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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 19 recordsLinked to original sources
PubMed2000

Treatment of diabetes in patients with severe obesity.

Besides genetic predisposition, obesity is the most important risk factor for the development of diabetes mellitus, and weight reduction has been shown to markedly improve blood glucose control in obese subjects with type 2 diabetes. Therapeutic strategies for the obese diabetic patient include: 1) promoting weight loss through lifestyle modifications (hypocaloric diet and exercise) and anti-obesity drugs (orlistat, sibutramine, etc.); 2) improving blood glucose control, essentially through the reduction of insulin resistance (metformin, eventually thiazolidinediones) or insulin need (alpha-glucosidase inhibitors) and, at a later stage, the correction of defective insulin secretion (sulphonylureas, repaglinide) or low circulating insulin levels (exogenous insulin); and 3) treating common associated risk factors, such as arterial hypertension and dyslipidaemias, to improve cardiovascular prognosis. When morbid obesity is present, both restoring a good glycemic control and correcting associated risk factors can only be obtained through marked and sustained weight loss. This primary objective justifies more aggressive weight reduction programmes, including very low-calorie diets and bariatric surgery, but only within a multidisciplinary approach and in well-selected patients.

Anti-Obesity Agents↗
PubMed2000

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.

BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

Adult↗
PubMed2000

No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.

Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein.

Adult↗
PubMed2000

[Antioxidant vitamins in the prevention of cardiovascular diseases. 2nd part: results of clinical trials].

Various epidemiological studies suggested that individuals with high intake of antioxidant vitamins (E, A and C) have a better cardiovascular prognosis than subjects with relative deficiencies in such vitamins. However, placebo-controlled randomized clinical trials did not demonstrate that a specific supplementation in either alpha-tocopherol (vitamin E) or beta-carotene (vitamin A) allows to reduce the incidence of major cardiovascular events, in the general population or even in various subgroups at high risk, and there is no such controlled trials with vitamin C alone. Some studies suggested that combined supplements of several antioxidant vitamins might be more efficacious, and these observations led to initiate several large controlled studies. Thus, until now, there is no convincing arguments in the literature in favour of artificial supplements of antioxidant vitamins. It seems preferable to encourage a well-balanced healthy diet while awaiting the results of the large prospective ongoing trials with combined supplementation.

Ascorbic Acid↗
PubMed2000

[Pharmacy clinics. Medication of the month. Cerivastatin (Lipobay, Cholstat)].

Cerivastatin, commercialized under the trade names of Lipobay by Bayer and Cholstat by Fournier Pharma, is a new synthetic statin. Because of its high affinity for HMG-CoA reductase enzyme that it specifically and selectively inhibited in the hepatocytes, cerivastatin exerts its cholesterol-lowering effect at very low doses, between 0.1 and 0.3 mg/day. Cerivastatin is indicated, after diet failure, in the treatment of primary forms of isolated hypercholesterolaemia or combined hyperlipidaemia. It is presented by the two pharmaceutical companies as 0.1, 0.2 and 0.3 mg filmed tablets. Usual dose is 0.3 mg, once daily, to be reduced in presence of renal failure. Cerivastatin is metabolised within the liver by two different families of cytochrome P450, which limits the risk of drug interferences. Besides this potential advantage as compared with some other statins, its pharmacodynamic activity and safety profile seem to be similar to those of other agents of the same pharmacological family.

Cytochrome P-450 Enzyme System↗
PubMed2000

[Clinical study of the month. The HOPE study, a two-by-two factorial clinical trial with contrasted results].

The results of the HOPE ("Heart Outcomes Prevention Evaluation") study, recently published in the New England Journal of Medicine, demonstrated a highly significant cardiovascular protection by an angiotensin converting enzyme inhibitor, ramipril at a dose of 10 mg/day, after a mean follow-up of 4.5 years, but not of vitamin E supplements at a dose of 400 UI/day in high-risk patients (> 55 years old) who had evidence of vascular disease (secondary prevention) or combined diabetes mellitus and another cardiovascular risk factor (primary prevention).

Aged↗
PubMed2000

[Antioxidant vitamins in the prevention of cardiovascular diseases. First part: epidemiologic studies].

The hypothesis of the atherogenic role of oxidized. LDL lipoproteins and the observation of the longevity of individuals on a "mediterranean diet" led to the concept that antioxidant vitamins may exert cardiovascular protective effects. In this first article, we summarize the results of the main epidemiological studies which analyzed the influence of dietary intakes (or resulting plasma concentrations) in vitamin E (alpha-tocopherol), vitamin A (beta-carotene) or vitamin C (ascorbic acid). The three types of studies available in the literature provided quite heterogeneous results, in favour of a protective role of antioxidant vitamins as far as cross-cultural and most prospective observational studies were concerned, but rather negative when considering case-control studies. However, in general, epidemiological studies tended to support, a beneficial role of these antioxidant vitamins to prevent cardiovascular diseases, at least in some subgroups of individuals.

Ascorbic Acid↗
PubMed2000

[Influenza: from vaccine prevention to antiviral therapy].

Influenza is a highly infectious disease responsible for dangerous epidemics, especially in patients at high risk. The vaccine exerts a valuable protective effect estimated up to 70% and is still considered as the key-approach against influenza. Antiviral agents of the first generation (amantadine, rimantadine, ribavirine) have limited use because of poor tolerance and occurrence of resistance. Zanamivir or Relenza, marketed by Glaxo Wellcome, is a new virostatic drug acting as a neuraminidase inhibitor. It prevents the release of new viruses and so stop the propagation of the infection. It must be taken orally by inhalation within 48 hours after the onset of symptoms. The treatment lasts 5 days (10 mg twice daily). Its efficacy has been demonstrated in controlled clinical trials, and its tolerance is generally excellent. However, caution is recommended in patients with asthma and chronic bronchitis because of the potential risk of bronchoconstriction. No resistance has been detected until now. Zanamivir is active on all strains of influenza A and B viruses.

Administration, Inhalation↗
PubMed2000

[Pharma-clinics. Medication of the month. Moxonidine (Moxon)].

Moxonidine (Moxon, Solvay Pharma) is the first member of a new class of centrally-acting antihypertensive agents. The selective activation of central I1 imidazoline receptors results in an inhibition of peripheral sympathetic activity and produces arterial vasodilatation. Moxonidine is indicated in the treatment of essential arterial hypertension, at a usual daily dose of 0.4 mg (initial dose of 0.2 mg/day), in one administration per day. Its tolerance profile is better than that of other centrally-acting antihypertensive agents which stimulate alpha-2 adrenergic receptors, and similar to that of medications of other classes. As monotherapy, the antihypertensive efficacy of moxonidine is similar to that of most other antihypertensive agents. In case of insufficient response, moxonidine may be associated with other antihypertensive compounds, which leads to a better efficacy with no deterioration of its good tolerance profile.

Antihypertensive Agents↗
PubMed2000

[Clinical study of the month. The STOP-2 study of arterial hypertension in the elderly].

After the demonstration of the efficacy of beta-blockers or diuretics versus placebo to prevent cardiovascular complications in elderly hypertensive patients in the first STOP-Hypertension study in 1991, a Swedish group published at the end of 1999 the STOP-2 Hypertension study. The latter randomised trial showed in a similar population that the cardiovascular protection of more recent antihypertensive agents such as calcium antagonists and angiotensin-converting-enzyme inhibitors is similar to that of the conventional antihypertensive drugs used in the first study. In fact, the degree of blood pressure control appears to be more important than the type of antihypertensive drugs used, and this conclusion is reinforced by the observation that numerous patients should rapidly be treated by more than one antihypertensive agent to reach blood pressure targets.

Adrenergic beta-Antagonists↗
PubMed2000

Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss.

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.

Diabetes Mellitus, Type 2↗
PubMed2000

[The dosage of anti-GAD and anti-IA2 autoantibodies: an aid to the early diagnosis of type 1 diabetes].

Diabetes mellitus is a frequent metabolic disease characterised by a complex and inconstant phenotypic expression that complicates the classification of patients and sometimes delays their optimal management. In that slowly progressive disease leading to severe and irreversible complications, the use of early and specific genetic, immunological and/or metabolic markers may help in the classification of diabetic patients and in the orientation of therapeutic strategies; furthermore, it is also an essential aid in the early screening of subjects at risk of developing the disease. The assessment of classical immunological markers, such as islet cell antibodies (ICA) or anti-insulin antibodies (IAA) has been recently completed by the screening of new promising markers such as GAD- and IA2-antibodies. The presence of these markers confirms the autoimmune component of the disease and thus supports the diagnosis of type 1 diabetes, even if clinical symptoms are absent or inconsistent. In addition, it represents a strong argument in favour of the initiation of specific immunological therapies to preserve B-cell number and function.

Autoantibodies↗
PubMed2000

[Pharma-clinics. Medication of the month. Glimepiride (Amarylle)].

Glimepiride, commercialized in Belgium under the trade name of Amarylle by Aventis, is a new sulphonylurea compound which is indicated in the treatment of type 2 diabetes, after diet and exercise failure. It is available as 2 mg tablets. The initial doses is 1 mg, to be progressively increased up to 4 mg per day, if necessary, with a maximal daily dose of 6 mg. It is recommended to take glimepiride once a day, with the first main meal. Because of a particular binding of this sulphonylurea to the B cells of Langerhans pancreatic islets and, perhaps, of the presence of some extrapancreatic effects, both hypoglycaemic risk and circulating plasma insulin levels are lower with glimepiride than with glibenclamide, the reference sulphonylurea agent used in comparative clinical trials.

Administration, Oral↗
PubMed2000

[Clinical study of the month. After DCCT, the EDIC study].

The "Diabetes Control and Complications Trial" (DCCT) demonstrated that intensive insulin therapy, by reducing HbA1c levels by about 2%, delays the onset and slows the progression of microangiopathic complications (by at least 50%) in patients with type 1 diabetes. The "Epidemiology of Diabetes Interventions and Complications" (EDIC) study recently showed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy during the DCCT not only persists, but is amplified for at least 4 years (reduction by about 80% when compared to diabetic patients previously treated with conventional therapy during the DCCT).

Diabetes Mellitus, Type 1↗
PubMed2000

[Assessment of therapeutic efficacy, an essential step in evidence-based medicine].

Evidence-based medicine relies on the results from clinical trials. We will describe the various modes of expression of the results (absolute risk reduction, relative risk reduction, odds ratios, number needed to treat to avoid one event,...) and we will insist upon the clinical significance and the pitfalls in the interpretation of these various indices of therapeutic efficacy.

Clinical Trials as Topic↗
PubMed2000

[Evidence-based medicine. Input of controlled clinical trials].

Controlled clinical trials are the support of Evidence-Based Medicine. In most instances, only them can indeed provide the demonstration of both the efficacy and safety of a pharmacological treatment, based upon rigorous scientific experimental observations avoiding potential bias due to subjective interpretation. In order to be able to extrapolate conclusions of drug trials to clinical practice and to positively influence physician's attitudes, "explanatory" trials, which aim at proving the intrinsic activity of the molecule, should be completed by "pragmatic" trials, which aim at demonstrating the clinical utility of the drug.

Attitude of Health Personnel↗
PubMed2000

[On the inapplicability of certain therapeutic guidelines in practice: the example of reimbursement for hypolipidemic agents in Belgium].

International guidelines from the Task Force of European and other Societies on Coronary Prevention and national guidelines from the Belgian Lipid Club recently emphasized the potential interest of adequate management of patients with even moderate hypercholesterolaemia. However, current criteria for the reimbursement of lipid-lowering drugs in Belgium do not allow to follow these guidelines. A solution should be urgently found in order to bridge the gap and permit practitioners, after diet failure, to effectively prescribe lipid-lowering agents in patients who should benefit in priority of such a treatment. It is certainly the case in secondary prevention as well as, in high risk individuals, in primary prevention, i.e. in situations where these drugs have provided enough evidence of their efficacy with an acceptable cost-benefit ratio.

Anticholesteremic Agents↗