The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
John T. Gwynne - One of the best experts on this subject based on the ideXlab platform.
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Natural History of Valvular Regurgitation 1 Year after Discontinuation of Dexfenfluramine Therapy
2016Co-Authors: Placebo-controlled Trial, John T. GwynneAbstract:Background: Previous studies have reported small increases in the prevalence of low-grade aortic and mitral regurgitation in patients treated with Dexfenfluramine compared with placebo. However, whether valvular abnormalities develop or progress 1 year after discontinuation of Dexfenfluramine therapy has not been determined. Objective: To assess change in valvular regurgitation and mor-phologic characteristics 1 year after discontinuation of dexfenflur-amine therapy. Design: Randomized, double-blind, placebo-controlled, multi-center study
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natural history of valvular regurgitation 1 year after discontinuation of Dexfenfluramine therapy a randomized double blind placebo controlled trial
Annals of Internal Medicine, 2001Co-Authors: Neil J. Weissman, John F. Tighe, Julio A Panza, John T. GwynneAbstract:Background: Previous studies have reported small increases in the prevalence of low-grade aortic and mitral regurgitation in patients treated with Dexfenfluramine compared with placebo. However, whether valvular abnormalities develop or progress 1 year after discontinuation of Dexfenfluramine therapy has not been determined. Objective: To assess change in valvular regurgitation and morphologic characteristics 1 year after discontinuation of Dexfenfluramine therapy. Design: Randomized, double-blind, placebo-controlled, multicenter study. Setting: Outpatient obesity centers. Patients: Obese persons who had been treated for 2 to 3 months with Dexfenfluramine, sustained-release Dexfenfluramine, or placebo. Blinding was maintained, and patients returned for repeated echocardiography at 1 year. Measurements: Pairs of echocardiograms were evaluated with a side-by-side reading method for change in grade of valvular regurgitation, structure, and function. A standardized acquisition and reading protocol was followed, and a core laboratory was used. Results: 914 patients who had initial echocardiography returned for repeated echocardiography 11.4 t 1.0 months (mean ± SD) after discontinuing study medication (10.0 ± 1.0 months after initial echocardiography). Compared with the placebo group, a greater proportion of patients in both Dexfenfluramine groups had decreased aortic regurgitation (p = 0.003 for the Dexfenfluramine group, p = 0.02 for the sustained-release group). No change in mitral regurgitation or any other measure of valvular structure or function was seen in any treatment group. Conclusions: After Dexfenfluramine therapy is taken for 2 to 3 months and discontinued, development or progression of any valvular regurgitation over the following year is unlikely. Echocardiographic evidence suggests that aortic regurgitation regresses in some previously treated patients.
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An Assessment of Heart-Valve Abnormalities in Obese Patients Taking Dexfenfluramine, Sustained-Release Dexfenfluramine, or Placebo
The New England journal of medicine, 1998Co-Authors: Neil J. Weissman, John F. Tighe, John S. Gottdiener, John T. GwynneAbstract:Background The appetite-suppressant drug fenfluramine, usually given in combination with phentermine, has been reported to be associated with cardiac valvular regurgitation. Concern has been raised that the d-enantiomer of fenfluramine, Dexfenfluramine, may also cause this problem. We were able to study the question by modifying an ongoing trial comparing sustained-release Dexfenfluramine with regular Dexfenfluramine and placebo. Methods We modified our randomized, double-blind, placebo-controlled study of Dexfenfluramine to include echocardiographic examinations of 1072 overweight patients within a median of one month after the discontinuation of treatment. The patients (approximately 80 percent of whom were women) had been randomly assigned to receive Dexfenfluramine (366 patients), investigational sustained-release Dexfenfluramine (352 patients), or placebo (354 patients). The average duration of treatment was 71 to 72 days in each of the three groups. Echocardiograms were assessed in a blinded fashion...
Luc Maroteaux - One of the best experts on this subject based on the ideXlab platform.
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Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT(2B) Receptors for Dexfenfluramine Anorectic Effects.
Neuropsychopharmacology, 2011Co-Authors: Sophie Banas, J M Launay, Stéphane Doly, Katia Boutourlinsky, Arnauld Belmer, Jacques Callebert, Corinne Collet, Silvina Diaz, Luc MaroteauxAbstract:The now-banned anorectic molecule, Dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in Dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in Dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to Dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to Dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22±0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the Dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon Dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependant-releasing effect of Dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.
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Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT2B Receptors for Dexfenfluramine Anorectic Effects
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010Co-Authors: Sophie Marie Banas, J M Launay, Stéphane Doly, Katia Boutourlinsky, Silvina L. Diaz, Arnauld Belmer, Jacques Callebert, Corinne Collet, Luc MaroteauxAbstract:The now-banned anorectic molecule, Dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in Dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in Dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to Dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to Dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22 ± 0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the Dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon Dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependent-releasing effect of Dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.
J M Launay - One of the best experts on this subject based on the ideXlab platform.
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Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT(2B) Receptors for Dexfenfluramine Anorectic Effects.
Neuropsychopharmacology, 2011Co-Authors: Sophie Banas, J M Launay, Stéphane Doly, Katia Boutourlinsky, Arnauld Belmer, Jacques Callebert, Corinne Collet, Silvina Diaz, Luc MaroteauxAbstract:The now-banned anorectic molecule, Dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in Dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in Dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to Dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to Dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22±0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the Dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon Dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependant-releasing effect of Dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.
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Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT2B Receptors for Dexfenfluramine Anorectic Effects
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010Co-Authors: Sophie Marie Banas, J M Launay, Stéphane Doly, Katia Boutourlinsky, Silvina L. Diaz, Arnauld Belmer, Jacques Callebert, Corinne Collet, Luc MaroteauxAbstract:The now-banned anorectic molecule, Dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in Dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in Dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to Dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to Dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22 ± 0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the Dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon Dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependent-releasing effect of Dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.
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Effect of Dexfenfluramine treatment in rats exposed to acute and chronic hypoxia.
American journal of respiratory and critical care medicine, 1998Co-Authors: S Eddahibi, B Raffestin, J M Launay, M Sitbon, S AdnotAbstract:The anorexiant Dexfenfluramine, which inhibits 5-hydroxytryptamine (5-HT) uptake, has been associated with an increase in the relative risk of developing primary pulmonary hypertension. The aim of this study was to investigate in rats whether Dexfenfluramine (1) alters the pulmonary vasomotor effects of 5-HT and (2) aggravates the development of pulmonary hypertension during exposure to various levels of chronic hypoxia. In isolated lungs from normoxic rats, Dexfenfluramine up to 10(-4) M did not elicit any vasoactive effects, and neither did pretreatment with Dexfenfluramine (10[-5] M in the perfusate) modify the vasoactive effects of 5-HT. In normoxic conscious rats, Dexfenfluramine given intravenously potentiated the pulmonary pressor response to acute hypoxia (10% O2). In rats chronically treated with Dexfenfluramine during a 2-wk exposure to 15% or 10% O2, plasma 5-HT concentrations were significantly increased compared with hypoxic controls, whereas no differences were found for pulmonary artery pressure, right ventricular hypertrophy, or pulmonary vessel muscularization. In contrast, a continuous 5-HT infusion providing a sustained increase in plasma 5-HT levels was associated with increased muscularization of distal pulmonary arteries in response to 10% O2. Simultaneous administration of Dexfenfluramine prevented the effect of exogenous 5-HT on vascular remodeling. Our findings show that Dexfenfluramine does not potentiate the development of pulmonary hypertension in rats exposed to chronic hypoxia, despite its effect on plasma 5-HT concentrations.
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Effect of Dexfenfluramine treatment in rats exposed to acute and chronic hypoxia.
American Journal of Respiratory and Critical Care Medicine, 1998Co-Authors: S Eddahibi, B Raffestin, J M Launay, M Sitbon, S AdnotAbstract:The anorexiant Dexfenfluramine, which inhibits 5-hydroxytryptamine (5-HT) uptake, has been associated with an increase in the relative risk of developing primary pulmonary hypertension. The aim of this study was to investigate in rats whether Dexfenfluramine (1) alters the pulmonary vasomotor effects of 5-HT and (2) aggravates the development of pulmonary hypertension during exposure to various levels of chronic hypoxia. In isolated lungs from normoxic rats, Dexfenfluramine up to 10− 4 M did not elicit any vasoactive effects, and neither did pretreatment with Dexfenfluramine (10− 5 M in the perfusate) modify the vasoactive effects of 5-HT. In normoxic conscious rats, Dexfenfluramine given intravenously potentiated the pulmonary pressor response to acute hypoxia (10% O2). In rats chronically treated with Dexfenfluramine during a 2-wk exposure to 15% or 10% O2 , plasma 5-HT concentrations were significantly increased compared with hypoxic controls, whereas no differences were found for pulmonary artery pres...
Neil J. Weissman - One of the best experts on this subject based on the ideXlab platform.
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natural history of valvular regurgitation 1 year after discontinuation of Dexfenfluramine therapy a randomized double blind placebo controlled trial
Annals of Internal Medicine, 2001Co-Authors: Neil J. Weissman, John F. Tighe, Julio A Panza, John T. GwynneAbstract:Background: Previous studies have reported small increases in the prevalence of low-grade aortic and mitral regurgitation in patients treated with Dexfenfluramine compared with placebo. However, whether valvular abnormalities develop or progress 1 year after discontinuation of Dexfenfluramine therapy has not been determined. Objective: To assess change in valvular regurgitation and morphologic characteristics 1 year after discontinuation of Dexfenfluramine therapy. Design: Randomized, double-blind, placebo-controlled, multicenter study. Setting: Outpatient obesity centers. Patients: Obese persons who had been treated for 2 to 3 months with Dexfenfluramine, sustained-release Dexfenfluramine, or placebo. Blinding was maintained, and patients returned for repeated echocardiography at 1 year. Measurements: Pairs of echocardiograms were evaluated with a side-by-side reading method for change in grade of valvular regurgitation, structure, and function. A standardized acquisition and reading protocol was followed, and a core laboratory was used. Results: 914 patients who had initial echocardiography returned for repeated echocardiography 11.4 t 1.0 months (mean ± SD) after discontinuing study medication (10.0 ± 1.0 months after initial echocardiography). Compared with the placebo group, a greater proportion of patients in both Dexfenfluramine groups had decreased aortic regurgitation (p = 0.003 for the Dexfenfluramine group, p = 0.02 for the sustained-release group). No change in mitral regurgitation or any other measure of valvular structure or function was seen in any treatment group. Conclusions: After Dexfenfluramine therapy is taken for 2 to 3 months and discontinued, development or progression of any valvular regurgitation over the following year is unlikely. Echocardiographic evidence suggests that aortic regurgitation regresses in some previously treated patients.
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An Assessment of Heart-Valve Abnormalities in Obese Patients Taking Dexfenfluramine, Sustained-Release Dexfenfluramine, or Placebo
The New England journal of medicine, 1998Co-Authors: Neil J. Weissman, John F. Tighe, John S. Gottdiener, John T. GwynneAbstract:Background The appetite-suppressant drug fenfluramine, usually given in combination with phentermine, has been reported to be associated with cardiac valvular regurgitation. Concern has been raised that the d-enantiomer of fenfluramine, Dexfenfluramine, may also cause this problem. We were able to study the question by modifying an ongoing trial comparing sustained-release Dexfenfluramine with regular Dexfenfluramine and placebo. Methods We modified our randomized, double-blind, placebo-controlled study of Dexfenfluramine to include echocardiographic examinations of 1072 overweight patients within a median of one month after the discontinuation of treatment. The patients (approximately 80 percent of whom were women) had been randomly assigned to receive Dexfenfluramine (366 patients), investigational sustained-release Dexfenfluramine (352 patients), or placebo (354 patients). The average duration of treatment was 71 to 72 days in each of the three groups. Echocardiograms were assessed in a blinded fashion...
Dennis K Yue - One of the best experts on this subject based on the ideXlab platform.
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obese patients with type 2 diabetes poorly controlled by insulin and metformin effects of adjunctive Dexfenfluramine therapy on glycaemic control
Diabetic Medicine, 1994Co-Authors: Karen A Willey, Lynda Molyneaux, Dennis K YueAbstract:Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional Dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the Dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in Dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with Dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive Dexfenfluramine can improve glycaemic control without exacerbating weight gain.
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The effects of Dexfenfluramine on blood glucose control in patients with type 2 diabetes.
Diabetic medicine : a journal of the British Diabetic Association, 1992Co-Authors: Karen A Willey, Lynda Molyneaux, Jane Overland, Dennis K YueAbstract:Dexfenfluramine has been shown to promote weight loss in overweight people. The present double-blind study was designed to test whether the addition of Dexfenfluramine to conventional oral hypoglycaemic treatment would promote weight loss and improve blood glucose control in overweight patients with Type 2 diabetes. The 34 patients studied were randomly assigned to Dexfenfluramine or placebo therapy which was added for 12 weeks to their existing treatment regimens of metformin with or without a sulphonylurea. Dexfenfluramine treatment was associated with a significant reduction in weight (98.7 +/- 5.0 (+/- SE) vs 94.9 +/- 5.2 kg; p less than 0.001), BMI (35.0 +/- 1.2 vs 33.6 +/- 1.9 kg m-2; p less than 0.001), HbA1c (7.5 +/- 0.3 vs 6.3 +/- 0.2%; p less than 0.001), fructosamine (313.9 +/- 17.6 vs 274.3 +/- 10.4 mumol l-1; p less than 0.01), systolic (137 +/- 5 vs 128 +/- 6 mmHg; p less than 0.05), and diastolic blood pressure (85 +/- 2 vs 73 +/- 3 mmHg; p less than 0.001). At the end of the study period, the Dexfenfluramine treated group had a significantly lower HbA1c (6.3 +/- 0.2 vs 7.2 +/- 0.4; p less than 0.05), fructosamine level (274.3 +/- 10.4 vs 313.3 +/- 16.1 mumol l-1; p less than 0.05) and diastolic blood pressure (73 +/- 3 vs 81 +/- 3 mmHg; p less than 0.03) when compared with the placebo group. In those patients treated with Dexfenfluramine, the reduction in HbA1c and blood pressure did not correlate with the decrease in BMI (r = 0.44 and 0.12, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)