RESUMEN
OBJECTIVE: To evaluate the efficacy of diethylpropion on a long-term basis, with emphasis in cardiovascular and psychiatric safety aspects. DESIGN: Randomized, double-blind, placebo-controlled trial. MEASUREMENTS: Following a 2-week screening period, 69 obese healthy adults received a hypocaloric diet and were randomized to diethylpropion 50 mg BID (n=37) or placebo (n=32) for 6 months. After this period, all participants received diethylpropion in an open-label extension for an additional 6 months. The primary outcome was percentage change in body weight. Electrocardiogram (ECG), echocardiography and clinical chemistry were performed at baseline and every 6 months. Psychiatric evaluation and application of Hamilton rating scales for depression and anxiety were also performed by experienced psychiatrists at baseline and every 3 months. RESULTS: After 6 months, the diethylpropion group lost an average of 9.8% (s.d. 6.9%) of initial body weight vs 3.2% (3.7%) in the placebo group (P<0.0001). From baseline to month 12, the mean weight loss produced by diethylpropion was 10.6% (8.3%). Participants in the placebo group who were switched to diethylpropion after 6 months lost an average of 7.0% (7.7%) of initial body weight. The difference between groups at month 12 was not significant (P=0.07). No differences in blood pressure, pulse rate, ECG and psychiatric evaluation were observed. Dry mouth and insomnia were the most frequent adverse events. CONCLUSION: Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year. It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population.
Asunto(s)
Depresores del Apetito/uso terapéutico , Dietilpropión/uso terapéutico , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Adulto , Peso Corporal , Dieta Reductora , Método Doble Ciego , Femenino , Humanos , Masculino , Obesidad/dietoterapia , Obesidad/fisiopatología , Placebos/uso terapéutico , Resultado del Tratamiento , Pérdida de Peso/fisiologíaRESUMEN
Obstructive sleep apnea-hypopnea syndrome involves recurring episodes of total obstruction (apnea) or partial obstruction (hypopnea) of airways during sleep. Obstructive sleep apnea-hypopnea syndrome affects mainly obese individuals and it is defined by an apnea-hypopnea index of five or more episodes per hour associated with daytime somnolence. In addition to anatomical factors and neuromuscular and genetic factors, sleep disorders are also involved in the pathogenesis of sleep apnea. Obesity affects upper airway anatomy because of fat deposition and metabolic activity of adipose tissue. Obstructive sleep apnea-hypopnea syndrome and metabolic syndrome have several characteristics such as visceral obesity, hypertension and insulin resistance. Inflammatory cytokines might be related to the pathogenesis of sleep apnea and metabolic syndrome. Sleep apnea treatment includes obesity treatment, use of equipment such as continuous positive airway pressure, drug therapy and surgical procedures in selected patients. Currently, there is no specific drug therapy available with proven efficacy for the treatment of obstructive sleep apnea-hypopnea syndrome. Body-weight reduction results in improvement of sleep apnea, and obesity treatment must be emphasized, including lifestyle changes, anti-obesity drugs and bariatric surgery.
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Obesidad/complicaciones , Obesidad/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/etiología , Comorbilidad , Citocinas/sangre , Humanos , Resistencia a la Insulina , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/terapia , Obesidad/terapia , Factores de Riesgo , Apnea Obstructiva del Sueño/terapiaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). METHODS: For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). RESULTS: The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m(2)). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. CONCLUSIONS: The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Derivación Gástrica/métodos , Laparoscopía/métodos , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugía , Adulto , Anciano , Anastomosis Quirúrgica/métodos , Glucemia/análisis , Índice de Masa Corporal , Estudios de Cohortes , Comorbilidad , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Íleon/cirugía , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Probabilidad , Calidad de Vida , Medición de Riesgo , Estómago/cirugía , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m(2), mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m(2), mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.
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Péptido Natriurético Encefálico/sangre , Obesidad Mórbida/sangre , Fragmentos de Péptidos/sangre , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Ecocardiografía , Femenino , Cardiopatías/sangre , Cardiopatías/etiología , Humanos , Mediciones Luminiscentes , Masculino , Obesidad Mórbida/complicaciones , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de Tiempo , Relación Cintura-CaderaRESUMEN
Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m², mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m², mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95 percent CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95 percent CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95 percent CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95 percent CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Péptido Natriurético Encefálico/sangre , Obesidad Mórbida/sangre , Fragmentos de Péptidos/sangre , Índice de Masa Corporal , Biomarcadores/sangre , Estudios de Casos y Controles , Ecocardiografía , Cardiopatías/sangre , Cardiopatías/etiología , Mediciones Luminiscentes , Obesidad Mórbida/complicaciones , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Relación Cintura-CaderaRESUMEN
Since neurovascular control is altered in obese subjects, we hypothesized that weight loss by diet (D) or diet plus exercise training (D + ET) would improve neurovascular control during mental stress in obese women. In a study with a dietary reduction of 600 kcal/day with or without exercise training for 4 months, 53 obese women were subdivided in D (N = 22, 33 +/- 1 years, BMI 34 +/- 1 kg/m2), D + ET (N = 22, 33 +/- 1 years, BMI 33 +/- 1 kg/m2), and nonadherent (NA, N = 9, 35 +/- 2 years, BMI 33 +/- 1 kg/m2) groups. Muscle sympathetic nerve activity (MSNA) was measured by microneurography and forearm blood flow by venous occlusion plethysmography. Mental stress was elicited by a 3-min Stroop color word test. Weight loss was similar between D and D + ET groups (87 +/- 2 vs 79 +/- 2 and 85 +/- 2 vs 76 +/- 2 kg, respectively, P < 0.05) with a significant reduction in MSNA during mental stress (58 +/- 2 vs 50 +/- 2, P = 0.0001, and 59 +/- 3 vs 50 +/- 2 bursts/100 beats, P = 0.0001, respectively), although the magnitude of the response was unchanged. Forearm vascular conductance during mental stress was significantly increased only in D + ET (2.74 +/- 0.22 vs 3.52 +/- 0.19 units, P = 0.02). Weight loss reduces MSNA during mental stress in obese women. The increase in forearm vascular conductance after weight loss provides convincing evidence for D + ET interventions as a nonpharmacologic therapy of human obesity.
Asunto(s)
Dieta Reductora , Ejercicio Físico , Obesidad/terapia , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Índice de Masa Corporal , Femenino , Antebrazo/irrigación sanguínea , Humanos , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Obesidad/fisiopatología , Obesidad/psicología , Pletismografía , Factores de TiempoRESUMEN
Since neurovascular control is altered in obese subjects, we hypothesized that weight loss by diet (D) or diet plus exercise training (D + ET) would improve neurovascular control during mental stress in obese women. In a study with a dietary reduction of 600 kcal/day with or without exercise training for 4 months, 53 obese women were subdivided in D (N = 22, 33 ± 1 years, BMI 34 ± 1 kg/m²), D + ET (N = 22, 33 ± 1 years, BMI 33 ± 1 kg/m²), and nonadherent (NA, N = 9, 35 ± 2 years, BMI 33 ± 1 kg/m²) groups. Muscle sympathetic nerve activity (MSNA) was measured by microneurography and forearm blood flow by venous occlusion plethysmography. Mental stress was elicited by a 3-min Stroop color word test. Weight loss was similar between D and D + ET groups (87 ± 2 vs 79 ± 2 and 85 ± 2 vs 76 ± 2 kg, respectively, P < 0.05) with a significant reduction in MSNA during mental stress (58 ± 2 vs 50 ± 2, P = 0.0001, and 59 ± 3 vs 50 ± 2 bursts/100 beats, P = 0.0001, respectively), although the magnitude of the response was unchanged. Forearm vascular conductance during mental stress was significantly increased only in D + ET (2.74 ± 0.22 vs 3.52 ± 0.19 units, P = 0.02). Weight loss reduces MSNA during mental stress in obese women. The increase in forearm vascular conductance after weight loss provides convincing evidence for D + ET interventions as a nonpharmacologic therapy of human obesity.
Asunto(s)
Humanos , Femenino , Adulto , Dieta Reductora , Terapia por Ejercicio , Obesidad/terapia , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Índice de Masa Corporal , Antebrazo/irrigación sanguínea , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Obesidad/fisiopatología , Obesidad/psicología , Pletismografía , Factores de TiempoRESUMEN
As perspectivas no tratamento medicamentoso da obesidade discutidaspodem ser divididas em duas categorias, a saber: medicamentos comercializados, em estudo clínico avançado ou em via deaprovação, ou drogas em início de investigação. Entre os primeiros destacam-se anticonvulsivantes como o topiramato (que embora tenha sido estudado na indicação de tratamento de obesidade foi descontinuado para esta indicação devido ao elevado número deabandono por efeitos adversos) e a zonisamida (com alguns estudosde curta duração em adultos obesos); antidepressivos como a bupropiona (que não somente leva a reduções de peso como minimiza o ganho de peso associado a cessação de tabagismo) e aradafaxina (metabólito da bupropiona, sem estudos documentados em obesos); análogos do glucagon-like peptide-1 como a exenatida (exendina-4), a pramlintida e a liraglutida (com estudos em diabéticos tipo 2 obesos) e um bloqueador seletivo do receptor canabinóide tipo 1, o rimonabant, cujos estudos (Rimonabant in Obesity), RIOEurope, RIO-North America, RIO-Lipids e RIO-Diabetes, envolvemmais de 6.600 pacientes com obesidade, com e sem diabetes e que se apresenta como perspectiva importante de tratamento da obesidade. Em início de investigação, estão moduladores da homeostase energética como antagonistas do neuropeptídeo Y, agonistas da melanocortina, leptina e análogos da leptina e fator neurotróficociliar (axokine); agentes termogênicos como os agonistas do receptor adrenérgico beta-3, agentes desacopladores da membranamitocondrial e moduladores periféricos da homeostase energética como a colecistoquinina.
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Humanos , Masculino , Femenino , Dexfenfluramina , Fenfluramina , Obesidad/fisiopatología , Obesidad/tratamiento farmacológicoRESUMEN
AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Lactonas/uso terapéutico , Obesidad , Adolescente , Adulto , Anciano , Antropometría , Fármacos Antiobesidad/efectos adversos , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Terapia Combinada , Diabetes Mellitus/sangre , Diabetes Mellitus/dietoterapia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Reductora , Método Doble Ciego , Inhibidores Enzimáticos/uso terapéutico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Lactonas/efectos adversos , Lipasa/antagonistas & inhibidores , Lípidos/sangre , Masculino , Persona de Mediana Edad , Orlistat , Factores de Riesgo , Pérdida de Peso/efectos de los fármacosRESUMEN
The information presented in this article provides an overview of physiological agents, therapeutics in current use, and medications that have been extensively used in the past but are no longer available, or are not classically considered as anti-obesity drugs. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral action energetic homeostasis (nutrients, monoamines and peptides), and on beta-phenethylamine pharmacological-derivative agents (fenfluramine, dexfenfluramine, phentermine, diethylpropion, fenproporex and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrine, phenylpropanolamine), a phenylpropanolamine oxy-tri-fluor-phenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials longer than 10 weeks in duration is also presented for medications used in the management of obesity.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Obesidad/tratamiento farmacológico , Fármacos Antiobesidad/farmacología , Depresores del Apetito/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Simpatomiméticos/uso terapéutico , Resultado del TratamientoRESUMEN
The principal objective of screening individuals at risk for melanoma is detection of cutaneous melanoma during the curable stages of its early evolution. Unaided visual inspection of the skin is often suboptimal at diagnosing melanoma. Improving the diagnostic accuracy for melanoma remains an area of active research. These research efforts have focused on both the detection of early melanoma and the in-depth evaluation of suspicious pigmented lesions for the presence or absence of melanoma...
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Melanoma/diagnóstico , Neoplasias/diagnósticoRESUMEN
OBJECTIVE: To study by doppler echocardiography the cardiac systolic and diastolic functions of health, uncomplicated obese subjects. METHODS: Fifty-nine obese women with an average body mass index (BMI) of 35 kg/m2 were evaluated and compared with 19 subjects with an average BMI of 23 kg/m2 (control group). RESULTS: In the obese group, a clear tendency was observed toward higher systolic pressure, increased wall thickness and, consequently, myocardial mass, elevation on the circumference stress of the left ventricular wall, and an indisputable presence of diastolic abnormalities. Filling abnormalities were observed with impaired relaxation, with prolonged isovolumic relaxation time (IVRT) and augmented atrium contribution representing early indexes of cardiac dysfunction when systolic performance is still normal. CONCLUSION: Obesity is generally a chronic condition, and doppler echocardiography can be used as a noninvasive instrument for early evaluation of left ventricular diastolic indexes.
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Presión Sanguínea/fisiología , Ecocardiografía Doppler/métodos , Obesidad/fisiopatología , Adulto , Índice de Masa Corporal , Superficie Corporal , Diástole/fisiología , Femenino , Humanos , Sístole/fisiología , Función Ventricular Izquierda/fisiologíaRESUMEN
Objetivo: Determinar a eficácia e tolerabilidade de 4 substâncias calorigênicas: ioimbina, triiodotironina (T3), combinação efedrina-aminofilina e fenilpropanolamina (FPA). Material, Métodos e Desenho da Pesquisa: 103 mulheres obesas (30 < BMI < 40kg/m 2 ), de 18 a 55 anos, foram submetidas a estudo cego comparativo das 4 substâncias associadas a uma dieta com 1.200 calorias (55 por cento HC, 30 por cento gordura e 15por cento proteínas). As doses utilizadas foram 8mg de ioimbina, 25mcg de T3, 100mg de aminofilina + 25mg de efedrina e 25mg de FPA. Foi ainda incluído um grupo placebo. Os 4 medicamentos e o placebo foram dados 3 vezes ao dia, antes do desjejum, do almoço e do jantar. O estudo se realizou num período de 12 semanas, para cada paciente e no início e o fim do mesmo foram avaliados peso, composição corpórea por bioimpedância, metabolismo de repouso (por calorimetria), pulso e pressão arterial e eventos adversos. Resultados: Houve perda de peso em todos os grupos, mas o único que perdeu peso significativamente em relação ao grupo placebo foi o que recebeu FPA (p < 0,05). Não houve diferença quanto à composição corpórea e metabolismo de repouso entre os 5 grupos. Conclusão: Em nossa amostra, a FPA se revelou mais eficaz, embora este fato não possa ser atribuído a uma maior queima energética em repouso, já que não houve diferença apreciável no metabolismo de repouso entre os grupos.
Asunto(s)
Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Antagonistas Adrenérgicos alfa/uso terapéutico , Aminofilina/uso terapéutico , Efedrina/uso terapéutico , Obesidad/tratamiento farmacológico , Fenilpropanolamina/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Triyodotironina/uso terapéutico , Método Doble Ciego , Combinación de Medicamentos , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacosRESUMEN
OBJECTIVE: In obese men, sex hormone-binding globulin (SHBG) as well as total testosterone (TT) levels are decreased. Data concerning serum free testosterone (FT) levels in obese men are discordant. FT levels are decreased in only some morbidly obese men, consistent with an impairment of the feedback regulatory mechanism. In this study we aimed to verify serum levels of TT and FT in two groups of obese men (BMI < 35.0 kg/m2 and BMI > 35.1 kg/m2) before and after weight loss. DESIGN: Two groups of obese men (group 1: BMI < or = 35 kg/m2; and group 2: BMI > or =35.1 kg/m2) were studied before and after 6 months of a low energy diet (1200 kcal/day). Every patient received a therapeutic prescription of dexfenfluramine (15 mg b.i.d.) that was maintained for 6 months. SUBJECTS: Thirty-seven obese men and 20 normal weight men. MEASUREMENTS: Serum sex hormones (TT and FT), serum luteinizing hormone (LH) and insulin were analyzed by RIA assays. Plasma insulin levels, serum TT, FT and LH concentrations were obtained before and after weight loss. RESULTS: Moderately obese men (BMI = 32.3+/- 1.9 kg/m2) presented significantly decreased TT levels (390+/-120ng/dl) as well as FT (mean+/-s.d.:16.0+/-4.8pg/ml) as compared with normal controls. FT serum levels had a significant and negative correlation with body mass index (BMI), whereas for TT concentrations this correlation was not significant. Serum LH concentrations (4.5+/-2.9mlU/ml) were normal. Insulin levels were elevated in all patients (46.3+/-30.1 microU/ml). After weight loss there was a significant (P< 0.01) increase in TT, FT and LH levels, whereas insulin concentrations significantly decreased. In massively obese men (BMI = 43.0 6.7 kg/m2), TT (320+/-110ng/dl), FT (11.0+/-2.1 pg/ml) and LH (3.1+/-1.3mlU/ml) were decreased and significantly lower as compared with the previous group and normal controls. As expected, after weight loss TT, FT and LH levels increased significantly while insulin concentrations decreased. CONCLUSIONS: We concluded that FT levels are dependent on the degree of obesity, massively obese men (BMI > or =35.1 kg/m2) being considered as candidates for consistently low FT levels. A functional decrease of LH pulse amplitude and serum LH levels as well as a possible negative action of excess of circulating leptin on the steroidogenesis may be related to the decreased androgens levels in massively obese men.
Asunto(s)
Dexfenfluramina/administración & dosificación , Dieta Reductora , Obesidad Mórbida/fisiopatología , Testículo/fisiopatología , Testosterona/sangre , Adulto , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Insulina/sangre , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Obesidad Mórbida/sangre , Obesidad Mórbida/dietoterapia , Radioinmunoensayo , Pérdida de Peso/fisiologíaRESUMEN
OBJECTIVE: The prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome. PATIENTS AND METHODS: We have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceded the adrenalectomy. RESULTS: The comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro-ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group. DISCUSSION: The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.
Asunto(s)
Adrenalectomía , Síndrome de Cushing/complicaciones , Síndrome de Nelson/etiología , Adolescente , Hormona Adrenocorticotrópica/sangre , Adulto , Síndrome de Cushing/sangre , Síndrome de Cushing/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Síndrome de Nelson/sangre , Síndrome de Nelson/diagnóstico , Trastornos de la Pigmentación/sangre , Trastornos de la Pigmentación/complicaciones , Trastornos de la Pigmentación/cirugía , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Periodo Posoperatorio , PrevalenciaRESUMEN
PURPOSE: We studied the clinical picture, sensitivity of the biochemical tests and imaging studies, pathological findings, surgical results and followup of patients with pheochromocytoma. MATERIALS AND METHODS: The records of 50 patients with pheochromocytoma were identified. Hyperadrenergic symptoms and signs; urinary dopamine, epinephrine, norepinephrine and vanillylmandelic acid levels; serum dopamine, epinephrine and norepinephrine levels; ultrasonography; computerized tomography; magnetic resonance imaging and 131iodine-metaiodobenzylguanidine images were analyzed. The size, weight and malignancy of the tumors, as well as the operative mortality, survival rate and clinical condition of the patients were also studied. RESULTS: The hyperadrenergic syndrome alone was found in 90% of the patients, Cushing's syndrome alone in 2%, both syndromes in 4%, a palpable abdominal tumor only in 2% and incidental tumors in 2%. The sensitivities of the urinary evaluation in the diagnosis were metanephrines 97%, vanillylmandelic acid 90%, epinephrine 64%, norepinephrine 93% and dopamine 66%. For serum assessment the sensitivities were epinephrine 67%, norepinephrine 93% and dopamine 63%. The sensitivities of the localization examinations were 89, 94, 100 and 88% for ultrasonography, computerized tomography, magnetic resonance imaging and 131I-metaiodobenzylquanidine, respectively. There was only 1 operative death. Of the patients with benign tumors 88% were cured and 12% remained hypertensive with no clinical or biochemical evidence of a hyperadrenergic profile. Of the 8 patients with malignant pheochromocytoma 1 was lost to followup and 3 died of widespread disease (1 without surgery and at 2, 24 and 78 months postoperatively). Of the 4 living patients 3 had no evidence of disease and 1 was well, although with pulmonary metastases.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Adolescente , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Feocromocitoma/complicaciones , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Feocromocitoma/cirugía , Cuidados Preoperatorios , Sensibilidad y EspecificidadRESUMEN
Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n = 13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n = 20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean +/- SEM 6.2 +/- 2.8 kg and Group II 13.4 +/- 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m2. However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.