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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 181 records · Page 10Linked to original sources
PubMed1999

Pharmacological treatment of obesity: present status.

OBJECTIVE: Obesity poses a serious health hazard and its treatment is often disappointing. This review describes the present status of pharmacological treatment of obesity in man. DESIGN: Obesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. The mode of action, efficacy and safety of each approach will be briefly discussed. RESULTS: All of the pharmacological possibilities have potential activities, but also serious limitations. While current anti-obesity pharmacotherapy essentially uses centrally-acting anorectic drugs, severe side-effects (more particularly pulmonary hypertension and valvular heart disease) have been reported, leading to the withdrawal of licensed fenfluramine and d-fenfluramine. New approaches have been recently proposed, such as sibutramine, an amine reuptake inhibitor which decreases food intake, and orlistat, an intestinal lipase inhibitor which decreases fat absorption. Obesity is a chronic disease and should be treated as such with reasonable expectations. Large-scale one-year placebo-controlled studies demonstrated that d-fenfluramine, sibutramine and orlistat significantly increased body weight loss by an average of 2-4 kg when compared to placebo and, more interestingly, multiplied by 2-3 the number of patients who succeeded in obtaining and maintaining a reduction of more than 10% of initial body weight. Interestingly, some of these compounds may also exert favourable effects on other vascular risk factors, independently of weight loss. CONCLUSIONS: Even if all anti-obesity pharmacological approaches can be helpful, they also have important limitations so that other strategies including either combined therapies or new drugs (peptides) are currently under investigation.

Anti-Obesity Agents↗
PubMed1999

Glucose metabolism and the postprandial state.

Disturbances of postprandial glucose metabolism are now thought to contribute to cardiovascular disease. Postprandial glucose excursions can be affected by a number of factors, such as the types of carbohydrates ingested and the way they are metabolized. In Type 2 diabetes, factors that contribute to excessive postprandial glucose excursions include disruption of insulin secretion, insufficient inhibition of hepatic glucose production and defective glucose storage in muscle. A number of measures may attenuate excessive postprandial blood glucose excursions. These include a diet high in 'low glycaemic index' foods and treatment with drugs that improve or restore the hormonal response (e.g. the sulphonylureas and the newer beta-cell mediated insulinotropic drugs such as repaglinide), that improve insulin sensitivity or that delay gastric emptying.

Diabetes Mellitus, Type 1↗
PubMed1999

Severe/extreme obesity: a medical disease requiring a surgical treatment?

Obesity poses a serious health hazard and its treatment is often disappointing. Surgical approaches have been proposed for treating severe obesity (body mass index or BMI > or = 35 kg/m2) with comorbidities or extreme obesity (BMI > or = 40 kg/m2). Before accepting bariatric surgery as alternative treatment, the four following prerequisites should be met: 1. the medical condition is serious enough; 2. it can not be treated satisfactorily with classical means; 3. the surgical treatment is effective in improving the clinical situation; and 4. bariatric surgery is safe enough, so that the benefits clearly outweigh the risks. On the basis of the literature and our own experience, it appears that gastric reduction surgery may be considered as a valuable alternative for treating severe/extreme obesity, despite the possible occurrence of perioperative and, more frequently, late complications, provided that it is performed by an experienced and multidisciplinary team in well-selected patients.

Anti-Obesity Agents↗
PubMed1999

Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes.

Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts an antihyperglycemic activity in a dose-dependent manner between 200 and 600 mg/day in type 2 diabetic patients treated with diet alone, sulfonylureas, or insulin. Additive antihyperglycemic effect may also be obtained by combining troglitazone and metformin. The antihyperglycemic effect of troglitazone as monotherapy is rather modest (reduction of HbA1c by 0.5-1.0%), but it appears to be somewhat greater when it is combined with other antidiabetic drugs. No double-blind studies have directly compared the activity of troglitazone with that of sulfonylureas or metformin. Troglitazone has been shown to exert additional beneficial effects on serum lipid profile and arterial blood pressure. It may be considered as a valuable alternative in insulin-resistant (obese and hyperinsulinemic) diabetic patients who appear to be the best responders to the drug. However, the efficacy of troglitazone is challenged by its safety profile, and the risk of hepatotoxicity still remains a major concern in clinical practice.

Administration, Oral↗
PubMed1999

Long-term effects of oral estradiol and dydrogesterone on carbohydrate metabolism in postmenopausal women.

OBJECTIVE: To determine in postmenopausal women the long-term effects on carbohydrate metabolism of the administration of oral micronized 17 beta-estradiol (2 mg/day continuously) and cyclical dydrogesterone (10 mg/day for 14 days per 28-day cycle). METHODS: A 2-year open-label prospective, non-comparative study was carried out of 13 healthy postmenopausal women receiving cyclical estradiol and dydrogesterone and serving as their own controls. Concentrations of blood glucose, plasma insulin, C-peptide, glucagon and free fatty acids (FFAs) were determined before treatment (base-line) and at 6, 12 and 24 months of hormone replacement therapy under fasting conditions and during a standard 75-g, 3-h, oral glucose tolerance test (OGTT). RESULTS: Fasting blood glucose levels were unchanged throughout the study, and the mean areas under the curves (AUCs) for glucose response increased slightly but non-significantly versus baseline; fasting plasma insulin levels tended a decrease, and AUCs for insulin responses to the glucose load fell by 23% from baseline (not significant); fasting C-peptide levels and AUCs were unchanged; plasma glucagon fasting levels and responses were in the normal range and stable throughout the study; and plasma FFA fasting levels decreased significantly, as well as FFA AUCs during OGTTs, at the 12th and 24th months of the study. CONCLUSIONS: During a 2-year treatment with oral estradiol and cyclical dydrogesterone, a direct progesterone derivative, tolerance to glucose was unchanged, fasting plasma insulin and insulin response to repeated glucose loads were decreased, and C-peptide levels remained unchanged, indicating a potential improvement in insulin sensitivity and clearance, as in younger women; additionally, a slightly enhanced antilipolytic activity of insulin was observed.

Blood Glucose↗
PubMed1999

[Clinical study of the month. The LIPID study: "long-term intervention with pravastatin in ischaemic disease"].

The LIPID study is a placebo-controlled, double-bind, randomized trial, performed in 9014 patients with coronary heart disease and total cholesterol levels of 155 to 271 mg/dl. After a mean follow-up of 6.1 years, patients receiving pravastatin (40 mg/day) had significantly (p < 0.001) lower death rate from coronary heart disease (24%), lower overall mortality (22%) and lower incidence of all cardiovascular outcomes (20 to 29% depending on the event). Interestingly enough, the reduction in death from coronary heart disease or nonfatal myocardial infarction was observed whatever the initial cholesterol concentration, and already significant if total cholesterol was < 213 mg/dl and LDL cholesterol was < 135 mg/dl. Thus, in secondary prevention, the favourable effect of the statin on the coronary heart disease outcomes is observed even in case of initial cholesterol levels yet considered as "normal".

Adult↗
PubMed1999

[Hypercholesterolemia-related cardiovascular risk: a continuum from a notion of normality, intervention threshold and therapeutic objectives].

There appears to be a continuum between the cardiovascular risk and the level of blood cholesterol, which hinders the definition of normal values, intervention threshold and therapeutic goals. The more and more convincing evidences provided by the "Evidence-Based Medicine" should be confronted to the pharmaco-economical constraints in order to first focus the essential of the efforts and resources on the target population with the highest risk. Unfortunately, the therapeutic strategy concerns a rather high percentage of the population of industrialized countries.

Anticholesteremic Agents↗
PubMed1999

[Pharma-clinics. The drug of the month. Aceclofenac (Biofenac)].

Aceclofenac, a phenylacetic acid derivative, is a new nonsteroidal anti-inflammatory drug (NSAID). It is indicated in the symptomatic treatment of pain and inflammatory or degenerative arthropathies: osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, abarticular inflammations, posttrauma or postoperative inflammations. The usual oral dosage of aceclofenac is 100 mg twice daily in adults. Its clinical efficacy seems to be similar to that of other NSAIDs, but its safety profile, especially gastro-intestinal tolerance, appears to be better. Finally, in vitro studies suggested that aceclofenac may exert positive effect on cartilage matrix metabolism.

Adult↗
PubMed1999

[The epidemic of metabolic diseases, a major problem of public health].

The industrialized world is confronted to a real epidemic of metabolic diseases triggered by overeating and sedentarity. Obesity, hypercholesterolaemia, diabetes mellitus and the metabolic syndrome associated to insulin resistance are well-known cardiovascular risk factors which all contribute to increase both morbidity and mortality, to alter the quality of life and to markedly increase the budget of the social security. Preventive measures should be taken urgently in order to correct such a dangerous trend for the public health.

Cardiovascular Diseases↗
PubMed1999

[How I study individual coronary risk extrapolated over 10 years].

The European Societies of Cardiology. Atherosclerosis and Hypertension agreed upon a table allowing to evaluate the coronary risk after 10 years according to five parameters (sex, age, smoking, total cholesterol, arterial blood pressure) and aggravating factors (familial history, diabetes mellitus, low HDL cholesterol, hypertriglyceridaemia). The risk level is based upon the equations of the prospective US study of Framingham. The calculation of such a risk is mainly interesting before considering intensified primary prevention in an individual free of any cardiovascular disease. The efforts should first focus on individuals with a high coronary risk, i.e. > 20% after 10 years. As far as secondary prevention is concerned, the patients should always be considered at high risk and beneficiate of all available therapeutic means.

Age Factors↗
PubMed1999

[How I treat ... an individual with severe obesity and metabolic abnormalities with gastroplasty].

Severe obesity, defined as a body mass index > or = 35 kg/m2, is frequently associated with various biological abnormalities, particularly in the presence of intra-abdominal adiposity. The most important disorders belong to the so-called insulin resistance syndrome, metabolic syndrome or syndrome X: hyperinsulinaemia, impaired glucose tolerance or type 2 diabetes, dyslipidaemias, hyperuricaemia, hyperfibrinogenaemia. All these metabolic abnormalities are considered as cardiovascular risk factors. They are also correlated with the severity of the liver steatosis which is commonly observed in individuals with severe obesity. We report our experience of the evolution of these metabolic abnormalities after a marked weight loss induced by gastroplasty. We will analyse the favourable effects of bariatric surgery on insulin sensitivity, biological components of the metabolic syndrome, type 2 diabetes and liver steatosis.

Cardiovascular Diseases↗
PubMed1999

[Pharmacy-clinic medication of the month. Naratriptan (naramig)].

Naratriptan, launched by Glaxo Wellcome under the trade name Naramig, is a potent and selective agonist of 5-HT1B and 5-HT1D vascular receptors. Available as tablets of 2.5 mg, it is indicated in the acute treatment of migraine, with or without aura. A single oral dose of 2.5 mg naratriptan is characterized by a satisfactory clinical efficacy (already significant after one hour, maximum after 4 hours and persisting during 24 hours), a reduction by half of the recurrence of the migraine crisis within the 24 hours and an excellent tolerance profile.

Drug Administration Schedule↗
PubMed1999

[Pharmacy-clinics medication of the month. Orlistate (xenical)].

Orlistat (tetrahydrolipstatin), launched by Roche under the trade name Xenical, is a selective inhibitor of pancreatic and gastro-intestinal lipases. It reduces the digestion of dietary fat and its resorption through digestive mucosa by around 30%. It is indicated, at a dose of 3 x 120 mg/day (one dose with each meal) and together with a moderately low-calorie and low-fat diet, for the treatment of obesity. It has been shown, in placebo-controlled two-year trials, to almost double the number of obese subjects who succeed in loosing at least 10% of initial body weight. Independently, it contributes to decrease serum cholesterol levels by 6-10%. Because of its mechanism of action, this drug can induce intestinal side-effects which tend to decrease with time and with the reduction of fat intake, thus improving diet compliance.

Dietary Fats↗