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Biomedical subjects

H Toplak

Publications and source records attributed to H Toplak.

At least 19 recordsLinked to original sources

Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging Study Group.

OBJECTIVE: To determine the weight-reducing efficacy of orlistat, a novel gastrointestinal lipase inhibitor, and to define the optimal dosage regimen and establish the tolerability of the drug when used for a 6-month treatment period. METHODS: The study was a multicentre randomised, double-blind, parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index between 28 and 43 kg x m(-2) Following a 5-week placebo run-in period, subjects were randomised to receive orlistat 30 mg, 60 mg, 120 mg, 240 mg or matching placebo three times a day (tid) for 24 weeks during meals. Patients were maintained on a mildly hypocaloric diet throughout the study period. The primary efficacy parameter was body weight change over time. RESULTS: Orlistat resulted in a significantly greater mean loss of body weight than observed in the placebo group. In absolute terms, mean weight loss was greatest in the 120 mg group (9.8%). More orlistat- than placebo-treated patients lost > 10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group). Orlistat was well tolerated. Predictably, in view of its known pharmacological effects, more orlistat-treated patients experienced gastrointestinal events. Mean levels of vitamins A, D and E, and beta-carotene remained within the clinical reference ranges in all treatment groups and rarely required supplementation. After 24 weeks, plasma concentrations of orlistat were either non-measurable or detected at the assay's limit of quantitation. CONCLUSION: Orlistat treatment results in a dose-dependent reduction in body weight in obese subjects and is well tolerated. Orlistat 120 mg tid represents the optimal dosage regimen.

Adult

Forearm composition contributes to differences in reactive hyperaemia between healthy men and women.

BACKGROUND: Post-ischaemic reactive hyperaemia in the forearm has been suggested as a marker of resistance vessel function. The contribution of forearm composition to the kinetics of reactive hyperaemia is largely unknown. The body composition of men and women differs in that women have a higher body fat content and less lean body mass. METHODS: In the present study, we investigated whether the kinetics of reactive hyperaemia in the forearm in 14 healthy subjects (seven men and seven women) show gender-specific differences and whether forearm composition contributes to such differences. RESULTS: Peak reactive hyperaemic flow as well as 1-min-flow debt repayment (measured by venous occlusion plethysmography) were significantly higher in male than in female study participants. This difference was explained to > 60% by gender-specific differences in forearm relative muscle mass (as determined by magnetic resonance imaging). The half-life of the reactive hyperaemic response, on the other hand, was not different between men and women and did not show an association with forearm muscle. CONCLUSION: Our results demonstrate that forearm composition must be considered if peak reactive hyperaemic or flow debt repayment is used as a target, and that dynamic measurements of the reactive hyperaemic process are more suitable to describe the function of resistance arteries than single-point observations.

Adipose Tissue

[Effect of fat distribution on risk].

About 10 years ago the WHO defined obesity as a separate disease whereas in Austria until now it is often regarded as a cosmetical problem only. Many diseases like those of joints and spine are correlated to the body weight and the body mass index (BMI), but macrovascular events (cardiovascular and cerebrovascular) and early death are closer associated with the waist to hip ratio (WHR), indicating an abdominal, android fat distribution. This fat distribution tends toward higher insulin levels, dys- and hyperlipidemia and disturbances in glucose metabolism which can in part explain these associations in the light of the metabolic syndrome. In conclusion, there is no healthy overweight, but not all overweight patients share the same risk.

Adipose Tissue

[Reduction of obesity and improvement in metabolic parameters by inhibition of intestinal lipases: current results with orlistat].

Until recently, obesity did not play a major role in considerations of physicians and public health authorities. The impact of health-threatening overweight was so far considered only as a risk factor for various other serious illnesses, such as hypertension, diabetes mellitus, hyperuricemia, elevated blood lipid levels and of vascular diseases of the heart, the brain and the kidneys. Recently however, obesity has been rated by the WHO as an unique disease, resulting in elevated morbidity and mortality. It is of constantly increasing importance because of the raising number of obese individuals in all industrial countries. In Austria an incidence of 8.5% of the adult population is estimated to be obese with a BMI > 30. Though the established concept for treatment of overweight consists of reduction of the caloric intake by diet, there is an obvious need for drugs making dieting easier acceptable to obese patients for prolonged periods. Orlistat is the first representative of a new class of such drugs, inhibiting intestinal acting lipase thus reducing the intestinal absorption of triglycerides; it contributes, therefore, to a reduced calorie intake. Preliminary results of treatment studies with Orlistat are presented, demonstrating its efficacy in inducing weight loss and improving metabolic parameters with tolerable intestinal side effects. After finalization of international studies, demonstrating efficacy and tolerability, orlistat has been registered in Austria in September 1998.

Adult

CAPRIE trial.

Explore the source record for details and available documents.

Aspirin

Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity.

The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.

Adult

[Effect of chromium yeast and chromium picolinate on body composition of obese, non-diabetic patients during and after a formula diet].

The objective of this study was to assess the effects of chromium yeast and chromium picolinate on lean body mass during and after weight reduction with a very-low-calorie diet. 36 obese (BMI 33.7 +/- 5.4 kg/m2), non-diabetic patients aged 45 +/- 6 years undergoing a 8-week very-low-calorie diet followed by a 18-week maintenance period. During the whole 26 week treatment period subjects received either placebo or chromium yeast (200 micrograms/d) or chromium-picolinate (200 micrograms/d) in a double-blind manner. Body weight was measured as BMI and body composition after calculation from skinfold thickness. As a result all three groups showed comparable weight loss after 8 and 26 weeks. Lean body mass was reduced in all groups after 8 weeks. However, after 26 weeks chromium picolinate supplemented subjects showed increased lean body mass (p < 0.029) whereas the other treatment groups still had reduced lean body mass. Chromium picolinate, but not chromium yeast, is able to increase lean body mass in obese patients in the maintenance period after a very-low-calorie diet without counteracting the weight loss achieved.

Adult

Increased prevalence of IgA-Chlamydia antibodies in NIDDM patients.

Chlamydia trachomatis oculogenital infection is a common disease in western societies. Despite the fact that diabetes is accompanied by increased risk for infections, no data on chlamydial infections in the non-insulin-dependent diabetic (NIDDM) patient exist. In our study Chlamydia antibodies were determined using an immunoperoxidase reaction in NIDDM patients (n = 79) and in a local nondiabetic control population (n = 125) which was randomly invited to a medical control visit without any preselection criteria. In total, 46% of diabetics and 55% of controls were IgG-Chlamydia antibody positive (ns). Using IgA-Chlamydia antibodies to define 'seroactive' chlamydial infection, 22% of NIDDM patients and 14% of controls were positive. Thus seroactive chlamydial infection of all patients with proven contact to Chlamydia (IgG-Chlamydia antibody positive) was 47% in diabetics versus 25% in controls, respectively (P < 0.05). Forming subgroups, significance was reached in females (52% vs. 32%, P < 0.05) only, but a similar trend was observed in males (36% vs. 21%, ns). Seroactivity was neither correlated with HbA1c nor with nephelometrically determined total serum immunoglobulins (IgG, IgA). Additionally we observed significantly elevated total IgM and IgA-levels in NIDDM patients whereas IgG-levels were comparable in both groups. In conclusion, seroactive chlamydial infections in subjects with proven contact to Chlamydia are more frequent in NIDDM patients than in nondiabetic controls. Additionally, higher IgM and IgA serum levels might indicate a higher susceptibility to active surface infections in NIDDM.

Adult

Involvement of the L-arginine-nitric oxide pathway in hyperglycaemia-induced coronary artery dysfunction of isolated guinea pig hearts.

The effects of hyperglycaemia and L-arginine on flow-induced reduction of coronary artery resistance were investigated in isolated guinea pig hearts. In the presence of indomethacin, hyperglycaemia caused an increase in flow-induced vasodilatation (P < 0.05). Hyperosmotic controls failed to mimic this effect. Addition of L-arginine strongly enhanced this effect. Addition of D-arginine failed to mimic the effects of L-arginine. The effect of L-arginine was abolished by co-administration of NG-nitro-L-arginine. In the absence of indomethacin and L-arginine, the effect of hyperglycaemia was blunted, suggesting the formation of vasoconstrictive prostanoids. Addition of L-arginine again resulted in a significant increase in flow-induced vasodilatation. In conclusion our results suggest that increased flow-induced vasodilatation under hyperglycaemic conditions depends on an adequate supply of L-arginine to maintain sufficient formation of nitric oxide.

Animals

Effects of treadmill exercise protocol with constant and ascending grade on levelling-off O2 uptake and VO2 max.

In order to investigate the effect of an exercise protocol on the levelling-off O2 uptake and VO2 max values, ten male subjects aged 28 +/- 5 yrs, height 1.8 +/- 0.05 m, body mass 76 +/- 6 kg performed two treadmill exercise protocols: 1) constant grade (CG) of 5%, with increasing running speed starting at 6 km.h-1 and increments of 2 km.h-1 every 3 minutes. 2) ascending grade (AG) starting at 0% and increments of 5% every 3 minutes, with constant running speed of 5 km.h-1. During each protocol oxygen uptake (VO2), pulmonary ventilation (VE), tidal volume (Vt), and breathing rate (BR) as well as blood lactate concentration (La) and heart rate (HR) were measured. In CG a levelling-off phenomenon of VO2 in all cases was observed. Aerobic capacity expressed as VO2 max in CG was 46.2 +/- 6.0 ml.min-1.kg-1. In contrast, VO2 max was 35% higher in AG (62.6 +/- 7.2 ml.min-1.kg-1). The behaviour of VO2 indicates a lower efficiency with increasing work load in AG as compared to CG. Regarding maximum performance it can be concluded that VO2 in CG seems to be limited by a mechanical or neuromuscular constraint on the depth of breathing, which is confirmed by a distinct flattening of Vt. The levelling-off of the VO2 in CG, something which is not observed in AG, can be explained plausibly this way.

Adult

Elevation of D-glucose impairs coronary artery autoregulation after slight reduction of coronary flow.

Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through D-glucose-induced alterations of intracellular metabolism. Therefore the effects of hyperglycaemia on coronary artery autoregulation under slight reduction of coronary flow were investigated in isolated perfused guinea-pig hearts. Under normal (10 mM) D-glucose concentrations coronary autoregulation was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL min-1) when L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF/NO) was available and formation of prostaglandines was intact. Under high (44 mM) D-glucose concentrations on the other hand, a sustained vasodilatation dependent on the availability of L-arginine was observed, when formation of prostaglandins was blocked. This effect was partially reduced in the presence of prostaglandin synthesis. Furthermore, the effect of L-arginine under both conditions could be antagonized by the L-arginine-analogue NG-nitro-L-arginine-methyl-ester (100 microM). Our results suggest that hyperglycaemia impairs coronary artery autoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the formation of vasodilatatory to vasoconstrictive prostaglandines was observed. These results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.

Animals

[Increased prevalence of serum IgA Chlamydia antibodies in obesity].

Obesity is metabolically related to diabetes type II. We have previously shown that seroactive (IgG- and IgA-Chlamydia antibody positive) chlamydial infection of asymptomatic patients is more frequent in type II diabetic patients than in nondiabetics, independent from metabolic control. Thus we investigated 119 nondiabetic patients (66 +/- 9 years, HbA1c < 6%) of our department for seroactive chlamydia infection using an immunoperoxidase reaction and compared the results to the anthropometric data. The prevalence of seroactive chlamydial infection was significantly (p < 0.05) higher in the considerably overweight patients with a BMI > 30 kg/m2, both when compared to lean patients (BMI < 24 kg/m2) and when compared to all those with BMI < 30 kg/m2. For slight to moderate obesity the prevalences were slightly (but not significantly) increased. Due to the fact that similar data were obtained for type II diabetic patients, an unknown relation to insulin resistance might be the underlying cause and should be further investigated.

Aged

[Effect of dexfenfluramine on eating behavior and body weight of obese patients: results of a field study of Isomeride in Austrian general practice].

In a multicenter study by 243 practicing physicians in Austria 819 severely obese subjects of both sexes without overt disease were encouraged to keep a calorie-restricted diet to reduce weight. After a run-in period of more than two weeks of dieting patients started taking 15 mg dexfenfluramine (Isomeride) twice daily for three month. While their weight was fairly stable during the run-in period progressive weight loss occurred during taking dexfenfluramine due to obvious changes in eating habits and appetite allowing to keep the reducing diet more strictly. Females lost 7.7 +/- 3.9 kg while obese men lost 9.32 +/- 4.6 kg. Laboratory tests obtained before starting dexfenfluramine and after 3 months at termination of medication showed blood glucose, cholesterol, LDL and triglycerides to decrease while HDL-cholesterol increased moderately. Dexfenfluramine was well tolerated by the majority of patients. Side effects such as fatigue, sedation, flatulence or diarrhea occurred in only 7.9% of the probands initially and dropped to 2.1% during the third month of the medication. It is concluded that Dexfenfluramine modifies eating habits and appetite thus making weight reducing diets easier acceptable and resulting in weight loss. It is suggested that Dexfenfluramine has a role in treatment regimes for morbid and refractory obesity.

Adult