[ { "pmid": "11105143", "target": "[\"Span: 2mg/kg daily for the first 4 days, followed by a single repeat dose of 2mg/kg at day 10 in 4 patients (total dose 10mg/kg); repeat doses on days 5, 6, and 10 in 13 patients (total dose 14mg/kg); or daily doses were continued on days 5 through 10 in 15 patients (total dose 20mg/kg) | Label: Dosage\", \"Span: mean age of 9 years, ranging between 3 and 26 years | Label: Age\", \"Span: mean weight was 25.9kg, ranging between 9.5kg and 75kg | Label: Body Type\"]", "text": "[Title]: Efficacy and Tolerability of Liposomal Amphotericin B (Ambisome) in the Treatment of Visceral Leishmaniasis in Brazil.\n[Abstract]: Thirty-two patients were enrolled in an open-label, dose/schedule ranging clinical trial to evaluate the efficacy and tolerability ofliposomal amphotericin B (Ambisome) in the treatment of visceral leishmaniasis. All patients received a dose of 2mg/kg daily for the first 4 days, followed by a single repeat dose of 2mg/kg at day 10 in 4 patients (total dose 10mg/kg); repeat doses on days 5, 6, and 10 in 13 patients (total dose 14mg/kg); or daily doses were continued on days 5 through 10 in 15 patients (total dose 20mg/kg). Patients had a mean age of 9 years, ranging between 3 and 26 years. Their mean weight was 25.9kg, ranging between 9.5kg and 75kg. All patients had splenomegaly, 31/32 had hepatomegaly, and 20 patients tested had leishmania documented on splenic aspirate. Six of the 32 patients were treated after relapse following antimony therapy. The duration of illness prior to therapy was a mean of 2 months, ranging between 2 weeks and 23 months. During and after treatment, there were significant reductions in liver and spleen sizes, and significant increases in body weight, hemoglobin levels and white blood cell counts. All patients showed initial cure at the 1 month follow-up. Seven patients relapsed between 2 and 6 months after the start of treatment. There was no dose relationship to the occurrence of relapse. The relapse rate in children 5 years of age or less was 7/15 (47%). Associated causes of relapse were refractory disease (i.e., previous relapses) in 2, severe malnutrition in 1, and concurrent disease (meningococcal meningitis) in 1. In the other 2 cases, no associated event was observed except young age (ages 3 and 5 years). One relapsed patient was treated successfully with 14 days of lipid amphotericin B, and the others were cured by use of antimony for 20 to 30 days. There were no dose related adverse events. The most common event was fever which occurred in 13/32 patients (41%); 3/4 patients in the 10mg dose group, 7/13 in the 14mg dose group, and 3/15 in the 20mg dose group. Three patients had cardiac arrhythmia, one also with myocarditis diagnosed 2 weeks after therapy was discontinued. One patient developed hepatitis after dose 3 and the drug was discontinued. We concluded that liposomal amphotericin B is effective in a daily dose of 2mg/kg given for 5-10 doses as an initial cure, but that relapse occurs in young children, particularly those with documented treatment resistant disease or concurrent malnutrition or infection. Patients should be carefully monitored for these risk factors before and during the months alter therapy, and for the occurrence of arrhythmia, cardio-pulmonary effects or hepatotoxicity. This treatment provides an important advance over previously used antimony therapy and appears to be more effective and well-tolerated than non-lipid amphotericin B.\n[Drug-Disease]: Ambisome - visceral leishmaniasis" }, { "pmid": "11109196", "target": "[]", "text": "[Title]: [Assessment of cardiotoxicity of high dose cyclophosphamide with electrocardiographic, echocardiographic, and troponin I monitoring in patients with breast tumors].\n[Abstract]: BACKGROUND: High-dose cyclophosphamide is the nucleus for virtually all high-dose chemotherapy protocols. Non-hematologic dose-limiting toxicity is represented by acute cardiomyopathy, even fatal in a minority of patients. The pathophysiology of such a cardiotoxicity is still poorly understood. Postmortem studies revealed hemorrhagic myocardial cell death, endothelial damage, and interstitial edema. Recently troponins, in particular troponin I, have been found to represent uniquely sensitive and specific markers of myocyte membrane integrity, thus to increase in response to myocardial cell damage in different clinical settings. METHODS: We performed a multiparametric monitoring in 16 consecutive breast cancer patients undergoing cyclophosphamide, by means of serial ECGs, cardiac enzymes determinations (creatine phosphokinase, MB mass and troponin I) through 0 to 72 hours, and echocardiography at baseline and after 48 hours. RESULTS: Neither overt cardiac failure nor enzyme elevation were recorded. Serial ECGs revealed a reduction in QRS voltage and/or ST segment abnormalities in 6 cases. Echocardiography showed an increase in left ventricular diastolic and/or systolic diameters and volumes in 4 cases but without any decrease in fractional shortening and ejection fraction under normal values: in 2 of them abnormalities of diastolic function (E/A mitral Doppler ratio, isovolumic relaxation time and deceleration time) were also recorded. CONCLUSIONS: Our protocol of cyclophosphamide administration did not cause cardiac toxicity by myocardial cell damage, as analyzed by troponin I levels, thus suggesting that myocyte membrane injury is not the first mechanism of it. ECG (i.e. QRS voltages) and echo-Doppler (i.e. E/A ratio) monitoring lead to hypothesize that endothelial injury and interstitial edema with subsequent reduction in left ventricular diastolic compliance may be the first signs of cardiac dysfunction in this clinical setting.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "11111143", "target": "[]", "text": "[Title]: Effects of a slow-release nifedipine on 24-hour ambulatory blood pressure and ischemic changes on 24-hour ambulatory electrocardiogram in patients with severe coronary artery disease.\n[Abstract]: Calcium antagonists have long been used as first-line drugs for hypertension and angina. However, deleterious effects have also been reported in patients treated with calcium antagonists. Thus, we evaluated the effect of a slow-release twice-daily formulation of nifedipine in 10 patients with severe coronary artery disease. Twenty-four-hour ambulatory electrocardiography (AECG) and blood pressure monitoring (ABPM) were performed simultaneously to detect any association between ischemic episodes on the ECG and changes in blood pressure (BP) and heart rate with and without nifedipine. Increased oxygen demand due to an increased systolic BP and heart rate was associated with ischemic episodes without nifedipine, while those with nifedipine were accompanied by a fall in diastolic BP and a rapid increase in heart rate. This slow-release twice-daily formulation of nifedipine may induce myocardial ischemia through a heart-rate increase and a decrease in coronary blood flow due to lower diastolic BP in patients with severe coronary artery disease. A once-daily formulation of nifedipine might be of great value for such patients.\n[Drug-Disease]: nifedipine - coronary artery disease" }, { "pmid": "11112032", "target": "[]", "text": "[Title]: Antiviral combination therapy for lamivudine-resistant hepatitis B reinfection after liver transplantation.\n[Abstract]: Development of resistance is a major issue in antiviral treatment of hepatitis B reinfection after liver transplantation. Antiviral combination therapy is discussed for therapy or prevention of this breakthrough of viral replication. Eight patients were enrolled into this retrospective analysis after liver transplantation for chronic hepatitis B infection. All had reinfection of the graft and breakthrough of HBV during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy with lamivudine and interferon-alpha 2a (group I, n = 4) or lamivudine and famciclovir (group II, n = 4) was initiated. Combination therapy was started 61 months (group I) and 25 months (group II) after liver transplantation. It markedly reduced the viral replication rate in all patients despite lamivudine resistance. In group I three of four patients and in group II two of four patients became HBV-DNA negative. Two long-term responders were observed in group I, and none in group II. No patient became HBsAg negative or lost HbeAg. Pretreatment elevated ALT and AST levels were significantly reduced. No severe complications, and especially no rejection episodes, occurred. Lamivudine in combination with other antiviral agents, especially interferon-alpha, might be a therapeutic option for hepatitis B reinfection after liver transplantation. Suppression of virus replication to the point of undetectable values is possible even in patients with lamivudine-resistant virus mutations.\n[Drug-Disease]: famciclovir - hepatitis B" }, { "pmid": "11112032", "target": "[]", "text": "[Title]: Antiviral combination therapy for lamivudine-resistant hepatitis B reinfection after liver transplantation.\n[Abstract]: Development of resistance is a major issue in antiviral treatment of hepatitis B reinfection after liver transplantation. Antiviral combination therapy is discussed for therapy or prevention of this breakthrough of viral replication. Eight patients were enrolled into this retrospective analysis after liver transplantation for chronic hepatitis B infection. All had reinfection of the graft and breakthrough of HBV during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy with lamivudine and interferon-alpha 2a (group I, n = 4) or lamivudine and famciclovir (group II, n = 4) was initiated. Combination therapy was started 61 months (group I) and 25 months (group II) after liver transplantation. It markedly reduced the viral replication rate in all patients despite lamivudine resistance. In group I three of four patients and in group II two of four patients became HBV-DNA negative. Two long-term responders were observed in group I, and none in group II. No patient became HBsAg negative or lost HbeAg. Pretreatment elevated ALT and AST levels were significantly reduced. No severe complications, and especially no rejection episodes, occurred. Lamivudine in combination with other antiviral agents, especially interferon-alpha, might be a therapeutic option for hepatitis B reinfection after liver transplantation. Suppression of virus replication to the point of undetectable values is possible even in patients with lamivudine-resistant virus mutations.\n[Drug-Disease]: lamivudine - hepatitis B" }, { "pmid": "11120421", "target": "[]", "text": "[Title]: Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.\n[Abstract]: BACKGROUND: A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. METHODS: Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). RESULTS: An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. CONCLUSIONS: In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.\n[Drug-Disease]: haloperidol - psychotic" }, { "pmid": "11120421", "target": "[]", "text": "[Title]: Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.\n[Abstract]: BACKGROUND: A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. METHODS: Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). RESULTS: An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. CONCLUSIONS: In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.\n[Drug-Disease]: risperidone - psychotic" }, { "pmid": "11121880", "target": "[\"Span: male | Label: Gender\"]", "text": "[Title]: Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: a positron emission tomography provocation study.\n[Abstract]: We report positron emission tomographic measurements of regional cerebral blood flow (rCBF) in a male patient with war and torture related post-traumatic stress disorder (PTSD) during symptom provocation. The subject was exposed to war related sounds before and after treatment with a selective serotonin reuptake inhibitor (SSRI; Fluoxetine; Fontex((R))). Therapy reduced PTSD symptoms, provoked anxiety and heart rate. Before treatment trauma reminders resulted in decreased rCBF in the insula, prefrontal, and inferior frontal cortices. Increased activity was evident in the cerebellum, precuneus and supplementary motor cortex. This was normalized after SSRI administration. Prefrontal and cingulate rCBF correlated with heart rate. Hence, the anxiolytic effect of SSRI for PTSD could be mediated by prefrontal and paralimbic cortices. Data suggest that SSRI treatment normalize provocation induced rCBF alterations in areas involved in memory, emotion, attention and motor-control.\n[Drug-Disease]: Fluoxetine - PTSD" }, { "pmid": "11130385", "target": "[]", "text": "[Title]: Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.\n[Abstract]: BACKGROUND: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.\n[Drug-Disease]: proguanil - falciparum malaria" }, { "pmid": "11130385", "target": "[]", "text": "[Title]: Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.\n[Abstract]: BACKGROUND: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.\n[Drug-Disease]: chloroquine - malaria" }, { "pmid": "11130385", "target": "[]", "text": "[Title]: Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.\n[Abstract]: BACKGROUND: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.\n[Drug-Disease]: atovaquone - falciparum malaria" }, { "pmid": "11131930", "target": "[\"Span: age > or = 65 years | Label: Age\", \"Span: titrated to 50 mg once daily | Label: Dosage\"]", "text": "[Title]: Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.\n[Abstract]: OBJECTIVE: To measure health-related quality-of-life (HRQoL) in elderly symptomatic heart failure patients following treatment with an angiotensin II receptor antagonist (losartan) vs. an angiotensin-converting-enzyme (ACE) inhibitor (captopril). METHODS: Patients (age > or = 65 years) were randomised to losartan, titrated to 50 mg once daily, or captopril, titrated to 50 mg three times daily, as tolerated. Sickness Impact Profile (SIP) and Minnesota Living with Heart Failure (LIhFE) questionnaires were administered at baseline, weeks 12 and 48. Composite hypothesis testing of change in HRQoL from baseline for completers, and withdrawal for unfavourable events (death, clinical/laboratory adverse experience) was used to account for differential dropout rates. RESULTS: In 203 patients completing the substudy (week 48), significant and comparable improvements in HRQoL from baseline were observed for both treatment groups (p < or = 0.001). Although there was a trend favouring losartan vs. captopril for the composite HRQoL endpoint (unadjusted p = 0.018, one-sided), this was not considered significant after adjusting for multiple testing. Significantly more captopril patients in the substudy subset withdrew for unfavourable reasons (19.6 vs. 10.9%, p = 0.038). CONCLUSIONS: Significant improvements in HRQoL were observed in elderly patients with symptomatic heart failure treated with losartan and captopril long-term. A trend favouring losartan in the composite measure of drug tolerability/quality of life was not significant, but losartan was generally better tolerated than captopril in that significantly fewer losartan patients discontinued therapy.\n[Drug-Disease]: losartan - heart failure" }, { "pmid": "11132533", "target": "[]", "text": "[Title]: [Effect of ribavirin on dynamics of hepatitis C viremia in interferon alpha-treated patiens with response or no response].\n[Abstract]: Combination therapy with interferon-alpha (IFN alpha) plus Ribavirin has been shown to improve the response rate in patients with chronic hepatitis C as compared to IFN alpha alone. However, the mode of anti-viral action of Ribavirin is still unknown. To prove, whether Ribavirin has any additional effect on the decline of hepatitis C viremia during the first weeks of treatment patients with and without combination therapy were compared. Kinetic studies were performed in patients who either responded to IFN alpha alone or IFN alpha plus Ribavirin combination as well as in nonresponders to both forms of therapeutic approaches. 64 IFN alpha naive patients with histologically proven chronic hepatitis C were included in the study. Patients were randomized to receive either IFN alpha-2a (Hoffmann-La Roche) 6 MU thrice weekly or IFN alpha 6 MU tiw plus Ribavirin (Meduna) 14 mg/kg/day for 12 weeks. 37 patients (58%) became HCV RNA-negative (= responders; 17 [46%] with IFN alpha alone, and 20 [54%] with combination therapy). 27 patients remained HCV RNA-positive (= non-responders; 13 [48%] with IFN alpha alone, and 14 [52%] with combination therapy). HCV RNA concentrations were measured in all patients at baseline as well as 1, 2, 4, and 12 weeks after the start of treatment (bDNA assay, Chiron). Using nonradioactive single-stranded conformation (SSCP)-analysis of the HCV hypervariable region 1 we investigated further whether initial viral decline is correlated with changes in viral quasispecies distribution. In primary responders, ribavirin did not influence hepatitis C viremia decline which was of biphasic nature. Also in nonresponders HCV RNA levels decreased after one week of treatment irrespectively of the mode of therapy (mean 10.0 +/- 2.3 to 5.5 +/- 1.1) (phase 1). In the following weeks, however, 2 types of HCV dynamics could be observed (phase 2). In patients with combination therapy, a further reduction of viremia level could be observed, whereas viremia levels in patients with IFN alpha alone slightly increased (week 12: 3.0 +/- 0.5 MEq/mL [combination, n = 15] vs. 7.5 +/- 2.9 MEq/mL [IFN alpha-mono, n = 12]). The individual response of these nonresponder patients showed, however, marked differences (range percentage decline after 4 weeks, 0-98%). Changes in the viral population (quasispecies distribution) as cause of these differences could be excluded by SSCP-analysis of PCR products of the HCV hypervariable region 1. Ribavirin in combination with IFN alpha exerts an additional anti-viral/immunmodulatory effect which manifests itself in phase 2 of hepatitis C viremia decline. The biphasic decline of hepatitis C viremia also observed in IFN alpha-nonresponders can not be explained by the selection of primary IFN alpha-resistant viral variants. The individual differences in the dynamic of hepatitis C viremia observed in the so called \"nonresponders\" imply that the term \"nonresponder\" should be redefined, considering our observation that a marked viral decline can occur in these patients.\n[Drug-Disease]: Ribavirin - hepatitis C viremia" }, { "pmid": "11132533", "target": "[]", "text": "[Title]: [Effect of ribavirin on dynamics of hepatitis C viremia in interferon alpha-treated patiens with response or no response].\n[Abstract]: Combination therapy with interferon-alpha (IFN alpha) plus Ribavirin has been shown to improve the response rate in patients with chronic hepatitis C as compared to IFN alpha alone. However, the mode of anti-viral action of Ribavirin is still unknown. To prove, whether Ribavirin has any additional effect on the decline of hepatitis C viremia during the first weeks of treatment patients with and without combination therapy were compared. Kinetic studies were performed in patients who either responded to IFN alpha alone or IFN alpha plus Ribavirin combination as well as in nonresponders to both forms of therapeutic approaches. 64 IFN alpha naive patients with histologically proven chronic hepatitis C were included in the study. Patients were randomized to receive either IFN alpha-2a (Hoffmann-La Roche) 6 MU thrice weekly or IFN alpha 6 MU tiw plus Ribavirin (Meduna) 14 mg/kg/day for 12 weeks. 37 patients (58%) became HCV RNA-negative (= responders; 17 [46%] with IFN alpha alone, and 20 [54%] with combination therapy). 27 patients remained HCV RNA-positive (= non-responders; 13 [48%] with IFN alpha alone, and 14 [52%] with combination therapy). HCV RNA concentrations were measured in all patients at baseline as well as 1, 2, 4, and 12 weeks after the start of treatment (bDNA assay, Chiron). Using nonradioactive single-stranded conformation (SSCP)-analysis of the HCV hypervariable region 1 we investigated further whether initial viral decline is correlated with changes in viral quasispecies distribution. In primary responders, ribavirin did not influence hepatitis C viremia decline which was of biphasic nature. Also in nonresponders HCV RNA levels decreased after one week of treatment irrespectively of the mode of therapy (mean 10.0 +/- 2.3 to 5.5 +/- 1.1) (phase 1). In the following weeks, however, 2 types of HCV dynamics could be observed (phase 2). In patients with combination therapy, a further reduction of viremia level could be observed, whereas viremia levels in patients with IFN alpha alone slightly increased (week 12: 3.0 +/- 0.5 MEq/mL [combination, n = 15] vs. 7.5 +/- 2.9 MEq/mL [IFN alpha-mono, n = 12]). The individual response of these nonresponder patients showed, however, marked differences (range percentage decline after 4 weeks, 0-98%). Changes in the viral population (quasispecies distribution) as cause of these differences could be excluded by SSCP-analysis of PCR products of the HCV hypervariable region 1. Ribavirin in combination with IFN alpha exerts an additional anti-viral/immunmodulatory effect which manifests itself in phase 2 of hepatitis C viremia decline. The biphasic decline of hepatitis C viremia also observed in IFN alpha-nonresponders can not be explained by the selection of primary IFN alpha-resistant viral variants. The individual differences in the dynamic of hepatitis C viremia observed in the so called \"nonresponders\" imply that the term \"nonresponder\" should be redefined, considering our observation that a marked viral decline can occur in these patients.\n[Drug-Disease]: Ribavirin - viremia" }, { "pmid": "11133605", "target": "[\"Span: older patients | Label: Age\"]", "text": "[Title]: Remifentanil versus meperidine for monitored anesthesia care: a comparison study in older patients undergoing ambulatory colonoscopy.\n[Abstract]: UNLABELLED: Colonoscopy is one of the most frequently performed outpatient procedures in the United States. This study was designed to test the hypothesis that a remifentanil infusion would be superior to boluses of meperidine in older patients undergoing ambulatory colonoscopy. One hundred ASA physical status I-IV patients undergoing colonoscopy were randomized in this double-blinded study to receive either remifentanil infusions (n = 49) or titrated boluses of meperidine (n = 51). Patient tolerance was assessed using physiologic variables and side effects associated with opioid analgesia. Verbal pain/anxiety and patient/operator satisfaction were also assessed. As a group, the physiologic characteristics demonstrated no significant differences in the response to the colonoscopy procedure. Although the patient and operator satisfaction surveys were similar between groups, the incidences of tachycardia, hypotension, and nausea were less and the adjusted verbal pain and anxiety scores were more in the Remifentanil group compared with the Meperidine group. This study demonstrates that remifentanil and meperidine were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. The differences in the pharmakinetics of remifentanil and meperidine most likely account for the differences noted between the two treatment groups. IMPLICATIONS: Remifentanil infusions and meperidine boluses are equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider.\n[Drug-Disease]: Remifentanil - pain" }, { "pmid": "11133605", "target": "[\"Span: older patients | Label: Age\"]", "text": "[Title]: Remifentanil versus meperidine for monitored anesthesia care: a comparison study in older patients undergoing ambulatory colonoscopy.\n[Abstract]: UNLABELLED: Colonoscopy is one of the most frequently performed outpatient procedures in the United States. This study was designed to test the hypothesis that a remifentanil infusion would be superior to boluses of meperidine in older patients undergoing ambulatory colonoscopy. One hundred ASA physical status I-IV patients undergoing colonoscopy were randomized in this double-blinded study to receive either remifentanil infusions (n = 49) or titrated boluses of meperidine (n = 51). Patient tolerance was assessed using physiologic variables and side effects associated with opioid analgesia. Verbal pain/anxiety and patient/operator satisfaction were also assessed. As a group, the physiologic characteristics demonstrated no significant differences in the response to the colonoscopy procedure. Although the patient and operator satisfaction surveys were similar between groups, the incidences of tachycardia, hypotension, and nausea were less and the adjusted verbal pain and anxiety scores were more in the Remifentanil group compared with the Meperidine group. This study demonstrates that remifentanil and meperidine were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. The differences in the pharmakinetics of remifentanil and meperidine most likely account for the differences noted between the two treatment groups. IMPLICATIONS: Remifentanil infusions and meperidine boluses are equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider.\n[Drug-Disease]: meperidine - pain" }, { "pmid": "11135021", "target": "[\"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study.\n[Abstract]: BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.\n[Drug-Disease]: sumatriptan - migraine" }, { "pmid": "11135021", "target": "[\"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study.\n[Abstract]: BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.\n[Drug-Disease]: sumatriptan - tension-type headache" }, { "pmid": "11135211", "target": "[\"Span: premenopausal women | Label: Gender\", \"Span: 600 mg/m(2) intravenously (i.v.) every 3 weeks | Label: Dosage\", \"Span: 100 mg/m(2) orally on Days 1 through 14 | Label: Dosage\"]", "text": "[Title]: Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.\n[Abstract]: BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.\n[Drug-Disease]: cyclophosphamide - breast carcinoma" }, { "pmid": "11135211", "target": "[\"Span: premenopausal women | Label: Gender\", \"Span: 40 mg/m(2) | Label: Dosage\", \"Span: intravenously (i.v.) every 3 weeks | Label: Dosage\"]", "text": "[Title]: Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.\n[Abstract]: BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.\n[Drug-Disease]: doxorubicin - breast carcinoma" }, { "pmid": "11135211", "target": "[\"Span: premenopausal women | Label: Gender\", \"Span: 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks | Label: Dosage\"]", "text": "[Title]: Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.\n[Abstract]: BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.\n[Drug-Disease]: 5-fluorouracil - breast carcinoma" }, { "pmid": "11135211", "target": "[\"Span: premenopausal women | Label: Gender\", \"Span: 40 mg/m(2) | Label: Dosage\", \"Span: intravenously (i.v.) every 3 weeks | Label: Dosage\"]", "text": "[Title]: Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.\n[Abstract]: BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.\n[Drug-Disease]: methotrexate - breast carcinoma" }, { "pmid": "11135224", "target": "[\"Span: 800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks | Label: Dosage\"]", "text": "[Title]: Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.\n[Abstract]: BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.\n[Drug-Disease]: gemcitabine - NSCLC" }, { "pmid": "11135224", "target": "[\"Span: 120 mg/m(2) given intravenously in 6 hours | Label: Dosage\"]", "text": "[Title]: Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.\n[Abstract]: BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.\n[Drug-Disease]: cisplatin - NSCLC" }, { "pmid": "11135224", "target": "[\"Span: 135 mg/m(2) given intravenously in 3 hours | Label: Dosage\"]", "text": "[Title]: Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.\n[Abstract]: BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.\n[Drug-Disease]: paclitaxel - NSCLC" }, { "pmid": "11135225", "target": "[\"Span: 100 mg/m(2) intravenously (i.v.) on Day 1 | Label: Dosage\", \"Span: 32 males and 28 females | Label: Gender\", \"Span: median age, 53 years | Label: Age\"]", "text": "[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.\n[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.\n[Drug-Disease]: FM - melanoma" }, { "pmid": "11135225", "target": "[\"Span: 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks | Label: Dosage\", \"Span: 32 males and 28 females | Label: Gender\", \"Span: median age, 53 years | Label: Age\"]", "text": "[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.\n[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.\n[Drug-Disease]: CDDP - melanoma" }, { "pmid": "11135225", "target": "[\"Span: 300 mg/m(2) i.v. on Days 2-4 | Label: Dosage\", \"Span: 32 males and 28 females | Label: Gender\", \"Span: median age, 53 years | Label: Age\"]", "text": "[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.\n[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.\n[Drug-Disease]: DTIC - melanoma" }, { "pmid": "11135723", "target": "[\"Span: 8, 16, and 32 mg | Label: Dosage\"]", "text": "[Title]: Pharmacodynamics of orally administered sustained- release hydromorphone in humans.\n[Abstract]: BACKGROUND: The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. METHODS: Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. RESULTS: The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. CONCLUSION: A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.\n[Drug-Disease]: hydromorphone - pain" }, { "pmid": "11147046", "target": "[\"Span: 2.5 mg oral | Label: Dosage\"]", "text": "[Title]: [Quality of life of migraine patients after treatment with 2.5 mg oral naratriptan].\n[Abstract]: OBJECTIVES: The primary objective of this prospective, open, non controlled, multicenter study was to collect data on migraine patient's health related quality of life before and after treatment of their migraine attacks b naratriptan orl 2.5 mg over a 12 week period. METHODS: The impact on health related quality of life was evaluated by the mean change from pre-treatment scores on the French migraine health related quality of life specific questionnaire (QVM). RESULTS: 244 patients have been included in the study. A statistically significant score improvement in health related quality of life, as measured by the global score and the four scores related to the four dimensions of the QVM questionnaire (functional, psychological, social and therapeutic) was observed compared to the pre-treatment score values. At the end of the treatment period, 67% of patients preferred naratriptan oral 2.5 mg to their usual treatment. CONCLUSION: Those data suggest that the use of naratriptan oral 2.5 mg for the treatment of migraine attacks during a 12 week period may be associated with a significant improvement in migraine patient's quality of life.\n[Drug-Disease]: naratriptan - migraine" }, { "pmid": "11149559", "target": "[\"Span: Fifty-two females and 75 males | Label: Gender\", \"Span: ages 20-69 | Label: Age\"]", "text": "[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.\n[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.\n[Drug-Disease]: olsalazine - ulcerative colitis" }, { "pmid": "11149559", "target": "[\"Span: Fifty-two females and 75 males | Label: Gender\", \"Span: ages 20-69 | Label: Age\"]", "text": "[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.\n[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.\n[Drug-Disease]: sulphasalazine - ulcerative colitis" }, { "pmid": "11149559", "target": "[\"Span: Fifty-two females and 75 males | Label: Gender\", \"Span: ages 20-69 | Label: Age\"]", "text": "[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.\n[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.\n[Drug-Disease]: mesalazine - ulcerative colitis" }, { "pmid": "11149742", "target": "[]", "text": "[Title]: Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.\n[Abstract]: This report describes two patients with germ cell tumors who underwent tandem autologous peripheral stem cell transplants. The chemotherapy consisted of high-dose carboplatin and etoposide. Both patients developed chemotherapy-related toxicities, which included nephrotoxicity in one case and febrile neutropenia, thrombocytopenia, ototoxicity and mucositis in both. During the second transplant, both patients received amifostine 15 min before and 2 h after each dose of carboplatin. The patients had less mucositis and nephrotoxicity. The duration of neutropenia and thrombocytopenia was less in both cases resulting in a decreased use of antibiotics and platelet transfusions. These cases suggest that the use of amifostine may be of benefit in minimizing toxicities associated with high-dose chemotherapy.\n[Drug-Disease]: amifostine - nephrotoxicity" }, { "pmid": "11149742", "target": "[]", "text": "[Title]: Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.\n[Abstract]: This report describes two patients with germ cell tumors who underwent tandem autologous peripheral stem cell transplants. The chemotherapy consisted of high-dose carboplatin and etoposide. Both patients developed chemotherapy-related toxicities, which included nephrotoxicity in one case and febrile neutropenia, thrombocytopenia, ototoxicity and mucositis in both. During the second transplant, both patients received amifostine 15 min before and 2 h after each dose of carboplatin. The patients had less mucositis and nephrotoxicity. The duration of neutropenia and thrombocytopenia was less in both cases resulting in a decreased use of antibiotics and platelet transfusions. These cases suggest that the use of amifostine may be of benefit in minimizing toxicities associated with high-dose chemotherapy.\n[Drug-Disease]: amifostine - mucositis" }, { "pmid": "11150359", "target": "[\"Span: infants | Label: Age\", \"Span: birth weight of 501 to 1000 g | Label: Body Type\", \"Span: at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days | Label: Dosage\"]", "text": "[Title]: Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.\n[Abstract]: BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.\n[Drug-Disease]: dexamethasone - lung disease" }, { "pmid": "11151749", "target": "[]", "text": "[Title]: Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia.\n[Abstract]: OBJECTIVE: A possible pharmacokinetic interaction between a CYP1A2 inhibitor, ciprofloxacin, and clozapine was studied in schizophrenia patients with stable clozapine treatment. METHODS: A randomised double-blind cross-over study design with two phases was used. Seven schizophrenic inpatients volunteered to receive, in addition to their previous drug regimen, either 250 mg ciprofloxacin or placebo twice daily (b.i.d.) for 7 days. The phases were separated by a 7-day wash-out period. Serum concentrations of clozapine and its main metabolite N-desmethylclozapine were measured during both phases before the first dose on day 1 and on days 3 and 8. RESULTS: Ciprofloxacin increased mean serum concentration of clozapine and N-desmethylclozapine by 29% (P < 0.01) and 31% (P < 0.05), respectively. There was a significant positive correlation (r = 0.90, P < 0.01) between the individual concentrations of serum ciprofloxacin and the increase in concentrations of clozapine plus N-desmethylclozapine. The increase in serum clozapine concentrations correlated significantly (r = 0.89, P < 0.01) with the ratios of N-desmethylclozapine to clozapine concentrations. CONCLUSION: Even a low dose of ciprofloxacin can moderately increase serum concentrations of clozapine and N-desmethylclozapine. A probable mechanism of interaction is an inhibition of CYP1A2 enzyme by ciprofloxacin. The possibility of clinically significant interaction should be considered, especially when higher doses of ciprofloxacin are used concomitantly with clozapine.\n[Drug-Disease]: N-desmethylclozapine - schizophrenic" }, { "pmid": "11151749", "target": "[]", "text": "[Title]: Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia.\n[Abstract]: OBJECTIVE: A possible pharmacokinetic interaction between a CYP1A2 inhibitor, ciprofloxacin, and clozapine was studied in schizophrenia patients with stable clozapine treatment. METHODS: A randomised double-blind cross-over study design with two phases was used. Seven schizophrenic inpatients volunteered to receive, in addition to their previous drug regimen, either 250 mg ciprofloxacin or placebo twice daily (b.i.d.) for 7 days. The phases were separated by a 7-day wash-out period. Serum concentrations of clozapine and its main metabolite N-desmethylclozapine were measured during both phases before the first dose on day 1 and on days 3 and 8. RESULTS: Ciprofloxacin increased mean serum concentration of clozapine and N-desmethylclozapine by 29% (P < 0.01) and 31% (P < 0.05), respectively. There was a significant positive correlation (r = 0.90, P < 0.01) between the individual concentrations of serum ciprofloxacin and the increase in concentrations of clozapine plus N-desmethylclozapine. The increase in serum clozapine concentrations correlated significantly (r = 0.89, P < 0.01) with the ratios of N-desmethylclozapine to clozapine concentrations. CONCLUSION: Even a low dose of ciprofloxacin can moderately increase serum concentrations of clozapine and N-desmethylclozapine. A probable mechanism of interaction is an inhibition of CYP1A2 enzyme by ciprofloxacin. The possibility of clinically significant interaction should be considered, especially when higher doses of ciprofloxacin are used concomitantly with clozapine.\n[Drug-Disease]: clozapine - schizophrenic" }, { "pmid": "11157560", "target": "[\"Span: The mean i.v. rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) | Label: Dosage\"]", "text": "[Title]: Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations.\n[Abstract]: Six patients with Parkinson's disease and refractory motor fluctuations, with severe subcutaneous (s.c.) nodule formation as a result of long-term s.c. apomorphine infusions, were switched to intravenous (i.v.) therapy via a long-term in-dwelling venous catheter. Five patients were followed-up for a mean of 7 months (range 0.5-18 months). All patients had plasma apomorphine concentrations measured at baseline during s.c. infusions and three had follow-up measurements when stabilized on i.v. therapy, to test the hypothesis that motor fluctuations in these patients are largely due to impaired absorption of apomorphine. The mean i.v. rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) of apomorphine were not significantly reduced compared with the s.c. route (9.24 mg/h and 243.4 mg). However, additional oral anti-parkinsonian medication was reduced by a mean of 59%, and 'off' time was virtually eliminated (mean reduction from 5.4 to 0.5 h per day, P< 0.05). There was also a significant reduction in dyskinesias and markedly improved quality of life. Pharmacokinetic analysis demonstrated more reliable and smoother delivery of apomorphine via the i.v. route, although 'off' periods were not always explained by low plasma apomorphine concentrations. Complication rates were high and included three unforeseen hazardous intravascular thrombotic complications, secondary to apomorphine crystal accumulation, necessitating cardiothoracic surgery. We conclude that i.v. apomorphine therapy holds promise as a more effective way of controlling motor fluctuations than the s.c. route. However, further preclinical research is required before i.v. Britaject apomorphine can be recommended for routine clinical practice. Even when stable plasma apomorphine concentrations were achieved, motor fluctuations could not be totally eradicated, suggesting that postsynaptic receptor changes may also play a role in the refractory 'off' periods in these patients.\n[Drug-Disease]: apomorphine - Parkinson's disease" }, { "pmid": "11157594", "target": "[\"Span: unrelated to left ventricular dysfunction | Label: Comorbidity\"]", "text": "[Title]: Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension.\n[Abstract]: STUDY OBJECTIVES: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. STUDY DESIGN: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. SETTING: Cardiac catheterization laboratory in a tertiary care teaching hospital. PATIENTS: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. MEASUREMENTS AND RESULTS: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). CONCLUSIONS: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.\n[Drug-Disease]: nitric oxide - chronic pulmonary hypertension" }, { "pmid": "11161370", "target": "[\"Span: 50 mg was injected once every 2 weeks for one month | Label: Dosage\"]", "text": "[Title]: Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.\n[Abstract]: DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.\n[Drug-Disease]: cytarabine - neoplastic meningitis" }, { "pmid": "1116418", "target": "[]", "text": "[Title]: Treatment of phenothiazine induced bulbar persistent dyskinesia with deanol acetamidobenzoate.\n[Abstract]: The late manifestation of neuroleptic-induced dyskinesia (persistent dyskinesia) is an irreversible complication of long-term treatment that is poorly understood and difficult to treat. Recently, a theory of dopamine receptor hypersensitivity in the dopaminergic-cholinergic system has suggested an explanation of choreiform movements and, thus, an implication for the management of persistent dyskinesia. The case presented is that of bulbar persistent dyskinesia in a patient who had been prescribed a phenothiazine derivative for eleven years; his symptoms improved with the use of deanol, which probably converts to acetylcholine after crossing the blood brain barrier. This improvement suggests that deanol may shift the neuroleptic-induced dopaminergic-cholinergic system unbalance toward equilibrium by matching predominant dopaminergic effect or by enhancing deficient cholinergic action in the dopaminergic-cholinergic system. This isolated finding needs to be confirmed by more research in neuropharmacology.\n[Drug-Disease]: deanol - dyskinesia" }, { "pmid": "11167954", "target": "[\"Span: 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) | Label: Age\"]", "text": "[Title]: Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years.\n[Abstract]: OBJECTIVE: Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double-blind, randomized, placebo-controlled trials with montelukast has not been previously reported. PATIENTS AND METHODS: A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long-term extension studies was performed. A total of 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated. RESULTS: The overall incidence of clinical and laboratory adverse events among montelukast-treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose-related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post-marketing safety experience seen to date. CONCLUSIONS: These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.\n[Drug-Disease]: montelukast - asthma" }, { "pmid": "11172345", "target": "[\"Span: 100 mg daily | Label: Dosage\"]", "text": "[Title]: A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B.\n[Abstract]: Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.\n[Drug-Disease]: lamivudine - HBV infection" }, { "pmid": "11174228", "target": "[\"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Diphenhydramine for the prevention of akathisia induced by prochlorperazine: a randomized, controlled trial.\n[Abstract]: STUDY OBJECTIVES: The utility of intravenous prochlorperazine as an antiemetic agent and abortive therapy for headache may be limited by the frequent occurrence of akathisia, the distressing effects of which have been shown to disrupt patient care. We tested the hypothesis that adjuvant diphenhydramine reduces the incidence of akathisia induced by prochlorperazine. METHODS: This randomized, double-blind, placebo-controlled trial was conducted in the emergency department of an academic tertiary care medical center with an annual census of 95,000 emergency patient visits. We enrolled a convenience sample of 100 adult patients who received 10 mg of intravenous prochlorperazine for the treatment of nausea/vomiting or headache. Subjects were randomly assigned to receive a 2-minute infusion of prochlorperazine with either 50 mg of diphenhydramine or placebo. The incidence of akathisia at 1 hour was measured by using explicit diagnostic criteria. To measure the influence of treatment on sedation, the subjects noted, on a 100-mm visual analog scale, their degree of sedation before and after treatment. RESULTS: Akathisia developed in 18 (36%) of 50 subjects in the control group and in 7 (14%) of 50 subjects in the diphenhydramine group, a 61% relative reduction. The addition of adjunct diphenhydramine resulted in an absolute reduction of 22% in the incidence of akathisia (95% confidence interval [CI] 6% to 38%; P = .01). The odds ratio for akathisia with the use of adjuvant diphenhydramine was 0.39 (95% CI 0.18 to 0.85). Mean sedation scores increased 12 mm after infusion of prochlorperazine alone (95% CI 3 to 21 mm) compared with a 33-mm increase after infusion of prochlorperazine with adjuvant diphenhydramine (95% CI 24 to 42 mm). The 12-mm difference between the groups was statistically significant (95% CI 9 to 34 mm, P < .001). CONCLUSION: Adjuvant diphenhydramine reduces the incidence of akathisia induced by prochlorperazine and is associated with an increase in sedation.\n[Drug-Disease]: diphenhydramine - akathisia" }, { "pmid": "11176729", "target": "[\"Span: 35.0 or 32.5 mg OD | Label: Dosage\", \"Span: 5.0 or 2.5 mg OD | Label: Dosage\", \"Span: age, > or =70 years | Label: Age\", \"Span: diabetes | Label: Comorbidity\"]", "text": "[Title]: Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.\n[Abstract]: BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.\n[Drug-Disease]: lisinopril - CHF" }, { "pmid": "11179262", "target": "[]", "text": "[Title]: Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials.\n[Abstract]: OBJECTIVE: To determine the cardiovascular and coronary risk thresholds at which aspirin for primary prevention of coronary heart disease is safe and worthwhile. DESIGN: Meta-analysis of four randomised controlled trials of aspirin for primary prevention. The benefit and harm from aspirin treatment were examined to determine: (1) the cardiovascular and coronary risk threshold at which benefit in prevention of myocardial infarction exceeds harm from significant bleeding; and (2) the absolute benefit expressed as number needed to treat (NNT) for aspirin net of cerebral haemorrhage and other bleeding complications at different levels of coronary risk. MAIN OUTCOME MEASURES: Benefit from aspirin, expressed as reduction in cardiovascular events, myocardial infarctions, strokes, and total mortality; harm caused by aspirin in relation to significant bleeds and major haemorrhages. RESULTS: Aspirin for primary prevention significantly reduced all cardiovascular events by 15% (95% confidence interval (CI) 6% to 22%) and myocardial infarctions by 30% (95% CI 21% to 38%), and non-significantly reduced all deaths by 6% (95% CI -4% to 15%). Aspirin non-significantly increased strokes by 6% (95% CI -24% to 9%) and significantly increased bleeding complications by 69% (95% CI 38% to 107%). The risk of major bleeding balanced the reduction in cardiovascular events when cardiovascular event risk was 0.22%/year. The upper 95% CI for this estimate suggests that harm from aspirin is unlikely to outweigh benefit provided the cardiovascular event risk is 0.8%/year, equivalent to a coronary risk of 0.6%/year. At coronary event risk 1.5%/year, the five year NNT was 44 to prevent a myocardial infarction, and 77 to prevent a myocardial infarction net of any important bleeding complication. At coronary event risk 1%/year the NNT was 67 to prevent a myocardial infarction, and 182 to prevent a myocardial infarction net of important bleeding. CONCLUSIONS: Aspirin treatment for primary prevention is safe and worthwhile at coronary event risk >/= 1.5%/year; safe but of limited value at coronary risk 1%/year; and unsafe at coronary event risk 0.5%/year. Advice on aspirin for primary prevention requires formal accurate estimation of absolute coronary event risk.\n[Drug-Disease]: aspirin - myocardial infarction" }, { "pmid": "11180027", "target": "[\"Span: 3.3 mg/70 kg of M6G | Label: Dosage\", \"Span: 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G | Label: Dosage\"]", "text": "[Title]: Randomized placebo-controlled trial of the activity of the morphine glucuronides.\n[Abstract]: BACKGROUND: Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. METHODS: We performed a double-blind placebo-controlled trial with 10 healthy volunteers. The trial had 6 arms: (1) placebo, (2) 10 mg/70 kg of morphine, (3) 3.3 mg/70 kg of M6G, (4) 30.6 mg/70 kg of M3G, (5) 30.6 mg/70 kg of M3G with 10 mg/70 kg of morphine, and (6) 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G; all were give by slow intravenous bolus. Analgesia was assessed with the use of the submaximal ischemic pain model. The effects were quantified on numerical and visual analogue scales. Respiratory parameters and response to steady state 5% carbon dioxide challenge were assessed with spirometry, mass spectroscopy, and earlobe blood gas analysis. RESULTS: Morphine and M6G produced significant pain relief compared with placebo (morphine, P < .0001; M6G, P = .033). Pain relief after M6G was less than after morphine (P = .009) and M3G was no better than placebo (P = .26). Pain relief with morphine and M6G were not significantly altered by M3G (P = .59 and P = .28, respectively). Significant and similar dysphoria and sedation occurred with both morphine (P < .002) and M6G (P < .016) but were absent with both M3G and placebo. Respiratory parameters suggested that M6G produced less respiratory depression than morphine. Both morphine and M6G caused a significant reduction in respiratory drive compared with placebo (morphine, P = .002; M6G, P = .013); this effect was not reversed by M3G (P = .35 and P = .83, respectively). CONCLUSIONS: M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.\n[Drug-Disease]: Morphine-6-glucuronide - Pain" }, { "pmid": "11181473", "target": "[\"Span: 30 mg/d | Label: Dosage\", \"Span: 300 mg/d | Label: Dosage\"]", "text": "[Title]: Effects of endothelin a receptor blockade on endothelial function in patients with chronic heart failure.\n[Abstract]: BACKGROUND: Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD). METHODS AND RESULTS: Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2+/-2%) when compared with the 11 controls (9.7+/-4.9%; P=0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0+/-2.0% to 4.9+/-2.9%; P=0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4+/-1.5% to 5.5+/-2.4%; P=0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8+/-0.4 to 5.1+/-0.7 mm; P=0.03). CONCLUSIONS: These results suggest that endothelin A receptor blockade improves FMD in CHF patients.\n[Drug-Disease]: LU 135252 - CHF" }, { "pmid": "11182704", "target": "[]", "text": "[Title]: Iodine-123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity.\n[Abstract]: BACKGROUND: We examined whether cardiac sympathetic imaging with iodine-123 metaiodobenzylguanidine (MIBG) would predict improvement of left ventricular (LV) function and exercise capacity in patients with heart failure after treatment with carvedilol. METHODS AND RESULTS: Eighteen patients with heart failure and 5 control subjects underwent I-123 MIBG imaging. Heart-to-mediastinum ratios at 20 minutes and 3 hours and myocardial washout rates (WR) were measured. Of the 18 patients, 11 were randomized to receive carvedilol medication, whereas the remaining 7 received a placebo. Only the carvedilol group demonstrated a significant improvement in both heart failure functional class and LV ejection fraction (EF) 1 year after the start of medication. Within the carvedilol group, MIBG WR showed a significant inverse correlation with improvement in LVEF (rho = -0.74, P =.02). The diagnostic accuracy of WR for predicting EF response to carvedilol was 91%. WR also appeared to be inversely related to the peak oxygen consumption rate (rho = -0.65, P =.08), although this did not reach statistical significance. CONCLUSION: I-123 MIBG imaging appears useful in predicting which patients with heart failure are likely to show the most improvement in LV function and exercise capacity after carvedilol treatment. Further studies in this area appear to be warranted.\n[Drug-Disease]: carvedilol - heart failure" }, { "pmid": "11189013", "target": "[]", "text": "[Title]: Rationale, design and organization of the Second Chinese Cardiac Study (CCS-2): a randomized trial of clopidogrel plus aspirin, and of metoprolol, among patients with suspected acute myocardial infarction. Second Chinese Cardiac Study (CCS-2) Collaborative Group.\n[Abstract]: Assessing combined anti-platelet therapy in suspected acute myocardial infarction Aspirin has been shown to be effective in the emergency treatment of acute myocardial infarction. It irreversibly inhibits platelet cyclo-oxygenase and thereby prevents the formation of the platelet aggregating agent thromboxane A2. Clopidogrel is an anti-platelet agent that acts by a different mechanism, inhibiting adenosine diphosphate-induced platelet aggregation. Simultaneous inhibition of both of these pathways might produce significantly greater anti-platelet effects than inhibition of either alone. The Second Chinese Cardiac Study (CCS-2) will reliably determine whether adding oral clopidogrel to aspirin for up to 4 weeks in hospital after suspected acute myocardial infarction can produce a greater reduction in the risk of major vascular events than can be achieved by giving aspirin alone. In order to be able to detect a further reduction of 10-15%, some 20,000-40,000 patients in over 1000 Chinese hospitals will be randomized. Assessing early beta-blocker therapy in suspected acute myocardial infarction Although over 27,000 patients have been studied previously in randomized trials of short-term beta-blocker therapy in acute myocardial infarction, the reduction in early mortality (513 (3.7%) for beta-blocker therapy deaths versus 586 (4.3%) for control deaths) was only just conventionally significant (P = 0.02) and, overall, the absolute benefits were small in the relatively low-risk patients studied. Although there might be worthwhile benefit in higher risk patients, there is currently little routine use of beta-blocker therapy in acute myocardial infarction. Hence, patients in CCS-2 will also be randomly allocated to receive metoprolol (intravenous then oral) or matching placebo for up to 4 weeks in hospital in a 2 x 2 factorial design. Such a design allows all patients to contribute fully to assessment of the separate effects of the anti-platelet regimen and the beta-blocker (without any material effect on study cost or sample size requirements) whilst also providing information about their combined effects. A streamlined trial in a wide range of patients In order to randomize 20,000-40,000 patients, the design of CCS-2 has been streamlined: data collection and other extra work for collaborators is minimal, allowing busy hospitals to take part easily. All patients presenting within 24 h of the onset of suspected acute myocardial infarction are eligible for the study provided they have a definite ECG abnormality and are not persistently hypotensive, and provided the doctor responsible considers there to be no clear indication for or contraindication to either of the trial treatments. Apart from administration of the trial treatments, all other aspects of individual patient management are entirely at the discretion of the doctor responsible. By including many different types of patient from many different types of hospital, with wide variation in ancillary management, the CCS-2 results will be of direct clinical relevance to the heterogeneous realities of future clinical practice. The trial began in July 1999 and is expected to be completed by the year 2003.\n[Drug-Disease]: aspirin - myocardial infarction" }, { "pmid": "11192362", "target": "[\"Span: during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily | Label: Dosage\"]", "text": "[Title]: MERIT-HF mortality and morbidity data.\n[Abstract]: This survival study was designed to address whether beta-1-blockade utilizing metoprolol CR/XL (controlled release/extended release) once daily added to standard therapy reduces mortality and morbidity in patients with decreased ejection fraction and symptoms of heart failure. Enrolled in a double-blind randomized study were 3991 patients with chronic heart failure in NYHA functional class II-IV and ejection fraction < or = 0.40 stabilized on optimal standard therapy. Randomization was preceded by a 2-week single blind placebo run-in period. The study medication was uptitrated during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily. The primary endpoints were all-cause mortality and combined all-cause mortality and hospitalization (time to first event) and other objectives were cause-specific data on hospitalization, NYHA functional class and quality of life. Mean follow-up time was 1 year. All-cause mortality was reduced in the metoprolol CR/XL group compared with the placebo group, 145 versus 217 deaths, 7.2% per patient year of follow-up versus 11.0% with a relative risk of 0.66 (95% CI 0.53-0.81, nominal p = 0.00009, p adjusted for interim analysis = 0.0062). This effect was consistent across all predefined subgroups. Sudden deaths were fewer in the metoprolol group (79 versus 132 deaths), RR 0.59 (p = 0.0002). Also deaths from worsening heart failure were fewer in the metoprolol group (30 versus 58 deaths), RR 0.51 (p = 0.0023). The combined endpoint total mortality or all-cause hospitalizations was also reduced by metoprolol (641 versus 767 events), RR 0.81 (p = 0.00012). Total mortality or hospitalizations due to worsening heart failure was also reduced (311 versus 439 events), RR 0.69 (p < 0.00001). The number of hospitalizations due to worsening heart failure (317 versus 451, p < 0.00001) and days in hospital due to worsening heart failure (3401 versus 5303 days, p < 0.00001) were also reduced by metoprolol. There was also an improvement in NYHA functional class, assessed by the physicians as well as the McMaster Overall Treatment Evaluation questionnaire (OTE), assessed by the patients (p = 0.028 and p = 0.089, respectively). Permanent early discontinuation was 13.9% in the metoprolol group and 15.3% in the placebo group (RR = 0.90). In conclusion, in patients with symptomatic heart failure metoprolol CR/XL once daily improved survival by 34%, sudden death by 41%, and deaths from worsening of heart failure by 49%. In addition to improvement of survival there was also a reduced need of hospitalizations for worsening heart failure and an improved NYHA functional class and of quality of life assessed in a substudy. Metoprolol was well tolerated with no difference in early discontinuation rate from placebo treatment.\n[Drug-Disease]: Metoprolol - heart failure" }, { "pmid": "11193132", "target": "[\"Span: 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% | Label: Dosage\", \"Span: a single 5 mg tablet of sublingual isosorbide dinitrate | Label: Dosage\"]", "text": "[Title]: Comparison between isosorbide dinitrate in aerosol and in tablet form for the treatment of hypertensive emergencies in the elderly.\n[Abstract]: BACKGROUND: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. METHODS: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% . Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. RESULTS: Blood pressure in Group A patients decreased from 193 +/- 13/123 +/- 6.6 mmHg to 154 +/- 15/92.5 +/- 7.6 mmHg (p < 0.005), the reduction beginning 10 min after drug administration; no adverse effects were found. Two patients in Group B did not respond but for the other patients in this group blood pressure decreased from 197 +/- 10/121 +/- 7 to 154 +/- 11/90 +/- 4 mmHg, (p < 0.005), the reduction beginning 45 min after receiving the medication; 8 patients suffered headache. CONCLUSION: Our results indicate that isosorbide dinitrate aerosol is more effective than tablets for the treatment of elderly patients with hypertensive emergencies.\n[Drug-Disease]: isosorbide dinitrate - hypertensive emergencies" }, { "pmid": "111940", "target": "[]", "text": "[Title]: Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.\n[Abstract]: A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.\n[Drug-Disease]: nifedipine - stable angina pectoris" }, { "pmid": "111940", "target": "[]", "text": "[Title]: Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.\n[Abstract]: A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.\n[Drug-Disease]: pindolol - stable angina pectoris" }, { "pmid": "11195228", "target": "[\"Span: paediatric or neonatal | Label: Age\"]", "text": "[Title]: Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.\n[Abstract]: UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.\n[Drug-Disease]: nitric oxide - hypoxaemia" }, { "pmid": "11195228", "target": "[\"Span: paediatric or neonatal | Label: Age\"]", "text": "[Title]: Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.\n[Abstract]: UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.\n[Drug-Disease]: nitric oxide - pulmonary hypertension" }, { "pmid": "11197214", "target": "[]", "text": "[Title]: Good prognosis of patients with acute promyelocytic leukemia who achieved second complete remission (CR) with a new retinoid, Am80, after relapse from CR induced by all-trans-retinoic acid.\n[Abstract]: A new synthetic retinoid, Am80, is effective in treating acute promyelocytic leukemia relapsed from all-trans-retinoic acid-induced complete remission (CR). We report here the long-term clinical outcomes of patients who achieved second CR with Am80. Of 24 evaluable patients, 14 achieved a second CR by Am80 therapy. Of those patients, 4 relapsed within 6 months, despite subsequent consolidation chemotherapy. Six patients underwent sibling or unrelated HLA-matched allogeneic bone marrow transplantation (BMT), and 4 are alive without relase for more than 49 months after achieving second CR. Four of 8 patients who did not receive BMT are alive without relapse for more than 49 months. Promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) fusion transcript was undetectable by reverse transcriptase-polymerase chain reaction in all living patients. Therefore, if patients achieve second CR with Am80 and HLA-matched donors are available, BMT is the treatment of choice. However, it is noteworthy that CR was maintained for more than 49 months in half of the patients who did not receive BMT.\n[Drug-Disease]: Am80 - Promyelocytic leukemia-retinoic" }, { "pmid": "11197585", "target": "[]", "text": "[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.\n[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.\n[Drug-Disease]: olanzapine - bipolar depressed" }, { "pmid": "11197585", "target": "[]", "text": "[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.\n[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.\n[Drug-Disease]: clonazepam - bipolar depressed" }, { "pmid": "11197585", "target": "[]", "text": "[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.\n[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.\n[Drug-Disease]: lithium - bipolar depressed" }, { "pmid": "11198485", "target": "[\"Span: female | Label: Gender\"]", "text": "[Title]: Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.\n[Abstract]: Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.\n[Drug-Disease]: fludrocortisone - Postural tachycardia syndrome" }, { "pmid": "11198485", "target": "[\"Span: female | Label: Gender\"]", "text": "[Title]: Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.\n[Abstract]: Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.\n[Drug-Disease]: bisoprolol - Postural tachycardia syndrome" }, { "pmid": "11202421", "target": "[\"Span: 300 micrograms | Label: Dosage\"]", "text": "[Title]: A clinical comparative study on effects of intracavernous injection of sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients.\n[Abstract]: AIM: To study the effect of intracavernous sodium nitroprusside (SNP), a nitric oxide (NO) donor, on penile erection. METHODS: Forty-two patients with erectile dysfunction (ED) were randomly assigned to receive SNP 300 micrograms or the control drugs (papaverine 30 mg + phentolamine 1 mg) intracavernously crosswise one week apart. The penile length, circumference and hardness after the administration of the experimental and control drugs were assessed and compared statistically. RESULTS: (1) There was no significant difference between the changes in penile length and circumference in the two occasions; (2) In 25 SNP and 28 control cases, the hardness of the penis was scored above 100 as evaluated by the Virag method (P > 0.05); (3) The duration of erection in the controls was longer than that in the SNP, but there were three priapism in the controls and not a single one in the SNP; (4) there was no apparent change in the heart rate and blood pressure in both occasions; other side effects were minimal except slight local pain in a few controls. CONCLUSION: SNP facilitates relaxation of the penile smooth muscle and penile erection without significant side effects. SNP may be used in ED patients that experience pain and priapism with papaverine/phentolamine.\n[Drug-Disease]: sodium nitroprusside - erectile dysfunction" }, { "pmid": "11202810", "target": "[]", "text": "[Title]: Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study.\n[Abstract]: Thirty-four patients with metastatic breast cancer (MBC) who had progression of disease after high-dose chemotherapy (HDCT) with peripheral blood progenitor cell support (PBPC) had methotrexate, uracil and tegafur (UFT), and leucovorin (MUL) therapy administered: methotrexate administered intramuscularly in combination with UFT given orally and leucovorin given orally. All patients had received extensive prior chemotherapy including a high-dose regimen with PBPC support. Two complete responses (CR) and 11 partial responses (PR) were observed (objective response rate: 13/34 or 38%, 95% confidence interval 22-56%). Seven additional patients had stable disease (SD), 4 of whom (12% of the total population) of 6 months or longer duration, with the clinical benefit rate (CR + PR + SD of at least 6-month duration) reaching 50%. Median follow-up was 38 months, and the median time to progression and the median overall survival time from the start of MUL were 5.5 and 11 months, respectively. Toxicity was mainly gastrointestinal. Eight patients (24%) had World Health Organization grade II or greater diarrhea and/or enteritis and, consequently, the UFT dose was reduced. Emesis was mild and easily manageable with thiethylperazine given orally. The regimen did not produce significant myelosuppression or alopecia. In conclusion, patients with MBC retain chemosensitivity even when they progress after HDCT/PBPC and can be treated again with chemotherapy. MUL is active and well tolerated in patients with MBC progressing after HDCT. Further studies with this regimen, as salvage chemotherapy or as maintenance chemotherapy after HDCT/PBPC, would appear to be warranted.\n[Drug-Disease]: leucovorin - MBC" }, { "pmid": "11202810", "target": "[]", "text": "[Title]: Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study.\n[Abstract]: Thirty-four patients with metastatic breast cancer (MBC) who had progression of disease after high-dose chemotherapy (HDCT) with peripheral blood progenitor cell support (PBPC) had methotrexate, uracil and tegafur (UFT), and leucovorin (MUL) therapy administered: methotrexate administered intramuscularly in combination with UFT given orally and leucovorin given orally. All patients had received extensive prior chemotherapy including a high-dose regimen with PBPC support. Two complete responses (CR) and 11 partial responses (PR) were observed (objective response rate: 13/34 or 38%, 95% confidence interval 22-56%). Seven additional patients had stable disease (SD), 4 of whom (12% of the total population) of 6 months or longer duration, with the clinical benefit rate (CR + PR + SD of at least 6-month duration) reaching 50%. Median follow-up was 38 months, and the median time to progression and the median overall survival time from the start of MUL were 5.5 and 11 months, respectively. Toxicity was mainly gastrointestinal. Eight patients (24%) had World Health Organization grade II or greater diarrhea and/or enteritis and, consequently, the UFT dose was reduced. Emesis was mild and easily manageable with thiethylperazine given orally. The regimen did not produce significant myelosuppression or alopecia. In conclusion, patients with MBC retain chemosensitivity even when they progress after HDCT/PBPC and can be treated again with chemotherapy. MUL is active and well tolerated in patients with MBC progressing after HDCT. Further studies with this regimen, as salvage chemotherapy or as maintenance chemotherapy after HDCT/PBPC, would appear to be warranted.\n[Drug-Disease]: methotrexate - MBC" }, { "pmid": "11204264", "target": "[\"Span: (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6-8 weeks | Label: Dosage\"]", "text": "[Title]: Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction.\n[Abstract]: Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6-8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37-69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6-8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.\n[Drug-Disease]: Testosterone - erectile dysfunction" }, { "pmid": "11204326", "target": "[]", "text": "[Title]: [Analysis of general and hemorrhagic complications after treatment of acute proximal deep venous thrombosis of the legs treated with anticoagulants, streptokinase and thrombectomy].\n[Abstract]: The aim of the study was to present general and haemorrhagic complications in 164 patients with acute DVT in ilio-femoral segment treated with different methods of pharmacological (heparins, streptokinase) and surgical (venous thrombectomy with temporary arterio-venous fistulae) therapy. There were no fatal complications in 48 UH or LMWH treated patients. One patient bled from stress stomach, one developed intramuscular haematoma, one mild pulmonary embolism and one rise of body. Among 84 patients treated with SK five fatal bleeding complications were recorded. From other non fatal complications we recorded one GI bleeding, one splenic rupture and three massive intramuscular haematoma. Three patients died in the early post thrombectomy period. Non fatal complications included one wound haematoma, two wound infection and one with marginal necrosis. The use of LMWH or UH treatment in acute ilio-femoral venous thrombosis is save as the frequency of massive bleeding and serious general complications is rather low. Fatal haemorrhagic episodes are the major hazards of thrombolytic therapy. Venous thrombectomy with temporary arterio-venous fistula may provide a good chance for treatment of acute proximal DVT associated with complete occlusion of the lumen of affected veins in patients with severe ischemic venous thrombosis or with contraindications to heparin treatment.\n[Drug-Disease]: heparin - ischemic venous thrombosis" }, { "pmid": "11204326", "target": "[]", "text": "[Title]: [Analysis of general and hemorrhagic complications after treatment of acute proximal deep venous thrombosis of the legs treated with anticoagulants, streptokinase and thrombectomy].\n[Abstract]: The aim of the study was to present general and haemorrhagic complications in 164 patients with acute DVT in ilio-femoral segment treated with different methods of pharmacological (heparins, streptokinase) and surgical (venous thrombectomy with temporary arterio-venous fistulae) therapy. There were no fatal complications in 48 UH or LMWH treated patients. One patient bled from stress stomach, one developed intramuscular haematoma, one mild pulmonary embolism and one rise of body. Among 84 patients treated with SK five fatal bleeding complications were recorded. From other non fatal complications we recorded one GI bleeding, one splenic rupture and three massive intramuscular haematoma. Three patients died in the early post thrombectomy period. Non fatal complications included one wound haematoma, two wound infection and one with marginal necrosis. The use of LMWH or UH treatment in acute ilio-femoral venous thrombosis is save as the frequency of massive bleeding and serious general complications is rather low. Fatal haemorrhagic episodes are the major hazards of thrombolytic therapy. Venous thrombectomy with temporary arterio-venous fistula may provide a good chance for treatment of acute proximal DVT associated with complete occlusion of the lumen of affected veins in patients with severe ischemic venous thrombosis or with contraindications to heparin treatment.\n[Drug-Disease]: LMWH - ischemic venous thrombosis" }, { "pmid": "11205470", "target": "[\"Span: four cycles ofcisplatin (cisDDP) 100 mg/m2 | Label: Dosage\"]", "text": "[Title]: Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.\n[Abstract]: PURPOSE: To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer. PATIENTS AND METHODS: Between January 1994 and February 1996, we recruited 30 patients to the pctx-then-cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials. RESULTS: Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx-then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then-cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then-cisDDP, 11 on cisDDP-then-pctx). CONCLUSION: The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs.\n[Drug-Disease]: cisDDP - epithelial ovarian cancer" }, { "pmid": "11205470", "target": "[\"Span: four cycles of paclitaxel (pctx) 200 mg/m2/3 hours | Label: Dosage\"]", "text": "[Title]: Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.\n[Abstract]: PURPOSE: To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer. PATIENTS AND METHODS: Between January 1994 and February 1996, we recruited 30 patients to the pctx-then-cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials. RESULTS: Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx-then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then-cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then-cisDDP, 11 on cisDDP-then-pctx). CONCLUSION: The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs.\n[Drug-Disease]: paclitaxel - epithelial ovarian cancer" }, { "pmid": "11206272", "target": "[]", "text": "[Title]: Neurotoxicity associated with a regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) employed in the treatment of gynecologic malignancies.\n[Abstract]: While the combination chemotherapy regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) is widely employed in the treatment of ovarian cancer, there are limited data available in the oncologic literature regarding the neurotoxic potential of the program. We retrospectively reviewed the clinical course of 87 patients treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center to address this important clinical issue. The overall incidence of peripheral neuropathy in this population was 25%, with 13% of women experiencing symptoms > or = grade 2 in severity. We conclude that while neurotoxicity is common following the use of this regimen, significant neurological dysfunction (> or = grade 2) is relatively infrequent.\n[Drug-Disease]: carboplatin - ovarian cancer+B184:B185+B184:B185" }, { "pmid": "11206272", "target": "[]", "text": "[Title]: Neurotoxicity associated with a regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) employed in the treatment of gynecologic malignancies.\n[Abstract]: While the combination chemotherapy regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) is widely employed in the treatment of ovarian cancer, there are limited data available in the oncologic literature regarding the neurotoxic potential of the program. We retrospectively reviewed the clinical course of 87 patients treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center to address this important clinical issue. The overall incidence of peripheral neuropathy in this population was 25%, with 13% of women experiencing symptoms > or = grade 2 in severity. We conclude that while neurotoxicity is common following the use of this regimen, significant neurological dysfunction (> or = grade 2) is relatively infrequent.\n[Drug-Disease]: paclitaxel - ovarian cancer" }, { "pmid": "11207403", "target": "[]", "text": "[Title]: Slow infusion for the prevention of akathisia induced by prochlorperazine: a randomized controlled trial.\n[Abstract]: The utility of intravenous prochlorperazine (PCZ) in the treatment of nausea, vomiting, and headache may be limited by the akathisia that occurs frequently with the recommended 2-min infusion rate. We tested the hypothesis that decreasing the rate of PCZ infusion to 15 min reduces the incidence of akathisia at 1 hour. This double-blinded, randomized, controlled trial was conducted in the Emergency Department of an academic tertiary-care medical center with an annual census of 95,000 emergency patient visits. We enrolled a convenience sample of adult patients who received 10 mg i.v. PCZ for the treatment of nausea, vomiting, or headache. Subjects were randomized to receive either a 2-min infusion of PCZ (10 mg) followed by a 15-min infusion of saline, or a 2-min infusion of saline followed by a 15-min infusion of prochlorperazine. The incidence of akathisia at 1 hour was measured by using explicit diagnostic criteria. One hundred sixty patients were randomly enrolled into two groups, which were comparable with respect to age, gender, weight, and complaint. Akathisia developed in 31 of 84 patients (36.9%) who received the 2-min infusion of PCZ and in 18 of 76 patients (23.7%) who received the 15-min infusion of PCZ (p = 0.07), a 36% (95% CI, -5% to 61%) relative reduction. The delta from pre-infusion to postinfusion scores between the two groups was not significant (p = 0.19). We conclude that slowing the rate of PCZ infusion does not decrease akathisia.\n[Drug-Disease]: PCZ - headache" }, { "pmid": "11207403", "target": "[]", "text": "[Title]: Slow infusion for the prevention of akathisia induced by prochlorperazine: a randomized controlled trial.\n[Abstract]: The utility of intravenous prochlorperazine (PCZ) in the treatment of nausea, vomiting, and headache may be limited by the akathisia that occurs frequently with the recommended 2-min infusion rate. We tested the hypothesis that decreasing the rate of PCZ infusion to 15 min reduces the incidence of akathisia at 1 hour. This double-blinded, randomized, controlled trial was conducted in the Emergency Department of an academic tertiary-care medical center with an annual census of 95,000 emergency patient visits. We enrolled a convenience sample of adult patients who received 10 mg i.v. PCZ for the treatment of nausea, vomiting, or headache. Subjects were randomized to receive either a 2-min infusion of PCZ (10 mg) followed by a 15-min infusion of saline, or a 2-min infusion of saline followed by a 15-min infusion of prochlorperazine. The incidence of akathisia at 1 hour was measured by using explicit diagnostic criteria. One hundred sixty patients were randomly enrolled into two groups, which were comparable with respect to age, gender, weight, and complaint. Akathisia developed in 31 of 84 patients (36.9%) who received the 2-min infusion of PCZ and in 18 of 76 patients (23.7%) who received the 15-min infusion of PCZ (p = 0.07), a 36% (95% CI, -5% to 61%) relative reduction. The delta from pre-infusion to postinfusion scores between the two groups was not significant (p = 0.19). We conclude that slowing the rate of PCZ infusion does not decrease akathisia.\n[Drug-Disease]: PCZ - nausea" }, { "pmid": "11207687", "target": "[\"Span: topical 5% topical imiquimod cream | Label: Dosage\"]", "text": "[Title]: Bowen's disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy.\n[Abstract]: BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies. OBJECTIVE: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL. METHODS: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day. RESULTS: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy. CONCLUSION: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies.\n[Drug-Disease]: imiquimod - Bowen's disease" }, { "pmid": "11207687", "target": "[\"Span: sulindac 200 mg twice a day | Label: Dosage\"]", "text": "[Title]: Bowen's disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy.\n[Abstract]: BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies. OBJECTIVE: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL. METHODS: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day. RESULTS: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy. CONCLUSION: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies.\n[Drug-Disease]: sulindac - Bowen's disease" }, { "pmid": "11230474", "target": "[\"Span: aged 18 to 75 years | Label: Age\", \"Span: infused over 1 hour, once every 3 weeks for six cycles maximum | Label: Dosage\"]", "text": "[Title]: Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Francais de Pneumo-Cancerologie study.\n[Abstract]: PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.\n[Drug-Disease]: carboplatin - small-cell lung cancer" }, { "pmid": "11230474", "target": "[\"Span: aged 18 to 75 years | Label: Age\", \"Span: (200 mg/m(2)) was infused over 3 hours | Label: Dosage\", \"Span: once every 3 weeks for six cycles maximum | Label: Dosage\"]", "text": "[Title]: Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Francais de Pneumo-Cancerologie study.\n[Abstract]: PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.\n[Drug-Disease]: paclitaxel - small-cell lung cancer" }, { "pmid": "11230490", "target": "[\"Span: 600 mg/m(2) of cyclophosphamide (C), every 3 weeks | Label: Dosage\"]", "text": "[Title]: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.\n[Abstract]: PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.\n[Drug-Disease]: cyclophosphamide - MBC" }, { "pmid": "11230490", "target": "[\"Span: either 60 mg/m(2) | Label: Dosage\", \"Span: every 3 weeks | Label: Dosage\"]", "text": "[Title]: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.\n[Abstract]: PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.\n[Drug-Disease]: doxorubicin - MBC" }, { "pmid": "11234897", "target": "[]", "text": "[Title]: Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells.\n[Abstract]: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel member of the tumor necrosis factor superfamily of cytokines that induces cell death by apoptosis. TRAIL has been shown to be effective in almost two-thirds of solid tumors tested thus far, but its effect on pancreatic cancer cells is unknown. We tested the effect of TRAIL on seven human pancreatic cancer cell lines (HPAF, Panc1, Miapaca2, Bxpc3, Panc89, SW979, and Aspc1) in vitro. Of these cell lines, all but Aspc1 showed a significant dose-dependent increase in apoptosis. The apoptotic rate, as detected by a terminal deoxynucleotidyl transferase-mediated nick end labeling assay, was highest in Bxpc3 (71.5%), followed by HPAF (38.0%), Miapaca2 (24.9%), Panc1 (16.1%), Panc89 (15.8%), SW979 (13.9%), and Aspc1 (5.2%). Multiple treatments were more effective than a single treatment and caused a sustained and profound cell death in all but Aspc1 cells. There was no correlation between the effect of TRAIL and the differentiation grade of the cell lines, p53 mutation, or bcl-2 or bax expression. The resistance of Aspc1 cells to TRAIL was not related to the lack of TRAIL receptors. The combination of actinomycin D and TRAIL induced an almost complete lysis of Aspc1 cells, whereas actinomycin D alone had no effect on cell survival but inhibited the expression of the Flice inhibitory protein, which is assumed to play a role in the apoptotic pathway of TRAIL. Thus, the combination of actinomycin D and TRAIL appears to be a promising approach for the therapy of pancreatic cancers resistant to TRAIL.\n[Drug-Disease]: actinomycin D - pancreatic cancers" }, { "pmid": "11235923", "target": "[\"Span: 1,200 mg/day | Label: Dosage\"]", "text": "[Title]: Gabapentin in the treatment of cocaine dependence: a case series.\n[Abstract]: BACKGROUND: Although multiple medications have been studied for the treatment of cocaine dependence, no medication has been shown to have a robust effect on craving and use. This pilot project was designed to evaluate the safety and tolerability of gabapentin in subjects with cocaine dependence. METHOD: Thirty cocaine-dependent subjects (DSM-IV criteria) were enrolled in an 8-week, open-label trial of 1,200 mg/day of gabapentin in divided doses. Urine drug screens, subjective measures of craving, and cocaine use interviews were conducted at each weekly visit. RESULTS: Baseline rating of amount and frequency of craving decreased significantly by week 8 (78% vs. 25% for amount, p = .000; 74% vs. 23% for frequency, p = .004). Positive urine drug screens for cocaine decreased from 86% at baseline to 29% at weeks 4 and 8. There were no reports of significant side effects or adverse events. CONCLUSION: This pilot study indicates that gabapentin is safe and well tolerated and may be beneficial in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.\n[Drug-Disease]: gabapentin - cocaine dependence" }, { "pmid": "11240075", "target": "[\"Span: 60 mg bid during the first 4 days of the 1 month treatment | Label: Dosage\"]", "text": "[Title]: Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.\n[Abstract]: Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.\n[Drug-Disease]: dihydrocodeine - osteoarthritis pain" }, { "pmid": "11240075", "target": "[\"Span: 60 mg bid during the first 4 days of the 1 month treatment | Label: Dosage\"]", "text": "[Title]: Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.\n[Abstract]: Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.\n[Drug-Disease]: dihydrocodeine - pain" }, { "pmid": "11240075", "target": "[\"Span: tramadol 100 mg bid | Label: Dosage\", \"Span: during the first 4 days of the 1 month treatment | Label: Dosage\"]", "text": "[Title]: Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.\n[Abstract]: Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.\n[Drug-Disease]: Tramadol - osteoarthritis pain" }, { "pmid": "11240075", "target": "[\"Span: tramadol 100 mg bid | Label: Dosage\", \"Span: during the first 4 days of the 1 month treatment | Label: Dosage\"]", "text": "[Title]: Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.\n[Abstract]: Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.\n[Drug-Disease]: Tramadol - pain" }, { "pmid": "11240090", "target": "[\"Span: 50, 100 and 150 ng/ml | Label: Dosage\", \"Span: seven males and five females | Label: Gender\"]", "text": "[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.\n[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.\n[Drug-Disease]: ketamine - hyperalgesic+B201:B204" }, { "pmid": "11240090", "target": "[\"Span: 50, 100 and 150 ng/ml | Label: Dosage\", \"Span: seven males and five females | Label: Gender\"]", "text": "[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.\n[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.\n[Drug-Disease]: ketamine - pain" }, { "pmid": "11240090", "target": "[\"Span: 25, 50 and 75 ng/ml | Label: Dosage\", \"Span: seven males and five females | Label: Gender\"]", "text": "[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.\n[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.\n[Drug-Disease]: alfentanil - hyperalgesic" }, { "pmid": "11240090", "target": "[\"Span: 25, 50 and 75 ng/ml | Label: Dosage\", \"Span: seven males and five females | Label: Gender\"]", "text": "[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.\n[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.\n[Drug-Disease]: alfentanil - pain" }, { "pmid": "11244274", "target": "[\"Span: 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day | Label: Dosage\"]", "text": "[Title]: Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.\n[Abstract]: Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator's global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.\n[Drug-Disease]: entacapone - Parkinson's Disease" }, { "pmid": "11244274", "target": "[]", "text": "[Title]: Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.\n[Abstract]: Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator's global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.\n[Drug-Disease]: levodopa - Parkinson's Disease" }, { "pmid": "1124744", "target": "[\"Span: subcutaneous (0.08 mg/kg) | Label: Dosage\", \"Span: oral (25 mg) | Label: Dosage\"]", "text": "[Title]: Cholinergic stimulation of the lower esophageal sphincter in patients with vagotomy and antrectomy.\n[Abstract]: Recently cholinergic stimulation of the lower esophageal sphincter (LES) with bethanechol has been shown to be effective in the treatment of chronic gastroesophageal reflux. Since chronic reflux and esophagitis also occur in patients with vagotomy and antrectomy, we studied the effect of bethanechol on sphincter pressure in 10 patients who had had vagotomy and antrectomy. Both subcutaneous (0.08 mg/kg) and oral (25 mg) administration of bethanechol caused significant increases in LES pressure in these patients. In addition, both subcutaneous and oral administration of bethanechol elevated hypotensive sphincter pressures to normal levels. Orally administered bethanechol produced a sustained increase in LES pressure throughout a 90-min study period. These studies suggest that cholinergic stimulation of the LES with bethanechol may be of therapeutic benefit in vagotomized and antrectomized patients with gastroesophageal reflux.\n[Drug-Disease]: bethanechol - gastroesophageal reflux" }, { "pmid": "11250985", "target": "[]", "text": "[Title]: Serious adverse events experienced by patients with chronic heart failure taking spironolactone.\n[Abstract]: In patients with chronic heart failure, spironolactone added to conventional treatment may lead to serious and, occasionally, fatal hyperkalaemia. In some cases this seems to happen because spironolactone causes diarrhoea. Four cases involving men with New York Heart Association functional class III heart failure are presented. As these cases revealed, close monitoring of blood chemistry is mandatory after starting spironolactone, and patients should be advised to stop spironolactone immediately if diarrhoea develops.\n[Drug-Disease]: spironolactone - heart failure" }, { "pmid": "11251344", "target": "[]", "text": "[Title]: Preventing venous thromboembolism in general medical inpatients and after an ischaemic stroke.\n[Abstract]: Clinical trials and meta-analyses have shown that low-molecular-weight heparin and unfractionated heparin are effective in preventing deep vein thrombosis (DVT) in acutely ill medical inpatients who are at risk as they are likely to be bedridden for 6 days or more. It is not known, however, if such prophylaxis can also reduce the likelihood of fatal pulmonary embolism or decrease all-causes mortality in this patient population. No recommendations can be made regarding thromboprophylaxis in those at a lower risk of venous thromboembolism or in short-stay inpatients, as these have not yet undergone clinical trial. Current evidence suggests that high doses of heparin should be avoided after an acute ischaemic stroke, as the results of recent large trials suggest any potential treatment benefit in preventing DVT is cancelled by the increased intracranial bleeding risk caused from the underlying disease.\n[Drug-Disease]: heparin - deep vein thrombosis" }, { "pmid": "11251433", "target": "[\"Span: 3-mg boluses | Label: Dosage\"]", "text": "[Title]: Induction with propofol target-concentration infusion vs. 8% sevoflurane inhalation and alfentanil in hypertensive patients.\n[Abstract]: Haemodynamic parameters during an inhalation induction with 8% sevoflurane were compared with those obtained with a target-controlled infusion of propofol in 50 hypertensive patients in a prospective randomised study. Heart rate and arterial pressure were recorded continuously. End-tidal sevoflurane and nitrous oxide concentration, SpO2 and bispectral index (BIS) were also collected from the beginning of anaesthesia until 8 min after tracheal intubation. Patients either received 4 mg.l-1 target-concentration propofol or performed a vital capacity inhalation of 8% sevoflurane in a high flow of oxygen (8 l.min-1) supplemented with 50% nitrous oxide at loss of consciousness. As soon as BIS was < 60, 20 microg.kg-1 alfentanil and 0.6 mg.kg-1 rocuronium were injected and orotracheal intubation was then performed 1 min later. Thereafter, the end-tidal concentration of sevoflurane was reduced to 1.3 minimum alveolar concentration (MAC). Hypotension was defined as a 30% decrease in arterial pressure and was treated with repeated 3-mg boluses of ephedrine. When 12 mg ephedrine was unable to correct hypotension, the concentration of propofol was reduced by 1 mg.l-1 and that of sevoflurane by 0.5%. Hypotension occurred in 22 patients in the sevoflurane group and 21 in the propofol group, and hypertension occurred in two and three patients in each group, respectively. The maximal reduction in mean (SD) arterial pressure was similar in the sevoflurane (45 (4) mmHg) and propofol (41.3 (2.6) mmHg) groups, as were the ephedrine requirements (9.6 (1.1) vs. 9.1 (1.1) mg, sevoflurane vs. propofol, p > 0.05), the duration of hypotension (276 (37) vs. 292 (38) s, sevoflurane vs. propofol, p > 0.05), and the number of hypotensive episodes or anaesthetic changes and depth of anaesthesia. Nevertheless, heart rate was lower during the 8 min following tracheal intubation in the sevoflurane group. In both groups, the duration of hypotension was easily controlled either by ephedrine or by adjusting the anaesthetic concentrations. Overall, haemodynamic tolerance appears to be similar in the two techniques. Because hypotension occurred after alfentanil in most patients, this study questioned which is the best opioid dose, if any, to associate with propofol or sevoflurane for the induction in hypertensive patients.\n[Drug-Disease]: ephedrine - hypotension" }, { "pmid": "11254118", "target": "[]", "text": "[Title]: Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials.\n[Abstract]: It is currently unclear whether any combination therapy for the treatment of metastatic melanoma is superior to standard single-agent dacarbazine (DTIC) in terms of tumour response and overall survival. The available randomized clinical trial data were combined in a meta-analysis to address this question. Initially a thorough MEDLARS search was conducted covering the time period from January 1970 to January 1999. This literature search was supplemented by manual searches of study bibliographies (including review articles) and review of relevant textbooks. The meta-analysis was performed according to a prospective protocol using strict study eligibility criteria. Data derived from randomized controlled trials comparing single-agent DTIC with combination chemo/immunotherapy were combined using a fixed effects model. Data were stratified into three combination therapy groups: DTIC-containing regimens, non-DTIC-containing therapy, and chemotherapy plus immunotherapy. The primary outcome of interest was the proportion of patients demonstrating a complete or partial response to treatment. A total of 20 randomized trials comprising 3273 patients were initially combined in a meta-analysis. This yielded an odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.02-1.48), demonstrating that combination drug therapies are associated with a 23% increase in response rate compared with single-agent DTIC. The combination of DTIC plus interferon-alpha produced a tumour response rate 53% greater (95% CI 1.10-2.13) than that seen with DTIC alone. This increase was greater than that seen with DTIC-containing multi-drug regimens, which had an OR of 1.33 (95% CI 0.99-1.78). No difference in overall survival was demonstrated. Non-DTIC-containing treatment programmes showed no advantage over DTIC in terms of tumour response rate (OR = 0.77, 95% CI 0.45-1.32). The combination of DTIC and interferon-alpha appears more active than standard single-agent DTIC in metastatic melanoma. Further randomized clinical trials employing a DTIC plus interferon arm are necessary to confirm these results.\n[Drug-Disease]: DTIC - melanoma" }, { "pmid": "11261747", "target": "[\"Span: 11 men and 10 women | Label: Dosage\", \"Span: mean age was 67.3 years +/- 10.0 (range 51-84) | Label: Age\"]", "text": "[Title]: Switching from pergolide to pramipexole in patients with Parkinson's disease.\n[Abstract]: OBJECTIVE/BACKGROUND: To compare the safety and efficacy of pramipexole and pergolide in the treatment of mild to moderate Parkinson's disease (PD). In contrast to pergolide, a D1 and D2 dopamine agonist, pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. No prospective head-to-head comparison studies of pergolide and pramipexole have been reported. METHODS: Patients with PD who were maintained on an optimal dose of pergolide were converted to pramipexole, typically over a one-month period. Clinical assessments were performed just prior to conversion and after an optimal dose of pramipexole was achieved. RESULTS: Twenty-five patients were converted from pergolide to pramipexole during the period of July, 1997 to January, 1999. Three patients were lost to follow-up, and one patient died. Of the remaining 21 patients there were 11 men and 10 women, mean age was 67.3 years +/- 10.0 (range 51-84). Mean duration of symptoms prior to conversion was 12.5 years +/- 3.4 (range 5-19). All patients (except one) were on concomitant carbidopa/ levodopa and experienced motor fluctuations. After a mean follow-up of 5.9 +/- 2.9 months on pramipexole, the mean levodopa daily dose was reduced from 618.7mg to 581.2mg (16.5% reduction, p = 0.61). The mean daily doses of pergolide and pramipexole (in milligrams per day) were 2.1 +/- 1.5 (0.15-6) and 3.2 +/- 1.1 (0.75-6) respectively. Thirteen patients (62%) reported overall improvement (subjective global response) on pramipexole as compared to pergolide, 5 (24%) were unchanged and 3 (14%) reported worsening. Eighteen of the 21 patients (86%) remained on pramipexole after the study period. Although there was a slight trend toward improved scores on pramipexole, the difference was not statistically significant. CONCLUSION: This open label study failed to provide evidence of superior efficacy of either dopamine agonist. It is possible, however, that while somepatients may benefit more from either pergolide or pramipexole, other patients may obtain additional benefit from other DA agonists or combination therapy. Future randomized, controlled, double-blinded therapeutic trials are needed to determine which, if any, dopamine agonist is superior in the treatment of PD.\n[Drug-Disease]: pramipexole - PD" }, { "pmid": "11261747", "target": "[\"Span: 11 men and 10 women | Label: Dosage\", \"Span: mean age was 67.3 years +/- 10.0 (range 51-84) | Label: Age\"]", "text": "[Title]: Switching from pergolide to pramipexole in patients with Parkinson's disease.\n[Abstract]: OBJECTIVE/BACKGROUND: To compare the safety and efficacy of pramipexole and pergolide in the treatment of mild to moderate Parkinson's disease (PD). In contrast to pergolide, a D1 and D2 dopamine agonist, pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. No prospective head-to-head comparison studies of pergolide and pramipexole have been reported. METHODS: Patients with PD who were maintained on an optimal dose of pergolide were converted to pramipexole, typically over a one-month period. Clinical assessments were performed just prior to conversion and after an optimal dose of pramipexole was achieved. RESULTS: Twenty-five patients were converted from pergolide to pramipexole during the period of July, 1997 to January, 1999. Three patients were lost to follow-up, and one patient died. Of the remaining 21 patients there were 11 men and 10 women, mean age was 67.3 years +/- 10.0 (range 51-84). Mean duration of symptoms prior to conversion was 12.5 years +/- 3.4 (range 5-19). All patients (except one) were on concomitant carbidopa/ levodopa and experienced motor fluctuations. After a mean follow-up of 5.9 +/- 2.9 months on pramipexole, the mean levodopa daily dose was reduced from 618.7mg to 581.2mg (16.5% reduction, p = 0.61). The mean daily doses of pergolide and pramipexole (in milligrams per day) were 2.1 +/- 1.5 (0.15-6) and 3.2 +/- 1.1 (0.75-6) respectively. Thirteen patients (62%) reported overall improvement (subjective global response) on pramipexole as compared to pergolide, 5 (24%) were unchanged and 3 (14%) reported worsening. Eighteen of the 21 patients (86%) remained on pramipexole after the study period. Although there was a slight trend toward improved scores on pramipexole, the difference was not statistically significant. CONCLUSION: This open label study failed to provide evidence of superior efficacy of either dopamine agonist. It is possible, however, that while somepatients may benefit more from either pergolide or pramipexole, other patients may obtain additional benefit from other DA agonists or combination therapy. Future randomized, controlled, double-blinded therapeutic trials are needed to determine which, if any, dopamine agonist is superior in the treatment of PD.\n[Drug-Disease]: pergolide - PD" }, { "pmid": "11264156", "target": "[]", "text": "[Title]: A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma.\n[Abstract]: We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 microg/m(2) daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood. 2001;97:1942-1946)\n[Drug-Disease]: topotecan - melanoma" }, { "pmid": "11268500", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: A paclitaxel-containing chemotherapy does not cause central nervous adverse effects: a prospective study in patients with ovarian cancer.\n[Abstract]: BACKGROUND: The objective of this study was to evaluate the possible effects of a paclitaxel containing chemotherapy on different neuropsychological parameters in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. The patients were tested with a battery of different neuropsychological tests before, after 3 cycles and at the end of the chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. The median values of 6 tests performed before the first chemotherapy cycle scored out of the normal range. These patients with deviant test results at the beginning of the paclitaxel/carboplatin infusions did not deteriorate during chemotherapy. We found a statistically significant improvement of the alphabetical cross out test from the first to the third measurement (mean increase = 4.07; 95% confidence interval = [0.99; 7.15]) (p < 0.05), indicating an improvement of the short-term attention, the concentration and the constancy of working during chemotherapy. The other tests failed to show statistically significant changes during chemotherapy (p > 0.05). CONCLUSION: According to our results, a chemotherapy consisting of paclitaxel/carboplatin caused no signs of acute central nervous toxicity or neuropsychological deterioration.\n[Drug-Disease]: carboplatin - epithelial ovarian carcinoma" }, { "pmid": "11268500", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: A paclitaxel-containing chemotherapy does not cause central nervous adverse effects: a prospective study in patients with ovarian cancer.\n[Abstract]: BACKGROUND: The objective of this study was to evaluate the possible effects of a paclitaxel containing chemotherapy on different neuropsychological parameters in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. The patients were tested with a battery of different neuropsychological tests before, after 3 cycles and at the end of the chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. The median values of 6 tests performed before the first chemotherapy cycle scored out of the normal range. These patients with deviant test results at the beginning of the paclitaxel/carboplatin infusions did not deteriorate during chemotherapy. We found a statistically significant improvement of the alphabetical cross out test from the first to the third measurement (mean increase = 4.07; 95% confidence interval = [0.99; 7.15]) (p < 0.05), indicating an improvement of the short-term attention, the concentration and the constancy of working during chemotherapy. The other tests failed to show statistically significant changes during chemotherapy (p > 0.05). CONCLUSION: According to our results, a chemotherapy consisting of paclitaxel/carboplatin caused no signs of acute central nervous toxicity or neuropsychological deterioration.\n[Drug-Disease]: paclitaxel - epithelial ovarian carcinoma" }, { "pmid": "11272779", "target": "[\"Span: 4 mg/0.1 mL | Label: Dosage\"]", "text": "[Title]: Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis.\n[Abstract]: PURPOSE: To report the safety and efficacy of intravitreal triamcinolone in the treatment of inflammatory cystoid macular oedema (CMO) in six patients who were resistant to other forms of therapy. METHODS: An open-label unmasked prospective nonrandomized pilot study of six patients with idiopathic uveitis and visually significant macular oedema, resistant to periocular and/or systemic corticosteroid treatment, was carried out. Baseline examination and investigations were performed, including fundus fluorescein angiography, and the patients were given a single intravitreal injection of triamcinolone (4 mg/0.1 mL). The primary outcome measure was angiographic resolution of CMO. Patients were reviewed at intervals of 2-4 weeks for 12 months. RESULTS: A single intravitreal injection of triamcinolone induced clinical and angiographic resolution of inflammatory macular oedema in all patients for varying periods of time up to 6 months. Five patients experienced increased intraocular pressure to 30 mmHg or greater which required treatment. Two patients developed posterior subcapsular cataract. CONCLUSION: One injection of intravitreal triamcinolone was an effective short-term treatment for resistant CMO in uveitis. As with steroids given by other routes, raised intraocular pressure and cataract may occur. As it was so effective in these eyes with resistant CMO, a larger study is warranted to evaluate this form of therapy.\n[Drug-Disease]: triamcinolone - uveitis" }, { "pmid": "11273312", "target": "[]", "text": "[Title]: Herpes zoster and post-herpetic neuralgia--a clinical trial of aspirin in chloroform for anodyne.\n[Abstract]: Pain associated with Herpes Zoster (HZ) and Post-herpetic Neuralgia (PHN) has been a challenging task to manage with ease. Topical aspirin dissolved in chloroform is an effective means of reducing pain due to HZ and PHN in most patients. The locus of pain origin and analgesia induced by topical aspirin is supposed to be at cutaneous free nerve ending pain receptors. The present study was conduced in fifty two patients of HZ and PHN. Pain intensity before and after the application of drug was measured with help of Sort Form McGill Pain Questionnaire (SE-MPQ). Most of the patients experienced relief of pain within 1-5 minutes after the aspirin-chloroform application. Maximum relief was achieved in about 30-40 minutes and persisted for 5-6 hrs. In the beginning 3-4 applications were required but frequency decreased gradually as the pain abated.\n[Drug-Disease]: aspirin - pain" }, { "pmid": "11273312", "target": "[]", "text": "[Title]: Herpes zoster and post-herpetic neuralgia--a clinical trial of aspirin in chloroform for anodyne.\n[Abstract]: Pain associated with Herpes Zoster (HZ) and Post-herpetic Neuralgia (PHN) has been a challenging task to manage with ease. Topical aspirin dissolved in chloroform is an effective means of reducing pain due to HZ and PHN in most patients. The locus of pain origin and analgesia induced by topical aspirin is supposed to be at cutaneous free nerve ending pain receptors. The present study was conduced in fifty two patients of HZ and PHN. Pain intensity before and after the application of drug was measured with help of Sort Form McGill Pain Questionnaire (SE-MPQ). Most of the patients experienced relief of pain within 1-5 minutes after the aspirin-chloroform application. Maximum relief was achieved in about 30-40 minutes and persisted for 5-6 hrs. In the beginning 3-4 applications were required but frequency decreased gradually as the pain abated.\n[Drug-Disease]: chloroform - pain" }, { "pmid": "11273923", "target": "[\"Span: 11.4 +/- 9.9 mo | Label: Age\", \"Span: 10, 20, and 40 mg/kg | Label: Dosage\"]", "text": "[Title]: Prophylactically-administered rectal acetaminophen does not reduce postoperative opioid requirements in infants and small children undergoing elective cleft palate repair.\n[Abstract]: UNLABELLED: Rectal acetaminophen (Ac) is often administered prophylactically at anesthesia induction for postoperative pain management in small children and is thought to have an opioid-sparing effect. We assessed in this double-blinded, prospective, randomized study early opioid requirements after three doses of Ac (10, 20, and 40 mg/kg versus placebo) in 80 children (ASA physical status I, age 11.4 +/- 9.9 mo) undergoing cleft palate repair. Single Ac plasma concentrations were measured. Pain scores assessed in the postanesthesia care unit of > or = 4 of 10 resulted in the IV administration of 25 microg/kg piritramide, a popular European mu receptor agonist (lockout time, 10 min; maximum 0.125 mg/kg). There were no significant differences between groups with regard to the early postoperative pain scores and the overall cumulative IV opioid requirements. Maximal plasma concentrations achieved were only subtherapeutic (Ac 10 mg/kg: 8 microg/mL; Ac 20 mg/kg: 13 microg/mL; Ac 40 mg/kg: 21 microg/mL after 122, 122, and 121 min, respectively). We conclude that rectal Ac up to 40 mg/kg has no opioid-sparing effect, does not result in analgesic Ac plasma concentrations, and lacks proof of its efficacy in infants and small children undergoing cleft palate repair, whereas titrated IV opioid boluses produced rapid and reliable pain relief. IMPLICATIONS: Acetaminophen is widely used prophylactically for postoperative analgesia in children and is thought to have an opioid-sparing effect. We showed that rectal acetaminophen up to 40 mg/kg administered at anesthesia induction lacked proof of efficacy, whereas IV opioid boluses resulted in reliable pain relief in children undergoing cleft palate repair.\n[Drug-Disease]: acetaminophen - pain" }, { "pmid": "11277962", "target": "[\"Span: aged 12-79 years | Label: Age\", \"Span: 5 mg | Label: Dosage\", \"Span: once daily for 6 weeks | Label: Dosage\"]", "text": "[Title]: Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study.\n[Abstract]: BACKGROUND: Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12-79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. RESULTS: Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. CONCLUSIONS: Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period.\n[Drug-Disease]: Desloratadine - pruritus" }, { "pmid": "11277962", "target": "[\"Span: aged 12-79 years | Label: Age\", \"Span: 5 mg | Label: Dosage\", \"Span: once daily for 6 weeks | Label: Dosage\"]", "text": "[Title]: Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study.\n[Abstract]: BACKGROUND: Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12-79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. RESULTS: Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. CONCLUSIONS: Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period.\n[Drug-Disease]: Desloratadine - urticaria" }, { "pmid": "11279639", "target": "[\"Span: daily dose of 10 mg | Label: Dosage\"]", "text": "[Title]: Arsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: clinicopathological and molecular features of a pilot study.\n[Abstract]: Arsenic trioxide (As2O3) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term administration is unknown. The anthracycline idarubicin is highly active alone or in combination chemotherapy for the treatment of APL. To minimize arsenic exposure and based on the high sensitivity of APL cells to anthracyclines, we conducted a prospective study to evaluate induction with As2O3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As2O3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m(2)/day for 5 days in the first course and 6 mg/m(2)/day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As2O3 treatment. During As2O3 therapy, an increase in white cell count peaking at a median of 17 days occurred in all the cases. Serial flow cytometric analysis of apoptosis, with mitochondrial APO2.7 antigen expression and the sub-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time quantitative polymerase chain reaction, all patients were shown to attain molecular remission after subsequent idarubicin treatment. With a median follow up of 13 months, seven of eight patients have remained in complete clinical remission, with six patients in molecular remission as well. One patient who was in third remission became PCR-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As2O3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As2O3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia.\n[Drug-Disease]: As2O3 - APL" }, { "pmid": "11279639", "target": "[\"Span: 6 mg/m(2)/day | Label: Dosage\"]", "text": "[Title]: Arsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: clinicopathological and molecular features of a pilot study.\n[Abstract]: Arsenic trioxide (As2O3) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term administration is unknown. The anthracycline idarubicin is highly active alone or in combination chemotherapy for the treatment of APL. To minimize arsenic exposure and based on the high sensitivity of APL cells to anthracyclines, we conducted a prospective study to evaluate induction with As2O3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As2O3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m(2)/day for 5 days in the first course and 6 mg/m(2)/day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As2O3 treatment. During As2O3 therapy, an increase in white cell count peaking at a median of 17 days occurred in all the cases. Serial flow cytometric analysis of apoptosis, with mitochondrial APO2.7 antigen expression and the sub-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time quantitative polymerase chain reaction, all patients were shown to attain molecular remission after subsequent idarubicin treatment. With a median follow up of 13 months, seven of eight patients have remained in complete clinical remission, with six patients in molecular remission as well. One patient who was in third remission became PCR-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As2O3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As2O3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia.\n[Drug-Disease]: idarubicin - APL" }, { "pmid": "11284463", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.\n[Abstract]: Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.\n[Drug-Disease]: rizatriptan - migraine" }, { "pmid": "11284463", "target": "[\"Span: 100 mg | Label: Dosage\"]", "text": "[Title]: Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.\n[Abstract]: Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.\n[Drug-Disease]: sumatriptan - migraine" }, { "pmid": "11285152", "target": "[\"Span: aged 3 months to 15 years | Label: Age\"]", "text": "[Title]: Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: a prospective and randomized study.\n[Abstract]: OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as effective as 7-day therapy for children hospitalized for parenteral antimicrobials. METHODS: A series of patients aged 3 months to 15 years who fulfilled strict criteria for bacterial pneumonia, other respiratory infections, sepsis-like infections, and other acute infections were prospectively randomized to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days. Besides blood and throat cultures, the etiology was searched by serology for 23 different agents. RESULTS: Of 154 children analyzed, a probable etiology was established in 96. Of those, a bacterial infection, with or without concomitant viral infection, was disclosed in 80% and 94% in the 4-day and 7-day treatment groups, respectively; pneumococcus being the commonest agent. There was one possible treatment failure in the 4-day group, but with a questionable relation to the short course. Three patients in the 4-day and two in the 7-day group underwent treatment changes, or were rehospitalized within 30 days. All children recovered entirely. CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in infections for which most parenteral antimicrobials are instituted, is not only safe, but reduces costs, is ecologically sound, and minimizes the risks of nosocomial infections and other adverse effects of treatment.\n[Drug-Disease]: cefuroxime - bacterial infection" }, { "pmid": "11285152", "target": "[\"Span: aged 3 months to 15 years | Label: Age\"]", "text": "[Title]: Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: a prospective and randomized study.\n[Abstract]: OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as effective as 7-day therapy for children hospitalized for parenteral antimicrobials. METHODS: A series of patients aged 3 months to 15 years who fulfilled strict criteria for bacterial pneumonia, other respiratory infections, sepsis-like infections, and other acute infections were prospectively randomized to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days. Besides blood and throat cultures, the etiology was searched by serology for 23 different agents. RESULTS: Of 154 children analyzed, a probable etiology was established in 96. Of those, a bacterial infection, with or without concomitant viral infection, was disclosed in 80% and 94% in the 4-day and 7-day treatment groups, respectively; pneumococcus being the commonest agent. There was one possible treatment failure in the 4-day group, but with a questionable relation to the short course. Three patients in the 4-day and two in the 7-day group underwent treatment changes, or were rehospitalized within 30 days. All children recovered entirely. CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in infections for which most parenteral antimicrobials are instituted, is not only safe, but reduces costs, is ecologically sound, and minimizes the risks of nosocomial infections and other adverse effects of treatment.\n[Drug-Disease]: penicillin - bacterial infection" }, { "pmid": "11286510", "target": "[\"Span: four male/five female | Label: Gender\", \"Span: age at diagnosis ranging from 6 days to 14 years | Label: Age\", \"Span: median dose 248 mg/kg/day; range 106-275 | Label: Dosage\"]", "text": "[Title]: Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients.\n[Abstract]: Ornithine transcarbamylase deficiency is a very heterogeneous urea cycle disorder resulting in hyperammonemia with various presentations from the neonatal period through adulthood. We performed a retrospective study in nine patients (four male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate the safety and efficacy of sodium phenylbutyrate (Ammonaps) in long-term treatment. All patients were diagnosed by DNA mutational analysis and/or liver enzyme measurement. They had previously been treated with sodium benzoate (median dose 248 mg/kg/day; range 106-275) and low protein diet (median 0.84 g/kg/day) and were switched to sodium phenylbutyrate (median dose of 352 mg/kg/day) at 8.9 and 4.9 years of age (median) in males and females, respectively. We analyzed clinical and biochemical data and the median follow-up duration was 26 months. During that time, there were no hyperammonemic episodes requiring hospitalization. Median plasma ammonia and glutamine levels were 30 and 902 micromol/L, respectively. Total protein intake could be increased to 0.95 g/kg/day after 18 months. No side effects related to therapy were observed. Further prospective studies should be performed to define the optimal dosage of sodium phenylbutyrate and the requirements for protein diet at different ages.\n[Drug-Disease]: sodium phenylbutyrate - hyperammonemia" }, { "pmid": "11286510", "target": "[\"Span: four male/five female | Label: Gender\", \"Span: age at diagnosis ranging from 6 days to 14 years | Label: Age\", \"Span: median dose of 352 mg/kg/day | Label: Dosage\"]", "text": "[Title]: Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients.\n[Abstract]: Ornithine transcarbamylase deficiency is a very heterogeneous urea cycle disorder resulting in hyperammonemia with various presentations from the neonatal period through adulthood. We performed a retrospective study in nine patients (four male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate the safety and efficacy of sodium phenylbutyrate (Ammonaps) in long-term treatment. All patients were diagnosed by DNA mutational analysis and/or liver enzyme measurement. They had previously been treated with sodium benzoate (median dose 248 mg/kg/day; range 106-275) and low protein diet (median 0.84 g/kg/day) and were switched to sodium phenylbutyrate (median dose of 352 mg/kg/day) at 8.9 and 4.9 years of age (median) in males and females, respectively. We analyzed clinical and biochemical data and the median follow-up duration was 26 months. During that time, there were no hyperammonemic episodes requiring hospitalization. Median plasma ammonia and glutamine levels were 30 and 902 micromol/L, respectively. Total protein intake could be increased to 0.95 g/kg/day after 18 months. No side effects related to therapy were observed. Further prospective studies should be performed to define the optimal dosage of sodium phenylbutyrate and the requirements for protein diet at different ages.\n[Drug-Disease]: sodium benzoate - hyperammonemia" }, { "pmid": "11288046", "target": "[\"Span: 400 mg/d | Label: Dosage\"]", "text": "[Title]: Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.\n[Abstract]: The aim of the present study was to investigate the effect of bezafibrate on insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2 diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL). Insulin sensitivity was measured with homeostasis model assessment insulin resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed by Matthews et al validated against minimal model-derived insulin secretion, was used to assess pancreatic insulin function. Twenty-two patients were treated with glibenclimide and the rest were treated with diet alone. All patients were treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet and the dose of any medications used throughout the study. Fasting glucose, insulin, triglycerides, HDL cholesterol, and total cholesterol levels were measured before and after treatment of bezafibrate. After treatment of bezafibrate for 3 months, serum triglyceride levels significantly decreased from 277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly decreased after the treatment with bezafibrate. HbA1c levels decreased, although not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no significant difference in body mass index (BMI) levels before and after the therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it can be concluded that bezafibrate reduces serum triglycerides, insulin resistance, and fasting blood glucose levels in non-obese Japanese type 2 diabetic patients.\n[Drug-Disease]: bezafibrate - insulin secretion" }, { "pmid": "11288046", "target": "[\"Span: 400 mg/d | Label: Dosage\"]", "text": "[Title]: Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.\n[Abstract]: The aim of the present study was to investigate the effect of bezafibrate on insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2 diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL). Insulin sensitivity was measured with homeostasis model assessment insulin resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed by Matthews et al validated against minimal model-derived insulin secretion, was used to assess pancreatic insulin function. Twenty-two patients were treated with glibenclimide and the rest were treated with diet alone. All patients were treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet and the dose of any medications used throughout the study. Fasting glucose, insulin, triglycerides, HDL cholesterol, and total cholesterol levels were measured before and after treatment of bezafibrate. After treatment of bezafibrate for 3 months, serum triglyceride levels significantly decreased from 277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly decreased after the treatment with bezafibrate. HbA1c levels decreased, although not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no significant difference in body mass index (BMI) levels before and after the therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it can be concluded that bezafibrate reduces serum triglycerides, insulin resistance, and fasting blood glucose levels in non-obese Japanese type 2 diabetic patients.\n[Drug-Disease]: bezafibrate - hypertriglyceridemia" }, { "pmid": "11291531", "target": "[]", "text": "[Title]: Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.\n[Abstract]: OBJECTIVE: To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia. DESIGN: Prospective, randomized, double-blind clinical trial. PATIENTS: 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated. RESULTS: Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills. CONCLUSIONS: These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.\n[Drug-Disease]: quetiapine - cognitive impairment" }, { "pmid": "11291531", "target": "[]", "text": "[Title]: Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.\n[Abstract]: OBJECTIVE: To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia. DESIGN: Prospective, randomized, double-blind clinical trial. PATIENTS: 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated. RESULTS: Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills. CONCLUSIONS: These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.\n[Drug-Disease]: quetiapine - schizophrenia" }, { "pmid": "11291531", "target": "[]", "text": "[Title]: Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.\n[Abstract]: OBJECTIVE: To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia. DESIGN: Prospective, randomized, double-blind clinical trial. PATIENTS: 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated. RESULTS: Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills. CONCLUSIONS: These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.\n[Drug-Disease]: haloperidol - schizophrenia" }, { "pmid": "11295089", "target": "[\"Span: 59 boys and 38 girls | Label: Gender\", \"Span: a median age of 13 +/- 4 years | Label: Age\", \"Span: continuous infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h | Label: Dosage\", \"Span: at a dosage of 75 mg/m2 over 72 h | Label: Dosage\"]", "text": "[Title]: Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction associated with continuous-infusion schedules.\n[Abstract]: We retrospectively reviewed the medical records of 97 children (59 boys and 38 girls) with a median age of 13 +/- 4 years who had been treated with continuous infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h (61 patients) or at a dosage of 75 mg/m2 over 72 h (36 patients). The drug was administered every 3 weeks. The cardiac status of patients was evaluated as a baseline and every 6 months during, and following therapy (median, 30.5 months). The evaluations included M-mode and two-dimensional echocardiography. Congestive heart failure developed in only one patient in this series, an 8-year-old girl who ultimately died of her cardiac complication. This incidence of doxorubicin-induced cardiotoxicity was compared with that seen in a control group of pediatric patients previously treated with doxorubicin at similar dosages but with a rapid infusion. The result compared favorably to the 13% incidence of cardiotoxicity (p = 0.03) and 7% mortality (p < 0.01) in the control group. No changes in the levels of tumor response were noted in children treated by continuous infusion when compared with historical controls. Continuous-infusion schedules of doxorubicin thus result in fewer incidences of cardiotoxicity in children and should be considered for wider application in pediatric cancer patients receiving doxorubicin.\n[Drug-Disease]: doxorubicin - pediatric cancer" }, { "pmid": "11296078", "target": "[\"Span: aged 6 to 18 years | Label: Age\", \"Span: 0.5 to 1 mg/kg | Label: Dosage\"]", "text": "[Title]: Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness.\n[Abstract]: OBJECTIVES: To evaluate the effectiveness of intravenous (IV) ketorolac tromethamine in the treatment of children with sickle cell disease with moderate to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that would determine who would need additional IV analgesics. DESIGN: A prospective case series. SETTING: The emergency department of an urban children's hospital in the southeastern United States. PATIENTS: A convenience sample of 51 children aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV analgesics. INTERVENTION: All patients were given 0.5 to 1 mg/kg IV ketorolac and IV fluids. MAIN OUTCOME MEASURES: Patients, parents, nurses, and physicians assessed pain before and after ketorolac using a standard 100-mm visual analog scale (VAS). RESULTS: Of the 70 episodes of VOP, 37 (53%) adequately resolved with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one episodes (47%) required the addition of an IV opioid (group B). Group B had a significantly greater proportion of episodes reporting 4 or more painful sites than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had significantly higher mean initial VAS scores than group A as assessed by the patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS score greater than 70, 69% (18/26) required the addition of an opioid. CONCLUSIONS: First-line therapy with IV ketorolac and IV fluids resulted in adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or more painful sites and an initial VAS score greater than 70 were predictors of the likelihood to need additional IV analgesics.\n[Drug-Disease]: ketorolac tromethamine - pain" }, { "pmid": "11297832", "target": "[]", "text": "[Title]: Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity.\n[Abstract]: Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.\n[Drug-Disease]: Propranolol - cocaine withdrawal symptoms" }, { "pmid": "11299845", "target": "[\"Span: aged < or = 70 years | Label: Age\", \"Span: 100 mg/m2, i.v., day 1, q3wks x 3 cycles | Label: Dosage\"]", "text": "[Title]: Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the adjuvant treatment of node positive breast cancer: results of a feasibility study.\n[Abstract]: BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. METHODS: The study included patients pts aged < or = 70 years, with operable node positive breast cancer. Two consecutive groups of patients received one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups. CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal treatment administration and limited incidence of G3-G4 side effects. 2) The concomitant use of lenograstin might partially explain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patients.\n[Drug-Disease]: docetaxel - breast cancer" }, { "pmid": "11299845", "target": "[\"Span: aged < or = 70 years | Label: Age\", \"Span: 75 mg/m2, i.v., day 1, q3wks x 3 cycles | Label: Dosage\"]", "text": "[Title]: Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the adjuvant treatment of node positive breast cancer: results of a feasibility study.\n[Abstract]: BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. METHODS: The study included patients pts aged < or = 70 years, with operable node positive breast cancer. Two consecutive groups of patients received one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups. CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal treatment administration and limited incidence of G3-G4 side effects. 2) The concomitant use of lenograstin might partially explain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patients.\n[Drug-Disease]: Doxorubicin - breast cancer" }, { "pmid": "11299847", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients.\n[Abstract]: BACKGROUND: The objective of this study was to evaluate possible effects of a paclitaxel containing chemotherapy, on the central nervous system (CNS) in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. Patients were tested with resting EEG (R-EEG) before and after chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of beta power and an increase of delta and theta power as well as a deceleration of the total centroid frequency clearly demonstrated a reduced vigilance in patients with ovarian cancer compared to healthy controls. On the other hand, the observed increase of beta power, a decrease of delta and theta power, and an acceleration of the total centroid from pre- to post-treatment demonstrated an improvement of vigilance in patients with ovarian cancer after treatment with paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that chemotherapy consisting of paclitaxel and carboplatin does not cause adverse effects on the central nervous system. Improved vigilance was measured in patients with ovarian cancer after chemotherapy.\n[Drug-Disease]: carboplatin - ovarian cancer" }, { "pmid": "11299847", "target": "[\"Span: women | Label: Gender\"]", "text": "[Title]: Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients.\n[Abstract]: BACKGROUND: The objective of this study was to evaluate possible effects of a paclitaxel containing chemotherapy, on the central nervous system (CNS) in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. Patients were tested with resting EEG (R-EEG) before and after chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of beta power and an increase of delta and theta power as well as a deceleration of the total centroid frequency clearly demonstrated a reduced vigilance in patients with ovarian cancer compared to healthy controls. On the other hand, the observed increase of beta power, a decrease of delta and theta power, and an acceleration of the total centroid from pre- to post-treatment demonstrated an improvement of vigilance in patients with ovarian cancer after treatment with paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that chemotherapy consisting of paclitaxel and carboplatin does not cause adverse effects on the central nervous system. Improved vigilance was measured in patients with ovarian cancer after chemotherapy.\n[Drug-Disease]: paclitaxel - ovarian cancer" }, { "pmid": "11300388", "target": "[\"Span: children | Label: Age\", \"Span: 2 microg ml(-1) | Label: Dosage\"]", "text": "[Title]: Postoperative epidural analgesia in children after major orthopaedic surgery. A randomised study of the effect on PONV of two anaesthetic techniques: low and high dose i.v. fentanyl and epidural infusions with and without fentanyl.\n[Abstract]: BACKGROUND: The study was performed in order to improve postoperative pain management in children after major orthopaedic surgery. Two different anaesthetic techniques (sevoflurane-low fentanyl and propofol-higher fentanyl) and two different epidural mixtures (bupivacaine 1.5 mg ml(-1) and adrenaline 2 microg ml(-1) compared with bupivacaine 1 mg ml(-1), adrenaline 2 microg ml(-1) and fentanyl 2 microg ml(-1)) were investigated with regard to postoperative analgesia and side effects, primarily postoperative nausea and vomiting (PONV). METHODS: Forty-two children were randomised into one of three groups: sevoflurane anaesthesia and epidural solution with fentanyl (SBAF); sevoflurane anaesthesia and epidural solution without fentanyl (SBA); propofol anaesthesia and epidural solution without fentanyl (PBA). RESULTS: Including fentanyl in the epidural mixture resulted in excellent postoperative analgesia without any need of i.v. opioids. However, 7 out of 16 children were nauseated and needed antiemetic drugs. On average, a 55-75% higher dose of bupivacaine was necessary to assure adequate analgesia when an epidural mixture without fentanyl was used. In addition, significantly more children needed i.v. opioids. Under these conditions there was no significant difference in pain scoring between the groups. There was significantly less nausea and less use of antiemetic drugs in children having epidurals without fentanyl in the sevoflurane groups. The same tendency, although not significant, was observed in the whole material. Sevoflurane anaesthesia resulted in less PONV than propofol anaesthesia, probably due to the higher amount of intravenous fentanyl used with the latter. This difference was not significant due to the small number of children included. Incidence of pruritus related significantly to epidural fentanyl. CONCLUSION: A satisfactory postoperative analgesia can be achieved with both epidural mixtures used in the study. Epidural fentanyl results in better analgesia, but significantly more PONV and greater use of antiemetic drugs. Omitting epidural fentanyl results in less PONV, but significantly less profound analgesia and a need for additional treatment with i.v. opioids, in addition to a 55-75% higher epidural bupivacaine infusion. Both epidural treatments result in high and similar patient satisfaction and no serious complications. The study could not show any significant difference between the effect of sevoflurane and propofol anaesthesia on PONV.\n[Drug-Disease]: fentanyl - postoperative pain" }, { "pmid": "11300427", "target": "[]", "text": "[Title]: Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure.\n[Abstract]: OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.\n[Drug-Disease]: spironolactone - CHF" }, { "pmid": "11304663", "target": "[\"Span: children | Label: Age\", \"Span: dose of approximately 2 mg/kg/d | Label: Dosage\", \"Span: for 3 to 10 days | Label: Dosage\"]", "text": "[Title]: Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report.\n[Abstract]: Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with alpha1-proteinase inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched controls; no significant changes in plasma alpha 2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/- 7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre- and posttreatment plasma AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.\n[Drug-Disease]: prednisone - NS" }, { "pmid": "11304663", "target": "[\"Span: children | Label: Age\", \"Span: orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days | Label: Dosage\"]", "text": "[Title]: Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report.\n[Abstract]: Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with alpha1-proteinase inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched controls; no significant changes in plasma alpha 2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/- 7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre- and posttreatment plasma AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.\n[Drug-Disease]: EACA - NS" }, { "pmid": "11305068", "target": "[\"Span: 200 mg i.v. | Label: Dosage\"]", "text": "[Title]: Prevention of vinorelbine phlebitis with cimetidine. A two-step design study.\n[Abstract]: One hundred eighteen patients with various malignancies received a total of 847 vinorelbine (VNR) infusions, during 25 of which episodes of vinorelbine phlebitis occurred (1 in each of the 25 patients concerned). Venous irritation was graded with reference to the scale devised by Rittenberg et al. To prevent these 25 patients against further venous toxicity, we pretreated them with cimetidine 200 mg i.v. prior to VNR administration in subsequent cycles of chemotherapy. In most (19, or 76%) complete prevention of recurrent phlebitis was observed, while partial prevention was observed in 5 patients (20%). Treatment was unsuccessful in 1 patient. In 127 VNR infusions given after cimetidine prophylaxis only 7 (6%) episodes of phlebitis occurred. These data show that i.v. administration of cimetidine prior to vinorelbine infusion can successfully prevent recurrence of phlebitis in patients who have shown venous irritation upon prior VNR treatment, at a rate of 94%.\n[Drug-Disease]: cimetidine - phlebitis" }, { "pmid": "11305704", "target": "[]", "text": "[Title]: A comparison of long-term outcome in first-episode schizophrenia following treatment with risperidone or a typical antipsychotic.\n[Abstract]: BACKGROUND: Most reports assessing the efficacy and tolerability of risperidone have involved patients previously treated with typical antipsychotics. Such patients are more likely to have a greater resistance or intolerance to treatment, thus restricting our interpretation of the impact a new treatment might have on the course of schizophrenia and possibly biasing the results. The present study examines the relative effectiveness of risperidone and typical antipsychotics in patients being treated for their first episode of schizophrenia. METHOD: From a cohort of 126 patients, 2 groups of 19 first-episode DSM-III-R/DSM-IV schizophrenia patients matched for age, gender, length of illness, and length of treatment and treated with either a typical antipsychotic or risperidone for a minimum of 1 year were compared on a number of outcome dimensions during their course of treatment and at follow-up. Treatment allocation was not random, and patients were judged to be compliant with medication. Patients treated with typical antipsychotics were followed up for a statistically nonsignificantly longer time (mean = 2.7 vs. 1.9 years). RESULTS: Six patients (31.6%) from the typical antipsychotic group were admitted to the hospital within the first year following the index admission compared with 1 patient (5.3%) in the risperidone group (admitted at month 14). Patients in the risperidone group showed a statistically significantly lower length of first hospitalization (p < .01), utilization of inpatient beds during the course of treatment (p < .001), and use of anticholinergic medication (p < .05). There were no statistically significant differences in symptom levels, either during the course of treatment or at follow-up; in the use of antidepressant, antianxiety, or mood-stabilizing drugs; or in changes in living circumstances or employment. CONCLUSION: These findings confirm at least equal long-term efficacy of typical antipsychotics and risperidone, but a possible advantage for risperidone in decreased service utilization and decreased use of anticholinergic drugs.\n[Drug-Disease]: risperidone - schizophrenia" }, { "pmid": "11307045", "target": "[\"Span: mean age was 63.5 +/- 9.66 years | Label: Dosage\"]", "text": "[Title]: The effect of levodopa on vocal function in Parkinson's disease.\n[Abstract]: Phonatory and articulatory dysfunctions are frequent observations in Parkinson's disease. We have investigated, using acoustic measures, the effects of levodopa treatment on vocal function in 20 patients with Parkinson's disease before and after levodopa. These patients were also compared with a matched control group. The mean age was 63.5 +/- 9.66 years, Hoehn-Yahr stage was 2.38 +/- 0.45, and onset mean age was 56.5 +/- 10.36 years. Paired Wilcoxon tests were performed to compare measurements before and after levodopa. The acoustic analysis using Computerized Speech Lab and MultiDimensional Voice Program software programs (Kay Elemetrics, Lincoln Park, NJ, USA) showed that measurements of fundamental frequency (p < 0.017) were significantly increased after medication, whereas short-term frequency perturbation jitter (p < 0.033), soft phonation index (noise parameter) (p < 0.015 ), and frequency tremor intensity index (p < 0.018) were significantly decreased after medication. The objective measurements of acoustic analysis are useful in evaluating the dopaminergic pharmacologic response in Parkinson's disease. The improvement in fundamental frequency and other vocal parameters may be a result of decrease in laryngeal hypokinesia and rigidity.\n[Drug-Disease]: levodopa - Parkinson's disease" }, { "pmid": "11314621", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Postoperative pain management using intravenous patient-controlled analgesia for pediatric patients.\n[Abstract]: Pain control is an important consideration after any surgical procedures. Especially in children, more attention and care are needed during the period of postoperative pain control, which must be both sufficiently safe and effective. In this respect, intravenous patient-controlled analgesia provides improved titration of analgesic drugs, thereby maintaining optimal analgesic status with few side effects. Thirty pediatric patients were randomly divided into two groups: the intravenous patient-controlled analgesia group (with nalbuphine HCl and ketorolac tromethamine) and the conventional pethidine HCl intramuscular group. The degree of analgesia was assessed every 4 hours until the second postoperative day. The intravenous patient-controlled analgesia group had significantly lower pain scores and took less time until they were able to walk to the bathroom, but as many side effects as the control group. We concluded that intravenous patient-controlled analgesia is safe and effective for pediatric patients who have moderate to severe pain after operations such as rib cartilage graft, iliac bone graft, and large flap surgeries.\n[Drug-Disease]: pethidine HCl - postoperative pain" }, { "pmid": "11314621", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Postoperative pain management using intravenous patient-controlled analgesia for pediatric patients.\n[Abstract]: Pain control is an important consideration after any surgical procedures. Especially in children, more attention and care are needed during the period of postoperative pain control, which must be both sufficiently safe and effective. In this respect, intravenous patient-controlled analgesia provides improved titration of analgesic drugs, thereby maintaining optimal analgesic status with few side effects. Thirty pediatric patients were randomly divided into two groups: the intravenous patient-controlled analgesia group (with nalbuphine HCl and ketorolac tromethamine) and the conventional pethidine HCl intramuscular group. The degree of analgesia was assessed every 4 hours until the second postoperative day. The intravenous patient-controlled analgesia group had significantly lower pain scores and took less time until they were able to walk to the bathroom, but as many side effects as the control group. We concluded that intravenous patient-controlled analgesia is safe and effective for pediatric patients who have moderate to severe pain after operations such as rib cartilage graft, iliac bone graft, and large flap surgeries.\n[Drug-Disease]: nalbuphine HCl - postoperative pain" }, { "pmid": "11314621", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Postoperative pain management using intravenous patient-controlled analgesia for pediatric patients.\n[Abstract]: Pain control is an important consideration after any surgical procedures. Especially in children, more attention and care are needed during the period of postoperative pain control, which must be both sufficiently safe and effective. In this respect, intravenous patient-controlled analgesia provides improved titration of analgesic drugs, thereby maintaining optimal analgesic status with few side effects. Thirty pediatric patients were randomly divided into two groups: the intravenous patient-controlled analgesia group (with nalbuphine HCl and ketorolac tromethamine) and the conventional pethidine HCl intramuscular group. The degree of analgesia was assessed every 4 hours until the second postoperative day. The intravenous patient-controlled analgesia group had significantly lower pain scores and took less time until they were able to walk to the bathroom, but as many side effects as the control group. We concluded that intravenous patient-controlled analgesia is safe and effective for pediatric patients who have moderate to severe pain after operations such as rib cartilage graft, iliac bone graft, and large flap surgeries.\n[Drug-Disease]: ketorolac tromethamine - postoperative pain" }, { "pmid": "11319569", "target": "[]", "text": "[Title]: Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.\n[Abstract]: The objective of this study was to assess the safety and efficacy of long-acting preparations of two commonly used calcium antagonists with particular reference to their effects on heart rate. Twenty patients with chronic stable angina were recruited to a double-blind, double-dummy crossover study of controlled-release diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and underwent clinical assessment, symptom and adverse event reporting, and repeated treadmill exercise tests over a 10- to 11-week period. The main outcome measures were heart rate at rest and exercise, incidence of angina and nitroglycerin use, treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment depression, heart rate at equivalent maximal exercise, and maximal ST-segment depression), and adverse events. Diltiazem CR significantly reduced heart rate at rest and equivalent exercise and incidence of angina and nitroglycerin use compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST-segment depression (but not maximal ST-segment depression) were all significantly improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse events than nifedipine SR. Calcium antagonists with negative chronotropic effects (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting formulation of the latter is used.\n[Drug-Disease]: Diltiazem - angina" }, { "pmid": "11323371", "target": "[]", "text": "[Title]: The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy.\n[Abstract]: UNLABELLED: Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, and we hypothesize that diltiazem can blunt this response. We measured the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure during ECT. Furthermore, we assessed seizure duration by using both the cuff method and two-lead electroencephalogram. We studied 18 patients with a randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem significantly reduced heart rate and mean arterial pressure just after medication, and it also significantly reduced the increases in these variables after ECT, as compared with the placebo. The use of diltiazem was, however, associated with a shortened seizure duration, possibly making ECT less effective. Because of the reduction in seizure duration, the routine administration of diltiazem may not be advisable because it can possibly interfere with the psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is potentially useful for reducing tachycardia and hypertension in high-risk patients. IMPLICATIONS: Diltiazem can blunt acute hyperdynamic responses after electroconvulsive therapy, but seizure duration is also significantly reduced, possibly making this therapy less effective.\n[Drug-Disease]: Diltiazem - seizure" }, { "pmid": "11325488", "target": "[\"Span: 22 M, eight F | Label: Gender\", \"Span: median age 62 | Label: Age\", \"Span: 25mg/m(2) | Label: Dosage\"]", "text": "[Title]: Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer.\n[Abstract]: The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.\n[Drug-Disease]: vinorelbine - non-small cell lung cancer" }, { "pmid": "11325488", "target": "[\"Span: 22 M, eight F | Label: Gender\", \"Span: median age 62 | Label: Age\", \"Span: 25mg/m(2) | Label: Dosage\"]", "text": "[Title]: Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer.\n[Abstract]: The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.\n[Drug-Disease]: carboplatin - non-small cell lung cancer" }, { "pmid": "11327628", "target": "[\"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Effect of acute blood pressure reduction on endothelial function in the brachial artery of patients with essential hypertension.\n[Abstract]: OBJECTIVES: To evaluate the effect of acute blood pressure reduction on endothelium-dependent vasodilation in the peripheral circulation of essential hypertensive patients. DESIGN: A parallel group study; endothelial function measured in 64 essential hypertensive patients before and after (2 h) treatment with nifedipine (20 mg, n = 32) or captopril (50 mg, n = 32), p.o., randomly assigned. METHODS: In hypertensive patients, we evaluated flow-mediated, endothelium-dependent dilation (FMD, high resolution ultrasound) of the brachial artery compared with endothelium-independent response to glyceryl trinitrate (GTN, 25 microg s.l.). Automatic computerized analysis was used to measure brachial artery diameter on end-diastolic frames acquired every second during the study. Sixty-six healthy normotensive subjects were also evaluated to assess the presence of endothelial dysfunction in hypertensive patients. RESULTS: Hypertensive patients showed a significantly (P< 0.01) lower FMD (5.9 +/- 2.5%) as compared to healthy controls (7.7 +/- 3.8%). The response to GTN was similar in normotensive subjects (7.5 +/- 3.1%) and hypertensive patients (7.2 +/- 6.5%). At baseline brachial artery diameter, FMD and response to GTN were similar in the nifedipine- and captopril-treated groups. Nifedipine and captopril similarly reduced blood pressure, but only nifedipine increased heart rate. Acute nifedipine, but not captopril, significantly (P< 0.01) increased brachial artery diameter, while FMD and response to GTN were not modified after nifedipine or captopril. CONCLUSIONS: Endothelial dysfunction in the brachial artery of essential hypertensive patients is not improved by acute blood pressure reduction.\n[Drug-Disease]: nifedipine - hypertensive" }, { "pmid": "11329400", "target": "[\"Span: 5-20 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder.\n[Abstract]: OBJECTIVE: The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. METHOD: Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks. RESULTS: The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants. CONCLUSIONS: Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.\n[Drug-Disease]: olanzapine - schizophrenia or schizoaffective disorder" }, { "pmid": "11329400", "target": "[\"Span: 2-6 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder.\n[Abstract]: OBJECTIVE: The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. METHOD: Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks. RESULTS: The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants. CONCLUSIONS: Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.\n[Drug-Disease]: risperidone - schizophrenia or schizoaffective disorder" }, { "pmid": "11331147", "target": "[\"Span: 6 mg | Label: Dosage\"]", "text": "[Title]: Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism.\n[Abstract]: Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms. Although often moderate to mild in severity, these symptoms are, nevertheless, associated with poorer over-all outcome. Recent studies suggest diminished nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit found in schizophrenia, failure of auditory sensory inhibition. Diminished inhibitory sensory gating also occurs in cocaine addicts, probably because of their increased catecholaminergic neurotransmission, which blocks the inhibition. In the present study, 11 cocaine addicts in the first week of detoxification were recorded electrophysiologically, after which the effects of 6 mg of nicotine gum, were assessed in a double-blind placebo-controlled crossover design. The test was repeated 10 days later. Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days. Although nicotine itself may not be a desirable therapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited therapeutic target for new drug development for the neuropsychiatric sequelae of cocaine addiction.\n[Drug-Disease]: nicotine - psychotic symptoms" }, { "pmid": "11332148", "target": "[]", "text": "[Title]: High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.\n[Abstract]: BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.\n[Drug-Disease]: docetaxel - breast cancer" }, { "pmid": "11332148", "target": "[]", "text": "[Title]: High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.\n[Abstract]: BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.\n[Drug-Disease]: epirubicin - breast cancer" }, { "pmid": "11333992", "target": "[\"Span: 217 black and 877 nonblack patients | Label: Body Type\", \"Span: 6.25 to 50 mg twice daily | Label: Dosage\"]", "text": "[Title]: Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.\n[Abstract]: BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta-blockers may be smaller in black patients than in patients of other races, but it is unknown whether race influences the response to carvedilol in patients with chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials Program, 217 black and 877 nonblack patients (in New York Heart Association class II, III, or IV and with a left ventricular ejection fraction of no more than 0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25 to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and nonblack patients. RESULTS: As compared with placebo, carvedilol lowered the risk of death from any cause or hospitalization for any reason by 48 percent in black patients and by 30 percent in nonblack patients. Carvedilol reduced the risk of worsening heart failure (heart failure leading to death, hospitalization, or a sustained increase in medication) by 54 percent in black patients and by 51 percent in nonblack patients. The ratios of the relative risks associated with carvedilol for these two outcome variables in black as compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42 to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively. Carvedilol also improved functional class, ejection fraction, and the patients' and physicians' global assessments in both the black patients and the nonblack patients. For all these measures of outcome and clinical status, carvedilol was superior to placebo within each racial cohort (P<0.05 in all analyses), and there was no significant interaction between race and treatment (P> 0.05 in all analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure.\n[Drug-Disease]: carvedilol - heart failure" }, { "pmid": "11334319", "target": "[]", "text": "[Title]: Mycophenolate mofetil therapy for children with lupus nephritis refractory to both intravenous cyclosphosphamide and cyclosporine.\n[Abstract]: We describe mycophenolate mofetil (MMF), a new immunosuppressive agent, to be a therapy of two children with lupus nephritis which were refractory to both cyclophosphamide (CyP) and cyclosporine (CsA). After 11- to 12-month course of MMF treatment, all clinical symptoms of lupus disappeared and serum antibodies became negative. MMF might be a promising curative for cyclophosphamide-resistant lupus nephritis in children. Cyclophosphamide intravenous bolus therapy is generally considered to be the treatment for patients with lupus nephritis. However, there is little guidance about what to do if such therapy fails. Recently, a new immunosuppressive agent, mycophenolate mofetil (MMF), has been used to treat cyclophosphamide-resistant lupus nephritis [Dooley et al. 1999, Gaubitz et al. 1999, Glicklich and Acharga 1998] in adults and has been recognized as a promising curative for lupus nephritis. Up to now, MMF has been adopted widely with solid organ transplantation to prevent or reverse acute rejection [Mathew 1998, Morris-Stiff and Jurewicz 1998] and has been used successfully to treat for rheumatoid arthritis refractory to a variety of other drugs. But there is no report about MMF treatment in children with cyclophosphamide-resistant lupus nephritis. We describe our experience with MMF treatment in two Chinese children with lupus nephritis that were refractory not only to cyclophosphamide but also to cyclosporine.\n[Drug-Disease]: MMF - lupus nephritis" }, { "pmid": "11341669", "target": "[\"Span: children | Label: Age\"]", "text": "[Title]: Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment.\n[Abstract]: To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy.\n[Drug-Disease]: famotidine - dyspepsia" }, { "pmid": "11343529", "target": "[\"Span: 50 to 200 mg | Label: Dosage\"]", "text": "[Title]: Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.\n[Abstract]: BACKGROUND: Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported. METHODS: Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings. RESULTS: Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%). CONCLUSION: The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.\n[Drug-Disease]: sertraline - PTSD" }, { "pmid": "11345386", "target": "[]", "text": "[Title]: Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.\n[Abstract]: BACKGROUND: Carvedilol reduces disease progression in heart failure, but to our knowledge, its effects on hospitalizations and costs have not been evaluated. OBJECTIVES: We examined the effects on hospitalization frequency and costs in the U.S. Carvedilol Heart Failure Trials Program. This program consisted of four concurrent, multicenter, double-blind, placebo-controlled studies involving 1,094 patients with New York Heart Association class II to IV heart failure, which treated patients with placebo or carvedilol for up to 15 months (median, 6.5 months). METHODS: Detailed resource utilization data were collected for all hospitalizations occurring between randomization and the end of follow-up. In-patient care costs were estimated based on observed levels of resource use. RESULTS: Compared with placebo, carvedilol reduced the risk of hospitalization for any reason by 29% (p = 0.009), cardiovascular hospitalizations by 28% (p = 0.034) and heart failure hospitalizations by 38% (p = 0.041). Carvedilol also decreased the mean number of hospitalizations per patient (for cardiovascular reasons 30% [p = 0.02], for heart failure 53% [p = 0.03]). Among hospitalized patients, carvedilol reduced severity of illness during hospital admission, as reflected by shorter length of stay and less frequent use of intensive care. For heart failure hospital admissions, carvedilol decreased mean length of stay by 37% (p = 0.03) and mean number of intensive care unit/coronary care unit days by 83% (p = 0.001), with similar effects on cardiovascular admissions. As a result, estimated inpatient care costs with carvedilol were 57% lower for cardiovascular admissions (p = 0.016) and 81% lower for heart failure admissions (p = 0.022). CONCLUSIONS: Carvedilol added to angiotensin-converting enzyme inhibition reduces hospitalization risk as well as severity of illness and resource utilization during admission in patients with chronic heart failure.\n[Drug-Disease]: Carvedilol - chronic heart failure" }, { "pmid": "11352968", "target": "[\"Span: median age, 46 years; range, 28 to 55 years | Label: Age\", \"Span: 90 mg/m2 | Label: Dosage\"]", "text": "[Title]: Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.\n[Abstract]: PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS: No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV. CONCLUSION: Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.\n[Drug-Disease]: epirubicin - breast cancer" }, { "pmid": "11375843", "target": "[\"Span: 5 mg morphine (body weight < or = 70 kg) | Label: Dosage\", \"Span: 10 mg morphine (body weight >70 kg) | Label: Dosage\"]", "text": "[Title]: Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation.\n[Abstract]: In this randomized, double-blinded, parallel-group study, we compared the efficacy of tramadol and morphine administered IV for the management of pain in trauma patients in the prehospital situation. One-hundred-five patients were randomly allocated to receive tramadol (Group T) or morphine (Group M). The initial dose was 100 mg tramadol in Group T and 5 mg morphine (body weight < or = 70 kg) or 10 mg morphine (body weight >70 kg) in Group M; this could be increased to 200 mg in Group T and 15 or 20 mg in Group M if necessary. Pain intensity was assessed with four-point verbal rating scales. Sedation, physiologic data, and adverse events were also recorded. Analgesia was similar in both groups; the 95% confidence interval for the difference between the decrease in pain intensity observed with tramadol or morphine was -0.26 to 0.30, which was within the predefined equivalence range (-0.50 to 0.50). Neither sedation scores nor physiologic data differed between groups. Tramadol is an acceptable alternative to morphine in the prehospital trauma setting.\n[Drug-Disease]: morphine - pain" }, { "pmid": "11375843", "target": "[\"Span: 100 mg | Label: Dosage\"]", "text": "[Title]: Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation.\n[Abstract]: In this randomized, double-blinded, parallel-group study, we compared the efficacy of tramadol and morphine administered IV for the management of pain in trauma patients in the prehospital situation. One-hundred-five patients were randomly allocated to receive tramadol (Group T) or morphine (Group M). The initial dose was 100 mg tramadol in Group T and 5 mg morphine (body weight < or = 70 kg) or 10 mg morphine (body weight >70 kg) in Group M; this could be increased to 200 mg in Group T and 15 or 20 mg in Group M if necessary. Pain intensity was assessed with four-point verbal rating scales. Sedation, physiologic data, and adverse events were also recorded. Analgesia was similar in both groups; the 95% confidence interval for the difference between the decrease in pain intensity observed with tramadol or morphine was -0.26 to 0.30, which was within the predefined equivalence range (-0.50 to 0.50). Neither sedation scores nor physiologic data differed between groups. Tramadol is an acceptable alternative to morphine in the prehospital trauma setting.\n[Drug-Disease]: Tramadol - pain" }, { "pmid": "11377349", "target": "[\"Span: 8 microg/kg | Label: Dosage\"]", "text": "[Title]: Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.\n[Abstract]: This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.\n[Drug-Disease]: dofetilide - arrhythmias" }, { "pmid": "11377349", "target": "[\"Span: 8 microg/kg | Label: Dosage\"]", "text": "[Title]: Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.\n[Abstract]: This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.\n[Drug-Disease]: dofetilide - heart failure" }, { "pmid": "11377349", "target": "[\"Span: 5 mg/kg | Label: Dosage\"]", "text": "[Title]: Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.\n[Abstract]: This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.\n[Drug-Disease]: amiodarone - arrhythmias" }, { "pmid": "11377349", "target": "[\"Span: 5 mg/kg | Label: Dosage\"]", "text": "[Title]: Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.\n[Abstract]: This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.\n[Drug-Disease]: amiodarone - heart failure" }, { "pmid": "11377651", "target": "[]", "text": "[Title]: Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.\n[Abstract]: Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.\n[Drug-Disease]: ifosfamide - pancreatic cancer" }, { "pmid": "11379810", "target": "[\"Span: 400 microg daily | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate.\n[Abstract]: BACKGROUND: Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel). OBJECTIVE: To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks. METHODS: This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy. RESULTS: Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference). CONCLUSIONS: BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.\n[Drug-Disease]: fluticasone propionate - asthma" }, { "pmid": "11379810", "target": "[\"Span: 400 microg daily | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate.\n[Abstract]: BACKGROUND: Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel). OBJECTIVE: To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks. METHODS: This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy. RESULTS: Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference). CONCLUSIONS: BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.\n[Drug-Disease]: BDP - asthma" }, { "pmid": "11379838", "target": "[]", "text": "[Title]: Antidepressant-induced mania in bipolar patients: identification of risk factors.\n[Abstract]: BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.\n[Drug-Disease]: lithium - manic" }, { "pmid": "11379842", "target": "[]", "text": "[Title]: Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study.\n[Abstract]: BACKGROUND: Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials. METHOD: In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension. RESULTS: The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%). CONCLUSION: During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.\n[Drug-Disease]: olanzapine - mania and depression symptoms" }, { "pmid": "11380911", "target": "[\"Span: 30 mg/kg per day | Label: Dosage\"]", "text": "[Title]: Re-treatment for immune globulin-resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy.\n[Abstract]: BACKGROUND: We compared the efficacy and safety of additional intravenous immune globulin (IVIG) therapy with steroid pulse therapy in patients with IVIG-resistant Kawasaki disease. METHODS: Two-hundred and sixty-two consecutive patients had been treated with a single dose of IVIG (2 g/kg) and aspirin (30 mg/kg per day). Thirty-five patients (13.4%) were not clinical responders to the initial IVIG treatment. They received an additional IVIG treatment (1 g/kg) within 48 h after the initial treatment. Seventeen patients (6.5%) did not respond to the additional IVIG treatment. We randomly divided these patients into two groups: group 1 consisted of eight patients who were treated with a single additional dose of IVIG (1 g/kg), while group 2 consisted of nine patients who were treated with steroid pulse therapy. RESULTS: The IVIG-resistant patients had a high incidence of coronary artery lesions (CAL; 48.6%). Five patients (62.5%) in group 1 had CAL, including two patients who each had a giant aneurysm and three patients who each had a small aneurysm. Seven patients (77.8%) in group 2 had CAL, including two patients who each had a giant aneurysm, two patients who each had a small coronary aneurysm and three patients who each showed transient dilatation during steroid pulse therapy. There was no significant difference in the incidence of CAL between the two groups. The duration of high fever in group 2 (1.4~0.7 days) was significantly shorter than in group 1 (4.8~3.4 days; P<0.05). The medical costs for the treatment of patients in group 2 (113, 012 yen +/- 22,084) were significantly lower than those for group 1 (144,194 yen +/- 12,914; P<0.05). CONCLUSIONS: Steroid pulse therapy may be useful in the treatment of patients with IVIG-resistant Kawasaki disease who experience prolonged fever. However, transient dilatation of the coronary artery is observed during steroid pulse therapy, so careful echocardiographic examination should be performed for those patients receiving steroid pulse therapy for the sake of early detection of coronary artery abnormalities.\n[Drug-Disease]: aspirin - Kawasaki disease" }, { "pmid": "11382140", "target": "[\"Span: 900 mg of clodronate in slow intravenous infusions on an outpatient basis in two-week intervals for at least 24 months | Label: Dosage\"]", "text": "[Title]: Bone mineral density in multiple myeloma patients after intravenous clodronate therapy.\n[Abstract]: Bisphosphonates inhibit osteoclastic bone destruction that may be stimulated by myeloma cells. By this way, bisphosphonates carry the potential to lower the number of new pathological fractures, of hypercalcaemic events, and of intensity of bone pain as was published earlier. Clodronate has been administered orally in most clinical studies so far despite of its poor bioavailability from the gastrointestinal tract. The aim of our study was to evaluate bone mineral density (BMD) changes in 34 newly diagnosed multiple myeloma patients regularly treated by 900 mg of clodronate in slow intravenous infusions on an outpatient basis in two-week intervals for at least 24 months. BMD was evaluated by CT scanning every six months. Initial values of trabecular BMD were only about 60 per cent of age- and sex-adjusted healthy population values. Clodronate therapy seemed to preserve BMD within the period of two or three years. This effect was seen not only in patients responding to chemotherapy but even in the small subgroup of patients with persisting active disease. We conclude that the long-term intravenous clodronate therapy may contribute to the preservation of BMD and thus calcium hydroxyapatite in bones in multiple myeloma patients concomitantly treated by chemotherapy. The administration of clodronate should start early in the course of disease, before BMD has been markedly reduced.\n[Drug-Disease]: clodronate - multiple myeloma" }, { "pmid": "11382140", "target": "[]", "text": "[Title]: Bone mineral density in multiple myeloma patients after intravenous clodronate therapy.\n[Abstract]: Bisphosphonates inhibit osteoclastic bone destruction that may be stimulated by myeloma cells. By this way, bisphosphonates carry the potential to lower the number of new pathological fractures, of hypercalcaemic events, and of intensity of bone pain as was published earlier. Clodronate has been administered orally in most clinical studies so far despite of its poor bioavailability from the gastrointestinal tract. The aim of our study was to evaluate bone mineral density (BMD) changes in 34 newly diagnosed multiple myeloma patients regularly treated by 900 mg of clodronate in slow intravenous infusions on an outpatient basis in two-week intervals for at least 24 months. BMD was evaluated by CT scanning every six months. Initial values of trabecular BMD were only about 60 per cent of age- and sex-adjusted healthy population values. Clodronate therapy seemed to preserve BMD within the period of two or three years. This effect was seen not only in patients responding to chemotherapy but even in the small subgroup of patients with persisting active disease. We conclude that the long-term intravenous clodronate therapy may contribute to the preservation of BMD and thus calcium hydroxyapatite in bones in multiple myeloma patients concomitantly treated by chemotherapy. The administration of clodronate should start early in the course of disease, before BMD has been markedly reduced.\n[Drug-Disease]: bisphosphonates - multiple myeloma" }, { "pmid": "11385229", "target": "[\"Span: aged 14-56 years | Label: Age\", \"Span: 8 mg/kg body weight | Label: Dosage\"]", "text": "[Title]: High-dose pulse corticosteroid therapy in the treatment of severe alopecia areata.\n[Abstract]: OBJECTIVE: The present monocenter prospective study was designed to evaluate the efficacy of intravenous high-dose methylprednisolone pulse therapy in patients with severe alopecia areata (AA). METHODS: 30 patients (aged 14-56 years) were treated with methylprednisolone (8 mg/kg body weight) intravenously on 3 consecutive days at 4-week intervals for at least 3 courses. RESULTS: 67% of patients with AA plurifocalis showed >50% regrowth of hair. None of the patients with AA totalis or universalis and only 1 patient with ophiasic AA responded to therapy. In patients with AA plurifocalis, higher response rates could be observed in those suffering from long-term disease compared to patients treated during their first episodes of AA (73 vs. 57%). CONCLUSION: High-dose methylprednisolone pulse therapy is an effective and well-tolerated treatment for patients with severe AA plurifocalis but might be less beneficial for patients with ophasic AA, AA totalis or universalis.\n[Drug-Disease]: methylprednisolone - alopecia areata" }, { "pmid": "11385257", "target": "[\"Span: 12.5 mg | Label: Dosage\"]", "text": "[Title]: Tolerability and efficacy of almotriptan in the long-term treatment of migraine.\n[Abstract]: BACKGROUND: Almotriptan is a highly specific 5-HT(1B/1D) receptor agonist, which acts selectively on blood vessels of the brain. Short-term studies have demonstrated that almotriptan provides rapid, effective and reliable relief of migraine attacks, while offering excellent tolerability. PURPOSE: To assess the long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for every migraine attack over a 1-year period. METHODS: A total of 762 patients treated 13,751 attacks (1-97 per patient); 61.5% of attacks were treated with one 12.5-mg dose, while for 38.5% of attacks, patients took a second dose within 24 h. RESULTS: Three hundred and ninety-one patients (51.3%) experienced a total of 1,617 adverse events (AEs). The majority (88.6%) of AEs were of mild-to-moderate intensity, and only 28.8% of AEs were considered to be related to the study drug. Only 2 patients experienced serious AEs possibly related to almotriptan, syncope and chest pain; both recovered without any sequelae. Patients reported at least 1 AE in 11% of attacks treated. The incidence of AEs decreased during the study. Only 6 (0.8%) study withdrawals were due to AEs considered to be related to almotriptan. Tolerability was not compromised in patients taking 2 doses of almotriptan or in those using migraine prophylactics. Patient age or sex did not influence the incidence of AEs. There was no evidence of tachyphylaxis in those patients completing the study. Pain relief at 2 h after the initial dose was achieved in 84.2% of moderate/severe attacks. Patients were pain free at 2 h after dose in 58.2% of all attacks. Older patients (> 40 years) tended to respond better than younger ones (< 40 years). Efficacy was not modified by use of migraine prophylactics or hormonal contraceptives. Efficacy measurements were consistent on treating repeated moderate/severe migraine attacks. CONCLUSION: This large, open study indicates that the new, specific 5-HT(1B/1D) agonist almotriptan, at a dose of 12.5 mg, is a well tolerated and effective treatment for migraine pain when used over a period of up to 1 year.\n[Drug-Disease]: almotriptan - migraine pain" }, { "pmid": "11385269", "target": "[\"Span: 10-mg | Label: Dosage\"]", "text": "[Title]: Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.\n[Abstract]: Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).\n[Drug-Disease]: rizatriptan - migraine" }, { "pmid": "11385269", "target": "[]", "text": "[Title]: Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.\n[Abstract]: Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).\n[Drug-Disease]: rizatriptan - nausea" }, { "pmid": "11385269", "target": "[]", "text": "[Title]: Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.\n[Abstract]: Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).\n[Drug-Disease]: rizatriptan - phonophobia" }, { "pmid": "11385269", "target": "[]", "text": "[Title]: Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.\n[Abstract]: Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).\n[Drug-Disease]: rizatriptan - photophobia" }, { "pmid": "11385269", "target": "[\"Span: 50-mg | Label: Dosage\"]", "text": "[Title]: Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.\n[Abstract]: Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).\n[Drug-Disease]: sumatriptan - migraine" }, { "pmid": "113900", "target": "[\"Span: 1200 mg daily | Label: Dosage\"]", "text": "[Title]: Demeclocycline in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone.\n[Abstract]: Fourteen patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been treated with demethylchlortetracycline (demeclocycline) 1200 mg daily. In 12 patients the underlying lesion was malignant. The serum sodium returned to normal (greater than 135 mmol/l) in all patients after a mean of 8.6 days (SD +/- 5.3 days). Blood urea rose significantly from the pretreatment level of 4.2 +/- 2.3 mmol/l to 10.1 +/- 5.1 mmol/l at ten days (P less than 0.001). The average maximum blood urea was 13.4 +/- 6.8 mmol/l. In four patients the urea rose above 20 mmol/l, and in two of these demecyocycline was discontinued because of thie rise. The azotaemia could be attributed to a combination of increased urea producation and a mild specific drug-induced nephrotoxicity. Discontinuation of demeclocycline in six patients led to a fall in serum sodium, in one case precipitously, and return of the urea towards normal levels. Demeclocycline appears therefore to be an effective maintenance treatment of SIADH, and the azotaemia that occurs is reversible and probably dose dependent.\n[Drug-Disease]: Demeclocycline - SIADH" }, { "pmid": "11391123", "target": "[\"Span: 100 mg (50 mg twice daily) at 2-week intervals to a final daily regimen of 400 mg twice daily | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind, placebo-controlled, ascending-dose tolerability and safety study of remacemide as adjuvant therapy in Parkinson's disease with response fluctuations.\n[Abstract]: The objective of this study was to establish the maximum tolerated dose of the low affinity non-competitive N-methyl-D-aspartate receptor antagonist remacemide in patients who have Parkinson's disease with response fluctuations or dyskinesias, or both. A total of 33 patients were randomly assigned in a 3-to-1 ratio to receive remacemide or placebo. Remacemide was administered orally at 150 mg twice daily, increasing incrementally by 100 mg (50 mg twice daily) at 2-week intervals to a final daily regimen of 400 mg twice daily or until a maximum tolerated dose was identified. The maximum total treatment period was 12 weeks. Of the 23 patients randomly selected to receive remacemide, four completed the study at the maximum permitted dose, compared with four of the 10 patients given placebo. The median maximum tolerated dose of remacemide was 450 mg/d. There was no clinically relevant change in percentage of \"on\" time between baseline and maximum tolerated dose in either group. At the maximum tolerated dose of remacemide for each patient, the mean Unified Parkinson's Disease Rating Scale (UPDRS) motor examination score (part III) decreased from 33 (SD = 18) to 26 (SD = 13) compared with a decrease from 28 (SD = 12) to 27 (SD = 8) in the placebo group. There was a decrease in the mean UPDRS \"complications of therapy\" score (part IV) in the remacemide group from 8 (SD = 4) to 6 (SD = 4), and the placebo group remained unchanged at 6 (SD = 4). The most common adverse events associated with remacemide were nausea, vomiting, dizziness, headache, abnormal vision, and hypokinesia. Remacemide was well tolerated at a dose level of 400 mg/d. There was a trend suggesting that remacemide was effective in improving symptoms at patients' individual maximum tolerated doses. These improvements occurred without exacerbating levodopa-induced dyskinesias.\n[Drug-Disease]: remacemide - Parkinson's Disease" }, { "pmid": "11391124", "target": "[\"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol.\n[Abstract]: In a series of earlier studies, an oral dose of 0.5 mg/kg d-amphetamine was administered to 81 patients with schizophrenia and eight normal control subjects. Seven more subjects with schizophrenia received placebo. Blood pressure and pulse rate were monitored before and 3 hours after drug administration. Blood pressure increased in both amphetamine groups, whereas placebo had no effect. However, pulse rate did not change in the schizophrenic group and only increased after 3 hours in normal control subjects as blood pressure began to decrease. Significant negative correlations between systolic blood pressure and pulse rate occurred at 2 and 3 hours, suggesting that the early cardiovascular response to amphetamine is an increase in blood pressure that recruits reflex control of heart rate. Eighteen of these subjects had hypertensive responses. Six subjects received 5 mg haloperidol intramuscularly, and 12 others had their blood pressure monitored until normalization. Haloperidol led to a more rapid decline of some but not all indices of blood pressure, suggesting that amphetamine-induced hypertension may have a dopaminergic component.\n[Drug-Disease]: Haloperidol - hypertension" }, { "pmid": "11391748", "target": "[\"Span: 200 mg | Label: Dosage\"]", "text": "[Title]: Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.\n[Abstract]: Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on levodopa-induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2-hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinson's Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa-induced dyskinesias by 50%without any loss of the anti-parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.\n[Drug-Disease]: amantadine - dyskinesias" }, { "pmid": "11391748", "target": "[]", "text": "[Title]: Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.\n[Abstract]: Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on levodopa-induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2-hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinson's Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa-induced dyskinesias by 50%without any loss of the anti-parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.\n[Drug-Disease]: levodopa - Parkinson's Disease" }, { "pmid": "11394734", "target": "[\"Span: RBC 400 mg BID | Label: Dosage\", \"Span: 2 weeks of RBC 400 mg BID | Label: Dosage\"]", "text": "[Title]: Lansoprazole-based triple therapy versus ranitidine bismuth citrate-based dual therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer: a multicenter, randomized, double-dummy study.\n[Abstract]: BACKGROUND: The optimal treatment regimen for eradication of Helicobacter pylori in patients with duodenal ulcer has yet to be determined. Based on a search of MEDLINE, no studies have been performed comparing a proton pump inhibitor-based triple therapy regimen with a ranitidine bismuth citrate (RBC)-based dual therapy regimen, both containing clarithromycin. OBJECTIVE: This study was undertaken to compare the efficacy of lansoprazole (LAN)-based triple therapy with that of RBC-based dual therapy in H pylori-infected patients with duodenal ulcer. METHODS: Patients were randomized to receive either 1 week of triple therapy with LAN 30 mg BID, clarithromycin 500 mg BID, and tinidazole 500 mg BID, followed by 3 weeks of LAN 30 mg BID, or 2 weeks of dual therapy with RBC 400 mg BID plus clarithromycin 500 mg BID, followed by 2 weeks of RBC 400 mg BID. Eradication of H pylori was defined as negative results on both the urease quick test and histologic examination > or =4 weeks after the end of treatment. Duodenal healing and recurrence rates were assessed endoscopically at 8 weeks and 6 months. A per-protocol (PP) analysis was conducted for each efficacy end point. Also conducted were an intent-to-treat (ITT) analysis in which patients with missing data were considered failures, and an observed analysis (OBS), which included patients with an evaluable result after treatment, regardless of compliance. RESULTS: One hundred eighty-five patients (126 men, 59 women; age range, 18-76 years; mean age, 43 years) were enrolled and randomized to treatment. In the LAN and RBC groups, respectively, H. pylori eradication rates were 92.6%, 93.1%, and 72.8% versus 78.6%, 77.9%, and 64.5% in the PP (P = 0.02), OBS (P = 0.01), and ITT analyses. The corresponding duodenal ulcer healing rates were 98.6%, 98.7%, and 83.7% versus 90.8%, 91.5%, and 81.7%; these differences were not statistically significant. Side effects were mild, occurring in 20.7% of LAN patients and 17.2% of RBC patients. Ulcer recurred in 2 RBC patients. No difference was observed between treatments in terms of the occurrence of gastritis or improvement of symptoms. CONCLUSION: Based on the results of the PP and OBS analyses, LAN-based triple therapy was superior to RBC-based dual therapy for the eradication of H. pylori in patients with duodenal ulcer.\n[Drug-Disease]: RBC - H pylori-infected" }, { "pmid": "11394734", "target": "[\"Span: 500 mg BID | Label: Dosage\"]", "text": "[Title]: Lansoprazole-based triple therapy versus ranitidine bismuth citrate-based dual therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer: a multicenter, randomized, double-dummy study.\n[Abstract]: BACKGROUND: The optimal treatment regimen for eradication of Helicobacter pylori in patients with duodenal ulcer has yet to be determined. Based on a search of MEDLINE, no studies have been performed comparing a proton pump inhibitor-based triple therapy regimen with a ranitidine bismuth citrate (RBC)-based dual therapy regimen, both containing clarithromycin. OBJECTIVE: This study was undertaken to compare the efficacy of lansoprazole (LAN)-based triple therapy with that of RBC-based dual therapy in H pylori-infected patients with duodenal ulcer. METHODS: Patients were randomized to receive either 1 week of triple therapy with LAN 30 mg BID, clarithromycin 500 mg BID, and tinidazole 500 mg BID, followed by 3 weeks of LAN 30 mg BID, or 2 weeks of dual therapy with RBC 400 mg BID plus clarithromycin 500 mg BID, followed by 2 weeks of RBC 400 mg BID. Eradication of H pylori was defined as negative results on both the urease quick test and histologic examination > or =4 weeks after the end of treatment. Duodenal healing and recurrence rates were assessed endoscopically at 8 weeks and 6 months. A per-protocol (PP) analysis was conducted for each efficacy end point. Also conducted were an intent-to-treat (ITT) analysis in which patients with missing data were considered failures, and an observed analysis (OBS), which included patients with an evaluable result after treatment, regardless of compliance. RESULTS: One hundred eighty-five patients (126 men, 59 women; age range, 18-76 years; mean age, 43 years) were enrolled and randomized to treatment. In the LAN and RBC groups, respectively, H. pylori eradication rates were 92.6%, 93.1%, and 72.8% versus 78.6%, 77.9%, and 64.5% in the PP (P = 0.02), OBS (P = 0.01), and ITT analyses. The corresponding duodenal ulcer healing rates were 98.6%, 98.7%, and 83.7% versus 90.8%, 91.5%, and 81.7%; these differences were not statistically significant. Side effects were mild, occurring in 20.7% of LAN patients and 17.2% of RBC patients. Ulcer recurred in 2 RBC patients. No difference was observed between treatments in terms of the occurrence of gastritis or improvement of symptoms. CONCLUSION: Based on the results of the PP and OBS analyses, LAN-based triple therapy was superior to RBC-based dual therapy for the eradication of H. pylori in patients with duodenal ulcer.\n[Drug-Disease]: tinidazole - H pylori-infected" }, { "pmid": "11394734", "target": "[\"Span: 500 mg BID | Label: Dosage\"]", "text": "[Title]: Lansoprazole-based triple therapy versus ranitidine bismuth citrate-based dual therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer: a multicenter, randomized, double-dummy study.\n[Abstract]: BACKGROUND: The optimal treatment regimen for eradication of Helicobacter pylori in patients with duodenal ulcer has yet to be determined. Based on a search of MEDLINE, no studies have been performed comparing a proton pump inhibitor-based triple therapy regimen with a ranitidine bismuth citrate (RBC)-based dual therapy regimen, both containing clarithromycin. OBJECTIVE: This study was undertaken to compare the efficacy of lansoprazole (LAN)-based triple therapy with that of RBC-based dual therapy in H pylori-infected patients with duodenal ulcer. METHODS: Patients were randomized to receive either 1 week of triple therapy with LAN 30 mg BID, clarithromycin 500 mg BID, and tinidazole 500 mg BID, followed by 3 weeks of LAN 30 mg BID, or 2 weeks of dual therapy with RBC 400 mg BID plus clarithromycin 500 mg BID, followed by 2 weeks of RBC 400 mg BID. Eradication of H pylori was defined as negative results on both the urease quick test and histologic examination > or =4 weeks after the end of treatment. Duodenal healing and recurrence rates were assessed endoscopically at 8 weeks and 6 months. A per-protocol (PP) analysis was conducted for each efficacy end point. Also conducted were an intent-to-treat (ITT) analysis in which patients with missing data were considered failures, and an observed analysis (OBS), which included patients with an evaluable result after treatment, regardless of compliance. RESULTS: One hundred eighty-five patients (126 men, 59 women; age range, 18-76 years; mean age, 43 years) were enrolled and randomized to treatment. In the LAN and RBC groups, respectively, H. pylori eradication rates were 92.6%, 93.1%, and 72.8% versus 78.6%, 77.9%, and 64.5% in the PP (P = 0.02), OBS (P = 0.01), and ITT analyses. The corresponding duodenal ulcer healing rates were 98.6%, 98.7%, and 83.7% versus 90.8%, 91.5%, and 81.7%; these differences were not statistically significant. Side effects were mild, occurring in 20.7% of LAN patients and 17.2% of RBC patients. Ulcer recurred in 2 RBC patients. No difference was observed between treatments in terms of the occurrence of gastritis or improvement of symptoms. CONCLUSION: Based on the results of the PP and OBS analyses, LAN-based triple therapy was superior to RBC-based dual therapy for the eradication of H. pylori in patients with duodenal ulcer.\n[Drug-Disease]: clarithromycin - H pylori-infected" }, { "pmid": "11394734", "target": "[\"Span: 30 mg BID | Label: Dosage\", \"Span: 3 weeks of LAN 30 mg BID | Label: Dosage\"]", "text": "[Title]: Lansoprazole-based triple therapy versus ranitidine bismuth citrate-based dual therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer: a multicenter, randomized, double-dummy study.\n[Abstract]: BACKGROUND: The optimal treatment regimen for eradication of Helicobacter pylori in patients with duodenal ulcer has yet to be determined. Based on a search of MEDLINE, no studies have been performed comparing a proton pump inhibitor-based triple therapy regimen with a ranitidine bismuth citrate (RBC)-based dual therapy regimen, both containing clarithromycin. OBJECTIVE: This study was undertaken to compare the efficacy of lansoprazole (LAN)-based triple therapy with that of RBC-based dual therapy in H pylori-infected patients with duodenal ulcer. METHODS: Patients were randomized to receive either 1 week of triple therapy with LAN 30 mg BID, clarithromycin 500 mg BID, and tinidazole 500 mg BID, followed by 3 weeks of LAN 30 mg BID, or 2 weeks of dual therapy with RBC 400 mg BID plus clarithromycin 500 mg BID, followed by 2 weeks of RBC 400 mg BID. Eradication of H pylori was defined as negative results on both the urease quick test and histologic examination > or =4 weeks after the end of treatment. Duodenal healing and recurrence rates were assessed endoscopically at 8 weeks and 6 months. A per-protocol (PP) analysis was conducted for each efficacy end point. Also conducted were an intent-to-treat (ITT) analysis in which patients with missing data were considered failures, and an observed analysis (OBS), which included patients with an evaluable result after treatment, regardless of compliance. RESULTS: One hundred eighty-five patients (126 men, 59 women; age range, 18-76 years; mean age, 43 years) were enrolled and randomized to treatment. In the LAN and RBC groups, respectively, H. pylori eradication rates were 92.6%, 93.1%, and 72.8% versus 78.6%, 77.9%, and 64.5% in the PP (P = 0.02), OBS (P = 0.01), and ITT analyses. The corresponding duodenal ulcer healing rates were 98.6%, 98.7%, and 83.7% versus 90.8%, 91.5%, and 81.7%; these differences were not statistically significant. Side effects were mild, occurring in 20.7% of LAN patients and 17.2% of RBC patients. Ulcer recurred in 2 RBC patients. No difference was observed between treatments in terms of the occurrence of gastritis or improvement of symptoms. CONCLUSION: Based on the results of the PP and OBS analyses, LAN-based triple therapy was superior to RBC-based dual therapy for the eradication of H. pylori in patients with duodenal ulcer.\n[Drug-Disease]: LAN - H pylori-infected" }, { "pmid": "11395245", "target": "[\"Span: 12 females, 25 males | Label: Gender\", \"Span: 0.8-13 years and 12-27 years | Label: Age\"]", "text": "[Title]: Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis.\n[Abstract]: PURPOSE: To evaluate the long-term brain metabolite changes on (1)H-MRS in acute lymphoblastic leukemia (ALL) patients who had intrathecal methotrexate (ITMTX) and cranial irradiation (CRT) for central nervous system (CNS) prophylaxis against CNS relapse. METHODS AND MATERIALS: Thirty-seven ALL patients (12 females, 25 males) with history of ITMTX and CRT for CNS prophylaxis were studied. Age ranges at the time of diagnosis and at magnetic resonance examination were 0.8-13 years and 12-27 years, respectively. The interval since diagnosis was 5.6-19 years. T2-weighted and gradient-recalled echo (GRE) magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H-MRS) were performed to assess brain injury. RESULTS: On MRI, 3 leukoencephalopathy (LEP) and 1 infarct were detected. Twenty-two patients had evidence of hemosiderin. On (1)H-MRS no statistically significant difference in choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cr was associated with LEP. A lower Cho/Cr (p = 0.006) and NAA/Cr (p = 0.078) was observed in brains with hemosiderin. Linear-regression analysis showed no statistically significant relationship between NAA/Cr or Cho/Cr with age at diagnosis, but there was a statistically significant decreasing trend of NAA/Cr and Cho/Cr with the interval since diagnosis. CONCLUSION: Long-term brain injury in ALL survivors after CNS prophylaxis with ITMTX and CRT was reflected by decreasing NAA/Cr and Cho/Cr with the interval since diagnosis. The lower Cho/Cr associated with hemosiderin but not LEP suggested a different pathophysiology for these brain lesions.\n[Drug-Disease]: methotrexate - acute lymphoblastic leukemia" }, { "pmid": "11398877", "target": "[\"Span: 80 mg/m2 i.v. | Label: Dosage\"]", "text": "[Title]: A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer.\n[Abstract]: BACKGROUND: Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC). In order to compare the TEP combination to cisplatin etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naive patients with histologically proven limited or extensive stage SCLC were randomised to receive either paclitaxel 175 mg/m2 i.v. three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v. on day 2 and etoposide 80 mg/m2 i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15) or cisplatin 80 mg/m2 i.v. on day 1 and etoposide 120 mg/m2 i.v. on days 1-3 in cycles every twenty-eight days. RESULTS: Due to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed. Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis. In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI): 37.5%-62.4%) for TEP and 48% (95%) CI: 36.2%-59.5%) for EP (P = 0.8). The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0.04). However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0.001). Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3-4 thrombocytopenia (P = 0.02), febrile neutropenia (P = 0.08), grade 3-4 diarrhea (P = 0.01), grade 3-4 asthenia (P = 0.05) and grade 3 neurotoxicity (P = 0.06). CONCLUSIONS: In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen. The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting. For future investigations, dose and schedule modifications are necessary to reduce toxicity.\n[Drug-Disease]: cisplatin - SCLC" }, { "pmid": "11398877", "target": "[\"Span: 120 mg/m2 i.v. | Label: Dosage\", \"Span: 80 mg/m2 i.v. | Label: Dosage\"]", "text": "[Title]: A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer.\n[Abstract]: BACKGROUND: Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC). In order to compare the TEP combination to cisplatin etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naive patients with histologically proven limited or extensive stage SCLC were randomised to receive either paclitaxel 175 mg/m2 i.v. three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v. on day 2 and etoposide 80 mg/m2 i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15) or cisplatin 80 mg/m2 i.v. on day 1 and etoposide 120 mg/m2 i.v. on days 1-3 in cycles every twenty-eight days. RESULTS: Due to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed. Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis. In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI): 37.5%-62.4%) for TEP and 48% (95%) CI: 36.2%-59.5%) for EP (P = 0.8). The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0.04). However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0.001). Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3-4 thrombocytopenia (P = 0.02), febrile neutropenia (P = 0.08), grade 3-4 diarrhea (P = 0.01), grade 3-4 asthenia (P = 0.05) and grade 3 neurotoxicity (P = 0.06). CONCLUSIONS: In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen. The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting. For future investigations, dose and schedule modifications are necessary to reduce toxicity.\n[Drug-Disease]: etoposide - SCLC" }, { "pmid": "11402364", "target": "[\"Span: 40 mg once a day | Label: Dosage\"]", "text": "[Title]: Prophylaxis of thromboembolism in spinal injuries--results of enoxaparin used in 276 patients.\n[Abstract]: OBJECTIVE: To evaluate the results of thromboembolic prophylaxis using enoxaparin in acute spinal injury patients. BACKGROUND: Deep vein thrombosis and pulmonary embolism are major causes of morbidity and mortality in patients with acute spinal injuries. A wide range of thromboprophylactic measures have been proposed. The present study describes the outcome of a regime of enoxaparin and antithromboembolic stockings in acute spinal injuries irrespective of neurological damage. SETTING: Scotland, UK. METHODS: Eighteen-month retrospective review of acute spinal injury patients admitted to a national spinal injuries unit. A thromboembolic prophylactic regimen of early mobilisation, use of antithromboembolic stockings, and subcutaneous administration of enoxaparin 40 mg once a day until patients could be mobilised for more than 4 h per day, was used. Patients with clinical suspicion of deep venous thrombosis or pulmonary embolism were investigated as appropriate. RESULTS: Out of 146 (53% of total) patients with spinal injuries with no neurological deficit only one patient (0.4%) developed clinical evidence of pulmonary embolism and out of 130 (47% of total) with spinal cord injury two (0.7%) developed clinical evidence of deep venous thrombosis while still on enoxaparin. Four patients (1.5%) developed deep venous thrombosis and one (0.4%) pulmonary embolism after discontinuing enoxaparin. There were no fatal pulmonary emboli and one suspected intraspinal bleeding. CONCLUSIONS: The present study suggests that, in addition to physical and mechanical measures, low molecular weight heparin in the form of enoxaparin 40 mg administered once daily compares favourably with previous studies for thromboprophylaxis in acute spinal injuries.\n[Drug-Disease]: enoxaparin - pulmonary emboli" }, { "pmid": "11402364", "target": "[\"Span: 40 mg once a day | Label: Dosage\"]", "text": "[Title]: Prophylaxis of thromboembolism in spinal injuries--results of enoxaparin used in 276 patients.\n[Abstract]: OBJECTIVE: To evaluate the results of thromboembolic prophylaxis using enoxaparin in acute spinal injury patients. BACKGROUND: Deep vein thrombosis and pulmonary embolism are major causes of morbidity and mortality in patients with acute spinal injuries. A wide range of thromboprophylactic measures have been proposed. The present study describes the outcome of a regime of enoxaparin and antithromboembolic stockings in acute spinal injuries irrespective of neurological damage. SETTING: Scotland, UK. METHODS: Eighteen-month retrospective review of acute spinal injury patients admitted to a national spinal injuries unit. A thromboembolic prophylactic regimen of early mobilisation, use of antithromboembolic stockings, and subcutaneous administration of enoxaparin 40 mg once a day until patients could be mobilised for more than 4 h per day, was used. Patients with clinical suspicion of deep venous thrombosis or pulmonary embolism were investigated as appropriate. RESULTS: Out of 146 (53% of total) patients with spinal injuries with no neurological deficit only one patient (0.4%) developed clinical evidence of pulmonary embolism and out of 130 (47% of total) with spinal cord injury two (0.7%) developed clinical evidence of deep venous thrombosis while still on enoxaparin. Four patients (1.5%) developed deep venous thrombosis and one (0.4%) pulmonary embolism after discontinuing enoxaparin. There were no fatal pulmonary emboli and one suspected intraspinal bleeding. CONCLUSIONS: The present study suggests that, in addition to physical and mechanical measures, low molecular weight heparin in the form of enoxaparin 40 mg administered once daily compares favourably with previous studies for thromboprophylaxis in acute spinal injuries.\n[Drug-Disease]: enoxaparin - deep venous thrombosis" }, { "pmid": "11403364", "target": "[\"Span: aged 40-79 | Label: Age\", \"Span: 50/ 100 mg | Label: Dosage\"]", "text": "[Title]: Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.\n[Abstract]: OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.\n[Drug-Disease]: atenolol - hypertensive" }, { "pmid": "11403364", "target": "[\"Span: aged 40-79 | Label: Age\", \"Span: 1.25/2.5 mg | Label: Dosage\"]", "text": "[Title]: Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.\n[Abstract]: OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.\n[Drug-Disease]: bendroflumethiazide - hypertensive" }, { "pmid": "11403364", "target": "[\"Span: aged 40-79 | Label: Age\", \"Span: 5/ 10 mg | Label: Dosage\"]", "text": "[Title]: Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.\n[Abstract]: OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.\n[Drug-Disease]: amlodipine - hypertensive" }, { "pmid": "11403364", "target": "[\"Span: aged 40-79 | Label: Age\", \"Span: 4/8 mg | Label: Dosage\"]", "text": "[Title]: Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.\n[Abstract]: OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.\n[Drug-Disease]: perindopril - hypertensive" }, { "pmid": "11403367", "target": "[\"Span: left ventricular hypertrophy | Label: Body Type\", \"Span: 150 mg q.d. | Label: Dosage\"]", "text": "[Title]: Regression of left ventricular hypertrophy in human hypertension with irbesartan.\n[Abstract]: BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.\n[Drug-Disease]: irbesartan - left ventricular hypertrophy" }, { "pmid": "11403367", "target": "[\"Span: left ventricular hypertrophy | Label: Body Type\", \"Span: 50 mg q.d. | Label: Dosage\"]", "text": "[Title]: Regression of left ventricular hypertrophy in human hypertension with irbesartan.\n[Abstract]: BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.\n[Drug-Disease]: atenolol - left ventricular hypertrophy" }, { "pmid": "11404165", "target": "[\"Span: 10 to 21 years old (mean age 16.9 years) | Label: Age\"]", "text": "[Title]: Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients.\n[Abstract]: BACKGROUND: Hyperlipidemia is common after cardiac transplantation and it is a risk factor for post-transplantation coronary artery disease. Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia. Pravastatin, a HMG-CoA reductase inhibitor, has been shown to be effective and safe for cholesterol reduction in adult heart transplant recipients. To our knowledge the safety and efficacy of pravastatin therapy in pediatric and adolescent heart transplant populations have not been previously analyzed. Therefore, we evaluated lipid profiles, liver transaminases, rejection data, and possible side effects in pediatric and adolescent cardiac transplant recipients treated with pravastatin. METHODS: The study group consisted of 40 cardiac transplant recipients 10 to 21 years old (mean age 16.9 years). Twenty-two patients received pravastatin in addition to an immunosuppressive regimen of either cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil, and prednisone. Serial determinations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides were available for all pravastatin-treated patients. Pre-treatment lipid values and hepatic transaminases were compared with those measured after therapy with pravastatin. Comparison of pravastatin-induced lipid reduction between groups treated with cyclosporine vs tacrolimus was also made. RESULTS: Patients receiving pravastatin experienced a mean 32 mg/dl decrease in TC (p < 0.005) and a mean 31 mg/dl decrease in LDL (p < 0.005), regardless of their immunosuppressive regimen. No statistical differences occurred in the magnitude of mean lipid reduction induced by pravastatin between the groups treated with cyclosporine vs tacrolimus. No significant changes in hepatic transaminase levels were noted, and no clinical evidence of pravastatin-induced myositis occurred in any subjects. CONCLUSION: Pravastatin therapy is effective and safe when used in pediatric and adolescent cardiac transplant recipients. Although the pravastatin-induced reduction in TC and LDL was more pronounced in patients receiving cyclosporine, the reduction was not statistically different from that in the tacrolimus group. No evidence of hepatic dysfunction or rhabdomyolysis in patients treated with pravastatin was noted. Long-term studies are required to evaluate the effect of pravastatin therapy on the incidence of accelerated coronary atherosclerosis in this population.\n[Drug-Disease]: pravastatin - hyperlipidemia" }, { "pmid": "11406335", "target": "[\"Span: 0, 50, and 100 mg | Label: Dosage\"]", "text": "[Title]: Analgesic profile of peroral and topical ketoprofen upon low pH-induced muscle pain.\n[Abstract]: Topical analgesics are widely marketed for treatment of muscle and joint pain. We have recently developed a model of muscle pain and have used this model to evaluate the efficacy of commercially available topical and peroral ketoprofen in order to evaluate the time- and dose-dependence of analgesia. In the present study, we examined the dose- (0, 50, and 100 mg) and time-dependence (hourly to 8 h) of commercially available peroral and topical ketoprofen. In order to achieve infusion times of 8 h (and thus study the time course of analgesic action), we adapted the model of low pH-induced muscle pain in humans to these requirements by applying the infusions continuously for 10 min every hour for 8 h. We found that the 10 min infusion produced reliable and consistent pain levels that were reproducible over the 8 h of the study. The study was performed double-blind, randomized, and with a 1-week interval between each of five different sessions (cross-over). Altogether six volunteers underwent intramuscular infusions of isotonic phosphate-buffered saline solution of pH 5.2; during each 8 h session the infusion was switched on eight times with a duration of 10 min at 50 min intervals (there was no infusion during the 50 min interval). The intramuscular infusion of low pH phosphate buffer induced a localized dull-aching or stinging muscle pain sensation; the flow rate of the pH infusion was individually adjusted to induce pain of a magnitude of 20% on a visual analogue scale (ranging from \"no pain\" (0%) to \"unbearable pain\" (100%)). Twenty minutes after starting the infusion the volunteers received a capsule with either a placebo or 50 or 100 mg ketoprofen perorally and, in addition, either placebo gel or 50 or 100 mg of a 2.5% commercial ketoprofen gel was applied topically to the skin. One of the sessions included a placebo gel and an oral placebo. The intensity of the recurrent pain stimulus was significantly reduced by 59% following administration of 100 mg peroral ketoprofen within the first 3 h (P<0.03, Wilcoxon test); this analgesia lasted up to the sixth hour of the experimental protocol. Oral ketoprofen (50 mg) was less effective and reduced the pain intensity by 45% (P<0.05) from only the second to the third hour. In contrast, pain reduction after topical ketoprofen application was not of the same magnitude but appeared to be faster to develop (with a maximum effect within 1 h) on average. The maximum pain suppression with 100 mg topical 2.5% ketoprofen gel was by 51% (significant with P<0.03), while 50 mg topical ketoprofen produced a non-significant reduction of 29%. The apparent analgesia was rapid to develop but transient and pain ratings increased back to baseline values within 3 h for the 100 mg dose and within 2 h for the 50 mg dose. This data suggests that topical application of commercial gel-based systems does not provide long-lasting analgesia in the muscle when compared to perorally-dosed ketoprofen. In addition, the data show that even doses of 100 mg peroral ketoprofen do not provide complete relief of muscle pain.\n[Drug-Disease]: ketoprofen - pain" }, { "pmid": "11410803", "target": "[]", "text": "[Title]: Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.\n[Abstract]: One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery \"good responder\" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while \"poor responder\" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.\n[Drug-Disease]: cisplatin - osteosarcoma" }, { "pmid": "11410803", "target": "[]", "text": "[Title]: Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.\n[Abstract]: One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery \"good responder\" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while \"poor responder\" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.\n[Drug-Disease]: doxorubicin - osteosarcoma" }, { "pmid": "11410803", "target": "[]", "text": "[Title]: Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.\n[Abstract]: One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery \"good responder\" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while \"poor responder\" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.\n[Drug-Disease]: methotrexate - osteosarcoma" }, { "pmid": "11411099", "target": "[\"Span: 125 mg x 2/day | Label: Dosage\"]", "text": "[Title]: [Clinical efficacy of treatment with low-dose flutamide in maximum androgen blockade therapy].\n[Abstract]: To prevent treatment withdrawal due to flutamide-induced liver dysfunction, we performed maximum androgen blockade (MAB) therapy by combining a luteinizing hormone-releasing hormone agonist or orchiectomy with low-dose flutamide (125 mg x 2/day) in patients with prostate cancer. In this study, the efficacy, adverse effects such as hepatotoxicity, and compliance were compared retrospectively between 35 patients who received low-dose flutamide therapy (1995-1999) and 27 patients who received flutamide at its ordinary dose (125 mg x 3/day). No significant difference was observed in the response rate (> or = PR) as determined from the prostate-specific antigen parameter (p = 0.6211) or the incidence of hepatotoxicity based on the aspartate aminotransferase and alanine aminotransferase levels. However, flutamide withdrawal due to liver dysfunction was less frequent in the low-dose group (2.9%) than in the ordinary dose group (18.5%) (p = 0.0386). MAB therapy using low-dose flutamide is expected to prevent the reduction in the compliance due to side effects and to improve the long-term prognosis in patients with prostate cancer, who are mostly elderly individuals.\n[Drug-Disease]: flutamide - prostate cancer" }, { "pmid": "11412729", "target": "[\"Span: 0.18% | Label: Dosage\", \"Span: 0.1% | Label: Dosage\"]", "text": "[Title]: [Comparison of ropivacaine and bupivacaine for epidural analgesia during labor].\n[Abstract]: OBJECTIVES: To compare the analgesic efficacy and level of motor block using two local anesthetics, ropivacaine and bupivacaine, during labor. MATERIAL AND METHODS: Sixty nulliparous women were enrolled during labor after full-term pregnancies. They were randomly assigned to receive epidural analgesia with ropivacaine (group R) or bupivacaine (group B). Group R patients received 10 ml of 0.18% ropivacaine with 5 microgram/ml of fentanyl followed by continuous epidural infusion of 0.1% ropivacaine with 2 microgram/ml of fentanyl at a rate of 10 ml/h. Group B patients received 10 ml of 0.15% bupivacaine with 5 microgram/ml of fentanyl followed by continuous epidural perfusion of 0.0625% bupivacaine with 2 microgram/ml of fentanyl at the same rate. Pain intensity was assessed on a visual analog scale, motor blockade on a Bromage scale, and level of sensory block at different moments. We also recorded total doses of local anesthetic employed during continuous epidural infusion, manner of final delivery, Apgar score, degree of maternal satisfaction and side effects. RESULTS: The demographic and delivery characteristics were similar in both groups. We found no statistically significant differences between the two groups for level of motor blockade, which was nil for 29 patients (96.66%) in group R and 28 patients (93.33%) in group B. No differences in degree of pain or level of sensory block (T8-T10 in both groups) were observed. The total doses of local anesthetic used were similar at 23.7 +/- 11.6 mg in group R and 16.5 +/- 7.3 mg in group B (non-significant difference). Nor did we find differences in manner of delivery, neonatal Apgar scores, degree of maternal satisfaction or side effects. CONCLUSION: Ropivacaine and bupivacaine are equally effective for epidural analgesia during labor at the doses used and they do not cause a relevant level of motor blockade.\n[Drug-Disease]: Ropivacaine - labor" }, { "pmid": "11412729", "target": "[\"Span: 0.15% | Label: Dosage\", \"Span: 0.0625% | Label: Dosage\"]", "text": "[Title]: [Comparison of ropivacaine and bupivacaine for epidural analgesia during labor].\n[Abstract]: OBJECTIVES: To compare the analgesic efficacy and level of motor block using two local anesthetics, ropivacaine and bupivacaine, during labor. MATERIAL AND METHODS: Sixty nulliparous women were enrolled during labor after full-term pregnancies. They were randomly assigned to receive epidural analgesia with ropivacaine (group R) or bupivacaine (group B). Group R patients received 10 ml of 0.18% ropivacaine with 5 microgram/ml of fentanyl followed by continuous epidural infusion of 0.1% ropivacaine with 2 microgram/ml of fentanyl at a rate of 10 ml/h. Group B patients received 10 ml of 0.15% bupivacaine with 5 microgram/ml of fentanyl followed by continuous epidural perfusion of 0.0625% bupivacaine with 2 microgram/ml of fentanyl at the same rate. Pain intensity was assessed on a visual analog scale, motor blockade on a Bromage scale, and level of sensory block at different moments. We also recorded total doses of local anesthetic employed during continuous epidural infusion, manner of final delivery, Apgar score, degree of maternal satisfaction and side effects. RESULTS: The demographic and delivery characteristics were similar in both groups. We found no statistically significant differences between the two groups for level of motor blockade, which was nil for 29 patients (96.66%) in group R and 28 patients (93.33%) in group B. No differences in degree of pain or level of sensory block (T8-T10 in both groups) were observed. The total doses of local anesthetic used were similar at 23.7 +/- 11.6 mg in group R and 16.5 +/- 7.3 mg in group B (non-significant difference). Nor did we find differences in manner of delivery, neonatal Apgar scores, degree of maternal satisfaction or side effects. CONCLUSION: Ropivacaine and bupivacaine are equally effective for epidural analgesia during labor at the doses used and they do not cause a relevant level of motor blockade.\n[Drug-Disease]: bupivacaine - labor" }, { "pmid": "11412729", "target": "[\"Span: 5 microgram/ml | Label: Dosage\", \"Span: 2 microgram/ml | Label: Dosage\"]", "text": "[Title]: [Comparison of ropivacaine and bupivacaine for epidural analgesia during labor].\n[Abstract]: OBJECTIVES: To compare the analgesic efficacy and level of motor block using two local anesthetics, ropivacaine and bupivacaine, during labor. MATERIAL AND METHODS: Sixty nulliparous women were enrolled during labor after full-term pregnancies. They were randomly assigned to receive epidural analgesia with ropivacaine (group R) or bupivacaine (group B). Group R patients received 10 ml of 0.18% ropivacaine with 5 microgram/ml of fentanyl followed by continuous epidural infusion of 0.1% ropivacaine with 2 microgram/ml of fentanyl at a rate of 10 ml/h. Group B patients received 10 ml of 0.15% bupivacaine with 5 microgram/ml of fentanyl followed by continuous epidural perfusion of 0.0625% bupivacaine with 2 microgram/ml of fentanyl at the same rate. Pain intensity was assessed on a visual analog scale, motor blockade on a Bromage scale, and level of sensory block at different moments. We also recorded total doses of local anesthetic employed during continuous epidural infusion, manner of final delivery, Apgar score, degree of maternal satisfaction and side effects. RESULTS: The demographic and delivery characteristics were similar in both groups. We found no statistically significant differences between the two groups for level of motor blockade, which was nil for 29 patients (96.66%) in group R and 28 patients (93.33%) in group B. No differences in degree of pain or level of sensory block (T8-T10 in both groups) were observed. The total doses of local anesthetic used were similar at 23.7 +/- 11.6 mg in group R and 16.5 +/- 7.3 mg in group B (non-significant difference). Nor did we find differences in manner of delivery, neonatal Apgar scores, degree of maternal satisfaction or side effects. CONCLUSION: Ropivacaine and bupivacaine are equally effective for epidural analgesia during labor at the doses used and they do not cause a relevant level of motor blockade.\n[Drug-Disease]: fentanyl - labor" }, { "pmid": "11412732", "target": "[\"Span: 2.5 mg | Label: Dosage\", \"Span: 0.125% | Label: Dosage\", \"Span: 0.25% | Label: Dosage\"]", "text": "[Title]: [The efficacy and safety of continuous epidural analgesia versus intradural-epidural analgesia during labor].\n[Abstract]: OBJECTIVE: To determine the efficacy and safety of intradural-epidural analgesia in comparison with continuous epidural analgesia during labor and childbirth. PATIENTS AND METHOD: Forty-two women whose labor began spontaneously were enrolled and distributed randomly in two groups. The intradural-epidural analgesia group (IEA, n = 21) received 25 microgram of intradural fentanyl with 2.5 mg of isobaric bupivacaine with adrenalin, after which analgesia was maintained with epidural administration of one 8 mL bolus of 0.125% bupivacaine, followed by perfusion of a balanced concentration at a rate of 8 ml/h. Patients in the continuous epidural analgesia group (CEA, n = 21) were given 8 ml of 0.25% bupivacaine with adrenalin; the epidural perfusion of 0.125% bupivacaine and 1 microgram/ml of fentanyl was started at the same rate as in the IEA group. We recorded pain as assessed on a visual analog scale, extension of sensory and motor block, maternal hemodynamic constants, number of boluses of bupivacaine used, total doses of bupivacaine and oxytocin, instruments needed for childbirth, and side effects (pruritus, nausea and vomiting). RESULTS: Analgesic efficacy during the first 30 minutes was greater in the IEA group. The total dose of bupivacaine, required top-up boluses, and the extension of sensory block at 30 minutes, one hour and two hours were also significantly less in the IEA group. The incidence of pruritus was higher in the IEA group. No significant differences were observed for other variables. CONCLUSIONS: Intradural-epidural analgesia provides effective analgesia for labor, with rapid onset, reduced extension of sensory block, lower total doses of local anesthetics and few side effects.\n[Drug-Disease]: bupivacaine - labor" }, { "pmid": "11412732", "target": "[]", "text": "[Title]: [The efficacy and safety of continuous epidural analgesia versus intradural-epidural analgesia during labor].\n[Abstract]: OBJECTIVE: To determine the efficacy and safety of intradural-epidural analgesia in comparison with continuous epidural analgesia during labor and childbirth. PATIENTS AND METHOD: Forty-two women whose labor began spontaneously were enrolled and distributed randomly in two groups. The intradural-epidural analgesia group (IEA, n = 21) received 25 microgram of intradural fentanyl with 2.5 mg of isobaric bupivacaine with adrenalin, after which analgesia was maintained with epidural administration of one 8 mL bolus of 0.125% bupivacaine, followed by perfusion of a balanced concentration at a rate of 8 ml/h. Patients in the continuous epidural analgesia group (CEA, n = 21) were given 8 ml of 0.25% bupivacaine with adrenalin; the epidural perfusion of 0.125% bupivacaine and 1 microgram/ml of fentanyl was started at the same rate as in the IEA group. We recorded pain as assessed on a visual analog scale, extension of sensory and motor block, maternal hemodynamic constants, number of boluses of bupivacaine used, total doses of bupivacaine and oxytocin, instruments needed for childbirth, and side effects (pruritus, nausea and vomiting). RESULTS: Analgesic efficacy during the first 30 minutes was greater in the IEA group. The total dose of bupivacaine, required top-up boluses, and the extension of sensory block at 30 minutes, one hour and two hours were also significantly less in the IEA group. The incidence of pruritus was higher in the IEA group. No significant differences were observed for other variables. CONCLUSIONS: Intradural-epidural analgesia provides effective analgesia for labor, with rapid onset, reduced extension of sensory block, lower total doses of local anesthetics and few side effects.\n[Drug-Disease]: adrenalin - labor" }, { "pmid": "11412732", "target": "[\"Span: 25 microgram | Label: Dosage\", \"Span: 1 microgram/ml | Label: Dosage\"]", "text": "[Title]: [The efficacy and safety of continuous epidural analgesia versus intradural-epidural analgesia during labor].\n[Abstract]: OBJECTIVE: To determine the efficacy and safety of intradural-epidural analgesia in comparison with continuous epidural analgesia during labor and childbirth. PATIENTS AND METHOD: Forty-two women whose labor began spontaneously were enrolled and distributed randomly in two groups. The intradural-epidural analgesia group (IEA, n = 21) received 25 microgram of intradural fentanyl with 2.5 mg of isobaric bupivacaine with adrenalin, after which analgesia was maintained with epidural administration of one 8 mL bolus of 0.125% bupivacaine, followed by perfusion of a balanced concentration at a rate of 8 ml/h. Patients in the continuous epidural analgesia group (CEA, n = 21) were given 8 ml of 0.25% bupivacaine with adrenalin; the epidural perfusion of 0.125% bupivacaine and 1 microgram/ml of fentanyl was started at the same rate as in the IEA group. We recorded pain as assessed on a visual analog scale, extension of sensory and motor block, maternal hemodynamic constants, number of boluses of bupivacaine used, total doses of bupivacaine and oxytocin, instruments needed for childbirth, and side effects (pruritus, nausea and vomiting). RESULTS: Analgesic efficacy during the first 30 minutes was greater in the IEA group. The total dose of bupivacaine, required top-up boluses, and the extension of sensory block at 30 minutes, one hour and two hours were also significantly less in the IEA group. The incidence of pruritus was higher in the IEA group. No significant differences were observed for other variables. CONCLUSIONS: Intradural-epidural analgesia provides effective analgesia for labor, with rapid onset, reduced extension of sensory block, lower total doses of local anesthetics and few side effects.\n[Drug-Disease]: fentanyl - labor" }, { "pmid": "11416610", "target": "[\"Span: 10 mg | Label: Dosage\", \"Span: mean age 53.9 | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.\n[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.\n[Drug-Disease]: benazepril - goal blood pressures" }, { "pmid": "11416610", "target": "[\"Span: 5 mg | Label: Dosage\", \"Span: mean age 52.1 | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.\n[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.\n[Drug-Disease]: enalapril - goal blood pressures" }, { "pmid": "11416610", "target": "[\"Span: 10 mg | Label: Dosage\", \"Span: mean age 52.4 | Label: Age\", \"Span: 5 mg | Label: Dosage\", \"Span: mean age 52.1 | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.\n[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.\n[Drug-Disease]: felodipine - goal blood pressures" }, { "pmid": "11416610", "target": "[\"Span: 5 mg | Label: Dosage\", \"Span: mean age 53.9 | Label: Age\", \"Span: male | Label: Gender\"]", "text": "[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.\n[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.\n[Drug-Disease]: amlodipine - goal blood pressures" }, { "pmid": "17344658", "target": "[\"Span: newborn infants | Label: Age\"]", "text": "[Title]: Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension.\n[Abstract]: BACKGROUND: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. OBJECTIVE: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. METHODS: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 +/- 1,019 g; gestational age = 35.6 +/- 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. RESULTS: Right cardiac output increased and left cardiac output tended to increase 1.5-4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. CONCLUSIONS: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.\n[Drug-Disease]: sildenafil - CDH" }, { "pmid": "17372175", "target": "[\"Span: African-American | Label: Body Type\"]", "text": "[Title]: Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.\n[Abstract]: BACKGROUND: We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS: Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.\n[Drug-Disease]: hydralazine hydrochloride - Heart Failure" }, { "pmid": "17372175", "target": "[\"Span: African-American | Label: Body Type\"]", "text": "[Title]: Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.\n[Abstract]: BACKGROUND: We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS: Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.\n[Drug-Disease]: isosorbide dinitrate - Heart Failure" }, { "pmid": "17388661", "target": "[\"Span: TP53 mutation | Label: Gene\", \"Span: 1,200 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.\n[Abstract]: BACKGROUND: In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. METHODS AND FINDINGS: In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. CONCLUSIONS: This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "17388661", "target": "[\"Span: TP53 mutation | Label: Gene\", \"Span: 75 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.\n[Abstract]: BACKGROUND: In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. METHODS AND FINDINGS: In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. CONCLUSIONS: This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.\n[Drug-Disease]: epirubicin - breast cancer" }, { "pmid": "17391164", "target": "[\"Span: drug-naive type 2 diabetes | Label: Comorbidity\"]", "text": "[Title]: Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes.\n[Abstract]: AIM: The aim of this study was to examine the efficacy and safety of topiramate as an adjunct to diet and exercise in drug-naive, obese subjects with type 2 diabetes. METHODS: Drug-naive individuals with type 2 diabetes, body mass index (BMI) of > or =27 and <50 kg/m(2) and haemoglobin A(1c) (HbA(1c)) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change((R)); Johnson & Johnson Healthcare Systems, Piscataway, NJ, USA) throughout the trial. After a 6-week placebo run-in, the subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Subjects were scheduled for 8-week titration and 52-week maintenance phases. The study was ended early; efficacy data were reported for a predefined modified intent-to-treat (MITT) population (n = 229), with 40 weeks of treatment. All the subjects who provided any safety data were included in the safety population (n = 535). RESULTS: Baseline mean weight was 103.7 kg, BMI 36 kg/m(2) and HbA(1c) 6.7% across all treatment groups. By the end of week 40, the placebo, the topiramate 96 mg/day and topiramate 192 mg/day groups lost 2.5, 6.6 and 9.1% of their baseline body weight respectively (p < 0.001 vs. placebo, MITT population using last observation carried forward). The decrease in HbA(1c) was 0.2, 0.6 and 0.7% respectively (p < 0.001 vs. placebo, MITT). Topiramate significantly reduced blood pressure and urinary albumin excretion; a weight-loss-independent HbA(1c) improving effect of topiramate was demonstrated. Adverse events were predominantly related to central nervous system (CNS). CONCLUSIONS: Topiramate as an add-on treatment to lifestyle improvements produced significant weight loss and improved glucose homeostasis in obese, drug-naive subjects with type 2 diabetes. These treatment advantages should be balanced against the occurrence of adverse events in the CNS.\n[Drug-Disease]: Topiramate - glucose homeostasis in obese" }, { "pmid": "17391744", "target": "[\"Span: male | Label: Gender\", \"Span: cocaine abusers | Label: Comorbidity\", \"Span: 5 mg/70 kg | Label: Dosage\", \"Span: 10 mg/70 kg | Label: Dosage\"]", "text": "[Title]: Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers.\n[Abstract]: Nalbuphine (Nubain) is a mixed action mu-kappa agonist used clinically for the management of pain. Nalbuphine and other mu-kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (P=.04) and reached peak levels of 22.1+/-7.1 ng/ml and 54.1+/-11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of \"Sick,\" \"Bad\" and \"Dizzy\" were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (P=.05-.0001), and were significantly correlated with increases in PRL (P=.05-.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.\n[Drug-Disease]: nalbuphine - pain" }, { "pmid": "17410198", "target": "[\"Span: folate | Label: Gene\", \"Span: pyrimidine | Label: Gene\", \"Span: purine metabolic enzymes | Label: Gene\"]", "text": "[Title]: Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis.\n[Abstract]: Methotrexate is the gold standard therapy for moderate to severe psoriasis, but there is marked interpersonal variation in its efficacy and toxicity. We hypothesized that in psoriasis patients, specific common polymorphisms in folate, pyrimidine, and purine metabolic enzymes are associated with methotrexate efficacy and/or toxicity. DNA from 203 retrospectively recruited psoriasis patients treated with methotrexate was collected and genotyped by restriction endonuclease digestion or length polymorphism assays. The reduced folate carrier (RFC) 80A allele and the thymidylate synthase (TS) 3'-untranslated region (3'-UTR) 6 bp deletion were associated with methotrexate-induced toxicity (P=0.025 and P=0.025, respectively). RFC 80A and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) 347G were associated with methotrexate discontinuation (P=0.048 and P=0.038). The TS 5'-UTR 28 bp 3R polymorphism correlated with poor clinical outcome (P=0.029), however, this was not the case when patients with palmoplantar pustular psoriasis were not included in the analysis. Stronger associations between specific polymorphisms and methotrexate-induced toxicity and discontinuation were found in a subanalysis of patients on methotrexate not receiving folic acid supplementation. We have demonstrated preliminary evidence that specific polymorphisms of enzymes involved in folate, pyrimidine, and purine metabolism could be useful in predicting clinical response to methotrexate in patients with psoriasis.\n[Drug-Disease]: methotrexate - psoriasis" }, { "pmid": "17419358", "target": "[\"Span: CYP2C9 genetic polymorphism | Label: Gene\"]", "text": "[Title]: [The influence of CYP2C9 genetic polymorphism on the pharmacokinetics and pharmacodynamics of warfarin in patients with constant atrial fibrillation].\n[Abstract]: CYP2C9 is the main enzyme participating in warfarin metabolism, of which genetic polymorphism is typical. The aim of the study was to investigate the influence of having allelic variants CYP2C9*2 and CYP2C9*3 on the pharmacokinetics, dosage regimen, and the rate of hemorrhage in patients with constant atrial fibrillation taking warfarin. Eighty-two patients with constant atrial fibrillation taking warfarin were included in the study. It was shown that in patients with CYP2C9*2 and CYP2C9*3 the clearance of warfarin and its dose were lower, while the episodes of excessive hypocoagulation and hemorrhage associated with warfarin were more frequent than in patients without these allelic variants. Basing on the results of the study, the authors propose an algorithm of choosing the initial warfarin dose depending on CYP2C9 genotype.\n[Drug-Disease]: warfarin - atrial fibrillation" }, { "pmid": "17425952", "target": "[\"Span: breast carcinomas | Label: Comorbidity\", \"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins.\n[Abstract]: OBJECTIVES: Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer. DESIGN AND METHODS: The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls. RESULTS: Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy. CONCLUSION: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.\n[Drug-Disease]: niacin - hypertriglyceridemia" }, { "pmid": "17425952", "target": "[\"Span: breast carcinomas | Label: Comorbidity\", \"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins.\n[Abstract]: OBJECTIVES: Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer. DESIGN AND METHODS: The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls. RESULTS: Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy. CONCLUSION: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.\n[Drug-Disease]: riboflavin - hypertriglyceridemia" }, { "pmid": "17454858", "target": "[\"Span: 75 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.\n[Abstract]: OBJECTIVE: To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU and Leucovorin for patients with advanced or recurrent colorectal cancer. MATERIAL AND METHODS: Irinotecan (75 mg/m(2)) was administered biweekly, while 5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6 weeks. RESULTS: The 21 consecutive patients subjected to this regimen showed a good response rate (43%) with minimal toxicity (incidence of grade 3/4: leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean survival time of all 21 patients was 15.7 months. This regimen could be a valid option for patients with advanced colorectal cancer, especially those seeking a good QoL (quality of life) for the remainder of their lives. We evaluated the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs, and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples. Expression of TS mRNA or sialyl Lewis X was negatively correlated with the response from chemotherapy. Patients with low DPD mRNA expression in the tumor showed a significant longer survival than those with high expression. In patients with high TP mRNA expression, there was a tendency towards a high incidence of leukopenia. CONCLUSIONS: Some predictive factors elucidated in this study could contribute to the progress of the tumor-biology based, individualized chemotherapy for colorectal cancer patients.\n[Drug-Disease]: Irinotecan - colorectal cancer" }, { "pmid": "17454858", "target": "[\"Span: 250 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.\n[Abstract]: OBJECTIVE: To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU and Leucovorin for patients with advanced or recurrent colorectal cancer. MATERIAL AND METHODS: Irinotecan (75 mg/m(2)) was administered biweekly, while 5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6 weeks. RESULTS: The 21 consecutive patients subjected to this regimen showed a good response rate (43%) with minimal toxicity (incidence of grade 3/4: leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean survival time of all 21 patients was 15.7 months. This regimen could be a valid option for patients with advanced colorectal cancer, especially those seeking a good QoL (quality of life) for the remainder of their lives. We evaluated the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs, and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples. Expression of TS mRNA or sialyl Lewis X was negatively correlated with the response from chemotherapy. Patients with low DPD mRNA expression in the tumor showed a significant longer survival than those with high expression. In patients with high TP mRNA expression, there was a tendency towards a high incidence of leukopenia. CONCLUSIONS: Some predictive factors elucidated in this study could contribute to the progress of the tumor-biology based, individualized chemotherapy for colorectal cancer patients.\n[Drug-Disease]: Leucovorin - colorectal cancer" }, { "pmid": "17454858", "target": "[\"Span: 600 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.\n[Abstract]: OBJECTIVE: To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU and Leucovorin for patients with advanced or recurrent colorectal cancer. MATERIAL AND METHODS: Irinotecan (75 mg/m(2)) was administered biweekly, while 5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6 weeks. RESULTS: The 21 consecutive patients subjected to this regimen showed a good response rate (43%) with minimal toxicity (incidence of grade 3/4: leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean survival time of all 21 patients was 15.7 months. This regimen could be a valid option for patients with advanced colorectal cancer, especially those seeking a good QoL (quality of life) for the remainder of their lives. We evaluated the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs, and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples. Expression of TS mRNA or sialyl Lewis X was negatively correlated with the response from chemotherapy. Patients with low DPD mRNA expression in the tumor showed a significant longer survival than those with high expression. In patients with high TP mRNA expression, there was a tendency towards a high incidence of leukopenia. CONCLUSIONS: Some predictive factors elucidated in this study could contribute to the progress of the tumor-biology based, individualized chemotherapy for colorectal cancer patients.\n[Drug-Disease]: 5FU - colorectal cancer" }, { "pmid": "17465473", "target": "[]", "text": "[Title]: Role of intravenously administered hyoscine butyl bromide in retrograde terminal ileoscopy: a randomized, double-blinded, placebo-controlled trial.\n[Abstract]: AIM: To evaluated the role of hyoscine butyl bromide in facilitating retrograde ileoscopy. METHODS: Retrograde terminal ileoscopy was attempted in 200 consecutive patients undergoing colonoscopy. After intubation of the cecum and visualization of the ileocecal valve, butyl bromide injection or normal saline was given intravenously to the patients in a double blind random fashion. The pulse rate and oxygen saturation were measured continuously. After completion of the procedure, endoscopists were then asked to score the ease of intubation and the ease of visualization of the terminal ileum on a visual scale of 1 to 10. The patients were also asked to score the pain after receiving hyoscine butyl bromide injection on a score of 1 to 10. RESULTS: Terminal ileoscopy could be performed in 188 patients. The mean (SD) visual analogue score for the ease of intubation of the cecum was 7.4 (0.65) in the injection group and 5.9 (0.8) in the placebo group (P < 0.001). The mean (SD) length of ileum visualized in the injection group was 14.4 (3.3) cm and 10.4 (2.7) cm in the placebo group (P < 0.001). The mean (SD) visual analogue score for ease of visualization of the terminal ileum was 7.5 (0.69) in the injection group and 5.9 (0.7) in the placebo group (P < 0.001). The pain score experienced by the patients was 6.5 (0.7) in the injection group and 6.7 (0.69) in the placebo group (P < 0.008). Although the pulse rate increased significantly in patients receiving the drug, no statistically significant difference was noted in the oxygen saturation between the two groups either before or after administration of the drug. No complications were observed in either of the groups. CONCLUSION: Hyoscine butyl bromide injection is a useful adjunct in helping the intubation and visualization of terminal ileum during colonoscopy.\n[Drug-Disease]: Hyoscine butyl bromide - pain" }, { "pmid": "17465867", "target": "[\"Span: 8.45 g | Label: Dosage\", \"Span: 4.5 g | Label: Dosage\"]", "text": "[Title]: Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy.\n[Abstract]: BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.\n[Drug-Disease]: methylprednisolone - Graves' ophthalmopathy" }, { "pmid": "17494885", "target": "[\"Span: 10 mg/d | Label: Dosage\", \"Span: median 20 mg/d; range 10 to 40 | Label: Dosage\"]", "text": "[Title]: Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.\n[Abstract]: The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.\n[Drug-Disease]: benazepril - ESRD" }, { "pmid": "17494885", "target": "[\"Span: 10 mg/d | Label: Dosage\", \"Span: median 20 mg/d; range 10 to 40 | Label: Dosage\"]", "text": "[Title]: Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.\n[Abstract]: The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.\n[Drug-Disease]: benazepril - proteinuria" }, { "pmid": "17494885", "target": "[\"Span: 50 mg/d | Label: Dosage\", \"Span: median 100 mg/d; range 50 to 200 | Label: Dosage\"]", "text": "[Title]: Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.\n[Abstract]: The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.\n[Drug-Disease]: losartan - ESRD" }, { "pmid": "17494885", "target": "[\"Span: 50 mg/d | Label: Dosage\", \"Span: median 100 mg/d; range 50 to 200 | Label: Dosage\"]", "text": "[Title]: Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.\n[Abstract]: The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.\n[Drug-Disease]: losartan - proteinuria" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: tropisetron - Nausea" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 5 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: tropisetron - emesis" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 8 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: ondansetron - Nausea" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 8 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: ondansetron - emesis" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 3 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: granisetron - Nausea" }, { "pmid": "17530482", "target": "[\"Span: Turkish | Label: Body Type\", \"Span: cancer | Label: Comorbidity\", \"Span: median age of 48 years | Label: Age\", \"Span: (72.8 percent) female | Label: Gender\", \"Span: (27.2 percent) male | Label: Gender\", \"Span: 3 mg | Label: Dosage\"]", "text": "[Title]: Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost.\n[Abstract]: BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. CONCLUSIONS: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.\n[Drug-Disease]: granisetron - emesis" }, { "pmid": "17532722", "target": "[\"Span: Caucasian | Label: Body Type\", \"Span: 50.5% were females | Label: Gender\", \"Span: mean age was 62.1 +/- 11.1 years | Label: Age\", \"Span: mean bodyweight was 88.6 +/- 15.4kg | Label: Body Type\", \"Span: mean body mass index (BMI) was 30.7 +/- 4.8 kg/m(2) | Label: Body Type\"]", "text": "[Title]: Antihypertensive effect of irbesartan and predictors of response in obesity-associated hypertension : a prospective, open-label study.\n[Abstract]: BACKGROUND: Obesity-associated hypertension is difficult to treat and puts patients at a substantially increased risk of cardiovascular events. Irbesartan has previously been shown to effectively lower blood pressure (BP) in high-risk groups including patients with type 2 diabetes mellitus or nephropathy, and may therefore also be suitable for the treatment of obesity-associated hypertension. In this study we aimed to: (a) assess the efficacy and tolerability of irbesartan alone and in combination with hydrochlorothiazide in patients with obesity-associated mild-to-moderate hypertension; and (b) investigate patient-associated determinants of poor BP control in this patient group. PATIENTS AND METHODS: This was a 3-month, prospective, open-label, multicentre, phase IV study in 72 479 hypertensive patients in 6989 general practices across Germany. Main outcome measures were BP reduction (primary parameter of effectiveness) and BP response rates after 3 months, as well as adverse events (AEs). Independent predictors of poor control were identified in a multivariate proportional odds model. RESULTS: All of the patients were Caucasian, 50.5% were females, mean age was 62.1 +/- 11.1 years, mean bodyweight was 88.6 +/- 15.4kg, and mean body mass index (BMI) was 30.7 +/- 4.8 kg/m(2). Almost all the patients were overweight or obese (92.3%). From a baseline value of 162/94mm Hg, systolic and diastolic BP were reduced by a mean of -23/-12mm Hg after 3 months. 66.1% of the patients were responders (reduction of diastolic BP >=10mm Hg), and 48.0% achieved BP normalisation (i.e. <140/90mm Hg). 79% of patients met their individual treatment goals as defined by the treating physician (mean 135/80mm Hg). AEs were reported in only 322 patients (0.4%). Factors requiring special attention in patients not achieving BP control were age (>55 years), high BMI category (>25 kg/m(2)), and increased waist circumference. CONCLUSION: Treatment with irbesartan (+/- hydrochlorothiazide) appeared to be effective and well tolerated in the study population of patients with obesity- associated hypertension. Easily recognisable characteristics allow physicians to identify patients whose BP is likely to be difficult to control.\n[Drug-Disease]: irbesartan - hypertension" }, { "pmid": "17532722", "target": "[\"Span: Caucasian | Label: Body Type\", \"Span: 50.5% were females | Label: Gender\", \"Span: mean age was 62.1 +/- 11.1 years | Label: Age\", \"Span: mean bodyweight was 88.6 +/- 15.4kg | Label: Body Type\", \"Span: mean body mass index (BMI) was 30.7 +/- 4.8 kg/m(2) | Label: Body Type\"]", "text": "[Title]: Antihypertensive effect of irbesartan and predictors of response in obesity-associated hypertension : a prospective, open-label study.\n[Abstract]: BACKGROUND: Obesity-associated hypertension is difficult to treat and puts patients at a substantially increased risk of cardiovascular events. Irbesartan has previously been shown to effectively lower blood pressure (BP) in high-risk groups including patients with type 2 diabetes mellitus or nephropathy, and may therefore also be suitable for the treatment of obesity-associated hypertension. In this study we aimed to: (a) assess the efficacy and tolerability of irbesartan alone and in combination with hydrochlorothiazide in patients with obesity-associated mild-to-moderate hypertension; and (b) investigate patient-associated determinants of poor BP control in this patient group. PATIENTS AND METHODS: This was a 3-month, prospective, open-label, multicentre, phase IV study in 72 479 hypertensive patients in 6989 general practices across Germany. Main outcome measures were BP reduction (primary parameter of effectiveness) and BP response rates after 3 months, as well as adverse events (AEs). Independent predictors of poor control were identified in a multivariate proportional odds model. RESULTS: All of the patients were Caucasian, 50.5% were females, mean age was 62.1 +/- 11.1 years, mean bodyweight was 88.6 +/- 15.4kg, and mean body mass index (BMI) was 30.7 +/- 4.8 kg/m(2). Almost all the patients were overweight or obese (92.3%). From a baseline value of 162/94mm Hg, systolic and diastolic BP were reduced by a mean of -23/-12mm Hg after 3 months. 66.1% of the patients were responders (reduction of diastolic BP >=10mm Hg), and 48.0% achieved BP normalisation (i.e. <140/90mm Hg). 79% of patients met their individual treatment goals as defined by the treating physician (mean 135/80mm Hg). AEs were reported in only 322 patients (0.4%). Factors requiring special attention in patients not achieving BP control were age (>55 years), high BMI category (>25 kg/m(2)), and increased waist circumference. CONCLUSION: Treatment with irbesartan (+/- hydrochlorothiazide) appeared to be effective and well tolerated in the study population of patients with obesity- associated hypertension. Easily recognisable characteristics allow physicians to identify patients whose BP is likely to be difficult to control.\n[Drug-Disease]: hydrochlorothiazide - hypertension" }, { "pmid": "17580253", "target": "[]", "text": "[Title]: Fluconazole coadministration concurrent with cyclophosphamide conditioning may reduce regimen-related toxicity postmyeloablative hematopoietic cell transplantation.\n[Abstract]: In a previous study comparing fluconazole and itraconazole administered as antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients, we found that fluconazole administration concurrent with cyclophosphamide (CY)-based conditioning was associated with fewer early toxicities compared to itraconazole. Fluconazole inhibits cytochrome P450 2C9, which is involved with the activation of CY, and so might provide protection from CY-related toxicities. To investigate this further, we compared CY and CY-metabolite data from patients who received fluconazole (n = 56) concurrent with CY-containing conditioning and in patients who did not (n = 17). The fluconazole group had greater exposure to CY, and lower peak serum concentration of CY-metabolite 4-hydroxycyclophosphamide. In a separate cohort, we examined outcomes in patients randomized to receive either fluconazole (n = 152) or placebo (n = 147) concurrent with CY-containing conditioning in a prior randomized trial. Patients who received fluconazole experienced less hepatic and renal toxicity, and had lower mortality. No difference in relapsed malignancy was apparent. These data support the hypothesis that fluconazole, when coadministered with CY, decreases CY-related toxicities by inhibiting cytochrome P450 2C9 metabolism.\n[Drug-Disease]: fluconazole - hepatic and renal toxicity" }, { "pmid": "1760829", "target": "[\"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Evaluation of effectiveness and tolerability of isosorbide mononitrate during a three-year period in patients with angina pectoris.\n[Abstract]: The antianginal effect and tolerability of isosorbide mononitrate (ISMN), 20 mg 2-3 times daily, orally were investigated in an open study in 28 patients, suffering from coronary heart disease and stable angina pectoris. Ergometric exercise tests were carried out before treatment and 2 h after drug intake, every 3 months during the first year and at 6-month intervals during the following 2 years. At the conclusion of the 3-year study the reduction of ST-segment depression, which had amounted to 58% after 1 year, could be improved to 78% (p less than 0.01). The frequency of angina was markedly reduced during the treatment with ISMN. While 14 of the patients had more than 3 episodes per day prior to the study, 16 patients were symptom-free at the end of the three years' therapy, and none of the patients had more than 1 or 2 attacks per day. The consumption of sublingual nitroglycerin diminished by 94% after one year and by 98% after 3 years of therapy (p less than 0.01). Headache was the only adverse effect observed in some of the patients (at the initiation of the treatment only). In conclusion this study demonstrated (1) the good tolerability of ISMN, at the doses used, and (2) the fact that the antianginal efficacy may be enhanced during the course of the therapy.\n[Drug-Disease]: ISMN - angina" }, { "pmid": "17649720", "target": "[]", "text": "[Title]: [Application of all-trans retinoic acid combining chemotherapy and As4S4 in the maintenance treatment of patients with acute promyelocytic leukemia].\n[Abstract]: OBJECTIVE: To compare the efficacy of all-trans retinoic acid (ATRA) combining chemotherapy and As4S4 with ATRA combining chemotherapy for the maintenance treatment of patients with acute promyelocytic leukemia (APL). METHODS: Sixty patients with APL induced to complete remission by ATRA and consolidated by chemotherapy were randomly divided into two groups. Thirty patients as As4S4 group received ATRA + As4S4 + chemotherapy, and another thirty patients as non-As4S4 group were treated only with ATRA + chemotherapy as maintenance therapy. The therapeutic effects, side effects and PML-RARalpha gene expression were analyzed. RESULTS: The three-year continuous complete remission (CCR) rate was 90.0% for As4S4 group and 61.1% for non-As4S4 group, the difference being statistically significant. Significant difference was also found in the positive rate of PML-RARalpha fusion gene between the two groups. The side effects were mild. CONCLUSION: APL patients in maintenance therapy with ATRA + 6-MP + MTX + As4S4 can obtain a higher CCR.\n[Drug-Disease]: ATRA - APL" }, { "pmid": "17654614", "target": "[\"Span: cardiac comorbidity | Label: Comorbidity\", \"Span: previous treatment with anthracycline-based regimens | Label: Body Type\", \"Span: 50 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines.\n[Abstract]: BACKGROUND: To assess the efficacy and safety of the combination of non-pegylated liposome-encapsulated doxorubicin (Myocet(R)) with cyclophosphamide, vincristine, prednisone and rituximab (R-COMP) in patients with aggressive non-Hodgkin's B-cell lymphomas. METHODS: Twenty-one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline-based regimens. Liposome-encapsulated doxorubicin at a dose of 50 mg/m(2) was administered in association with cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), prednisone (40 mg/m(2)) and rituximab (375 mg/m(2)) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred. RESULTS: A complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow-up of 13 months (range 2-36 months), 2/16 CR patients relapsed, with a disease-free survival (DFS) of 78%. CONCLUSIONS: The replacement of doxorubicin with its non-pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients.\n[Drug-Disease]: doxorubicin - aggressive non-Hodgkin's B-cell lymphomas" }, { "pmid": "1768975", "target": "[]", "text": "[Title]: Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin.\n[Abstract]: Regimens using cyclosporin (CSP) and either methylprednisolone (MP) or methotrexate (MTX) have been useful in the prophylaxis of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). However, CSP produces a number of side effects, including neurologic toxicity. A retrospective review of recipients of 239 BMTs given CSP-based prophylactic regimens revealed that 10 patients (4.2%, 95% confidence interval 0% to 10.4%) experienced a syndrome characterized by hypertension, severe visual disturbances, seizures and occipital lobe density changes on brain computed tomography (nine patients) or nuclear magnetic resonance imaging (one patient). Neurologic findings were reversible in all cases, usually after temporary discontinuation of CSP. Univariate analysis identified the following risk factors for neurotoxicity: use of unrelated or HLA-mismatched related donors, administration of etoposide (VP-16) or total body irradiation as part of conditioning, use of corticosteroids for prophylaxis or treatment of acute GVHD, or development of either acute GVHD or clinically significant microangiopathic hemolytic anemia (MAHA) post-BMT. In multivariate analysis, the most important predictors were the use of VP-16 (p = 0.008), the use of a continuous infusion CSP plus MP prophylactic regimen for GVHD (p = 0.003) and the development of MAHA after BMT (p less than 0.001). The strong association with MAHA suggests that endothelial damage is related to the development of this complication.\n[Drug-Disease]: MTX - GVHD" }, { "pmid": "1768975", "target": "[]", "text": "[Title]: Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin.\n[Abstract]: Regimens using cyclosporin (CSP) and either methylprednisolone (MP) or methotrexate (MTX) have been useful in the prophylaxis of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). However, CSP produces a number of side effects, including neurologic toxicity. A retrospective review of recipients of 239 BMTs given CSP-based prophylactic regimens revealed that 10 patients (4.2%, 95% confidence interval 0% to 10.4%) experienced a syndrome characterized by hypertension, severe visual disturbances, seizures and occipital lobe density changes on brain computed tomography (nine patients) or nuclear magnetic resonance imaging (one patient). Neurologic findings were reversible in all cases, usually after temporary discontinuation of CSP. Univariate analysis identified the following risk factors for neurotoxicity: use of unrelated or HLA-mismatched related donors, administration of etoposide (VP-16) or total body irradiation as part of conditioning, use of corticosteroids for prophylaxis or treatment of acute GVHD, or development of either acute GVHD or clinically significant microangiopathic hemolytic anemia (MAHA) post-BMT. In multivariate analysis, the most important predictors were the use of VP-16 (p = 0.008), the use of a continuous infusion CSP plus MP prophylactic regimen for GVHD (p = 0.003) and the development of MAHA after BMT (p less than 0.001). The strong association with MAHA suggests that endothelial damage is related to the development of this complication.\n[Drug-Disease]: MP - GVHD" }, { "pmid": "1768975", "target": "[]", "text": "[Title]: Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin.\n[Abstract]: Regimens using cyclosporin (CSP) and either methylprednisolone (MP) or methotrexate (MTX) have been useful in the prophylaxis of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). However, CSP produces a number of side effects, including neurologic toxicity. A retrospective review of recipients of 239 BMTs given CSP-based prophylactic regimens revealed that 10 patients (4.2%, 95% confidence interval 0% to 10.4%) experienced a syndrome characterized by hypertension, severe visual disturbances, seizures and occipital lobe density changes on brain computed tomography (nine patients) or nuclear magnetic resonance imaging (one patient). Neurologic findings were reversible in all cases, usually after temporary discontinuation of CSP. Univariate analysis identified the following risk factors for neurotoxicity: use of unrelated or HLA-mismatched related donors, administration of etoposide (VP-16) or total body irradiation as part of conditioning, use of corticosteroids for prophylaxis or treatment of acute GVHD, or development of either acute GVHD or clinically significant microangiopathic hemolytic anemia (MAHA) post-BMT. In multivariate analysis, the most important predictors were the use of VP-16 (p = 0.008), the use of a continuous infusion CSP plus MP prophylactic regimen for GVHD (p = 0.003) and the development of MAHA after BMT (p less than 0.001). The strong association with MAHA suggests that endothelial damage is related to the development of this complication.\n[Drug-Disease]: cyclosporin - GVHD" }, { "pmid": "17700361", "target": "[\"Span: polymorphisms in the large-conductance calcium and voltage-dependent potassium (BK) channel beta1 subunit gene, KCNMB1 | Label: Gene\"]", "text": "[Title]: KCNMB1 genotype influences response to verapamil SR and adverse outcomes in the INternational VErapamil SR/Trandolapril STudy (INVEST).\n[Abstract]: OBJECTIVES: We sought to determine whether polymorphisms in the large-conductance calcium and voltage-dependent potassium (BK) channel beta1 subunit gene, KCNMB1, are associated with blood pressure response to verapamil SR or adverse outcomes in the GENEtic substudy of the INternational VErapamil SR/trandolapril STudy (INVEST-GENES). BACKGROUND: KCNMB1 is involved in calcium sensitivity and hypertension. The association between variability in KCNMB1 and calcium antagonist response, however, has not been assessed. METHODS: Genetic samples were collected from 5979 patients in INVEST. Blood pressure response to verapamil SR and time to achieve blood pressure control was assessed in relation to Glu65Lys and Val110Leu genotypes. The primary outcome (all cause mortality, nonfatal myocardial infarction or nonfatal stroke) was compared between genotype groups, and interaction with verapamil SR therapy was assessed. RESULTS: Systolic blood pressure response to verapamil SR did not differ by KCNMB1 genotype. Lys65 variant carriers, however, achieved blood pressure control earlier than Glu65Glu individuals [1.47 (interquartile ratio 2.77) versus 2.83 (interquartile ratio 4.17) months, P=0.01] and were less likely to require multiple drugs at the time of blood pressure control (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.95). Leu110 variant carriers had a reduced risk of primary outcome (hazard ratio 0.68, 95% confidence interval 0.47-0.998). Subgroup analysis revealed this finding to be more pronounced in verapamil SR-assigned patients (hazard ratio 0.587, 95% confidence interval 0.33-1.04) compared with atenolol-assigned patients (hazard ratio 0.946, 95% confidence interval 0.56-1.59). No difference was seen in the occurrence of the primary outcome compared by codon 65 genotype. CONCLUSIONS: Our findings suggest that KCNMB1 genotype influences responsiveness to verapamil SR and risk of adverse cardiovascular outcomes.\n[Drug-Disease]: verapamil - hypertension" }, { "pmid": "17710662", "target": "[\"Span: 4-year-old | Label: Age\", \"Span: boy | Label: Gender\", \"Span: acute lymphoblastic leukemia | Label: Comorbidity\"]", "text": "[Title]: Pyridoxine and pyridostigmine treatment in vincristine-induced neuropathy.\n[Abstract]: Vincristine is a commonly used antineoplastic drug and frequently causes neurotoxicity. Here the authors report a 4-year-old boy with acute lymphoblastic leukemia in whom vincristine-induced peripheral and cranial neuropathy developed during remission induction therapy. The patient seemed to benefit from pyridoxine and pyridostigmine therapy greatly and this therapy is recommended in patients with severe vincristine-induced neuropathy.\n[Drug-Disease]: pyridostigmine - cranial neuropathy" }, { "pmid": "17710662", "target": "[\"Span: 4-year-old | Label: Age\", \"Span: boy | Label: Gender\", \"Span: acute lymphoblastic leukemia | Label: Comorbidity\"]", "text": "[Title]: Pyridoxine and pyridostigmine treatment in vincristine-induced neuropathy.\n[Abstract]: Vincristine is a commonly used antineoplastic drug and frequently causes neurotoxicity. Here the authors report a 4-year-old boy with acute lymphoblastic leukemia in whom vincristine-induced peripheral and cranial neuropathy developed during remission induction therapy. The patient seemed to benefit from pyridoxine and pyridostigmine therapy greatly and this therapy is recommended in patients with severe vincristine-induced neuropathy.\n[Drug-Disease]: pyridoxine - cranial neuropathy" }, { "pmid": "17728426", "target": "[\"Span: 15 mg/day | Label: Dosage\", \"Span: 30 mg/day | Label: Dosage\", \"Span: 11 female | Label: Gender\"]", "text": "[Title]: Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial.\n[Abstract]: OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.\n[Drug-Disease]: Aripiprazole - menstrual disturbances" }, { "pmid": "1778090", "target": "[\"Span: African | Label: Body Type\", \"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Clinical efficacy and tolerability of tenoxicam in African patients with osteoarthritis, rheumatoid arthritis, tendinitis and/or bursitis: an open study.\n[Abstract]: An open clinical evaluation was carried out in 736 African out-patients suffering from rheumatic and inflammatory disorders to assess the efficacy and tolerability of tenoxicam in relieving the signs and symptoms of their condition. On entry, all previous treatment was discontinued and patients received a simple daily dose of 20 mg tenoxicam orally for 15 days in the case of those with rheumatoid arthritis or tendinitis, or for 30 days in those with osteoarthritis. Paracetamol was allowed as a rescue analgesic. Subjective verbal scale assessments were used to determine levels of pain at rest, on movement and at night, sleep disturbance and functional incapacity, on entry and during treatment. At the end of the study period, both physicians and patients gave an overall opinion of the clinical response to tenoxicam, and patients were asked how their current compared with their previous treatment. The results showed that approximately 90% of patients had an excellent or good response to tenoxicam with marked improvement in all the signs and symptoms evaluated. Moreover, tenoxicam proved to be well tolerated, only a small number of patients reporting adverse events, mainly gastro-intestinal.\n[Drug-Disease]: tenoxicam - rheumatoid arthritis" }, { "pmid": "1778090", "target": "[\"Span: African | Label: Body Type\", \"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Clinical efficacy and tolerability of tenoxicam in African patients with osteoarthritis, rheumatoid arthritis, tendinitis and/or bursitis: an open study.\n[Abstract]: An open clinical evaluation was carried out in 736 African out-patients suffering from rheumatic and inflammatory disorders to assess the efficacy and tolerability of tenoxicam in relieving the signs and symptoms of their condition. On entry, all previous treatment was discontinued and patients received a simple daily dose of 20 mg tenoxicam orally for 15 days in the case of those with rheumatoid arthritis or tendinitis, or for 30 days in those with osteoarthritis. Paracetamol was allowed as a rescue analgesic. Subjective verbal scale assessments were used to determine levels of pain at rest, on movement and at night, sleep disturbance and functional incapacity, on entry and during treatment. At the end of the study period, both physicians and patients gave an overall opinion of the clinical response to tenoxicam, and patients were asked how their current compared with their previous treatment. The results showed that approximately 90% of patients had an excellent or good response to tenoxicam with marked improvement in all the signs and symptoms evaluated. Moreover, tenoxicam proved to be well tolerated, only a small number of patients reporting adverse events, mainly gastro-intestinal.\n[Drug-Disease]: tenoxicam - osteoarthritis" }, { "pmid": "1778090", "target": "[\"Span: African | Label: Body Type\", \"Span: 20 mg | Label: Dosage\"]", "text": "[Title]: Clinical efficacy and tolerability of tenoxicam in African patients with osteoarthritis, rheumatoid arthritis, tendinitis and/or bursitis: an open study.\n[Abstract]: An open clinical evaluation was carried out in 736 African out-patients suffering from rheumatic and inflammatory disorders to assess the efficacy and tolerability of tenoxicam in relieving the signs and symptoms of their condition. On entry, all previous treatment was discontinued and patients received a simple daily dose of 20 mg tenoxicam orally for 15 days in the case of those with rheumatoid arthritis or tendinitis, or for 30 days in those with osteoarthritis. Paracetamol was allowed as a rescue analgesic. Subjective verbal scale assessments were used to determine levels of pain at rest, on movement and at night, sleep disturbance and functional incapacity, on entry and during treatment. At the end of the study period, both physicians and patients gave an overall opinion of the clinical response to tenoxicam, and patients were asked how their current compared with their previous treatment. The results showed that approximately 90% of patients had an excellent or good response to tenoxicam with marked improvement in all the signs and symptoms evaluated. Moreover, tenoxicam proved to be well tolerated, only a small number of patients reporting adverse events, mainly gastro-intestinal.\n[Drug-Disease]: tenoxicam - pain" }, { "pmid": "17868276", "target": "[\"Span: mutations of the dysferlin gene | Label: Gene\"]", "text": "[Title]: A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene.\n[Abstract]: Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.\n[Drug-Disease]: dantrolene - Miyoshi myopathy" }, { "pmid": "17906454", "target": "[]", "text": "[Title]: Flavopiridol in the treatment of chronic lymphocytic leukemia.\n[Abstract]: PURPOSE OF REVIEW: The synthetic flavone flavopiridol induces apoptosis of chronic lymphocytic leukemia cells in vitro; however, initial studies administering flavopiridol by a 24- to 72-h continuous intravenous infusion demonstrated no clinical activity. This review focuses on a novel dosing regimen that has achieved significant clinical activity in relapsed, poor-risk chronic lymphocytic leukemia. RECENT FINDINGS: Binding to human plasma proteins reduces free flavopiridol concentration and makes continuous intravenous infusion dosing ineffective. Pharmacokinetic modeling indicated that administering flavopiridol by a 30-min intravenous bolus followed by a 4-h continuous intravenous infusion would achieve serum concentrations necessary to induce in-vivo apoptosis. Our institution conducted a phase I study in relapsed chronic lymphocytic leukemia. Dose-limiting toxicity was acute tumor lysis syndrome resulting in fatal hyperkalemia. Careful monitoring and aggressive intervention for hyperkalemia, including hemodialysis if necessary, allowed flavopiridol to be given safely. Nineteen of 42 patients responded (45%), including five of 12 patients (42%) with del(17p13) and 13 of 18 patients (72%) with del(11q22). SUMMARY: Flavopiridol, when administered by a 30-min intravenous bolus followed by a 4-h continuous intravenous infusion, is active in high-risk, refractory chronic lymphocytic leukemia. Careful monitoring and aggressive intervention for tumor lysis syndrome and hyperkalemia is necessary for safe drug administration. Further studies to optimize the dose and schedule of administration, and to study this drug in other hematologic malignancies, are ongoing.\n[Drug-Disease]: Flavopiridol - chronic lymphocytic leukemia" }, { "pmid": "17943569", "target": "[]", "text": "[Title]: Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial.\n[Abstract]: In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M. In the non-African-American cohort, an abnormal phenotype occurred in 12% and 2.9% were mildly deficient. Baseline pulmonary function and asthma scores were not significantly different between those with normal and abnormal AAT phenotype. However those with the deficiency tended to show a greater bronchodilator response.\n[Drug-Disease]: montelukast - asthma" }, { "pmid": "17943569", "target": "[]", "text": "[Title]: Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial.\n[Abstract]: In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M. In the non-African-American cohort, an abnormal phenotype occurred in 12% and 2.9% were mildly deficient. Baseline pulmonary function and asthma scores were not significantly different between those with normal and abnormal AAT phenotype. However those with the deficiency tended to show a greater bronchodilator response.\n[Drug-Disease]: theophylline - asthma" }, { "pmid": "17959037", "target": "[]", "text": "[Title]: Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide.\n[Abstract]: AIM: To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide. METHODS: Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 was measured by RT-PCR. RESULTS: Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%+/-0.67%) was significantly higher than that in the control group (6.23%+/-1.29%, P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05). CONCLUSION: Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.\n[Drug-Disease]: celecoxib - gastric adenocarcinoma" }, { "pmid": "17959037", "target": "[]", "text": "[Title]: Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide.\n[Abstract]: AIM: To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide. METHODS: Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 was measured by RT-PCR. RESULTS: Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%+/-0.67%) was significantly higher than that in the control group (6.23%+/-1.29%, P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05). CONCLUSION: Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.\n[Drug-Disease]: octreotide - gastric adenocarcinoma" }, { "pmid": "18008242", "target": "[\"Span: 3, 9, and 15 months of age | Label: Age\", \"Span: 250 and 12.5 mg | Label: Dosage\"]", "text": "[Title]: Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: Intermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects. METHODS: In Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age. RESULTS: In the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated. CONCLUSIONS: The intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00167843.\n[Drug-Disease]: SP - anemia" }, { "pmid": "18008242", "target": "[\"Span: 3, 9, and 15 months of age | Label: Age\", \"Span: 250 and 12.5 mg | Label: Dosage\"]", "text": "[Title]: Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial.\n[Abstract]: BACKGROUND: Intermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects. METHODS: In Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age. RESULTS: In the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated. CONCLUSIONS: The intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00167843.\n[Drug-Disease]: SP - malaria" }, { "pmid": "18037770", "target": "[]", "text": "[Title]: Impact of adenosine receptor signaling and metabolism on pathophysiology in patients with chronic heart failure.\n[Abstract]: Adenosine is well known to be a cardioprotective substance in ischemic heart disease. However, the modulation of adenosine receptors and the production and degradation of endogenous adenosine in chronic heart failure (CHF) are not fully understood. We analyzed the gene expression patterns of adenosine-related genes in human failing and nonfailing myocardium using DNA microarray analysis and quantitative real time-polymerase chain reaction (RT-PCR). DNA microarray analysis revealed that the gene expression of adenosine A2a, A2b, and A3 receptors (A2aR, A2bR, and A3R) as well as that of adenosine deaminase (ADA) decreased in failing myocardium. The down-regulation of these genes was verified by quantitative RT-PCR. We also measured the activities of these adenosine metabolism-related enzymes in failing myocardium and cardiac adenosine levels in patients with CHF. In CHF patients, we observed the decreased enzyme activity of ADA and the elevation of cardiac adenosine levels in CHF patients. To enhance the signaling of adenosine receptors, we increased plasma adenosine levels using dipyridamole, which decreased the severity of CHF. The gene expression of A2aR, A2bR, A3R, and ADA was decreased in the failing hearts, and this decrease may impair adenosine-related signal transduction. The activities of adenosine-related enzymes were altered, thus increasing the myocardial adenosine levels; this increase may compensate for the impairment of adenosine-related signal transduction in patients with CHF. The impairment of adenosine-related signal transmission contributes to the pathophysiology of CHF.\n[Drug-Disease]: dipyridamole - CHF" }, { "pmid": "18037772", "target": "[]", "text": "[Title]: Renal-protective effect of T-and L-type calcium channel blockers in hypertensive patients: an Amlodipine-to-Benidipine Changeover (ABC) study.\n[Abstract]: Both strict blood pressure control and efferent artery dilatation are critical in reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine, an L- and T-type calcium channel blocker, has the potential for increased effectiveness compared with L-type-dominant calcium channel blockers such as amlodipine. Therefore, we evaluated blood pressure and proteinuria after changeover from amlodipine to benidipine in poorly controlled hypertensive patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment and unable to achieve optimal blood pressure as determined by Japanese Society of Hypertension Guidelines for the Management of Hypertention (JSH 2004) were changed over to benidipine treatment. We measured blood pressure and pulse rate and assessed urinary protein excretion before and after changeover. Systolic and diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55 g/g creatinine (p=0.0119). The urinary protein reduction was observed only in patients with renin-angiotensin inhibition (p=0.0216). By switching from amlodipine to benidipine treatment, more than 80% of patients reduced their blood pressure, and more than 40% achieved optimal blood pressure. Higher urinary protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and presence of diabetes (p=0.0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria.\n[Drug-Disease]: benidipine - Hypertension" }, { "pmid": "18037772", "target": "[]", "text": "[Title]: Renal-protective effect of T-and L-type calcium channel blockers in hypertensive patients: an Amlodipine-to-Benidipine Changeover (ABC) study.\n[Abstract]: Both strict blood pressure control and efferent artery dilatation are critical in reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine, an L- and T-type calcium channel blocker, has the potential for increased effectiveness compared with L-type-dominant calcium channel blockers such as amlodipine. Therefore, we evaluated blood pressure and proteinuria after changeover from amlodipine to benidipine in poorly controlled hypertensive patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment and unable to achieve optimal blood pressure as determined by Japanese Society of Hypertension Guidelines for the Management of Hypertention (JSH 2004) were changed over to benidipine treatment. We measured blood pressure and pulse rate and assessed urinary protein excretion before and after changeover. Systolic and diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55 g/g creatinine (p=0.0119). The urinary protein reduction was observed only in patients with renin-angiotensin inhibition (p=0.0216). By switching from amlodipine to benidipine treatment, more than 80% of patients reduced their blood pressure, and more than 40% achieved optimal blood pressure. Higher urinary protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and presence of diabetes (p=0.0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria.\n[Drug-Disease]: benidipine - proteinuria" }, { "pmid": "1803833", "target": "[\"Span: 1 mg | Label: Dosage\", \"Span: 0.5 mg | Label: Dosage\"]", "text": "[Title]: Clinical evaluation of the short half-life injectable benzodiazepine midazolam, and of the specific antagonist flumazenil in upper digestive tract endoscopy.\n[Abstract]: In a first step, midazolam 0.1 mg/kg, midazolam 0.05 mg/kg and diazepam 0.15 mg/kg administered intravenously were blindly evaluated as a sedating preparation in 3 groups of each 30 patients undergoing gastroscopy. Although amnesia is better with midazolam 0.1 mg/kg, the induced sedation is protracted, which is not to be wished in ambulatory patients. On the other side, diazepam 0.15 mg/kg was locally less well tolerated. Taking into consideration the efficacy and the general and local tolerance, the dose of midazolam 0.05 mg/kg seems the best compromise. In a second step, the specific benzodiazepine antagonist flumazenil was blindly evaluated at two intravenous doses, 1 mg and 0.5 mg, against placebo for reversal of midazolam (0.1 mg/kg) induced sedation in gastroscopy patients. 1 mg of flumazenil (and to a lesser degree 0.5 mg) suppresses the sedation and amnesia induced by midazolam and normalizes attention and sensori-motor functions. However a certain degree of resedation can reappear 45-60 min. after the administration of flumazenil. Though this phenomenon did not alter the tests measuring attention and sensorimotor functions and the recovery of memory (contrary to placebo), it incites to be cautious when the drug is given to ambulatory patients.\n[Drug-Disease]: flumazenil - amnesia" }, { "pmid": "18075464", "target": "[]", "text": "[Title]: Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol.\n[Abstract]: OBJECTIVE: Administration of the beta-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both beta1-adrenergic and beta2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. METHODS: We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype beta1-adrenergic and beta2-adrenergic receptor polymorphisms. RESULTS: When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other beta1-adrenergic and beta2-adrenergic receptor polymorphisms (P>0.05). CONCLUSION: In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.\n[Drug-Disease]: carvedilol - dilated cardiomyopathy" }, { "pmid": "18075464", "target": "[]", "text": "[Title]: Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol.\n[Abstract]: OBJECTIVE: Administration of the beta-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both beta1-adrenergic and beta2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. METHODS: We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype beta1-adrenergic and beta2-adrenergic receptor polymorphisms. RESULTS: When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other beta1-adrenergic and beta2-adrenergic receptor polymorphisms (P>0.05). CONCLUSION: In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.\n[Drug-Disease]: carvedilol - heart failure" }, { "pmid": "18082302", "target": "[\"Span: schizophrenic | Label: Comorbidity\", \"Span: 1500 mg/day | Label: Dosage\"]", "text": "[Title]: Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine.\n[Abstract]: The second generation antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the effect of metformin treatment on the olanzapine-induced metabolic disturbance in schizophrenic patients. Twenty-four schizophrenic subjects who had received olanzapine treatment at least 3 months were assigned to the therapy with metformin 1500 mg/day for 8 weeks. The metabolic parameters were quantitatively assessed at baseline, weeks 2, 4, and 8 by using the intravenous glucose tolerance test. After an 8-week treatment with metformin, the body weight, fasting levels of glucose, triglyceride, and insulin, insulin secretion, and insulin resistance significantly decreased. Half of study subjects with metabolic syndrome obtained improvement after the metformin trial. Subjects' psychopathological condition remained unchanged during the study period. The olanzapine-induced metabolic disturbance could be reversed after 8-week metformin treatment. Based on the results of this study, we hypothesize that metformin could modulate the effect of olanzapine-induced metabolic disturbance.\n[Drug-Disease]: metformin - metabolic syndrome" }, { "pmid": "18172266", "target": "[\"Span: under the age of 65 years | Label: Age\", \"Span: 25 mg/m(2) i.v. | Label: Dosage\"]", "text": "[Title]: Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication.\n[Abstract]: PURPOSE: Fludarabine, cyclophosphamide, and mitoxantrone (FCM) results in a high response rate in previously treated patients with chronic lymphocytic leukemia (CLL). The aim of this study was to investigate FCM as frontline therapy in CLL. EXPERIMENTAL DESIGN: Sixty-nine patients under the age of 65 years with active CLL were treated. Patients received six cycles of fludarabine 25 mg/m(2) i.v. x 3 days, cyclophosphamide 200 mg/m(2) i.v. x 3 days, and mitoxantrone 6 mg/m(2) i.v. x 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating minimal residual disease (MRD) was also analyzed. RESULTS: The overall response, MRD-negative complete response (CR), MRD-positive CR, nodular partial response (PR), and PR rates were 90%, 26%, 38%, 14%, and 12%, respectively. Severe (grades 3 or 4) neutropenia developed in 10% of the patients. Major and minor infections were reported in 1% and 8% of cases, respectively. Median response duration was 37 months. Patients with del(17p) failed to attain CR. Patients achieving MRD-negative CR had a longer response duration and overall survival than patients with an inferior response. Low serum lactate dehydrogenase levels, low ZAP-70 expression, and mutated IgV(H) genes predicted longer response duration. Finally, both low ZAP-70 and CD38 expression in leukemic cells correlated with MRD-negativity achievement. CONCLUSION: FCM induces a high response rate, including MRD-negative CRs in untreated patients with active CLL. Treatment toxicity is acceptable. Both high ZAP-70 and increased CD38 expression predict failure to obtain MRD-negative response. Patients in whom MRD can be eradicated have longer response duration and overall survival than those with inferior response. These results indicate that FCM can be an ideal companion for chemoimmunotherapy of patients with CLL.\n[Drug-Disease]: fludarabine - chronic lymphocytic leukemia" }, { "pmid": "18172266", "target": "[\"Span: under the age of 65 years | Label: Age\", \"Span: 200 mg/m(2) i.v. | Label: Dosage\"]", "text": "[Title]: Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication.\n[Abstract]: PURPOSE: Fludarabine, cyclophosphamide, and mitoxantrone (FCM) results in a high response rate in previously treated patients with chronic lymphocytic leukemia (CLL). The aim of this study was to investigate FCM as frontline therapy in CLL. EXPERIMENTAL DESIGN: Sixty-nine patients under the age of 65 years with active CLL were treated. Patients received six cycles of fludarabine 25 mg/m(2) i.v. x 3 days, cyclophosphamide 200 mg/m(2) i.v. x 3 days, and mitoxantrone 6 mg/m(2) i.v. x 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating minimal residual disease (MRD) was also analyzed. RESULTS: The overall response, MRD-negative complete response (CR), MRD-positive CR, nodular partial response (PR), and PR rates were 90%, 26%, 38%, 14%, and 12%, respectively. Severe (grades 3 or 4) neutropenia developed in 10% of the patients. Major and minor infections were reported in 1% and 8% of cases, respectively. Median response duration was 37 months. Patients with del(17p) failed to attain CR. Patients achieving MRD-negative CR had a longer response duration and overall survival than patients with an inferior response. Low serum lactate dehydrogenase levels, low ZAP-70 expression, and mutated IgV(H) genes predicted longer response duration. Finally, both low ZAP-70 and CD38 expression in leukemic cells correlated with MRD-negativity achievement. CONCLUSION: FCM induces a high response rate, including MRD-negative CRs in untreated patients with active CLL. Treatment toxicity is acceptable. Both high ZAP-70 and increased CD38 expression predict failure to obtain MRD-negative response. Patients in whom MRD can be eradicated have longer response duration and overall survival than those with inferior response. These results indicate that FCM can be an ideal companion for chemoimmunotherapy of patients with CLL.\n[Drug-Disease]: cyclophosphamide - chronic lymphocytic leukemia" }, { "pmid": "18172266", "target": "[\"Span: under the age of 65 years | Label: Age\", \"Span: 6 mg/m(2) i.v. | Label: Dosage\"]", "text": "[Title]: Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication.\n[Abstract]: PURPOSE: Fludarabine, cyclophosphamide, and mitoxantrone (FCM) results in a high response rate in previously treated patients with chronic lymphocytic leukemia (CLL). The aim of this study was to investigate FCM as frontline therapy in CLL. EXPERIMENTAL DESIGN: Sixty-nine patients under the age of 65 years with active CLL were treated. Patients received six cycles of fludarabine 25 mg/m(2) i.v. x 3 days, cyclophosphamide 200 mg/m(2) i.v. x 3 days, and mitoxantrone 6 mg/m(2) i.v. x 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating minimal residual disease (MRD) was also analyzed. RESULTS: The overall response, MRD-negative complete response (CR), MRD-positive CR, nodular partial response (PR), and PR rates were 90%, 26%, 38%, 14%, and 12%, respectively. Severe (grades 3 or 4) neutropenia developed in 10% of the patients. Major and minor infections were reported in 1% and 8% of cases, respectively. Median response duration was 37 months. Patients with del(17p) failed to attain CR. Patients achieving MRD-negative CR had a longer response duration and overall survival than patients with an inferior response. Low serum lactate dehydrogenase levels, low ZAP-70 expression, and mutated IgV(H) genes predicted longer response duration. Finally, both low ZAP-70 and CD38 expression in leukemic cells correlated with MRD-negativity achievement. CONCLUSION: FCM induces a high response rate, including MRD-negative CRs in untreated patients with active CLL. Treatment toxicity is acceptable. Both high ZAP-70 and increased CD38 expression predict failure to obtain MRD-negative response. Patients in whom MRD can be eradicated have longer response duration and overall survival than those with inferior response. These results indicate that FCM can be an ideal companion for chemoimmunotherapy of patients with CLL.\n[Drug-Disease]: mitoxantrone - chronic lymphocytic leukemia" }, { "pmid": "18218293", "target": "[]", "text": "[Title]: Long-term remission in schizophrenia and related psychoses with long-acting risperidone: results obtained in an open-label study with an observation period of 18 months.\n[Abstract]: OBJECTIVE: To monitor long-term symptomatic tolerability and remission in patients with stable but suboptimally treated psychoses after switching to risperidone long-acting injectable (RLAI). METHOD: This subgroup analysis of the Switch to Risperidone Microspheres (StoRMi) open-label trial followed up patients with psychoses who were converted to RLAI for a period of 18 months or until RLAI became commercially available in their country of residence. It included patients from seven European countries. Dosage adjustments were performed as clinically necessary. The efficacy endpoint was achieving and maintaining remission, defined as absent to mild core schizophrenia symptoms for > or = 6 months. A schizophrenia assessment was also completed and patients were monitored for the development of adverse events (AEs). Discontinuation rates were calculated based on Kaplan-Meier estimates where patients switching to commercial RLAI were used as censored observations. RESULTS: A total of 529 patients were followed for up to 18 months. At 18 months, the discontinuation rate was 55.7% based on Kaplan-Meier estimates. The median time to discontinuation was 15.7 months (95% CI (14.0; 17.5)). RLAI was generally well tolerated with most AEs mild-to-moderate in severity. 13% of patients discontinued treatment because of an AE. Body weight of patients increased by a mean A+/- SD of 1.0 A+/- 6.1 kg from treatment initiation to endpoint (p = 0.0001). Glucose-related AEs occurred in four patients (0.8%). Among those patients not meeting severity remission criteria at baseline, 44.8% were in remission at endpoint. Among those patients meeting severity criteria for remission at baseline, 84.2% were in remission at endpoint. A total of 93.7% of the patients who achieved or maintained remission at 6 months were in remission at endpoint. CONCLUSIONS: RLAI is safe during long-term treatment up to 18 months in adults requiring antipsychotics. Conversion to RLAI resulted in improved symptom control. Most patients achieved and maintained a sustained remission (> or = 6 months) after conversion to RLAI.\n[Drug-Disease]: Risperidone - schizophrenia" }, { "pmid": "18250251", "target": "[\"Span: polymorphism of the mu-opioid receptor gene (OPRM1) | Label: Gene\", \"Span: 100 mg | Label: Dosage\"]", "text": "[Title]: An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study.\n[Abstract]: CONTEXT: Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the mu-opioid receptor gene (OPRM1), might predict naltrexone response. OBJECTIVE: To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone. DESIGN: Pharmacogenetic analysis conducted between January 1, 2001, and January 31, 2004. SETTING: Eleven academic sites in the COMBINE Study. PARTICIPANTS: Recently abstinent volunteers who met all 3 of the following conditions: (1) DSM-IV criteria for primary alcohol dependence; (2) participation in the COMBINE Study; and (3) availability of DNA. INTERVENTIONS: Alcoholic subjects were treated for 16 weeks with 100 mg of naltrexone hydrochloride (234 Asn40 homozygotes and 67 with at least 1 copy of the Asp40 allele) or placebo (235 Asn40 homozygotes and 68 with at least 1 copy of the Asp40 allele). All participants received medical management (MM) alone or with combined behavioral intervention (CBI). MAIN OUTCOME MEASURES: Time trends in percentage of days abstinent, percentage of heavy drinking days, and rates of good clinical outcome. RESULTS: Alcoholic subjects with an Asp40 allele receiving MM alone (no CBI) had an increased percentage of days abstinent (P = .07) and a decreased percentage of heavy drinking days (P = .04) if treated with naltrexone vs placebo, while those with the Asn40/Asn40 genotype showed no medication differences. If treated with MM alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of individuals with the Asn40/Asn40 genotype (odds ratio, 5.75; confidence interval, 1.88-17.54), while, if treated with placebo, 48.6% of Asp40 carriers and 54.0% of individuals with the Asn40/Asn40 genotype had a good clinical outcome (interaction between medication and genotype, P = .005). No gene x medication interactions were observed in those treated with both MM and CBI. CONCLUSIONS: These results confirm and extend the observation that the functionally significant OPRM1 Asp40 allele predicts naltrexone treatment response in alcoholic individuals. This relationship might be obscured, however, by other efficacious treatments. OPRM1 genotyping in alcoholic individuals might be useful to assist in selecting treatment options. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.\n[Drug-Disease]: naltrexone - primary alcohol dependence" }, { "pmid": "18256692", "target": "[\"Span: ABCC1 (ATP-binding cassette, subfamily C, member 1) | Label: Gene\", \"Span: ABCG2 (ATP-binding cassette, subfamily G, member 2) | Label: Gene\"]", "text": "[Title]: Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis.\n[Abstract]: Methotrexate, an inexpensive first-line systemic therapy for moderate-to-severe psoriasis, is limited in its use by unpredictable efficacy and toxicity. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and/or toxicity of the drug. DNA was collected from 374 patients with chronic plaque psoriasis who had been treated with methotrexate. Phenotypic data on efficacy and toxicity were available. Haplotype tagging SNPs (r(2)>0.8) across the relevant genes, with a minor allele frequency of >5%, were selected from the HAPMAP phase II data. SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity. With one SNP in ABCC1, rs246240, the carriage of two copies of allele 1 gives an odds ratio of 2.2 (95% confidence interval: 1.3-3.6; P=0.001) for developing toxicity to methotrexate. These data indicate that knowledge of SNPs in genes relevant to methotrexate efflux may be important in selecting patients suitable for this therapy.\n[Drug-Disease]: methotrexate - psoriasis" }, { "pmid": "18278980", "target": "[]", "text": "[Title]: Spotlight on risperidone in irritability associated with autistic disorder in children and adolescents.\n[Abstract]: Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin 5-HT(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioural symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence and hyperglycaemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents.\n[Drug-Disease]: risperidone - autistic disorder" }, { "pmid": "18278980", "target": "[]", "text": "[Title]: Spotlight on risperidone in irritability associated with autistic disorder in children and adolescents.\n[Abstract]: Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin 5-HT(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioural symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence and hyperglycaemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents.\n[Drug-Disease]: risperidone - bipolar I disorder" }, { "pmid": "18278980", "target": "[]", "text": "[Title]: Spotlight on risperidone in irritability associated with autistic disorder in children and adolescents.\n[Abstract]: Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin 5-HT(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioural symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence and hyperglycaemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents.\n[Drug-Disease]: risperidone - schizophrenia" }, { "pmid": "18315450", "target": "[\"Span: mean age 14.5 +/- 1.8 years | Label: Age\", \"Span: 20 to 160 mg/day (mean, 98.3 +/- 40.4 mg/day) | Label: Dosage\"]", "text": "[Title]: Ziprasidone in adolescents with autism: an open-label pilot study.\n[Abstract]: INTRODUCTION: The antipsychotic drugs are the best-studied agents shown to reduce symptoms in autism, including hyperactivity, aggression, self-abusive behavior, temper tantrums, lability, irritability, social withdrawal, and stereotypical behaviors. However, significant weight gain has been associated with use of many atypical agents. Ziprasidone has been weight neutral in adult populations, but data from adolescents and patients with autism are sparse. However, ziprasidone administration has been associated with increases in the QTc. The purpose of this study was to collect pilot data on the efficacy and safety of ziprasidone in adolescents with autism, focusing on safety issues of weight gain and QTc. METHODS: Twelve adolescents with autism (mean age 14.5 +/- 1.8 years) were treated in a 6-week open pilot study. Ziprasidone dosage ranged from 20 to 160 mg/day (mean, 98.3 +/- 40.4 mg/day). The primary efficacy measure was the Clinical Global Impressions-Improvement item (CGI-I); other efficacy measures included the Aberrant Behavior Checklist and the Children's Psychiatric Rating Scale. RESULTS: Based on the CGI-I, 9 of 12 (75%) patients were treatment responders. Ziprasidone was weight neutral, and the QTc increased by a mean of 14.7 msec. Two subjects had acute dystonic reactions. Cholesterol decreased and prolactin remained the same. CONCLUSIONS: Ziprasidone shows promise as a treatment for adolescents with autism. More definitive trials are needed.\n[Drug-Disease]: Ziprasidone - autism" }, { "pmid": "18323546", "target": "[\"Span: 60/600 mg/m(2) | Label: Dosage\", \"Span: median age was 49 years (range, 27 to 72 years) | Label: Age\"]", "text": "[Title]: The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer.\n[Abstract]: PURPOSE: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival. METHODS: Patients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of >or= 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m(2)) x 4 followed by P (175 mg/m(2)) x 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T x1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18. RESULTS: From January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced congestive heart failure (CHF). There were no cardiac deaths. CONCLUSION: Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.\n[Drug-Disease]: cyclophosphamide - breast cancer" }, { "pmid": "18323546", "target": "[\"Span: 175 mg/m(2) | Label: Dosage\", \"Span: median age was 49 years (range, 27 to 72 years) | Label: Age\"]", "text": "[Title]: The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer.\n[Abstract]: PURPOSE: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival. METHODS: Patients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of >or= 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m(2)) x 4 followed by P (175 mg/m(2)) x 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T x1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18. RESULTS: From January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced congestive heart failure (CHF). There were no cardiac deaths. CONCLUSION: Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.\n[Drug-Disease]: P - breast cancer" }, { "pmid": "1835291", "target": "[\"Span: 36 micrograms | Label: Dosage\"]", "text": "[Title]: Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.\n[Abstract]: The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.\n[Drug-Disease]: ipratropium - chronic airflow obstruction" }, { "pmid": "1835291", "target": "[\"Span: dose titrated to produce serum levels of 10-20 micrograms/mL | Label: Dosage\"]", "text": "[Title]: Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.\n[Abstract]: The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.\n[Drug-Disease]: theophylline - chronic airflow obstruction" }, { "pmid": "18378520", "target": "[\"Span: 80 mg | Label: Dosage\"]", "text": "[Title]: Telmisartan, ramipril, or both in patients at high risk for vascular events.\n[Abstract]: BACKGROUND: In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS: After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS: Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).\n[Drug-Disease]: Telmisartan - diabetes" }, { "pmid": "18378520", "target": "[\"Span: 10 mg | Label: Dosage\"]", "text": "[Title]: Telmisartan, ramipril, or both in patients at high risk for vascular events.\n[Abstract]: BACKGROUND: In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS: After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS: Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).\n[Drug-Disease]: ramipril - diabetes" }, { "pmid": "18382427", "target": "[\"Span: Indian | Label: Body Type\", \"Span: women | Label: Gender\", \"Span: 1200 mg m(-2) | Label: Dosage\", \"Span: 1000 mg | Label: Dosage\"]", "text": "[Title]: A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.\n[Abstract]: This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.\n[Drug-Disease]: gemcitabine - breast cancer" }, { "pmid": "18382427", "target": "[\"Span: Indian | Label: Body Type\", \"Span: women | Label: Gender\", \"Span: 70 mg m(-2) | Label: Dosage\"]", "text": "[Title]: A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.\n[Abstract]: This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.\n[Drug-Disease]: cisplatin - breast cancer" }, { "pmid": "18382427", "target": "[\"Span: Indian | Label: Body Type\", \"Span: women | Label: Gender\", \"Span: 60 mg m(-2) | Label: Dosage\"]", "text": "[Title]: A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.\n[Abstract]: This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.\n[Drug-Disease]: Dox - breast cancer" }, { "pmid": "18482155", "target": "[\"Span: polymorphism of the mu-opioid receptor gene (OPRM1) | Label: Gene\", \"Span: 101 Alaskans | Label: Body Type\", \"Span: 68 American Indians/Alaska Natives | Label: Body Type\", \"Span: 50 mg | Label: Dosage\"]", "text": "[Title]: Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial.\n[Abstract]: BACKGROUND: Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians. METHODS: Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. RESULTS: Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. CONCLUSIONS: Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.\n[Drug-Disease]: Naltrexone - alcoholism" }, { "pmid": "17032661", "target": "[]", "text": "[Title]: The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function.\n[Abstract]: BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass elicits a potent reperfusion injury and inflammatory response, more intense in patients with impaired myocardial function. Propofol has antioxidant properties which may attenuate such a response. METHODS: In total, 27 patients with impaired left ventricular function undergoing CABG were randomly allocated to receive either target-controlled infusion propofol (P) or saline (S) immediately before aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18 expression) were measured. RESULTS: Propofol decreased MDA coronary sinus concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after reperfusion a significant difference between the two groups in systemic MDA concentrations was also seen. IL-6 concentration increases were significantly greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs 228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase significantly in either group. Compared with baseline values IL-10 concentrations decreased after reperfusion but the values were higher in the propofol group than in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in leucocyte function or urinary isoprostane concentrations was demonstrated. CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and systemic inflammation in patients with impaired myocardial function undergoing CABG.\n[Drug-Disease]: Propofol - inflammation" }, { "pmid": "17076980", "target": "[\"Span: 10 mg/day | Label: Dosage\"]", "text": "[Title]: Lipid-lowering effects of colesevelam HCl in combination with ezetimibe.\n[Abstract]: OBJECTIVE: The primary aim of this study was to compare the effect of colesevelam HCl in combination with ezetimibe to ezetimibe monotherapy on low-density lipoprotein cholesterol (LDL-C) levels in subjects with primary hypercholesterolemia. METHODS: Subjects with primary hypercholesterolemia (N = 86) were enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a 4- to 8-week washout period, subjects received colesevelam HCl 3.8 g/day plus ezetimibe 10 mg/day or colesevelam HCl placebo plus ezetimibe 10 mg/day for 6 weeks. The primary efficacy endpoint was the mean percent change in LDL-C during randomized treatment. Secondary endpoints included mean absolute change in LDL-C, mean absolute and mean percent change in levels of high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), apolipoprotein (apo) A-I and apo B, and median absolute and percent changes in triglycerides (TG) and high-sensitivity C-reactive protein from baseline to end of treatment. Of the 86 subjects randomized to treatment, 85 were included in the intent-to-treat analysis. RESULTS: After 6 weeks of treatment, colesevelam HCl plus ezetimibe produced a mean percent change in LDL-C of -32.3% versus -21.4% with ezetimibe monotherapy (p < 0.0001). Colesevelam HCl plus ezetimibe was significantly more effective than ezetimibe alone at producing mean percent reductions in TC, non-HDL-C, and apo B and increases in apo A-I (p < 0.005 for all). Neither treatment regimen resulted in significant changes in median TG levels compared with baseline (p = NS). Both treatments were safe and generally well tolerated. CONCLUSIONS: Colesevelam HCl plus ezetimibe combination therapy significantly reduced mean LDL-C, TC, non-HDL-C, and apo B levels and increased apo A-I levels (p < 0.005 for all) without significantly increasing median TG levels in hypercholesterolemic subjects compared with ezetimibe alone. Although limited in that atherosclerotic coronary heart disease outcomes were not evaluated, this study demonstrated that combining colesevelam HCl with ezetimibe is a therapeutic option in hypercholesterolemic patients, such as those in whom statins are contraindicated and/or who may have intolerances to statin therapy.\n[Drug-Disease]: ezetimibe - hypercholesterolemia" }, { "pmid": "17076980", "target": "[\"Span: 3.8 g/day | Label: Dosage\"]", "text": "[Title]: Lipid-lowering effects of colesevelam HCl in combination with ezetimibe.\n[Abstract]: OBJECTIVE: The primary aim of this study was to compare the effect of colesevelam HCl in combination with ezetimibe to ezetimibe monotherapy on low-density lipoprotein cholesterol (LDL-C) levels in subjects with primary hypercholesterolemia. METHODS: Subjects with primary hypercholesterolemia (N = 86) were enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a 4- to 8-week washout period, subjects received colesevelam HCl 3.8 g/day plus ezetimibe 10 mg/day or colesevelam HCl placebo plus ezetimibe 10 mg/day for 6 weeks. The primary efficacy endpoint was the mean percent change in LDL-C during randomized treatment. Secondary endpoints included mean absolute change in LDL-C, mean absolute and mean percent change in levels of high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), apolipoprotein (apo) A-I and apo B, and median absolute and percent changes in triglycerides (TG) and high-sensitivity C-reactive protein from baseline to end of treatment. Of the 86 subjects randomized to treatment, 85 were included in the intent-to-treat analysis. RESULTS: After 6 weeks of treatment, colesevelam HCl plus ezetimibe produced a mean percent change in LDL-C of -32.3% versus -21.4% with ezetimibe monotherapy (p < 0.0001). Colesevelam HCl plus ezetimibe was significantly more effective than ezetimibe alone at producing mean percent reductions in TC, non-HDL-C, and apo B and increases in apo A-I (p < 0.005 for all). Neither treatment regimen resulted in significant changes in median TG levels compared with baseline (p = NS). Both treatments were safe and generally well tolerated. CONCLUSIONS: Colesevelam HCl plus ezetimibe combination therapy significantly reduced mean LDL-C, TC, non-HDL-C, and apo B levels and increased apo A-I levels (p < 0.005 for all) without significantly increasing median TG levels in hypercholesterolemic subjects compared with ezetimibe alone. Although limited in that atherosclerotic coronary heart disease outcomes were not evaluated, this study demonstrated that combining colesevelam HCl with ezetimibe is a therapeutic option in hypercholesterolemic patients, such as those in whom statins are contraindicated and/or who may have intolerances to statin therapy.\n[Drug-Disease]: colesevelam HCl - hypercholesterolemia" }, { "pmid": "17113426", "target": "[\"Span: 60 mg or 90 mg daily | Label: Dosage\"]", "text": "[Title]: Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.\n[Abstract]: BACKGROUND: Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. METHODS: We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445. FINDINGS: 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32). INTERPRETATION: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.\n[Drug-Disease]: etoricoxib - rheumatoid arthritis" }, { "pmid": "17113426", "target": "[\"Span: 60 mg or 90 mg daily | Label: Dosage\"]", "text": "[Title]: Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.\n[Abstract]: BACKGROUND: Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. METHODS: We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445. FINDINGS: 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32). INTERPRETATION: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.\n[Drug-Disease]: etoricoxib - osteoarthritis" }, { "pmid": "17113426", "target": "[\"Span: 150 mg daily | Label: Dosage\"]", "text": "[Title]: Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.\n[Abstract]: BACKGROUND: Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. METHODS: We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445. FINDINGS: 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32). INTERPRETATION: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.\n[Drug-Disease]: diclofenac - rheumatoid arthritis" }, { "pmid": "17113426", "target": "[\"Span: 150 mg daily | Label: Dosage\"]", "text": "[Title]: Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.\n[Abstract]: BACKGROUND: Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. METHODS: We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445. FINDINGS: 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32). INTERPRETATION: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.\n[Drug-Disease]: diclofenac - osteoarthritis" }, { "pmid": "17146452", "target": "[]", "text": "[Title]: Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.\n[Abstract]: BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.\n[Drug-Disease]: Fenfluramine - obesity" }, { "pmid": "17146452", "target": "[]", "text": "[Title]: Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.\n[Abstract]: BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.\n[Drug-Disease]: fluoxetine - obesity" }, { "pmid": "17146452", "target": "[]", "text": "[Title]: Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.\n[Abstract]: BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.\n[Drug-Disease]: phentermine - obesity" }, { "pmid": "17196055", "target": "[\"Span: 5-20 mg/day | Label: Dosage\", \"Span: 14.7 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine versus risperidone in the treatment of manic or mixed States in bipolar I disorder: a randomized, double-blind trial.\n[Abstract]: OBJECTIVE: To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes. METHOD: This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002. The primary outcome measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP) severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of life (Short Form Health Survey [SF-12]), psychological well-being (Psychological General Well-Being [PGWB] inventory), and sexual functioning were also compared. RESULTS: Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day, respectively. Between treatments, there was no difference in mean change in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response rates. Significantly more olanzapine-treated patients completed the study compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine-treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score improvement across the study. Olanzapine-treated patients experienced greater elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs. 1.6 kg; p = .004), while risperidone-treated patients were more likely to experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual dysfunction (total score increase of 1.75 vs. 0.64; p = .049). CONCLUSION: Both olanzapine and risperidone treatment yielded similar improvements in mania. The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain.\n[Drug-Disease]: olanzapine - mania" }, { "pmid": "17196055", "target": "[\"Span: 1-6 mg/day | Label: Dosage\", \"Span: 3.9 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine versus risperidone in the treatment of manic or mixed States in bipolar I disorder: a randomized, double-blind trial.\n[Abstract]: OBJECTIVE: To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes. METHOD: This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002. The primary outcome measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP) severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of life (Short Form Health Survey [SF-12]), psychological well-being (Psychological General Well-Being [PGWB] inventory), and sexual functioning were also compared. RESULTS: Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day, respectively. Between treatments, there was no difference in mean change in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response rates. Significantly more olanzapine-treated patients completed the study compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine-treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score improvement across the study. Olanzapine-treated patients experienced greater elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs. 1.6 kg; p = .004), while risperidone-treated patients were more likely to experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual dysfunction (total score increase of 1.75 vs. 0.64; p = .049). CONCLUSION: Both olanzapine and risperidone treatment yielded similar improvements in mania. The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain.\n[Drug-Disease]: risperidone - mania" }, { "pmid": "17201610", "target": "[\"Span: adolescents | Label: Age\", \"Span: 400-600 mg/day | Label: Dosage\"]", "text": "[Title]: The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s).\n[Abstract]: OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders. METHOD: Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point. RESULTS: Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28]. CONCLUSIONS: Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.\n[Drug-Disease]: Quetiapine - impulsivity" }, { "pmid": "17201610", "target": "[\"Span: adolescents | Label: Age\", \"Span: serum level 80-120 microg/mL | Label: Dosage\"]", "text": "[Title]: The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s).\n[Abstract]: OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders. METHOD: Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point. RESULTS: Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28]. CONCLUSIONS: Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.\n[Drug-Disease]: divalproex - impulsivity" }, { "pmid": "17236224", "target": "[\"Span: 600 mg orally daily | Label: Dosage\", \"Span: BCR-ABL kinase mutations | Label: Gene\"]", "text": "[Title]: Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia.\n[Abstract]: BACKGROUND: Resistance to imatinib is a frequent clinical problem in advanced phase chronic myelogenous leukemia (CML). A Phase II study was performed on low-dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP). METHODS: Patients received decitabine 15 mg/m(2) intravenously daily, 5 days a week for 2 weeks, and imatinib 600 mg orally daily. Global DNA methylation was measured by long interspersed nucleotide element (LINE) bisulfite/pyrosequencing. RESULTS: Twenty-eight patients were enrolled (25 with imatinib resistance; 18 in AP, 10 in BP). A total of 91 cycles (median, 2.5 cycles per patient) was administered. Complete hematologic responses, partial hematologic responses, and hematologic improvement were observed in 9 (32%), 1 (4%), and 2 (7%) patients. Major and minor cytogenetic responses were observed in 5 (18%) and 3 (11%) patients. The hematologic response rate was higher in patients without BCR-ABL kinase mutations (10 of 19, 53%) than in those with mutations (1 of 7, 14%). Median duration of hematologic response was 18 (range, 4 to 107+) weeks. Myelosuppression was the major adverse effect, with neutropenic fever in 9 patients (32%). LINE methylation decreased from 71.6% +/- 0.9% (mean +/- standard error of the mean) to 60.4% +/- 2.0% on Day 5, 60.5% +/- 1.8% on Day 12, and returned to 68.8% +/- 1.4% at peripheral blood recovery. A decrease in LINE methylation tended to be greater in nonresponders than in responders on Days 5 and 12. CONCLUSIONS: Combination therapy with decitabine and imatinib is well tolerated and active in advanced phase CML without BCR-ABL kinase mutations.\n[Drug-Disease]: imatinib - myeloid blastic" }, { "pmid": "17236224", "target": "[\"Span: 15 mg/m(2) intravenously daily | Label: Dosage\", \"Span: BCR-ABL kinase mutations | Label: Gene\"]", "text": "[Title]: Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia.\n[Abstract]: BACKGROUND: Resistance to imatinib is a frequent clinical problem in advanced phase chronic myelogenous leukemia (CML). A Phase II study was performed on low-dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP). METHODS: Patients received decitabine 15 mg/m(2) intravenously daily, 5 days a week for 2 weeks, and imatinib 600 mg orally daily. Global DNA methylation was measured by long interspersed nucleotide element (LINE) bisulfite/pyrosequencing. RESULTS: Twenty-eight patients were enrolled (25 with imatinib resistance; 18 in AP, 10 in BP). A total of 91 cycles (median, 2.5 cycles per patient) was administered. Complete hematologic responses, partial hematologic responses, and hematologic improvement were observed in 9 (32%), 1 (4%), and 2 (7%) patients. Major and minor cytogenetic responses were observed in 5 (18%) and 3 (11%) patients. The hematologic response rate was higher in patients without BCR-ABL kinase mutations (10 of 19, 53%) than in those with mutations (1 of 7, 14%). Median duration of hematologic response was 18 (range, 4 to 107+) weeks. Myelosuppression was the major adverse effect, with neutropenic fever in 9 patients (32%). LINE methylation decreased from 71.6% +/- 0.9% (mean +/- standard error of the mean) to 60.4% +/- 2.0% on Day 5, 60.5% +/- 1.8% on Day 12, and returned to 68.8% +/- 1.4% at peripheral blood recovery. A decrease in LINE methylation tended to be greater in nonresponders than in responders on Days 5 and 12. CONCLUSIONS: Combination therapy with decitabine and imatinib is well tolerated and active in advanced phase CML without BCR-ABL kinase mutations.\n[Drug-Disease]: decitabine - myeloid blastic" }, { "pmid": "17256746", "target": "[]", "text": "[Title]: Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B.\n[Abstract]: UNLABELLED: We studied the long-term efficacy of adefovir dipivoxil (ADV) treatment in 42 HBeAg-negative patients with chronic hepatitis B (CHB) who had developed genotypical lamivudine (LAM) resistance with virological and clinical breakthroughs under long-term LAM treatment. Patients were allocated in 2 treatment groups. In the first (n = 14), LAM was switched to ADV monotherapy whereas in the second (n = 28) ADV was added to LAM. The two groups did not differ in patients' characteristics, all of them having HBV genotype D infection with the precore stop codon mutation. Within 12 months from start of ADV treatment, serum HBV DNA became nondetectable and ALT normalized in 71% and 90% of patients, respectively, with no difference between the 2 arms. Patients with baseline HBV DNA levels less than 10(7) copies/ml experienced a significantly earlier and more frequent decline in serum HBV DNA to nondetectable levels as compared with patients with greater than 10(7) HBV DNA copies/ml at baseline (P = 0.0013) This response has hitherto been maintained (median treatment duration 40 months) in all patients with ADV added to LAM, whereas virological and biochemical breakthroughs due to development of ADV signature resistance mutations occurred in 3 of 14 patients (21%) on ADV monotherapy 15 to 18 months from start of treatment (P = 0.0174). CONCLUSION: Adding ADV to LAM in HBeAg-negative CHB patients with LAM resistance effectively suppresses HBV replication inmost of them and induces biochemical remission that can be maintained in all of them at least for 3 years without any evidence of development of resistance to ADV.\n[Drug-Disease]: ADV - chronic hepatitis B" }, { "pmid": "17256746", "target": "[]", "text": "[Title]: Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B.\n[Abstract]: UNLABELLED: We studied the long-term efficacy of adefovir dipivoxil (ADV) treatment in 42 HBeAg-negative patients with chronic hepatitis B (CHB) who had developed genotypical lamivudine (LAM) resistance with virological and clinical breakthroughs under long-term LAM treatment. Patients were allocated in 2 treatment groups. In the first (n = 14), LAM was switched to ADV monotherapy whereas in the second (n = 28) ADV was added to LAM. The two groups did not differ in patients' characteristics, all of them having HBV genotype D infection with the precore stop codon mutation. Within 12 months from start of ADV treatment, serum HBV DNA became nondetectable and ALT normalized in 71% and 90% of patients, respectively, with no difference between the 2 arms. Patients with baseline HBV DNA levels less than 10(7) copies/ml experienced a significantly earlier and more frequent decline in serum HBV DNA to nondetectable levels as compared with patients with greater than 10(7) HBV DNA copies/ml at baseline (P = 0.0013) This response has hitherto been maintained (median treatment duration 40 months) in all patients with ADV added to LAM, whereas virological and biochemical breakthroughs due to development of ADV signature resistance mutations occurred in 3 of 14 patients (21%) on ADV monotherapy 15 to 18 months from start of treatment (P = 0.0174). CONCLUSION: Adding ADV to LAM in HBeAg-negative CHB patients with LAM resistance effectively suppresses HBV replication inmost of them and induces biochemical remission that can be maintained in all of them at least for 3 years without any evidence of development of resistance to ADV.\n[Drug-Disease]: LAM - chronic hepatitis B" }, { "pmid": "17262810", "target": "[\"Span: multidrug resistance 1 (MDR1) gene | Label: Gene\", \"Span: G2677T/A | Label: Gene\", \"Span: C3435T | Label: Gene\", \"Span: Spanish | Label: Body Type\"]", "text": "[Title]: MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease.\n[Abstract]: BACKGROUND: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. RESULTS: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6-12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8-22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82-3.9; P = 0.14). CONCLUSIONS: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy.\n[Drug-Disease]: azathioprine - Crohn's disease" }, { "pmid": "17294898", "target": "[]", "text": "[Title]: [Therapeutic results with apl 93 protocol in acute promyelocytic leukemia (34 cases)].\n[Abstract]: BACKGROUND: Acute promyelocytic leukaemia (APL) account for approximately 10% to 15% of all AML in most reports. Clinical features includes the presence in 80% to 90% of patients of a severe hemorrhagic syndrome, a specific balanced translocation between chromosomes 15 and 17 with a fusion of a large pert of the retinoic acid receptor a gene (RARa) on chromosome 17 to a part of the promyelocytic leukaemia (PML) gene on chromosome 15. More than 75% of patients (under 65 years of age) can be cured, with the application of a combination of anthracyclines and all-trans retinoic acid (ATRA), followed by maintenance therapy. AIM: of the study was to assess of the therapeutic management of APL 93 protocol in acute promyelocytic leukemia. METHODS: We present here the results of a retrospective study concerning 34 patients with APL included between 1998 and 2004 in the APL 93 protocol : 20 in group B and 14 in group C. CR was 82 %. RESULTS: Failure is only due to toxic death (18%) Event free survival at 4 years is 63,47% with relapse rate at 14.25%. Overall survival at 4 years is 69,72%. Our results are acceptable and can be improved with reduction of failure due to toxic death, probably with omission of cytarabine from induction and consolidation adapted by the Spanish PETHEMA Group.\n[Drug-Disease]: ATRA - acute promyelocytic leukemia" }, { "pmid": "17294898", "target": "[]", "text": "[Title]: [Therapeutic results with apl 93 protocol in acute promyelocytic leukemia (34 cases)].\n[Abstract]: BACKGROUND: Acute promyelocytic leukaemia (APL) account for approximately 10% to 15% of all AML in most reports. Clinical features includes the presence in 80% to 90% of patients of a severe hemorrhagic syndrome, a specific balanced translocation between chromosomes 15 and 17 with a fusion of a large pert of the retinoic acid receptor a gene (RARa) on chromosome 17 to a part of the promyelocytic leukaemia (PML) gene on chromosome 15. More than 75% of patients (under 65 years of age) can be cured, with the application of a combination of anthracyclines and all-trans retinoic acid (ATRA), followed by maintenance therapy. AIM: of the study was to assess of the therapeutic management of APL 93 protocol in acute promyelocytic leukemia. METHODS: We present here the results of a retrospective study concerning 34 patients with APL included between 1998 and 2004 in the APL 93 protocol : 20 in group B and 14 in group C. CR was 82 %. RESULTS: Failure is only due to toxic death (18%) Event free survival at 4 years is 63,47% with relapse rate at 14.25%. Overall survival at 4 years is 69,72%. Our results are acceptable and can be improved with reduction of failure due to toxic death, probably with omission of cytarabine from induction and consolidation adapted by the Spanish PETHEMA Group.\n[Drug-Disease]: anthracyclines - acute promyelocytic leukemia" }, { "pmid": "17324145", "target": "[\"Span: Male | Label: Gender\", \"Span: age range 40-55 years | Label: Age\", \"Span: 5 mg once daily | Label: Dosage\"]", "text": "[Title]: Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men.\n[Abstract]: 1. Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two beta(1)-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men. 2. Male out-patients (age range 40-55 years) with newly diagnosed or existing stage 1 essential hypertension (mean seated systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg) were enrolled in the study. All patients lived in a stable, heterosexual partnership and had no history of sexual dysfunction. After a 2-week placebo run-in period, patients were randomized double-blind to either Treatment group A (comprising nebivolol 5 mg once daily for 12 weeks, followed by placebo for 2 weeks and then metoprolol succinate 95 mg once daily for 12 weeks) or Treatment group B (comprising metoprolol succinate 95 mg for 12 weeks, placebo for 2 weeks and then nebivolol 5 mg for 12 weeks). An international index of erectile function (IIEF) questionnaire and a diary documented patients' sexual function and activity. 3. Nebivolol and metoprolol lowered blood pressure to a similar extent. Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores. 4. Despite similar antihypertensive efficacy of the cardioselective beta(1)-adrenoceptor antagonists nebivolol and metoprolol, nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term beta-adrenoceptor antagonist therapy.\n[Drug-Disease]: nebivolol - hypertensive" }, { "pmid": "17324145", "target": "[\"Span: Male | Label: Gender\", \"Span: age range 40-55 years | Label: Age\", \"Span: 95 mg once daily | Label: Dosage\"]", "text": "[Title]: Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men.\n[Abstract]: 1. Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two beta(1)-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men. 2. Male out-patients (age range 40-55 years) with newly diagnosed or existing stage 1 essential hypertension (mean seated systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg) were enrolled in the study. All patients lived in a stable, heterosexual partnership and had no history of sexual dysfunction. After a 2-week placebo run-in period, patients were randomized double-blind to either Treatment group A (comprising nebivolol 5 mg once daily for 12 weeks, followed by placebo for 2 weeks and then metoprolol succinate 95 mg once daily for 12 weeks) or Treatment group B (comprising metoprolol succinate 95 mg for 12 weeks, placebo for 2 weeks and then nebivolol 5 mg for 12 weeks). An international index of erectile function (IIEF) questionnaire and a diary documented patients' sexual function and activity. 3. Nebivolol and metoprolol lowered blood pressure to a similar extent. Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores. 4. Despite similar antihypertensive efficacy of the cardioselective beta(1)-adrenoceptor antagonists nebivolol and metoprolol, nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term beta-adrenoceptor antagonist therapy.\n[Drug-Disease]: metoprolol - hypertensive" }, { "pmid": "17363756", "target": "[\"Span: type 2 diabetes | Label: Comorbidity\", \"Span: up to 175 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of topiramate controlled release in the treatment of obese type 2 diabetic patients.\n[Abstract]: OBJECTIVE: This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes, BMI > or =27 kg/m2, A1C >6.5 and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase. RESULTS: A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P < 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P < 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related. CONCLUSIONS: Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.\n[Drug-Disease]: Topiramate - obesity" }, { "pmid": "17383295", "target": "[]", "text": "[Title]: Exercise capacity in atrial fibrillation: a substudy of the Sotalol-Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).\n[Abstract]: BACKGROUND: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. METHODS: Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. RESULTS: Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (approximately 25 beat/min) and peak exercise (approximately 40 beat/min) heart rates at 6 months and 1 year (P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. CONCLUSION: Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.\n[Drug-Disease]: amiodarone - AF" }, { "pmid": "17383295", "target": "[]", "text": "[Title]: Exercise capacity in atrial fibrillation: a substudy of the Sotalol-Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).\n[Abstract]: BACKGROUND: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. METHODS: Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. RESULTS: Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (approximately 25 beat/min) and peak exercise (approximately 40 beat/min) heart rates at 6 months and 1 year (P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. CONCLUSION: Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.\n[Drug-Disease]: sotalol - AF" }, { "pmid": "17401013", "target": "[\"Span: thymidylate synthase | Label: Gene\", \"Span: methylenetetrahydrofolate reductase | Label: Gene\", \"Span: xeroderma pigmentosum group D (XPD) | Label: Gene\", \"Span: excision repair cross complementing group 1 (ERCC1) | Label: Gene\", \"Span: x-ray cross complementing group 1 | Label: Gene\", \"Span: x-ray cross complementing protein 3 | Label: Gene\", \"Span: glutathione S-transferases (GSTs) | Label: Gene\", \"Span: ERCC1-118 T/T | Label: Gene\", \"Span: XPD-751 A/C | Label: Gene\", \"Span: XPD-751 C/C | Label: Gene\", \"Span: GSTP1-105 A/G | Label: Gene\", \"Span: GSTP1-105 G/G | Label: Gene\"]", "text": "[Title]: Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy.\n[Abstract]: PURPOSE: The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy. MATERIALS AND METHODS: Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS). RESULTS: In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes. CONCLUSION: A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.\n[Drug-Disease]: oxaliplatin - colorectal cancer" }, { "pmid": "17401013", "target": "[\"Span: thymidylate synthase | Label: Gene\", \"Span: methylenetetrahydrofolate reductase | Label: Gene\", \"Span: xeroderma pigmentosum group D (XPD) | Label: Gene\", \"Span: excision repair cross complementing group 1 (ERCC1) | Label: Gene\", \"Span: x-ray cross complementing group 1 | Label: Gene\", \"Span: x-ray cross complementing protein 3 | Label: Gene\", \"Span: glutathione S-transferases (GSTs) | Label: Gene\", \"Span: ERCC1-118 T/T | Label: Gene\", \"Span: XPD-751 A/C | Label: Gene\", \"Span: XPD-751 C/C | Label: Gene\", \"Span: GSTP1-105 A/G | Label: Gene\", \"Span: GSTP1-105 G/G | Label: Gene\"]", "text": "[Title]: Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy.\n[Abstract]: PURPOSE: The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy. MATERIALS AND METHODS: Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS). RESULTS: In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes. CONCLUSION: A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.\n[Drug-Disease]: folinic acid - colorectal cancer" }, { "pmid": "17401013", "target": "[\"Span: thymidylate synthase | Label: Gene\", \"Span: methylenetetrahydrofolate reductase | Label: Gene\", \"Span: xeroderma pigmentosum group D (XPD) | Label: Gene\", \"Span: excision repair cross complementing group 1 (ERCC1) | Label: Gene\", \"Span: x-ray cross complementing group 1 | Label: Gene\", \"Span: x-ray cross complementing protein 3 | Label: Gene\", \"Span: glutathione S-transferases (GSTs) | Label: Gene\", \"Span: ERCC1-118 T/T | Label: Gene\", \"Span: XPD-751 A/C | Label: Gene\", \"Span: XPD-751 C/C | Label: Gene\", \"Span: GSTP1-105 A/G | Label: Gene\", \"Span: GSTP1-105 G/G | Label: Gene\"]", "text": "[Title]: Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy.\n[Abstract]: PURPOSE: The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy. MATERIALS AND METHODS: Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS). RESULTS: In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes. CONCLUSION: A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.\n[Drug-Disease]: fluorouracil - colorectal cancer" }, { "pmid": "17408102", "target": "[\"Span: multiple myeloma | Label: Comorbidity\", \"Span: 100 to 300 mg | Label: Dosage\"]", "text": "[Title]: [Thalidomide-associated bradycardia in patients with hematologic diseases: a single institution experience].\n[Abstract]: Thalidomide, an immunomodulatory and antiangiogenic agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstrom macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.\n[Drug-Disease]: thalidomide - non-Hodgkin's lymphoma" }, { "pmid": "17408102", "target": "[\"Span: multiple myeloma | Label: Comorbidity\", \"Span: 100 to 300 mg | Label: Dosage\"]", "text": "[Title]: [Thalidomide-associated bradycardia in patients with hematologic diseases: a single institution experience].\n[Abstract]: Thalidomide, an immunomodulatory and antiangiogenic agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstrom macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.\n[Drug-Disease]: thalidomide - macroglobulinemia" }, { "pmid": "17408102", "target": "[\"Span: 100 to 300 mg | Label: Dosage\"]", "text": "[Title]: [Thalidomide-associated bradycardia in patients with hematologic diseases: a single institution experience].\n[Abstract]: Thalidomide, an immunomodulatory and antiangiogenic agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstrom macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.\n[Drug-Disease]: thalidomide - multiple myeloma" }, { "pmid": "17408102", "target": "[\"Span: multiple myeloma | Label: Comorbidity\", \"Span: 100 to 300 mg | Label: Dosage\"]", "text": "[Title]: [Thalidomide-associated bradycardia in patients with hematologic diseases: a single institution experience].\n[Abstract]: Thalidomide, an immunomodulatory and antiangiogenic agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstrom macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.\n[Drug-Disease]: thalidomide - myelodysplastic syndrome" }, { "pmid": "17414239", "target": "[\"Span: major Axis I psychiatric disorder | Label: Comorbidity\", \"Span: (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression | Label: Comorbidity\"]", "text": "[Title]: Naltrexone and disulfiram in patients with alcohol dependence and current depression.\n[Abstract]: OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.\n[Drug-Disease]: disulfiram - alcohol dependence" }, { "pmid": "17414239", "target": "[\"Span: major Axis I psychiatric disorder | Label: Comorbidity\", \"Span: (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression | Label: Comorbidity\"]", "text": "[Title]: Naltrexone and disulfiram in patients with alcohol dependence and current depression.\n[Abstract]: OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.\n[Drug-Disease]: naltrexone - alcohol dependence" }, { "pmid": "17496732", "target": "[]", "text": "[Title]: Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.\n[Abstract]: BACKGROUND: The atherogenic index of plasma (AIP), defined as logarithm [log] of the ratio of plasma concentration of triglycerides to high-density lipoprotein (HDL) cholesterol, has recently been proposed as a predictive marker for plasma atherogenicity and is positively correlated with cardiovascular disease risk. The nutrient combination of chromium picolinate and biotin (CPB) has been previously shown to reduce insulin resistance and hyperglycemia in patients with type 2 diabetes (T2DM). METHODS: Thirty-six moderately obese subjects with T2DM and with impaired glycemic control were randomized to receive CPB or placebo in addition to their oral hyperglycemic agents for 4 weeks. Measurements of blood lipids (including ratio of triglycerides to HDL cholesterol), fructosamine, glucose, and insulin were taken at baseline and after 4 weeks. RESULTS: At the final visit, the active group had a significantly lower AIP compared to the placebo group (P < 0.05). A significant difference in triglyceride level (P < 0.02) and the ratio of low-density lipoprotein (LDL) to HDL cholesterol (P < 0.05) was also observed between the groups at the final visit. In the active group, the changes in urinary chromium levels were inversely correlated with the change in AIP (P < 0.05). Urinary chromium levels were significantly increased in the CPB group. In the CPB group, glucose levels decreased at 1 hour and 2 hours and glucose area under the curve and fructosamine level were significantly decreased. Ratios of total to HDL cholesterol, LDL to HDL cholesterol, and non-HDL to HDL cholesterol were significantly decreased between the treatments at final visit. No significant adverse events were observed in the CPB or placebo groups. CONCLUSIONS: These results suggest that the combination of chromium picolinate and biotin may be a valuable nutritional adjuvant therapy to reduce AIP and correlated CVD risk factors in people with T2DM.\n[Drug-Disease]: chromium picolinate - hyperglycemia" }, { "pmid": "17496732", "target": "[]", "text": "[Title]: Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.\n[Abstract]: BACKGROUND: The atherogenic index of plasma (AIP), defined as logarithm [log] of the ratio of plasma concentration of triglycerides to high-density lipoprotein (HDL) cholesterol, has recently been proposed as a predictive marker for plasma atherogenicity and is positively correlated with cardiovascular disease risk. The nutrient combination of chromium picolinate and biotin (CPB) has been previously shown to reduce insulin resistance and hyperglycemia in patients with type 2 diabetes (T2DM). METHODS: Thirty-six moderately obese subjects with T2DM and with impaired glycemic control were randomized to receive CPB or placebo in addition to their oral hyperglycemic agents for 4 weeks. Measurements of blood lipids (including ratio of triglycerides to HDL cholesterol), fructosamine, glucose, and insulin were taken at baseline and after 4 weeks. RESULTS: At the final visit, the active group had a significantly lower AIP compared to the placebo group (P < 0.05). A significant difference in triglyceride level (P < 0.02) and the ratio of low-density lipoprotein (LDL) to HDL cholesterol (P < 0.05) was also observed between the groups at the final visit. In the active group, the changes in urinary chromium levels were inversely correlated with the change in AIP (P < 0.05). Urinary chromium levels were significantly increased in the CPB group. In the CPB group, glucose levels decreased at 1 hour and 2 hours and glucose area under the curve and fructosamine level were significantly decreased. Ratios of total to HDL cholesterol, LDL to HDL cholesterol, and non-HDL to HDL cholesterol were significantly decreased between the treatments at final visit. No significant adverse events were observed in the CPB or placebo groups. CONCLUSIONS: These results suggest that the combination of chromium picolinate and biotin may be a valuable nutritional adjuvant therapy to reduce AIP and correlated CVD risk factors in people with T2DM.\n[Drug-Disease]: biotin - hyperglycemia" }, { "pmid": "17503984", "target": "[\"Span: 300 mg/day | Label: Dosage\", \"Span: S/L genotype of the 5-HTTLPR polymorphism | Label: Gene\"]", "text": "[Title]: Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial.\n[Abstract]: OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD). Still, up to 40% to 60% of OCD patients do not respond to SRI treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1B, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. METHOD: 91 outpatients with OCD according to DSM-IV criteria consented to the study and were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive Compulsive Scale (YBOCS), and response was defined as a > or = 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5-HT2A genotypes and differentiated in paroxetine-or venlafaxine-treated groups. The study was conducted from August 1998 to July 2002. RESULTS: In the whole group, 64% of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 8.66, df = 2, p = .013), whereas in the venlafaxine-treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 9.72, df = 2, p = .008). CONCLUSIONS: The results of this study suggest that response in venlafaxine-treated OCD patients is associated with the S/L genotype of the 5-HTTLPR polymorphism and in paroxetine-treated OCD patients with the G/G genotype of the 5-HT2A polymorphism.\n[Drug-Disease]: venlafaxine - OCD" }, { "pmid": "17503984", "target": "[\"Span: 60 mg/day | Label: Dosage\", \"Span: G/G genotype of the 5-HT2A polymorphism | Label: Gene\"]", "text": "[Title]: Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial.\n[Abstract]: OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD). Still, up to 40% to 60% of OCD patients do not respond to SRI treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1B, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. METHOD: 91 outpatients with OCD according to DSM-IV criteria consented to the study and were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive Compulsive Scale (YBOCS), and response was defined as a > or = 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5-HT2A genotypes and differentiated in paroxetine-or venlafaxine-treated groups. The study was conducted from August 1998 to July 2002. RESULTS: In the whole group, 64% of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 8.66, df = 2, p = .013), whereas in the venlafaxine-treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 9.72, df = 2, p = .008). CONCLUSIONS: The results of this study suggest that response in venlafaxine-treated OCD patients is associated with the S/L genotype of the 5-HTTLPR polymorphism and in paroxetine-treated OCD patients with the G/G genotype of the 5-HT2A polymorphism.\n[Drug-Disease]: paroxetine - OCD" }, { "pmid": "17522103", "target": "[]", "text": "[Title]: Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin.\n[Abstract]: BACKGROUND: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP. METHODS: Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers. RESULTS: Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043). CONCLUSION: The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.\n[Drug-Disease]: cisplatin - gastric cancer" }, { "pmid": "17522103", "target": "[]", "text": "[Title]: Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin.\n[Abstract]: BACKGROUND: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP. METHODS: Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers. RESULTS: Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043). CONCLUSION: The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.\n[Drug-Disease]: 5-FU - gastric cancer" }, { "pmid": "17531327", "target": "[\"Span: 5-20 mg/day | Label: Dosage\"]", "text": "[Title]: Olanzapine versus lithium in the acute treatment of bipolar mania: a double-blind, randomized, controlled trial.\n[Abstract]: BACKGROUND: This multicenter, double-blind, randomized, controlled study conducted in China examined the efficacy and safety of olanzapine versus lithium in the treatment of patients with bipolar manic/mixed episodes. METHODS: Patients with bipolar manic or mixed episode (DSM-IV criteria) and Young Mania Rating Scale (YMRS) score> or =20 at screening received olanzapine (5-20 mg/day, n=69) or lithium carbonate (600-1800 mg/day, n=71) for 4 weeks. The primary outcome was mean change from baseline in Clinical Global Impressions-Bipolar Version Overall Severity of Illness (CGI-BP) score. Secondary efficacy measures included YMRS, Brief Psychiatric Rating Scale (BPRS), and Montgomery-Asberg Depression Rating Scale (MADRS) scores. Safety was also assessed. RESULTS: A significantly greater mean change was observed in olanzapine versus lithium patients in CGI-BP (Overall Severity) (P=0.009), YMRS (P=0.013), BPRS (P=0.032), and CGI-BP (Severity of Mania) (P=0.012) scores. More olanzapine than lithium patients experienced at least one adverse event possibly related to study drug (P=0.038). More olanzapine patients had a clinically significant weight increase (> or =7% of baseline weight) compared to lithium patients (P=0.009). More olanzapine patients completed the study than lithium patients, although this difference was not statistically significant (olz, 91.3%; lith, 78.9%; P=0.057). LIMITATIONS: No placebo arm was included; however both treatments have previously been reported to be more effective than placebo. CONCLUSIONS: These results suggest that olanzapine has superior efficacy to lithium in the acute treatment of patients with bipolar mania over a 4-week period. However, adverse events were experienced by a greater number of olanzapine patients than lithium patients.\n[Drug-Disease]: olanzapine - bipolar mania" }, { "pmid": "17557453", "target": "[\"Span: 3 mg | Label: Dosage\"]", "text": "[Title]: Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.\n[Abstract]: BACKGROUND: Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD. METHODS: Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo. RESULTS: Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD-17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were maintained at Week 10 (p < .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p < .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (p < .05). CONCLUSIONS: In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.\n[Drug-Disease]: eszopiclone - MDD" }, { "pmid": "17557453", "target": "[\"Span: 3 mg | Label: Dosage\"]", "text": "[Title]: Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.\n[Abstract]: BACKGROUND: Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD. METHODS: Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo. RESULTS: Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD-17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were maintained at Week 10 (p < .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p < .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (p < .05). CONCLUSIONS: In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.\n[Drug-Disease]: eszopiclone - insomnia" }, { "pmid": "17557453", "target": "[]", "text": "[Title]: Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.\n[Abstract]: BACKGROUND: Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD. METHODS: Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo. RESULTS: Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD-17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were maintained at Week 10 (p < .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p < .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (p < .05). CONCLUSIONS: In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.\n[Drug-Disease]: fluoxetine - MDD" }, { "pmid": "17557453", "target": "[]", "text": "[Title]: Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.\n[Abstract]: BACKGROUND: Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD. METHODS: Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo. RESULTS: Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD-17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were maintained at Week 10 (p < .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p < .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (p < .05). CONCLUSIONS: In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.\n[Drug-Disease]: fluoxetine - insomnia" }, { "pmid": "17563214", "target": "[\"Span: 50 mg/day | Label: Dosage\"]", "text": "[Title]: Family history and antisocial traits moderate naltrexone's effects on heavy drinking in alcoholics.\n[Abstract]: Naltrexone's (NAL) effects on alcohol consumption are generally modest, so identifying patients likely to benefit would improve treatment utility. Several studies indicate that potentially significant moderators of NAL's effects might include family history of alcohol problems (FH), age of onset of alcohol problems, degree of antisocial traits, and comorbid drug use. Data from 128 alcoholic patients enrolled in a 12-week NAL treatment study (50 mg/day) were reanalyzed to determine the role of FH, age of onset, antisocial traits, and comorbid drug use in NAL's treatment effects on heavy drinking days. Dichotomized FH, age of onset of alcohol problems, and comorbid cocaine or marijuana use had no interaction effect with medication. Percentage of relatives with problem drinking (family history percentage [FHP]) moderated the effects of NAL on drinking such that NAL resulted in lower drinking rates only for patients with higher FHP. Antisocial traits also moderated the effects of medication on drinking for patients compliant with =70% of medication. Patients with more antisocial traits had less heavy drinking on NAL than on placebo, whereas patients low on antisocial traits had no benefit from NAL. Covarying antisociality in regressions of drinking outcome on FHP showed that the effects of FHP were not attributable to antisociality. Thus, NAL may selectively benefit alcoholics with antisocial traits or 20% or more relatives with problem drinking.\n[Drug-Disease]: NAL - alcoholic" }, { "pmid": "17575230", "target": "[\"Span: 600 mg/m(2) | Label: Dosage\", \"Span: 900 mg/m(2) | Label: Dosage\"]", "text": "[Title]: A randomized, double-blind, phase II study of two doses of pemetrexed as first-line chemotherapy for advanced breast cancer.\n[Abstract]: PURPOSE: Pemetrexed has shown varied response rates in advanced breast cancer. This randomized, double-blind, phase II study was conducted to assess the efficacy and safety of two doses of pemetrexed in a homogeneous population. A secondary objective was to identify molecular biomarkers correlating with response and toxicity. EXPERIMENTAL DESIGN: Patients with newly diagnosed metastatic breast cancer or locally recurrent breast cancer received 600 mg/m(2) (P600 arm) or 900 mg/m(2) (P900 arm) of pemetrexed on day 1 of a 21-day cycle. All patients received folic acid and vitamin B(12) supplementation. RESULTS: The P600 (47 patients) and P900 (45 patients) arms had response rates of 17.0% (95% confidence interval, 7.7-30.8%) and 15.6% (95% confidence interval, 6.5-29.5%) with approximately 50% stable disease per arm, median progression-free survival of 4.2 and 4.1 months, and median times to tumor progression of 4.2 and 4.6 months, respectively. Both arms exhibited minimal toxicity (grade 3/4 neutropenia <20%, leukopenia <9%, and other toxicities <5%). Tumor samples from 49 patients were assessed for the expression levels of 12 pemetrexed-related genes. Folylpolyglutamate synthetase and thymidine phosphorylase correlated with efficacy. Best response rates and median time to tumor progression for high versus low thymidine phosphorylase expression were 27.6% versus 6.3% (P = 0.023) and 5.4 versus 1.9 months (P = 0.076), and for folylpolyglutamate synthetase were 37.5% versus 10.0% (P = 0.115) and 8.6 versus 3.0 months (P = 0.019), respectively. gamma-Glutamyl hydrolase expression correlated with grade 3/4 toxicities: 78.6% for high versus 27.3% for low gamma-glutamyl hydrolase (P = 0.024). CONCLUSION: The two pemetrexed doses yielded similar efficacy and safety profiles. Exploratory biomarker analysis identified efficacy and toxicity correlations and warrants further evaluation.\n[Drug-Disease]: pemetrexed - breast cancer" }, { "pmid": "17614302", "target": "[]", "text": "[Title]: Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study.\n[Abstract]: BACKGROUND: The optimal trastuzumab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzumab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens. METHODS: Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or docetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane. RESULTS: Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P = .09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity. Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention. CONCLUSIONS: Both vinorelbine/trastuzumab and taxane/trastuzumab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting.\n[Drug-Disease]: taxane - breast cancer" }, { "pmid": "17614302", "target": "[]", "text": "[Title]: Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study.\n[Abstract]: BACKGROUND: The optimal trastuzumab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzumab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens. METHODS: Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or docetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane. RESULTS: Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P = .09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity. Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention. CONCLUSIONS: Both vinorelbine/trastuzumab and taxane/trastuzumab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting.\n[Drug-Disease]: vinorelbine - breast cancer" }, { "pmid": "17634861", "target": "[\"Span: mean age, 63 years | Label: Age\", \"Span: 4 mg | Label: Dosage\"]", "text": "[Title]: Quantitative evaluation of reduction of plaque-like hard exudates in diabetic macular edema after intravitreal triamcinolone injection.\n[Abstract]: BACKGROUND: To describe a new method of quantifying the amount of plaque-like hard exudates after intravitreal triamcinolone acetonide injection in diabetic macular edema. METHODS: This study included 22 eyes of 14 patients (mean age, 63 years) with chronic diabetic macular edema and plaque-like hard exudates. The patients were injected with a single dose of 4 mg intravitreal triamcinolone acetonide. The optic disc size as relative size unit was taken to quantify the hard exudates: Total areas of exudates and the optic nerve head were computed from fundus pictures with a digital analysis program on magnified images. The former was divided by the latter, and the results were expressed as a percentage value. The ratio was used to track improvements in a given eye over 6 months. RESULTS: Average ratio of hard exudates to optic nerve head area reduced to 81% of its initial value at 1 month (P=0.007), to 54% at 3 months (P<0.001) and to 41% at 6 months (P<0.001). CONCLUSIONS: The new method allowed detection of a significant reduction of ratio of hard exudates to optic disc area of diabetic plaque-like hard exudates following 4 mg intravitreal triamcinolone.\n[Drug-Disease]: triamcinolone acetonide - diabetic macular edema" }, { "pmid": "17653228", "target": "[\"Span: 600 mg | Label: Dosage\"]", "text": "[Title]: N-Acetylcysteine in the prevention of ototoxicity.\n[Abstract]: Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin-induced ototoxicity in hemodialysis patients. That approach may help to prevent aminoglycoside-induced hearing loss in these high-risk patients in daily practice.\n[Drug-Disease]: N-acetylcysteine - hearing loss" }, { "pmid": "17658394", "target": "[]", "text": "[Title]: Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial.\n[Abstract]: BACKGROUND: Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine. METHODS: 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. FINDINGS: There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38%vs 15%, respectively; overall response rate 94%vs 80%, respectively; p<0.0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0.006 and 0.04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0.00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (V(H)) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. INTERPRETATION: Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.\n[Drug-Disease]: Fludarabine - chronic lymphocytic leukaemia" }, { "pmid": "17658394", "target": "[]", "text": "[Title]: Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial.\n[Abstract]: BACKGROUND: Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine. METHODS: 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. FINDINGS: There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38%vs 15%, respectively; overall response rate 94%vs 80%, respectively; p<0.0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0.006 and 0.04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0.00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (V(H)) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. INTERPRETATION: Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.\n[Drug-Disease]: cyclophosphamide - chronic lymphocytic leukaemia" }, { "pmid": "17663920", "target": "[\"Span: 200-400 mg/day | Label: Dosage\"]", "text": "[Title]: Safety of celecoxib in patients with cutaneous reactions due to ASA-NSAIDs intolerance.\n[Abstract]: BACKGROUND: Pseudo-allergic reactions against aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are quite frequent. OBJECTIVE: Our aim was to determine tolerance of Celecoxib, a selective inhibitor of cyclooxygenase-2 (Cox-2), by oral challenge test in patients who showed skin reactions (diffuse erythema or urticaria/angioedema) after taking ASA and/or NSAIDs. METHODS: The oral challenge test was carried out in single-blind on 86 patients treated with a 200 mg cumulative dose of Celebrex, administered in 3 or 4 visits at 48-72 hours interval. RESULTS: Only 4 patients showed mild skin reactions. In addition, we observed 37 patients with osteoarthrosis taking a 200-400 mg/day dose of Celebrex 5-6 times a week, over a period of 75 days. At day 36, we observed in a single patient urticarial phenomena appeared on the chest and the back. CONCLUSIONS: Our study proves therefore Celecoxib safety on a 72-hour observation period.\n[Drug-Disease]: Celecoxib - osteoarthrosis" }, { "pmid": "17673219", "target": "[\"Span: 10-80 mg/day | Label: Dosage\"]", "text": "[Title]: Modulation of arterial reactivity using amlodipine and atorvastatin measured by ultrasound examination (MARGAUX).\n[Abstract]: OBJECTIVE: To evaluate the effect of the calcium channel blocker amlodipine on endothelial function in normotensive patients with coronary disease taking concomitant atorvastatin therapy. METHODS AND RESULTS: Atorvastatin was titrated (10-80 mg/day) to maintain LDL-C<2.5 mmol/L and patients were randomized to receive amlodipine (5-10mg/day, n=64) or placebo (n=70) for 12 months. Brachial artery flow-mediated vasodilation (FMD) was assessed using vascular ultrasound. Inflammatory markers were also measured. At 12 months there was a significant decrease in mean low-density lipoprotein cholesterol (LDL-C) (4.4-2.1 mmol/L, P<0.0001), high-sensitivity C-reactive protein (hsCRP) (3.8-2.3mg/L, P<0.0001) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (710-665 ng/mL, P<0.0001) for all patients, compared with baseline. Amlodipine was associated with a mean blood pressure reduction of 8/3 mm Hg (P<0.0001) whereas patients on placebo had no significant change. In the atorvastatin-placebo group, mean FMD increased (7.3-9.5%, P<0.05) with no change in nitroglycerin-mediated dilation. No further benefit on FMD or inflammatory markers was observed with the addition of amlodipine. CONCLUSIONS: Intensive reduction of LDL-C with atorvastatin improves endothelium-dependent vasodilation and reduces markers of inflammation in patients with coronary disease. Amlodipine was not associated with a significant additional benefit on these variables.\n[Drug-Disease]: atorvastatin - inflammation" }, { "pmid": "17679676", "target": "[\"Span: 200 mg/day | Label: Dosage\", \"Span: total dose: 21 g | Label: Dosage\", \"Span: total dose over three months: 18 g | Label: Dosage\"]", "text": "[Title]: Neuropathy in multiple myeloma treated with thalidomide: a prospective study.\n[Abstract]: BACKGROUND: Thalidomide is effective as a first-line therapy for the treatment of multiple myeloma (MM), but its use is limited by peripheral neurotoxicity. OBJECTIVE: To study the occurrence of both myeloma-related neuropathy and thalidomide-induced neuropathy in 31 patients with newly diagnosed MM. METHODS: Clinical and electrophysiologic examinations were performed in 31 patients with newly diagnosed MM before and after 4 months of therapy with thalidomide (200 mg/day, total dose: 21 g) aimed at debulking MM, before autologous transplantation. After transplantation, the patients took thalidomide, 200 mg/day for another 3 months (total dose over three months: 18 g) and then underwent a final clinical and electrophysiologic checkup. RESULTS: At baseline, four patients presented a mild sensorimotor peripheral neuropathy related to MM, which tended to worsen slightly during treatment with thalidomide. At the end of treatment, 83% of the patients had clinical and electrophysiologic evidence of a mild sensory rather than motor, axonal, length-dependent polyneuropathy, whereas 100% of the patients showed improvement to the basic pathology (>or=partial response). CONCLUSIONS: Peripheral neuropathy, sometimes subclinical, and mild in our patients, is a common, early side effect of thalidomide therapy. The high doses (21 g) used in all patients for a relatively short time (4 months) rule out any correlations between neuropathy, total dose, and duration of treatment.\n[Drug-Disease]: thalidomide - myeloma-related neuropathy" }, { "pmid": "17711797", "target": "[\"Span: 12 +/- 8 mg | Label: Dosage\", \"Span: Taiwanese | Label: Body Type\", \"Span: beta1-adrenoceptor | Label: Gene\"]", "text": "[Title]: Predictors of therapeutic response to beta-blockers in patients with heart failure in Taiwan.\n[Abstract]: BACKGROUND/PURPOSE: Chinese are more sensitive to beta-blockers than Caucasians. However, data regarding beta-blocker therapy in heart failure (HF) patients in Taiwan are lacking. We aimed to evaluate the improvement of left ventricular function and the potential predictors of response to beta-blocker therapy in Taiwanese HF patients. METHODS: We enrolled 34 HF patients with baseline left ventricular ejection fraction (LVEF) </= 40%. Beta-blockers were titrated up to the maximum tolerable dose. LVEF prior to beta-blocker usage and at the stable dose were obtained. We also sequenced the entire gene encoding beta1-adrenoceptor to assess the relationships between LVEF improvement and gene polymorphisms. RESULTS: Beta-blocker therapy (25 +/- 22 months) with a mean stable dose of 12 +/- 8 mg carvedilol/day significantly improved LVEF (from 28 +/- 8% to 40 +/- 15%, p < 0.001). Stepwise multiple linear regression analysis identified dilated cardiomyopathy (beta = 18.32, p = 0.0004), baseline LVEF (beta = -0.85, p = 0.0020), use of amiodarone (beta = -22.58, p = 0.0034) and square of digoxin dose (beta = -314.25, p = 0.0059) at stable beta-blocker dose as independent predictors of LVEF improvement, where beta is the estimated regression coefficient. We did not find any novel variant of beta1-adrenoceptor gene other than those previously reported at codons 49 and 389, with the allele distributions similar to those found in Caucasians, and these polymorphisms did not imply therapeutic response to beta-blocker. CONCLUSION: We demonstrated the therapeutic effects of beta-blockers in Taiwanese HF patients with a dose lower than what has been reported in Western people. Moreover, patients with the etiology of dilated cardiomyopathy or lower baseline LVEF predicted a greater LVEF improvement. The beta1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to beta-blockers in this Taiwanese population.\n[Drug-Disease]: carvedilol - dilated cardiomyopathy" }, { "pmid": "17713159", "target": "[]", "text": "[Title]: A novel mutation pattern emerging during lamivudine treatment shows cross-resistance to adefovir dipivoxil treatment.\n[Abstract]: AIMS: This study was conducted to clarify the resistance profile of a novel mutation pattern emerging during lamivudine (3TC) therapy and showing cross-resistance to adefovir dipivoxil (ADV) in a patient with chronic hepatitis B. METHODS AND RESULTS: Successful suppression of hepatitis B virus (HBV) replication by sequential therapy of 9 MU thrice weekly interferon (IFN) and 3TC was followed by genotypical resistance detected at month 28 of therapy (month 19 of lamivudine treatment). ADV was added to 3TC therapy on month 44 of antiviral treatment. Neither alanine aminotransferase normalization nor a stable decrease in HBV viral load was observed, although ADV was used for more than 40 months. The HBV pol region was amplified from serum samples obtained before and after ADV treatment. The complete genome was cloned into a TA vector. PCR products and 7-10 clones from each cloned vector were sequenced. A novel mutation, A181S, in the reverse transcriptase gene leading to a conversion of W172C in the overlapping surface antigen gene was detected along with a M2041 mutation. The complete genome comprising the A181S+M2041 pattern was cloned into an expression vector and its in vitro susceptibility to 3TC, ADV, tenofovir (PMPA), clevudine (L-FMAU) and emtricitabine (FTC) were determined in transiently transfected Huh7 cells. This mutation pattern displayed more than 1000-fold resistance to the nucleoside analogues 3TC and FTC and approximately sixfold resistance to L-FMAU, while it confers 28.23- and 5.57-fold resistance for the nucleotide analogues ADV and PMPA, respectively. CONCLUSION: A new mutation pattern, A181S+M2041, arising under lamivudine treatment confers cross-resistance to ADV both in vivo and in vitro.\n[Drug-Disease]: ADV - chronic hepatitis B" }, { "pmid": "17713159", "target": "[]", "text": "[Title]: A novel mutation pattern emerging during lamivudine treatment shows cross-resistance to adefovir dipivoxil treatment.\n[Abstract]: AIMS: This study was conducted to clarify the resistance profile of a novel mutation pattern emerging during lamivudine (3TC) therapy and showing cross-resistance to adefovir dipivoxil (ADV) in a patient with chronic hepatitis B. METHODS AND RESULTS: Successful suppression of hepatitis B virus (HBV) replication by sequential therapy of 9 MU thrice weekly interferon (IFN) and 3TC was followed by genotypical resistance detected at month 28 of therapy (month 19 of lamivudine treatment). ADV was added to 3TC therapy on month 44 of antiviral treatment. Neither alanine aminotransferase normalization nor a stable decrease in HBV viral load was observed, although ADV was used for more than 40 months. The HBV pol region was amplified from serum samples obtained before and after ADV treatment. The complete genome was cloned into a TA vector. PCR products and 7-10 clones from each cloned vector were sequenced. A novel mutation, A181S, in the reverse transcriptase gene leading to a conversion of W172C in the overlapping surface antigen gene was detected along with a M2041 mutation. The complete genome comprising the A181S+M2041 pattern was cloned into an expression vector and its in vitro susceptibility to 3TC, ADV, tenofovir (PMPA), clevudine (L-FMAU) and emtricitabine (FTC) were determined in transiently transfected Huh7 cells. This mutation pattern displayed more than 1000-fold resistance to the nucleoside analogues 3TC and FTC and approximately sixfold resistance to L-FMAU, while it confers 28.23- and 5.57-fold resistance for the nucleotide analogues ADV and PMPA, respectively. CONCLUSION: A new mutation pattern, A181S+M2041, arising under lamivudine treatment confers cross-resistance to ADV both in vivo and in vitro.\n[Drug-Disease]: lamivudine - chronic hepatitis B" }, { "pmid": "17846226", "target": "[\"Span: 20 mg/m(2) | Label: Dosage\"]", "text": "[Title]: Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma.\n[Abstract]: Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m(2)) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T(1)S(1)). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at (http://www.clinicaltrials.gov) as no. NCT00020449.\n[Drug-Disease]: doxorubicin - Kaposi sarcoma" }, { "pmid": "17873684", "target": "[\"Span: Bipolar disorder | Label: Comorbidity\"]", "text": "[Title]: A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence.\n[Abstract]: INTRODUCTION: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric disorder. Cocaine use is particularly common in patients with bipolar disorder. Both cocaine use and bipolar disorder are associated with mood symptoms and cognitive impairment. Therefore, treatments that stabilize mood, improve cognition, and reduce cocaine use would be useful. Citicoline modulates phospholipids metabolism and neurotransmitter levels and appears to improve cognition in some central nervous system disorders. A 12-week, randomized, placebo-controlled, parallel-group, add-on, proof-of-concept trial of citicoline was conducted in 44 outpatients with a history of mania or hypomania and cocaine dependence. The primary aim was to examine memory, but mood and cocaine use were also assessed. METHOD: Participants were evaluated with a structured diagnostic interview; Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, and Rey Auditory Verbal Learning Test. Cocaine use was assessed with urine drug screens. Data were analyzed using mixed-model analysis of covariance, generalized estimating equations, and logistic regression analyses that used all of the available data. RESULTS: A significant group effect (P = 0.006) favoring citicoline was observed on the Rey Auditory Verbal Learning Test alternative word list. No significant between-group differences were found on the Inventory of Depressive Symptomatology-Self-Report or Young Mania Rating Scale. The citicoline group had a significantly lower probability of a cocaine-positive urine at exit (P = 0.026). The covariate-adjusted odds ratio estimate was 6.41, suggesting that those who took placebo had 6.41-times higher odds of testing positive for cocaine at exit than those who took citicoline. Citicoline was well tolerated, with no participants to our knowledge discontinuing because of medication side effects. CONCLUSIONS: The use of citicoline was associated with improvement relative to placebo in some aspects of declarative memory and cocaine use, but not mood. The findings are promising and suggest that larger trials of citicoline are warranted.\n[Drug-Disease]: citicoline - cocaine dependence" }, { "pmid": "17933497", "target": "[\"Span: 590.0 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial.\n[Abstract]: This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.\n[Drug-Disease]: quetiapine - schizophrenia" }, { "pmid": "17933497", "target": "[\"Span: 15.1 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial.\n[Abstract]: This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.\n[Drug-Disease]: olanzapine - schizophrenia" }, { "pmid": "17933497", "target": "[\"Span: 5.1 mg/day | Label: Dosage\"]", "text": "[Title]: A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial.\n[Abstract]: This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.\n[Drug-Disease]: risperidone - schizophrenia" }, { "pmid": "1794742", "target": "[]", "text": "[Title]: Prednisone versus deflazacort in the treatment of autoimmune thrombocytopenic purpura: evaluation of clinical response and immunological modifications.\n[Abstract]: We report the results of a randomized clinical trial of two different coricosteroids (prednisone versus deflazacort) in patients affected by autoimmune thrombocytopenic purpura (ATP). We have evaluated the efficacy of the two steroids on platelet count, antiplatelet antibodies, lymphocyte subsets and the occurrence of side effects. Twenty-seven patients were evaluable: 13 were treated with PDN and 14 with DFC. After 24 weeks of treatment, 4/12 (33%), subjects treated with PDN were refractory while complete responses were obtained in 2/12 (17%) and partial responses in 6/12 (50%). Among patients treated with DFC, 4/11 (36%) were considered as refractory, 2/11 (18%) had a complete response and 5/11 (46%) a partial response. A statistically significant decrease of antiplatelet antibodies was recorded in both groups after 4 weeks of therapy, but only in subjects receiving PDN did the reduction last until the 24th week. We observed an increase of T lymphocyte subsets (CD3, CD2, CD4, CD8) in absolute number, due to an increase in circulating lymphocytes, after 4 weeks. No substantial modifications were observed in these populations regarding the percentage or the CD4/CD8 ratio. After 24 weeks, 91% (10/11) of patients treated with PDN presented an increase of body weight and 1 had a stable increase in blood pressure. Among the subjects treated with DFC, 64% (7/11) showed an increase of body weight after the same follow-up. In conclusion, no difference was observed the two steroids studied.\n[Drug-Disease]: deflazacort - autoimmune thrombocytopenic purpura" }, { "pmid": "1794742", "target": "[]", "text": "[Title]: Prednisone versus deflazacort in the treatment of autoimmune thrombocytopenic purpura: evaluation of clinical response and immunological modifications.\n[Abstract]: We report the results of a randomized clinical trial of two different coricosteroids (prednisone versus deflazacort) in patients affected by autoimmune thrombocytopenic purpura (ATP). We have evaluated the efficacy of the two steroids on platelet count, antiplatelet antibodies, lymphocyte subsets and the occurrence of side effects. Twenty-seven patients were evaluable: 13 were treated with PDN and 14 with DFC. After 24 weeks of treatment, 4/12 (33%), subjects treated with PDN were refractory while complete responses were obtained in 2/12 (17%) and partial responses in 6/12 (50%). Among patients treated with DFC, 4/11 (36%) were considered as refractory, 2/11 (18%) had a complete response and 5/11 (46%) a partial response. A statistically significant decrease of antiplatelet antibodies was recorded in both groups after 4 weeks of therapy, but only in subjects receiving PDN did the reduction last until the 24th week. We observed an increase of T lymphocyte subsets (CD3, CD2, CD4, CD8) in absolute number, due to an increase in circulating lymphocytes, after 4 weeks. No substantial modifications were observed in these populations regarding the percentage or the CD4/CD8 ratio. After 24 weeks, 91% (10/11) of patients treated with PDN presented an increase of body weight and 1 had a stable increase in blood pressure. Among the subjects treated with DFC, 64% (7/11) showed an increase of body weight after the same follow-up. In conclusion, no difference was observed the two steroids studied.\n[Drug-Disease]: prednisone - autoimmune thrombocytopenic purpura" }, { "pmid": "17978870", "target": "[\"Span: 60 mg/m(2) | Label: Dosage\"]", "text": "[Title]: The development of a predictive model to estimate cardiotoxic risk for patients with metastatic breast cancer receiving anthracyclines.\n[Abstract]: BACKGROUND: Cardiac toxicity from anthracyclines (ACH) can lead to therapy discontinuation, hospitalization or congestive heart failure (CHF). Since such risk may vary by patient, we developed and tested a risk-prediction tool for cardiac toxicity in metastatic breast cancer (MBC) patients receiving chemotherapy with doxorubicin, either in its traditional (DOX) or pegylated liposomal (PLD) formulation. METHODS: Data was obtained (n = 509) from a randomized clinical trial of MBC patients assigned either DOX (60 mg/m(2) every 3 weeks) or PLD (50 mg/m(2) every 4 weeks) (O'Brien Ann Oncol 15, 440-449, 2004). Patient, disease and treatment factors were identified for each cycle of therapy. Factors with a P-value of <or=0.25 with >or=grade 2 cardiac toxicity following a cycle were retained and included in a generalized estimating equations (GEE) regression model A risk scoring algorithm (range 0-62) was then developed from the final model. RESULTS: Factors predictive of cardiac toxicity included an interaction effect between DOX and the number of cumulative cycles, patient age and weight, previous ACH exposure and poor performance status. A ROC analysis had an area under the curve (AUC) of 0.84 (95% CI: 0.79-0.89). A precycle risk score cutoff of >or=30 to <40 was identified to optimally balance sensitivity (58.5%) and specificity (89.0%). Patients with a score in a given cycle, within or above this threshold, would be considered at high risk for cardiac toxicity. CONCLUSION: Our model provides patient specific risk information that could be helpful in assessing the risks and benefits of anthracyclines in the MBC patients.\n[Drug-Disease]: DOX - MBC" }, { "pmid": "18000507", "target": "[\"Span: 1000 mg m(-2) b.i.d. | Label: Dosage\"]", "text": "[Title]: Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial.\n[Abstract]: Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m(-2) b.i.d. on days 1-14, docetaxel 40 mg m(-2) i.v. day 1, mitomycin C 4 or 6 mg m(-2) i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received >/=3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m(-2)) and mitomycin C (4 mg m(-2)). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.\n[Drug-Disease]: capecitabine - pancreatic cancer" }, { "pmid": "18000507", "target": "[\"Span: 40 mg m(-2) i.v. | Label: Dosage\"]", "text": "[Title]: Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial.\n[Abstract]: Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m(-2) b.i.d. on days 1-14, docetaxel 40 mg m(-2) i.v. day 1, mitomycin C 4 or 6 mg m(-2) i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received >/=3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m(-2)) and mitomycin C (4 mg m(-2)). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.\n[Drug-Disease]: docetaxel - pancreatic cancer" }, { "pmid": "18000507", "target": "[\"Span: 4 or 6 mg m(-2) i.v. | Label: Dosage\"]", "text": "[Title]: Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial.\n[Abstract]: Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m(-2) b.i.d. on days 1-14, docetaxel 40 mg m(-2) i.v. day 1, mitomycin C 4 or 6 mg m(-2) i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received >/=3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m(-2)) and mitomycin C (4 mg m(-2)). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.\n[Drug-Disease]: mitomycin C - pancreatic cancer" }, { "pmid": "18038714", "target": "[\"Span: 8 year-old | Label: Age\", \"Span: boy | Label: Gender\"]", "text": "[Title]: Effect of metformin and rosiglitazone in a prepubertal boy with Alstrom syndrome.\n[Abstract]: UNLABELLED: Alstrom syndrome (AS) is an autosomal recessive disorder characterized by progressive pigmentary retinopathy, sensorineural hearing loss, fatty liver infiltration, obesity, insulin resistance and early-onset type 2 diabetes mellitus (DM2). Early onset of insulin resistance and DM2 are key components of this syndrome. AIM: To study the effect of early initiation of the insulin sensitizer metformin combined with rosiglitazone in a patient with AS with impaired glucose tolerance. PATIENT: An 8 year-old boy with AS presented with acanthosis nigricans and insulin resistance at the age of 6 years. He had progressive excessive weight gain from 9 months of age. By the age of 1 year he developed photosensitivity, blindness and nystagmus. At the age of 5.5 years, his body mass index (BMI) was above the 95th percentile. He developed impaired glucose tolerance at 6 years of age and treatment with metformin was initiated. After 8 months of treatment with metformin he developed DM2. The dose of metformin was increased, and rosiglitazone added. METHODS: A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR). For mutation analysis, all exons and splice site sequences of the ALMS1 gene were amplified and sequenced. RESULTS: Metformin treatment alone at the stage of impaired glucose tolerance did not prevent progression to DM2. However, metformin at a higher dose and in combination with rosiglitazone resulted in improvement of pancreatic beta-cell function, shown by markedly improved first-phase insulin response to glucose measured by AIR. The patient was found to have two heterozygous nonsense mutations in ALMS1, 8008 C-->T Ter, R2670X, and 11449 C-->T Ter, Q3817X. These alterations cause premature stops and result in a truncated ALMS1 protein. CONCLUSION: We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.\n[Drug-Disease]: rosiglitazone - Alstrom syndrome" }, { "pmid": "18038714", "target": "[\"Span: 8 year-old | Label: Age\", \"Span: boy | Label: Gender\"]", "text": "[Title]: Effect of metformin and rosiglitazone in a prepubertal boy with Alstrom syndrome.\n[Abstract]: UNLABELLED: Alstrom syndrome (AS) is an autosomal recessive disorder characterized by progressive pigmentary retinopathy, sensorineural hearing loss, fatty liver infiltration, obesity, insulin resistance and early-onset type 2 diabetes mellitus (DM2). Early onset of insulin resistance and DM2 are key components of this syndrome. AIM: To study the effect of early initiation of the insulin sensitizer metformin combined with rosiglitazone in a patient with AS with impaired glucose tolerance. PATIENT: An 8 year-old boy with AS presented with acanthosis nigricans and insulin resistance at the age of 6 years. He had progressive excessive weight gain from 9 months of age. By the age of 1 year he developed photosensitivity, blindness and nystagmus. At the age of 5.5 years, his body mass index (BMI) was above the 95th percentile. He developed impaired glucose tolerance at 6 years of age and treatment with metformin was initiated. After 8 months of treatment with metformin he developed DM2. The dose of metformin was increased, and rosiglitazone added. METHODS: A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR). For mutation analysis, all exons and splice site sequences of the ALMS1 gene were amplified and sequenced. RESULTS: Metformin treatment alone at the stage of impaired glucose tolerance did not prevent progression to DM2. However, metformin at a higher dose and in combination with rosiglitazone resulted in improvement of pancreatic beta-cell function, shown by markedly improved first-phase insulin response to glucose measured by AIR. The patient was found to have two heterozygous nonsense mutations in ALMS1, 8008 C-->T Ter, R2670X, and 11449 C-->T Ter, Q3817X. These alterations cause premature stops and result in a truncated ALMS1 protein. CONCLUSION: We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.\n[Drug-Disease]: metformin - Alstrom syndrome" }, { "pmid": "18055864", "target": "[\"Span: 100 mg/m(2) | Label: Dosage\", \"Span: JAK2 | Label: Gene\", \"Span: NPM1 | Label: Gene\"]", "text": "[Title]: Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia.\n[Abstract]: Decitabine's mechanism of action in chronic myelomonocytic leukemia remains incompletely understood. We studied the dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m(2) per course every 4 weeks) using quantitative monitoring of mutant alleles by pyrosequencing. Patients with chronic myelomonocytic leukemia were first screened for JAK2 and NPM1 mutations, and 3 patients with mutations were identified. Mutant allele percentages in mononuclear cell DNA were followed after treatment, along with methylation of LINE1 and 10 other genes. The clearance of mutant alleles was modest after the first cycle, despite induction of hypomethylation. Delayed substantial clearance was observed after 2 to 4 cycles that correlated with clinical response. Two patients had complete disappearance of mutant alleles and sustained clinical remissions. In another patient, mutant allele was detectable at clinical remission, which lasted for 8 months. Our data suggest a predominantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.gov as #NCT00067808.\n[Drug-Disease]: decitabine - chronic myelomonocytic leukemia" }, { "pmid": "18078449", "target": "[\"Span: 5 mg | Label: Dosage\", \"Span: age range 2-18 years | Label: Age\"]", "text": "[Title]: A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.\n[Abstract]: The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.\n[Drug-Disease]: melatonin - sleep phase syndrome" }, { "pmid": "18235151", "target": "[\"Span: diabetes | Label: Comorbidity\", \"Span: nephropathy | Label: Comorbidity\", \"Span: arteriosclerosis obliterans | Label: Comorbidity\", \"Span: 300 mg/d | Label: Dosage\"]", "text": "[Title]: Reduced albuminuria with sarpogrelate is accompanied by a decrease in monocyte chemoattractant protein-1 levels in type 2 diabetes.\n[Abstract]: BACKGROUND AND OBJECTIVES: Sarpogrelate has been shown to reduce albuminuria in diabetic nephropathy. For examination of whether this is based on the same mechanisms as angiotensin II receptor blockers or thiazolidinedione, effects of sarpogrelate on atherosclerotic inflammatory molecules and their relations to albuminuria in patients who had diabetes and had already been treated with angiotensin II receptor blockers and with or without thiazolidinedione were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Forty patients who had diabetes with nephropathy and arteriosclerosis obliterans and had already been treated with angiotensin II receptor blocker (n = 40) were randomly assigned to sarpogrelate (300 mg/d; n = 20) or aspirin group (100 mg/d; n = 20). Plasma monocyte chemoattractant protein-1 and urinary albumin-to-creatinine ratio and monocyte chemoattractant protein-1 were measured at baseline and 16 wk after administration. RESULTS: Only the sarpogrelate group showed increases in plasma adiponectin and decreases in both plasma and urinary monocyte chemoattractant protein-1 and albumin-to-creatinine ratio levels. Moreover, percentage change of monocyte chemoattractant protein-1 level correlated positively to that of albumin-to-creatinine ratio. Even when the sarpogrelate group was further divided into two groups with (n = 9) or without thiazolidinedione (n = 11), changes in monocyte chemoattractant protein-1 or albumin-to-creatinine ratio did not differ. CONCLUSIONS: Sarpogrelate can reduce albuminuria and plasma and urinary monocyte chemoattractant protein-1 levels while increasing plasma adiponectin in diabetic nephropathy. These effects seem to be mediated via mechanisms that are different from those of angiotensin II receptor blocker or thiazolidinedione.\n[Drug-Disease]: sarpogrelate - albuminuria" }, { "pmid": "18235151", "target": "[\"Span: arteriosclerosis obliterans | Label: Comorbidity\", \"Span: 300 mg/d | Label: Dosage\"]", "text": "[Title]: Reduced albuminuria with sarpogrelate is accompanied by a decrease in monocyte chemoattractant protein-1 levels in type 2 diabetes.\n[Abstract]: BACKGROUND AND OBJECTIVES: Sarpogrelate has been shown to reduce albuminuria in diabetic nephropathy. For examination of whether this is based on the same mechanisms as angiotensin II receptor blockers or thiazolidinedione, effects of sarpogrelate on atherosclerotic inflammatory molecules and their relations to albuminuria in patients who had diabetes and had already been treated with angiotensin II receptor blockers and with or without thiazolidinedione were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Forty patients who had diabetes with nephropathy and arteriosclerosis obliterans and had already been treated with angiotensin II receptor blocker (n = 40) were randomly assigned to sarpogrelate (300 mg/d; n = 20) or aspirin group (100 mg/d; n = 20). Plasma monocyte chemoattractant protein-1 and urinary albumin-to-creatinine ratio and monocyte chemoattractant protein-1 were measured at baseline and 16 wk after administration. RESULTS: Only the sarpogrelate group showed increases in plasma adiponectin and decreases in both plasma and urinary monocyte chemoattractant protein-1 and albumin-to-creatinine ratio levels. Moreover, percentage change of monocyte chemoattractant protein-1 level correlated positively to that of albumin-to-creatinine ratio. Even when the sarpogrelate group was further divided into two groups with (n = 9) or without thiazolidinedione (n = 11), changes in monocyte chemoattractant protein-1 or albumin-to-creatinine ratio did not differ. CONCLUSIONS: Sarpogrelate can reduce albuminuria and plasma and urinary monocyte chemoattractant protein-1 levels while increasing plasma adiponectin in diabetic nephropathy. These effects seem to be mediated via mechanisms that are different from those of angiotensin II receptor blocker or thiazolidinedione.\n[Drug-Disease]: sarpogrelate - diabetic nephropathy" }, { "pmid": "18286688", "target": "[]", "text": "[Title]: Predictive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy.\n[Abstract]: AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen. METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage II/III) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system. RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression. CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.\n[Drug-Disease]: 5-FU - rectal adenocarcinoma" }, { "pmid": "18344623", "target": "[\"Span: 160 mg/day | Label: Dosage\"]", "text": "[Title]: Renal protective effect in hypertensive patients: the high doses of angiotensin II receptor blocker (HARB) study.\n[Abstract]: Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.\n[Drug-Disease]: valsartan - Hypertension" }, { "pmid": "18344623", "target": "[\"Span: 160 mg/day | Label: Dosage\"]", "text": "[Title]: Renal protective effect in hypertensive patients: the high doses of angiotensin II receptor blocker (HARB) study.\n[Abstract]: Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.\n[Drug-Disease]: valsartan - proteinuria" }, { "pmid": "18344723", "target": "[]", "text": "[Title]: A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.\n[Abstract]: Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.\n[Drug-Disease]: ALA - weight gain" }, { "pmid": "18349306", "target": "[\"Span: 20-year-old | Label: Age\", \"Span: 27-week pregnant | Label: Body Type\", \"Span: 260 mg (4 mg/kg) daily | Label: Dosage\"]", "text": "[Title]: Successful treatment of vancomycin-resistant Enterococcus faecium pyelonephritis with daptomycin during pregnancy.\n[Abstract]: OBJECTIVE: To report successful treatment using daptomycin for pyelonephritis associated with vancomycin-resistant Enterococcus faecium (VRE) in a 27-week pregnant woman. CASE SUMMARY: A 20-year-old 27-week pregnant patient with a history of spina bifida, neurogenic bladder, and multiple hospitalizations for recurrent urinary tract infections (UTIs) was diagnosed with pyelonephritis. She was treated with daptomycin 260 mg (4 mg/kg) daily for 14 days on the basis of a urine culture that revealed E. faecium resistant to ampicillin, nitrofurantoin, and vancomycin. All cultures following treatment revealed no growth, and the patient as well as the neonate displayed no adverse effects. DISCUSSION: VRE UTIs can be treated safely in pregnancy with nitrofurantoin, if the organism is susceptible. Other viable options in the treatment of VRE, including linezolid, doxycycline, and quinupristin/dalfopristin, have lower urinary concentrations, teratogenic risk, or limited findings regarding their safety in pregnancy. Daptomycin was selected in this case due to its efficacy in the treatment of VRE, high urinary concentrations, pregnancy category B, and one case report indicating its successful use in pregnancy. CONCLUSIONS: Treatment of VRE in pregnancy can be challenging due to the teratogenicity or unknown safety of available options. The use of daptomycin in our patient enabled a successful outcome of multidrug-resistant E. faecium in a complicated pregnant patient without observed neonatal abnormalities.\n[Drug-Disease]: daptomycin - pyelonephritis" }, { "pmid": "18360012", "target": "[\"Span: Japanese | Label: Body Type\", \"Span: early-stage type-2 diabetes | Label: Comorbidity\", \"Span: 20 mg/day | Label: Dosage\"]", "text": "[Title]: Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension.\n[Abstract]: Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan.\n[Drug-Disease]: olmesartan - hypertension" }, { "pmid": "18381794", "target": "[\"Span: folate-dependent gene polymorphisms | Label: Gene\", \"Span: MTX transporter gene polymorphisms | Label: Gene\", \"Span: ATP-binding cassette transporter B1 (ABCB1) | Label: Gene\", \"Span: C1 (ABCC1) | Label: Gene\", \"Span: C2 (ABCC2) | Label: Gene\", \"Span: folylpolyglutamyl synthase (FPGS) | Label: Gene\", \"Span: methylenetetrahydrofolate reductase (MTHFR) | Label: Gene\", \"Span: thymidylate synthase (TYMS) | Label: Gene\", \"Span: Caucasian American | Label: Body Type\", \"Span: African American | Label: Body Type\"]", "text": "[Title]: Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis.\n[Abstract]: OBJECTIVE: Research has examined the association of folate-dependent gene polymorphisms with methotrexate (MTX) toxicity in racially homogenous patients with rheumatoid arthritis (RA). We examined the influence of MTX transporter gene polymorphisms on MTX toxicity in 2 racial groups of patients with RA. METHODS: Using a retrospective cross-validation approach, the association of polymorphisms in 6 genes in the MTX cellular pathway with MTX toxicity was examined in training and validation cohorts. The genes analyzed were ATP-binding cassette transporter B1 (ABCB1), C1 (ABCC1), C2 (ABCC2), folylpolyglutamyl synthase (FPGS), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TYMS). Both cohorts included Caucasian Americans and African Americans. Statistical analyses consisted of Fisher exact tests, multivariable logistic regression models, and survival analyses. RESULTS: Four of 25 variants displayed significant associations with MTX toxicity in the training cohort. The intronic single-nucleotide polymorphism (SNP) ABCC2 IVS 23+56 T --> C was associated with alopecia in Caucasians (p = 0.035). ABCB1 1236 C --> T was associated with overall toxicity (p = 0.013); ABCC2 1249 G --> A with gastrointestinal toxicity (p = 0.009); and ABCC2 1058 G --> A with hepatotoxicity (p = 0.04) in African Americans. These 4 SNP and the MTHFR 677 C --> T variant were assessed in the validation cohort. Of these, only the MTHFR 677 C --> T SNP was associated with alopecia, and only in African Americans (p = 0.032). The ABCC2 IVS 23+56 T --> C genotype influenced toxicity-related time to discontinuation or dose decrease in the Caucasian validation cohort (p < 0.0001). CONCLUSION: In addition to SNP in folate-dependent genes, MTX transporter gene SNP may be important markers of MTX toxicity in RA. Such pharmacogenetic associations are race-specific.\n[Drug-Disease]: MTX - RA" }, { "pmid": "18394743", "target": "[\"Span: 176 men | Label: Gender\", \"Span: 75 women | Label: Gender\", \"Span: 4 mg | Label: Dosage\"]", "text": "[Title]: Rosiglitazone improves insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus.\n[Abstract]: Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARgamma is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6+/-0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFT(max)) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82+/-1.94 vs. 2.01+/-1.58), while BMI and SFT(max) increased, and leptin (4.72+/-3.77 vs. 5.69+/-4.30 ng/ml) and adiponectin levels (7.54+/-10.20 vs. 12.89+/-10.13 microg/ml) increased. The increase in serum leptin correlated with an increase in SFT(max) (r=0.511, p<0.001) and with a reduction in HOMA-IR (r=-0.368, p<0.001). The correlation of Delta leptin with Delta HOMA-IR and with Delta SFT(max) was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.\n[Drug-Disease]: RSG - diabetes mellitus" }, { "pmid": "18464745", "target": "[\"Span: AT1R C5245T polymorphism | Label: Gene\", \"Span: AT1R 5245 TT | Label: Gene\"]", "text": "[Title]: The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial.\n[Abstract]: BACKGROUND: The aim of this study was to investigate the effect of the plasma concentration of irbesartan, a specific angiotensin II type 1 receptor (AT1R) antagonist, and the blood pressure response in relation to AT1R gene polymorphisms. METHODS: Plasma irbesartan was analyzed in 42 patients with mild-to-moderate hypertension and left ventricular hypertrophy from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) trial, who were treated with irbesartan as monotherapy for 12 weeks. Blood pressure and irbesartan concentration were measured at trough, i.e., 24 +/- 3 h after the last dose. Five AT1R gene polymorphisms were analyzed by minisequencing. RESULTS: Neither the plasma concentration of irbesartan, nor any of the AT1R polymorphisms were associated with the blood pressure response to irbesartan treatment. However, the interaction term between the plasma concentration of irbesartan and the AT1R C5245T polymorphism was related to the reduction in systolic blood pressure after 12 weeks of treatment (P = 0.025). Furthermore, the plasma concentration of irbesartan was related to the change in systolic blood pressure in individuals homozygous for the AT1R 5245 T allele (r = -0.56, P = 0.030), but not for other genotypes. CONCLUSIONS: There was an association between plasma concentrations of irbesartan and the blood pressure response for hypertensive patients with AT1R 5245 TT. Because of the small sample size, this study needs to be viewed as hypothesis generating. This is the first study, to our knowledge, indicating that the concentration-response relationship of an antihypertensive drug may be genotype dependent.\n[Drug-Disease]: irbesartan - hypertensive" }, { "pmid": "18480965", "target": "[\"Span: 11 men | Label: Gender\", \"Span: 11 women | Label: Gender\", \"Span: ages 26-65 (median 40) | Label: Age\"]", "text": "[Title]: CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma.\n[Abstract]: OBJECTIVE: A Phase II study of CPT-11 in adults with recurrent, temozolomide (TMZ)-refractory, 1p19q co-deleted, anaplastic oligodendroglioma (AO) with a primary objective of determining 6-month progression free survival (PFS). BACKGROUND: There is no standard therapy for alkylator-resistant AO. METHODS: Twenty-two patients (11 men; 11 women) ages 26-65 (median 40), with radiographically recurrent AO were enrolled. All patients had previously been treated with surgery, involved-field radiotherapy, and adjuvant chemotherapy (TMZ in 15; BCNU in 6). Fifteen patients were treated at first recurrence with an alternative chemotherapy. 13 patients underwent repeat surgery. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks. Neurological and neuroradiographic evaluations were performed every 8-9 weeks. RESULTS: All patients were evaluable for toxicity and response. A total of 141 cycles of CPT-11 (median 3 cycles; range 3-18) were administered. CPT-11 related toxicity included diarrhea (14 patients; 4 grade 3), neutropenia (8; 4 grade 3), fatigue (12; 3 grade 3), and delayed nausea/vomiting (12; 3 grade 3). 5 patients (23%) demonstrated a partial radiographic response, 8 (36%) demonstrated stable disease and 9 (41%) had progressive disease following three cycles of CPT-11. Time to tumor progression ranged from 2 to 13.5 months (median: 4.5 months). Survival ranged from 3 to 21 months (median: 5.5 months). Six-month and 12-month PFS were 33% and 4.5% respectively. CONCLUSIONS: CPT-11 demonstrated modest efficacy (similar to other salvage glioma regimens) with acceptable toxicity in this cohort of adults with recurrent, 1p19q co-deleted AO all of whom had failed prior TMZ chemotherapy.\n[Drug-Disease]: CPT-11 - oligodendroglioma" }, { "pmid": "18500220", "target": "[\"Span: 2 tablets of 0.5 mg dutasteride/die | Label: Dosage\"]", "text": "[Title]: [Dutasteride in the treatment of hormone refractory prostate cancer].\n[Abstract]: AIM: Most patients with advanced prostate cancer respond to androgen inhibition with or without antiandrogens. Progression to androgen-independent prostate cancer takes 5-7 years and is characterized by biochemical or diagnostic changes, despite testosteronemia levels similar to those after castration. Dutasteride, a 5-alfa-reductase types 1 and 2 inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). In prostate cancer, 5-alfa-reductase type 1 expression is greater than in BPH, but no differences in 5-alfa-reductase type 2 expression have been observed between metastatic prostate cancer and BPH. The higher levels of the two isozymes in metastatic and in recurrent prostate cancer after androgen withdrawal may reflect a selective adaptive mechanism to the amplification of remaining androgen signals. The aim of this prospective study was to evaluate the clinical utility of dutasteride in the treatment of hormone refractory prostate cancer. METHODS: Between March 2005 and December 2007, 8 patients with hormone refractory prostate cancer were evaluated prospectively. Following antiandrogen withdrawal and subsequent increase in PSA, 5 patients received docetaxel plus prednisone and 3 received ketoconazole plus hydrocortisone. The regimen was a single administration of 2 tablets of 0.5 mg dutasteride/die. Therapeutic response was defined as a >50% reduction in PSA or a 75% reduction at 4 weeks after the start of therapy. RESULTS: The mean duration of follow-up was 9 months (range, 21-24 months). A reduction >50% or >75% in PSA was noted in 4 and 6 patients, respectively. Bone scintigraphy detected no normalization of bone lesions; computed tomography scanning showed no partial response to treatment. The mean duration of response was 6.9 months (range, 0-21 months). Two (25%) of the 8 patients died at 6 and 10 months, respectively, neither of which had responded to dutasteride treatment. Only 1/8 patients reported experiencing dyspepsia during the study period. CONCLUSION: The activity of 5-alfa-reductase types 1 and 2 is expressed in the epithelial cells of the prostate, the stroma, and the prostate tumor. The genetic expression of fatty acid synthesis is influenced by dutasteride, which inhibits it by blocking the pathway that regulates sterol protein binding which, in turn, regulates androgen stimulation. The addition of a dual inhibitor of 5-a-reductase types 1 and 2 to antiandrogen therapy may further inhibit tumor growth, thus reducing the concentration of intracellular dihydrotestosterone, which is the primary androgen mediator of PSA gene expression in prostate tumor cell lines. These data support the rationale for the use of dutasteride in the treatment of hormone refractory prostate cancer. The study findings show that dutasteride is useful in the treatment of hormone refractory prostate cancer.\n[Drug-Disease]: dutasteride - benign prostatic hyperplasia" }, { "pmid": "18500220", "target": "[\"Span: 2 tablets of 0.5 mg dutasteride/die | Label: Dosage\"]", "text": "[Title]: [Dutasteride in the treatment of hormone refractory prostate cancer].\n[Abstract]: AIM: Most patients with advanced prostate cancer respond to androgen inhibition with or without antiandrogens. Progression to androgen-independent prostate cancer takes 5-7 years and is characterized by biochemical or diagnostic changes, despite testosteronemia levels similar to those after castration. Dutasteride, a 5-alfa-reductase types 1 and 2 inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). In prostate cancer, 5-alfa-reductase type 1 expression is greater than in BPH, but no differences in 5-alfa-reductase type 2 expression have been observed between metastatic prostate cancer and BPH. The higher levels of the two isozymes in metastatic and in recurrent prostate cancer after androgen withdrawal may reflect a selective adaptive mechanism to the amplification of remaining androgen signals. The aim of this prospective study was to evaluate the clinical utility of dutasteride in the treatment of hormone refractory prostate cancer. METHODS: Between March 2005 and December 2007, 8 patients with hormone refractory prostate cancer were evaluated prospectively. Following antiandrogen withdrawal and subsequent increase in PSA, 5 patients received docetaxel plus prednisone and 3 received ketoconazole plus hydrocortisone. The regimen was a single administration of 2 tablets of 0.5 mg dutasteride/die. Therapeutic response was defined as a >50% reduction in PSA or a 75% reduction at 4 weeks after the start of therapy. RESULTS: The mean duration of follow-up was 9 months (range, 21-24 months). A reduction >50% or >75% in PSA was noted in 4 and 6 patients, respectively. Bone scintigraphy detected no normalization of bone lesions; computed tomography scanning showed no partial response to treatment. The mean duration of response was 6.9 months (range, 0-21 months). Two (25%) of the 8 patients died at 6 and 10 months, respectively, neither of which had responded to dutasteride treatment. Only 1/8 patients reported experiencing dyspepsia during the study period. CONCLUSION: The activity of 5-alfa-reductase types 1 and 2 is expressed in the epithelial cells of the prostate, the stroma, and the prostate tumor. The genetic expression of fatty acid synthesis is influenced by dutasteride, which inhibits it by blocking the pathway that regulates sterol protein binding which, in turn, regulates androgen stimulation. The addition of a dual inhibitor of 5-a-reductase types 1 and 2 to antiandrogen therapy may further inhibit tumor growth, thus reducing the concentration of intracellular dihydrotestosterone, which is the primary androgen mediator of PSA gene expression in prostate tumor cell lines. These data support the rationale for the use of dutasteride in the treatment of hormone refractory prostate cancer. The study findings show that dutasteride is useful in the treatment of hormone refractory prostate cancer.\n[Drug-Disease]: dutasteride - hormone refractory prostate cancer" }, { "pmid": "18503564", "target": "[]", "text": "[Title]: Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy.\n[Abstract]: Rufinamide is a new, orally active antiepileptic drug (AED), which has been found to be effective in the treatment of partial seizures and drop attacks associated with the Lennox-Gastaut syndrome. When taken with food, rufinamide is relatively well absorbed in the lower dose range, with approximately dose-proportional plasma concentrations up to 1,600 mg/day, but less than dose-proportional plasma concentrations at higher doses due to reduced oral bioavailability. Rufinamide is not extensively bound to plasma proteins. During repeated dosing, steady state is reached within 2 days, consistent with its elimination half-life of 6-10 h. The apparent volume of distribution (V(d)/F) and apparent oral clearance (CL/F) are related to body size, the best predictor being body surface area. Rufinamide is not a substrate of cytochrome P450 (CYP450) enzymes and is extensively metabolized via hydrolysis by carboxylesterases to a pharmacologically inactive carboxylic acid derivative, which is excreted in the urine. Rufinamide pharmacokinetics are not affected by impaired renal function. Potential differences in rufinamide pharmacokinetics between children and adults have not been investigated systematically in formal studies. Although population pharmacokinetic modeling suggests that in the absence of interacting comedication rufinamide CL/F may be higher in children than in adults, a meaningful comparison of data across age groups is complicated by age-related differences in doses and in proportion of patients receiving drugs known to increase or to decrease rufinamide CL/F. A study investigating the effect of rufinamide on the pharmacokinetics of the CYP3A4 substrate triazolam and an oral contraceptive interaction study showed that rufinamide has some enzyme-inducing potential in man. Findings from population pharmacokinetic modeling indicate that rufinamide does not modify the CL/F of topiramate or valproic acid, but may slightly increase the CL/F of carbamazepine and lamotrigine and slightly decrease the CL/F of phenobarbital and phenytoin (all predicted changes were <20%). These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but valproic acid may increase plasma rufinamide concentrations, especially in children in whom plasma rufinamide concentrations could be increased substantially. Conversely, comedication with carbamazepine, vigabatrin, phenytoin, phenobarbital, and primidone was associated with a slight-to-moderate decrease in plasma rufinamide concentrations, ranging from a minimum of -13.7% in female children comedicated with vigabatrin to a maximum of -46.3% in female adults comedicated with phenytoin, phenobarbital, or primidone. In population modeling using data from placebo-controlled trials, a positive correlation has been identified between reduction in seizure frequency and steady-state plasma rufinamide concentrations. The probability of adverse effects also appears to be concentration-related.\n[Drug-Disease]: rufinamide - seizure" } ]