/D) polymorphism of ACE gene | Label: Gene\"]", "text": "[Title]: A study of the relationships between angiotensin- converting enzyme gene, chymase gene polymorphisms, pharmacological treatment with ACE inhibitor and regression of left ventricular hypertrophy in essential hypertension patients treated with benazepril.\n[Abstract]: BACKGROUND: About 15-37% of the adult population worldwide suffers from hypertension. Hypertension is responsible for one-third of all global deaths. Left ventricular hypertrophy (LVH) is one of the most important characteristics of hypertension target organ damage and is also an independent risk factor for cardiovascular events. Therefore, effective regression of LVH is a main aim of hypertension treatment and also an important public health concern. However, few studies of the regression of LVH have been reported. In particular, little is known about the relationship between the genotypes of angiotensin-converting enzyme (ACE) and chymase (CMA) genes, and the effectiveness of antihypertensive drugs in regression of LVH. AIM: The study investigated whether the insertion/deletion (I/D) polymorphism of ACE gene and the A/B polymorphism of the CMA gene are related to the regression of LVH in essential hypertension patients who were participants in a long-term trial of therapy with benazepril. SUBJECTS AND METHODS: Data from 157 patients was collected and used in the analysis. The genotypes of ACE and CMA genes were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Left ventricular mass (LVM) was measured by echocardiography, and left ventricular mass index (LVMI) was calculated. RESULTS: Blood pressure was markedly reduced and heart rate was unchanged by long-term treatment with benazepril. Regression of LVH was observed. The mean reduction in LVMI was 41.50+/-28.48 g m-2. Reduction of LVM, LVMI and percentage reduction of LVMI were more in the DD group than in the II and ID groups (P<0.05). No significant difference in other indices was found in the different genotype groups of ACE (P>0.05). No significant difference in all indices was found among the different genotype groups of CMA (P>0.05). No interaction was found between the genotypes of ACE and CMA. CONCLUSION: Hypertension patients with the DD genotype are more likely to have regression of LVH when treated with benazepril than patients with other genotypes of ACE. No evidence was found to support an association between CMA genotype and regression of LVH in patients or to support the interaction between the two genes in regression of LVH.\n[Drug-Disease]: benazepril - Left ventricular hypertrophy" }, { "pmid": "15790438", "target": "[\"Span: 740 mg/m(2) | Label: Dosage\"]", "text": "[Title]: A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma.\n[Abstract]: OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline values of hemoglobin, leukocyte, and platelets were slightly lower in the amifostine group, but the mean percentual decrease of these parameters after each treatment cycle showed no difference between both arms. Symptoms of neurotoxicity remained absent in 40% PC vs. 49% PC + A cycles; sensory neurotoxicity grade I occurred in 45% vs. 48% and grade II in 12% PC vs. 2% of PC + A cycles (overall P < 0.001). Nausea grade II was reported in 2% vs. 6% (P = 0.007) and vomiting grade II in 1% of PC vs. 8% PC + A cycles (P < 0.001). Amifostine was temporarily interrupted in five patients due to hypotension, but no dose reductions were indicated. Quality of life questionnaires showed no difference in neurotoxicity scores between both study arms at treatment completion. The median progression-free survival was 16 vs. 22 months (n.s.) for PC and PC + A patients. In a pooled analysis of four randomized studies, amifostine diminished the risk of developing neurotoxicity grade II-III (Odds Ratio 0.3, 95% confidence interval 0.15-0.63, P < 0.05), but had no effect on the risk for bone marrow toxicity. CONCLUSION: Amifostine shows only minor but significant activity in diminishing neurotoxicity without preventing paclitaxel + carboplatin-induced bone marrow toxicity.\n[Drug-Disease]: Amifostine - bone marrow toxicity" }, { "pmid": "15846279", "target": "[\"Span: 25 mg | Label: Dosage\"]", "text": "[Title]: Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.\n[Abstract]: BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol. METHODS: In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.\n[Drug-Disease]: carvedilol - myocardial infarctions" }, { "pmid": "15863797", "target": "[\"Span: mean age=25.4 years | Label: Age\", \"Span: mean modal dose=2.9 mg | Label: Dosage\"]", "text": "[Title]: Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.\n[Abstract]: OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.\n[Drug-Disease]: haloperidol - psychotic illness" }, { "pmid": "15863797", "target": "[\"Span: mean age=25.4 years | Label: Age\", \"Span: mean modal dose=3.3 mg | Label: Dosage\"]", "text": "[Title]: Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.\n[Abstract]: OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.\n[Drug-Disease]: risperidone - psychotic illness" }, { "pmid": "15863969", "target": "[\"Span: 68 year-old | Label: Age\", \"Span: woman | Label: Gender\", \"Span: Hashimoto's thyroiditis | Label: Comorbidity\", \"Span: primary biliary cirrhosis | Label: Comorbidity\"]", "text": "[Title]: [Efficacy of anti-thymocyte globulin and cyclosporin A combined therapy in aplastic anemia complicated with limited cutaneous systemic sclerosis].\n[Abstract]: We reported here on a case of limited cutaneous systemic sclerosis (lcSSc) with aplastic anemia treated by anti-thymocyte globulin and cyclosporin A. The use of this therapy resulted not only in marrow recovery but also in resolution of the skin sclerosis. A 68 year-old woman was diagnosed as lcSSc accompanied by Hashimoto's thyroiditis and primary biliary cirrhosis. Treatment by D-penicillamine was started. After 11 months, She complained of nasal bleeding and subcutaneous bleeding. Her laboratory data revealed pancytopenia. White blood cell count, hemoglobin concentration and platelet count were decreased at 2300/microl, 8.2 g/dl, and 3000/microl respectively. Bone marrow was severely hypoplastic, suggesting aplastic anemia. The etiology of hypopastic marrow was considered to be D-penicillamine which had been frequently reported to cause hematopoietic cell suppression. We immediately started methylprednisolone pulse therapy combined with G-CSF and cyclosporin A, which showed little effectiveness. Next we tried the anti-thymocyte globulin therapy combined with G-CSF and cyclosporin A. Her blood cell counts gradually improved. After 4 months, she did not need the blood transfusion anymore. Furthermore, the sclerosis of her skin began to improve gradually, and the titer of anti-centromere antibody also decreased. Thus, anti-thymocyte globulin and cyclosporin A combined therapy can be considered among the therapies of systemic sclerosis.\n[Drug-Disease]: cyclosporin A - aplastic anemia" }, { "pmid": "15903126", "target": "[\"Span: 24, 36, 48, or 60 mg twice daily | Label: Dosage\"]", "text": "[Title]: Pharmacokinetics of ximelagatran and relationship to clinical response in acute deep vein thrombosis.\n[Abstract]: OBJECTIVE: Our objective was to characterize the pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, and the relationship between melagatran exposure and clinical outcome in patients with acute deep vein thrombosis. METHODS: A population pharmacokinetic analysis was performed on samples from patients with deep vein thrombosis participating in a randomized dose-finding study (THRombin Inhibitor in Venous thrombo-Embolism [THRIVE I]). Patients received fixed doses of oral ximelagatran (24, 36, 48, or 60 mg twice daily) for 12 to 16 days. Thrombus size was evaluated by venography before and after treatment. Exposure-response curves were characterized for the probability of regression, no change, and progression of the thrombus extension and of having a bleeding-related event, by use of logistic regression models. RESULTS: The pharmacokinetics of melagatran (1836 samples in 264 patients) was predictable, without significant time or dose dependencies. Clearance after oral administration (population mean, 27.3 L/h) was correlated with creatinine clearance (P < 10(-6)), and volume of distribution (population mean, 176 L) was correlated with body weight (P = 2 x 10(-5)). Gender, age, or smoking did not significantly influence melagatran pharmacokinetics after the influence of renal function and body weight was accounted for. Unexplained interpatient variability values in total plasma clearance and bioavailability were 19% and 21%, respectively. The median area under the plasma melagatran concentration versus time curve across all patients and dose levels was 3.22 h x micromol/L (5th-95th percentiles, 1.35-7.69). There was no significant relationship between area under the plasma concentration versus time curve and change in thrombus extension (P = .59) or bleeding-related events (P = .77), and the estimated exposure-response curves were relatively flat. CONCLUSIONS: The pharmacokinetics of melagatran in patients with acute deep vein thrombosis was predictable after oral ximelagatran administration. Shallow exposure-response curves for efficacy and bleeding indicate that there is no need for individualized dosing or therapeutic drug monitoring in the patient population studied.\n[Drug-Disease]: ximelagatran - deep vein thrombosis" }, { "pmid": "15920378", "target": "[\"Span: Cocaine abuse | Label: Comorbidity\"]", "text": "[Title]: Cocaine abuse in schizophrenic patients treated with olanzapine versus haloperidol.\n[Abstract]: Comorbid cocaine abuse adversely affects clinical outcomes in schizophrenia. Using a prospective, randomized, parallel group design (N = 24), we tested the hypothesis that patients with schizophrenia treated with olanzapine have reduced cocaine craving and abuse compared with those treated with haloperidol. In addition, we examined whether this differential effect correlated with reductions in extrapyramidal symptoms, positive and negative symptoms, and/or depression. There were no significant differences overall in proportions of positive drug screens between treatment groups; no differences in positive, negative, or depressive symptoms; and few differences between treatment conditions in extrapyramidal symptoms. However, craving for cocaine was rated significantly lower by patients treated with haloperidol compared with patients treated with olanzapine. Important study limitations include a small sample size and high attrition rates. Larger controlled studies are necessary to determine optimal antipsychotic therapy for patients with schizophrenia and comorbid cocaine abuse.\n[Drug-Disease]: olanzapine - schizophrenia" }, { "pmid": "15920378", "target": "[\"Span: Cocaine abuse | Label: Comorbidity\"]", "text": "[Title]: Cocaine abuse in schizophrenic patients treated with olanzapine versus haloperidol.\n[Abstract]: Comorbid cocaine abuse adversely affects clinical outcomes in schizophrenia. Using a prospective, randomized, parallel group design (N = 24), we tested the hypothesis that patients with schizophrenia treated with olanzapine have reduced cocaine craving and abuse compared with those treated with haloperidol. In addition, we examined whether this differential effect correlated with reductions in extrapyramidal symptoms, positive and negative symptoms, and/or depression. There were no significant differences overall in proportions of positive drug screens between treatment groups; no differences in positive, negative, or depressive symptoms; and few differences between treatment conditions in extrapyramidal symptoms. However, craving for cocaine was rated significantly lower by patients treated with haloperidol compared with patients treated with olanzapine. Important study limitations include a small sample size and high attrition rates. Larger controlled studies are necessary to determine optimal antipsychotic therapy for patients with schizophrenia and comorbid cocaine abuse.\n[Drug-Disease]: haloperidol - schizophrenia" }, { "pmid": "15943844", "target": "[\"Span: 15 mg/day | Label: Dosage\"]", "text": "[Title]: Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies.\n[Abstract]: BACKGROUND: The treatment of functional dyspepsia is controversial. AIM: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. PATIENTS AND METHODS: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. RESULTS: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively, without any significant improvement. CONCLUSIONS: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.\n[Drug-Disease]: mosapride - functional dyspepsia" }, { "pmid": "15943844", "target": "[\"Span: 40 mg/day | Label: Dosage\"]", "text": "[Title]: Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies.\n[Abstract]: BACKGROUND: The treatment of functional dyspepsia is controversial. AIM: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. PATIENTS AND METHODS: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. RESULTS: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively, without any significant improvement. CONCLUSIONS: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.\n[Drug-Disease]: famotidine - functional dyspepsia" }, { "pmid": "15943850", "target": "[\"Span: 20 mg bd | Label: Dosage\"]", "text": "[Title]: Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine.\n[Abstract]: BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.\n[Drug-Disease]: famotidine - peptic ulcers" }, { "pmid": "15943850", "target": "[\"Span: 15 mg daily | Label: Dosage\"]", "text": "[Title]: Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine.\n[Abstract]: BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.\n[Drug-Disease]: lansoprazole - peptic ulcers" }, { "pmid": "15965573", "target": "[]", "text": "[Title]: A review of carvedilol arrhythmia data in clinical trials.\n[Abstract]: beta-Blockers are currently being evaluated more intensively to define their role in clinical use as antiarrhythmic agents. beta-Adrenergic blockade has been studied in relation to atrial fibrillation, ventricular arrhythmias, and sudden death; however, it is apparent from a number of studies that not all beta-blockers are equally effective. Randomized clinical trial data, both in heart failure and post-myocardial infarction (MI) patients, have shown differences in mortality benefits in addition to a variable effect on arrhythmias and sudden death. Carvedilol, a third-generation beta-blocker with proven clinical benefit in the management of heart failure and post-MI patients, has properties that may make it an effective antiarrhythmic agent. This paper reviews the current clinical arrhythmia data available for carvedilol from large-scale clinical trials and small studies. The trial evidence demonstrates that carvedilol therapy can be an effective adjunctive rate-control therapy in patients with atrial fibrillation, prevent mortality in patients with heart failure or post-MI with left ventricular dysfunction, with or without atrial fibrillation, and reduce its onset and the incidence of ventricular arrhythmia and sudden death.\n[Drug-Disease]: carvedilol - atrial fibrillation" }, { "pmid": "15965573", "target": "[]", "text": "[Title]: A review of carvedilol arrhythmia data in clinical trials.\n[Abstract]: beta-Blockers are currently being evaluated more intensively to define their role in clinical use as antiarrhythmic agents. beta-Adrenergic blockade has been studied in relation to atrial fibrillation, ventricular arrhythmias, and sudden death; however, it is apparent from a number of studies that not all beta-blockers are equally effective. Randomized clinical trial data, both in heart failure and post-myocardial infarction (MI) patients, have shown differences in mortality benefits in addition to a variable effect on arrhythmias and sudden death. Carvedilol, a third-generation beta-blocker with proven clinical benefit in the management of heart failure and post-MI patients, has properties that may make it an effective antiarrhythmic agent. This paper reviews the current clinical arrhythmia data available for carvedilol from large-scale clinical trials and small studies. The trial evidence demonstrates that carvedilol therapy can be an effective adjunctive rate-control therapy in patients with atrial fibrillation, prevent mortality in patients with heart failure or post-MI with left ventricular dysfunction, with or without atrial fibrillation, and reduce its onset and the incidence of ventricular arrhythmia and sudden death.\n[Drug-Disease]: carvedilol - heart failure" } ]