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See detailPharma-clinics. Le medicament du mois. L'alendronate (Fosamax).
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(4), 220-2

Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which inhibits bone turnover by suppressing the activity of osteoclasts without increasing the risk of osteomalacia. Alendronate is ... [more ▼]

Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which inhibits bone turnover by suppressing the activity of osteoclasts without increasing the risk of osteomalacia. Alendronate is highly effective at preventing bone loss associated to absence of endogenous estrogen and induces a sustained increase in bone mass. Fosamax is indicated and reimbursed in the treatment of osteoporosis in postmenopausal women, with either an history of bone fracture confirmed by X-ray exam or obvious osteoporosis assessed by bone mineral density measurement. The recommended dosage is 10 mg once daily, continuously. The drug should be absorbed after an overnight fast to improve its bioavailability and with a big glass of plain water to reduce the risk of oesophageal ulcerations. Large randomized controlled trials for up to 3 years have demonstrated that alendronate is able to reduce the risk and rate of occurrence of vertebral and nonvertebral fractures in postmenopausal women. [less ▲]

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See detailImplications virales dans l'etiopathogenie du diabete de type 1: donnees actuelles.
Radermecker, Régis ULg; Scheen, André ULg; Letiexhe, Michel ULg et al

in Revue Médicale de Liège (1998), 53(10), 597-602

Type 1 diabetes mellitus results from autoimmune destruction of pancreatic beta cells. After having described genetic, immunological and metabolic factors, some researchers have hypothezised that ... [more ▼]

Type 1 diabetes mellitus results from autoimmune destruction of pancreatic beta cells. After having described genetic, immunological and metabolic factors, some researchers have hypothezised that environmental factors might trigger the autoimmune process. Based on epidemiological, anatomoclinical and animal studies, they suggest a role for virus infections. [less ▲]

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See detailPharma clinics. Comment je traite.... Certaines maladies metaboliques grace a une intervention pharmacologique ciblee sur l'intestin.
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(11), 646-50

Besides the classical dietary regimen, it is possible to use specific pharmacological approaches, targeted at the intestine, in order to treat some metabolic disorders. Three approaches will be described ... [more ▼]

Besides the classical dietary regimen, it is possible to use specific pharmacological approaches, targeted at the intestine, in order to treat some metabolic disorders. Three approaches will be described: anionic resins for treating hypercholesterolaemia, alpha-glucosidase inhibitors for treating diabetes mellitus and reactive hypoglycaemia, and intestinal lipase inhibitors for treating obesity. All these drugs are based on original concepts, but their clinical use is often limited by the occurrence of digestive side-effects. The latter may generally be reduced by progressive and individual titration of the dosage of each drug and/or by following an appropriate diet. [less ▲]

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See detailPharma-clinics. Le medicament du mois. Premelle (oestrogenes conjugues + medroxyprogesterone).
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(10), 638-40

Premelle, commercialised by Wyeth-Lederle, is a combination of conjugated estrogens 0.625 mg and medroxyprogesterone acetate 5 mg which is indicated in the treatment of menopause-associated problems ... [more ▼]

Premelle, commercialised by Wyeth-Lederle, is a combination of conjugated estrogens 0.625 mg and medroxyprogesterone acetate 5 mg which is indicated in the treatment of menopause-associated problems, among which vasomotor symptoms, atrophic vaginitis and/or urethritis, and in the prevention and treatment of post-menopausal osteoporosis. It is presented in two formulations, Premelle cyclic 5 and Premelle 5. The former, in which the progestagen is only given during the last 14 out of 28 days of the treatment cycle, is accompanied by regular bleeding and thus preferably indicated during perimenopause whereas the latter, in which the progestagen is given continuously and results in amenorrhea, is mostly indicated after menopause in order to improve long-term compliance. [less ▲]

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See detailComment j'explore ... un sujet avec une concentration basse de cholesterol HDL.
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(11), 711-4

A decrease in plasma HDL cholesterol concentration is considered as a major cardiovascular risk factor and is a prevalent lipid abnormality among patients with coronary heart disease. This condition is ... [more ▼]

A decrease in plasma HDL cholesterol concentration is considered as a major cardiovascular risk factor and is a prevalent lipid abnormality among patients with coronary heart disease. This condition is most often observed in the presence of hypertriglyceridaemia, generally linked to the insulin resistance syndrome, but may also be associated to elevated LDL cholesterol level or even be present alone (hypoalphalipoproteinaemia). The decision to treat a patient with low HDL level depends on the individual overall cardiovascular risk which should be evaluated as carefully as possible. The investigation should look for causes which may favour this metabolic condition, such as bad life habits or possible pharmacological interferences. [less ▲]

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See detailPharma-clinics. Le medicament du mois. Le formoterol (Oxis Turbohaler).
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(11), 715-8

Formoterol, commercialized by Astra under the trade name Oxis, is a new potent and selective agonist of beta-2 adrenergic receptors, which is used with a specific device (Turbohaler) allowing effective ... [more ▼]

Formoterol, commercialized by Astra under the trade name Oxis, is a new potent and selective agonist of beta-2 adrenergic receptors, which is used with a specific device (Turbohaler) allowing effective inhalation. Bronchodilatation occurs rapidly, within 1-3 minutes after inhalation, and lasts about 12 hours after the administration of a unique dose. Oxis Turbohaler is indicated to reduce symptoms associated with bronchial obstruction in asthmatic patients when the control of asthma is not achieved with inhaled corticoid therapy. It is not indicated for the treatment of acute crisis. It is presented as powder vials for inhalation (4.5 or 9 micrograms per dose). The usual dose in adults is 1-2 inhalations 1-2 times per day, in the morning and/or in the evening (bedtime administration should be recommended in case of nocturnal asthma). There is not enough data for treating children. The lowest dose allowing adequate control of asthma should be selected for chronic treatment. [less ▲]

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See detailInfo-congres. Les lecons de la "United Kingdom Prospective Diabetes Study".
Scheen, André ULg; Lefebvre, Pierre ULg

in Revue Médicale de Liège (1998), 53(9), 576-8

The United Kingdom Prospective Diabetes Study (UKPDS) is the largest study ever performed in the field of diabetes. It has been carried on in more than 5000 patients with newly diagnosed type 2 diabetes ... [more ▼]

The United Kingdom Prospective Diabetes Study (UKPDS) is the largest study ever performed in the field of diabetes. It has been carried on in more than 5000 patients with newly diagnosed type 2 diabetes and followed during almost 15 years. The main goals of the study were to investigate the effects of improving blood glucose and/or blood pressure control on diabetic complications, and to compare the advantages and inconvenients of the most important pharmacological approaches. The results of the UKPDS have been presented at the last Congress of the European Association for the Study of Diabetes (EASD) in Barcelona, September 10-11, 1998. They essentially showed that improving blood glucose or arterial blood pressure control allows to significantly reduce the incidence of complications associated to diabetes. Best results were observed in individuals in whom treatments of both hyperglycemia and hypertension were intensified. For each risk factor, no threshold has been found so that every reduction in blood glucose or arterial pressure is accompanied by a nearly linear diminution in the incidence of diabetic complications. The type of pharmacological treatment appears to have a less prominent influence, even if metformin appears to exert the most favourable effects in the group of obese patients with type 2 diabetes. [less ▲]

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See detailPharma clinics. Comment je traite ... un patient diabetique avec obesite severe.
Scheen, André ULg; Triches, K.; Luyckx, Françoise ULg et al

in Revue Médicale de Liège (1998), 53(7), 386-9

Obesity plays a crucial role in type 2 diabetes pathophysiology and a major weight loss markedly improves glycaemic control. The common failure of classical treatments leads to the use of more aggressive ... [more ▼]

Obesity plays a crucial role in type 2 diabetes pathophysiology and a major weight loss markedly improves glycaemic control. The common failure of classical treatments leads to the use of more aggressive weight-reduction approaches, such as very-low-calorie diets (VLCDs), anti-obesity drugs or even bariatric surgery. VLCDs are very successful in the short-term but rather disappointing in the long-term. Anti-obesity compounds only induce a modest mean weight reduction, even if some patients appear to be better responders. Interestingly, serotoninergic agents increase insulin sensitivity and glycaemic control, independently of weight loss. Bariatric surgery provides the most impressive results. In well-selected subjects, gastroplasty (either vertical ring gastroplasty or adjustable silicone gastric banding) generally induces a considerable weight loss which results in a remarkable and sustained glycaemic control improvement and allows the reduction, or even the suppression, of any antidiabetic treatment. This ultimate solution should not be neglected after failure of medical approaches, provided that the indication is correct, the surgical procedure is performed in a specialized centre and the followup is well organized by a multidisciplinary team. [less ▲]

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See detailPharma-clinics. Comment je traite ... un sujet avec une concentration basse de cholesterol HDL.
Scheen, André ULg

in Revue Médicale de Liège (1998), 53(12), 727-31

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile ... [more ▼]

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile (isolated abnormality, associated hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment must favour diet and exercise, before considering a possible pharmacological approach. Results are usually acceptable with better life habits and appropriate diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From a pharmacological point of view, the best results are obtained with fibrates or nicotinic acid. However, results are often disappointing when low HDL cholesterol level is isolated. [less ▲]

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See detailInfluence of the A-->G (-3826) uncoupling protein-1 gene (UCP1) variant on the dynamics of body weight before and after gastroplasty in morbidly obese subjects.
Luyckx, Françoise ULg; Scheen, André ULg; Proenza, A. M. et al

in International Journal of Obesity & Related Metabolic Disorders (1998), 22(12), 1244-5

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See detailLiver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty.
Luyckx, Françoise ULg; Desaive, Claude ULg; Thiry, Albert ULg et al

in International Journal of Obesity & Related Metabolic Disorders (1998), 22(3), 222-6

OBJECTIVE: To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss. DESIGN: Retrospective clinical study ... [more ▼]

OBJECTIVE: To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss. DESIGN: Retrospective clinical study. SUBJECT: 528 obese patients before bariatric surgery and 69 obese subjects of the initial cohort evaluated before and 27+/-15 months after gastroplasty. MEASUREMENTS: Fatty deposition (scored as mild, moderate or severe) and inflammatory changes were evaluated in liver biopsies; clinical (body mass index (BMI), age, gender, duration of obesity) and biological (glucose, triglycerides, liver enzymes) parameters were related to histological findings. RESULTS: 74% of the 528 biopsies showed fatty change, estimated as mild in 41% of cases, moderate in 32% and severe in 27%. The prevalence of steatosis was significantly higher in men than in women (91% vs 70%, P = 0.001) and in patients with impaired glucose tolerance or type 2 diabetes compared with nondiabetics (89% vs 69% P = 0.001). The severity of the steatosis was associated with BMI (P = 0.002) but not with the duration of obesity or the age of the patient. When compared with patients without fatty change, those with liver steatosis had significantly higher fasting plasma glucose (5.5 mmol/l vs 5.1 mmol/l, P = 0.007) and triglycerides (1.8 mmol/l vs 1.3 mmol/l, P = 0.002). Mean serum liver enzyme activities (alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transpeptidase (gammaGT) were significantly (P < 0.001) increased in patients with fatty change but remained within laboratory reference values. In the 69 patients who have been evaluated after a marked weight reduction (-32+/-19kg), 45% of the biopsies were considered as normal (vs 13% before, P < 0.001) while pure fatty change was still observed in 38% of the patients (vs 83% before, P = 0.001). However, the severity of the steatosis was significantly (P < 0.001) reduced (mild: 62% vs 21%; moderate: 23% vs 37%; severe: 15% vs 42%). In addition, a significant increase of hepatitis was observed in 26% of the biopsies (vs 14% before, P < 0.05). CONCLUSIONS: Liver steatosis in obese subjects is associated with men, diabetic status, BMI, higher fasting glucose and hypertriglyceridaemia. Postgastroplasty weight loss reduces liver steatosis, but seems to increase the incidence of inflammatory lobular hepatitis. [less ▲]

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See detailIA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings. The Belgian Diabetes Registry.
Gorus, F. K.; Goubert, P.; Semakula, C. et al

in Diabetologia (1997), 40(1), 95-9

IA-2 has been identified as an autoantigen that is recognized by immunoglobulins from insulin-dependent diabetic (IDDM) patients. Using a liquid phase radiobinding assay, we performed an IA-2-autoantibody ... [more ▼]

IA-2 has been identified as an autoantigen that is recognized by immunoglobulins from insulin-dependent diabetic (IDDM) patients. Using a liquid phase radiobinding assay, we performed an IA-2-autoantibody (IA-2-Ab) assay in 474 IDDM patients and 482 non-diabetic control subjects aged 0-3 years. IA-2-Ab were detected in 58% of the patients and 0.8% of control subjects. Their prevalence in patients was lower than that of islet cell autoantibodies (ICA; 73%) or glutamic acid decarboxylase (M(r) 65 kDa)-autoantibodies (GAD65-Ab; 82%) but higher than that of insulin autoantibodies (IAA; 42%). IA-2-Ab were more frequent in patients under age 20 years (70%) than between 20 and 40 years (45%; p < 0.001). In the whole IDDM group, 92% of patients were positive for at least one of the three molecular assays, which is higher than the positivity for the ICA assay (73%). Only 1% was negative in the molecular assays and positive in the ICA assay. IA-2-Ab levels were positively correlated with ICA titres (p < 0.001) and HLA DQ A1*0301-DQ B1*0.02 (p < 0.003) by multivariate analysis. In a group of 481 non-diabetic siblings (age 0-39 years) of IDDM patients only 7 were IA-2-Ab positive (1.5%). All seven were under age 20 years and positive for at least two other autoantibodies and for DQ A1*0301-DQB1*0302. Four of these seven developed IDDM during the 6-70-month follow-up period. The positive predictive value of IA-2-Ab (57%) was higher than that of ICA, GAD65-Ab or IAA alone, or in combination (< or = 20%) but these calculations are restricted by the relatively short observation period and the small number of cases. The only IA-2-Ab-negative case of pre-diabetes was also negative for IAA and GAD65-Ab, while it was strongly positive for ICA. In conclusion, IA-2-Ab show a high diagnostic specificity for IDDM and are predictive markers of impending diabetes in siblings of patients. In combination with other molecular antibody assays they may replace ICA testing in future. Our data also indicate that other autoantibodies than IA-2-Ab, GAD65-Ab and IAA contribute to ICA. [less ▲]

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See detailA propos de quelques utilisations non conventionnelles de la metformine
SCHEEN, André ULg; PAQUOT, Nicolas ULg; LETIEXHE, Michel ULg et al

in Médecine et Hygiène (1997), 55

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See detailAcute Functional Iron Deficiency in Obese Subjects During a Very-Low-Energy All-Protein Diet
Beguin, Yves ULg; Grek, Vincent; Weber, Georges ULg et al

in American Journal of Clinical Nutrition (1997), 66(1), 75-9

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 ... [more ▼]

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone. [less ▲]

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See detailPerspective in the treatment of insulin resistance.
Scheen, André ULg

in Human Reproduction (1997), 12 Suppl 1

Improving the action of insulin is a relatively new concept in therapy. It should, however, become more and more important because of the rapid expansion of the insulin resistance syndrome (including ... [more ▼]

Improving the action of insulin is a relatively new concept in therapy. It should, however, become more and more important because of the rapid expansion of the insulin resistance syndrome (including upper body adiposity, glucose intolerance, hypertension, dyslipidaemia, etc.) in industrialized countries and its dramatic consequences for public health. Insulin sensitivity can be improved by non-pharmacological means, essentially reduction of excessive body weight, promotion of regular physical activity and modification of dietary habits, as well as, possibly, cessation of smoking and correction of subclinical magnesium deficiency. Currently available pharmacological means mainly include the biguanide compound metformin and possibly anti-obesity agents, such as (d-) fenfluramine, fluoxetine and benfluorex. New compounds aiming at improving the action of insulin are in development, especially the thiazolidinedione derivatives (e.g. troglitazone), known as 'insulin sensitizers'. Treatment of insulin resistance may have important gynaecological applications, essentially in polycystic ovary syndrome and, possibly, after menopause. Hopefully, improving insulin sensitivity could ameliorate the cardiovascular prognosis of numerous individuals having some or all components of insulin resistance syndrome. [less ▲]

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See detailNon-insulin-dependent diabetes mellitus in the elderly.
Scheen, André ULg

in Bailliere's Clinical Endocrinology and Metabolism (1997), 11(2), 389-406

The prevalence of non-insulin-dependent diabetes mellitus dramatically increases with age. Older diabetic subjects have an increased frequency of complications from diabetes compared with their younger ... [more ▼]

The prevalence of non-insulin-dependent diabetes mellitus dramatically increases with age. Older diabetic subjects have an increased frequency of complications from diabetes compared with their younger counterparts and higher morbidity and mortality rates compared with age-matched non-diabetic controls. Elderly patients with diabetes are generally treated following the same approach as in younger patients: dietary therapy first, followed by oral hypoglycaemic agents and ultimately insulin. However, several specificities should be pointed out. Changes associated with ageing may affect the pharmacokinetics and pharmacodynamics of both sulphonylureas (increasing the risk of severe hypoglycaemia) and biguanides (increasing the risk of lactic acidosis). The best insulin regimen in old age is not known, but a twice-daily injection of a pre-mixed insulin preparation is usually recommended. Goals of therapy must be realistic and not cause disabling side-effects. The general practitioner plays a crucial role in the care of elderly diabetic patients, but access to a multidisciplinary specialized team may be necessary. [less ▲]

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See detailGlucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models.
Overkamp, D.; Gautier, J. F.; Renn, W. et al

in American Journal of Physiology (1997), 273(2 Pt 1), 284-96

This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were ... [more ▼]

This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were studied after an overnight fast. Two bolus injections of [U-13C]glucose were given 150 min apart, the first without and the second together with concomitant injection of unlabeled glucose. [3-3H]glucose was constantly infused throughout the study and served to provide an independent means for evaluation of system responses. A linear time-invariant three-compartmental model and the two-compartment time-variant model proposed by Caumo and Cobelli were used to interpret measured time courses of [U-13C]glucose and to reconstruct endogenous glucose production and glucose removal. The ability of the two models to describe the glucose tracer time course was comparable. Simulation studies showed that the two-compartmental time-variant system better predicted measured [3-3H]glucose concentration profiles than did the three-compartmental time-invariant model. However, endogenous glucose production and the integral of excess glucose removal over basal during the IVGTT derived from the two models were almost identical. [less ▲]

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See detailLa lamotrigine (Lamictal).
Scheen, André ULg

in Revue Médicale de Liège (1997), 52(11), 738-40

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