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Biomedical subjects

M Guillaume

Publications and source records attributed to M Guillaume.

At least 37 records · Page 2Linked to original sources

Obesity and nutrition in children. The Belgian Luxembourg Child Study IV.

OBJECTIVE: To analyse the association between nutritional and familial factors and obesity in boys and girls. DESIGN: Randomized, cross-sectional population study. SETTING: Province de Luxembourg, Belgium. SUBJECTS: One thousand and twenty-eight boys and girls in age strata 6-8, 8-10 and 10-12 y, comprising 70.3% of primary cohort. METHODS: Examinations included anthropometric measurements and questionnaires covering familial, socioeconomic and psychosocial factors. A three day dietary record was obtained in 955 children. This was analysed in relation to the anthropometric data. RESULTS: In comparison with similar studies from other regions and recommended allowances, the intakes of total energy, fat, particularly saturated fat and cholesterol, were high, while consumption of carbohydrate and fiber was low, as well as the polyunsaturated/saturated ratio of fat. Total energy intake showed no or weakly significant correlations with anthropometric factors. However, total fat (P=0.045) and saturated fat (P=0.0005) intake showed consistent positive correlations with body mass index (BMI, kg/m2) and skinfold thickness, with corresponding negative relationships to carbohydrate intake (P=0.034) in boys. Such relationships were also found when calculated as energy density. These associations were not statistically significant in girls. The high fat, low carbohydrate pattern of the nutritional status seemed to be more pronounced in families where the father had a low level of education (lipids, boys, P=0.0007), and where both parents were obese (saturated fat, boys, P=0.023), suggesting involvement of socioeconomic and familial factors. CONCLUSION: The lack of correlation between factors indicating obesity and total energy intake suggests that the positive energy balance causing obesity is due mainly to a low energy output. However, since energy intake measurements are imprecise, overeating can not be excluded, particularly since elevated consumption of food with high contents of fat, found in these children seems to be poorly regulated.

Belgium↗

Physical activity, obesity, and cardiovascular risk factors in children. The Belgian Luxembourg Child Study II.

Physical activity was measured in relation to cardiovascular (CV) risk factors in a randomly selected population of 1028 children from Province de Luxembourg in Belgium, a mainly rural area with a high prevalence of such risk factors among adults and children. Physical activity was estimated as participation in sport activities, a major indicator of leisure-time physical activity in schoolchildren, and physical inactivity was estimated as frequency and duration of television (TV) watching. Boys participated more frequently in sport activities than girls did (p = 0.001). A majority of the children watched TV daily. After age adjustment, bodyweight (girls, p < 0.012; boys, p < 0.027) and, in boys, body mass index (BMI) (p < 0.039) were related to days per week of TV watching. No significant relationships with other CV risk factors remained after adjustments for BMI. In analyses of independent contributions of age, TV watching, and sports activity on CV risk factors, age showed highly significant relationships. In boys, TV showed relationships with BMI (p < 0.04) and (borderline) with systolic blood pressure, independent of age and sports activity, whereas the latter was significantly related to subscapular skinfold (p < 0.04) and (borderline) with triceps skinfold and cholesterol. In girls, no significant independent contributions to risk factor associations were found. The father's education was directly associated with sports activities, whereas the mother being a housewife showed negative relationships to physical activity and positive to TV watching in their children, suggesting socioeconomic influence on the activity patterns of children. Furthermore, registrations suggested less physical activity in the most rural part of the area. It is concluded that children in this mainly rural area watch TV frequently. In boys, physical inactivity, measured both as TV watching and as registrations of sports activities, contributes independently to body fat mass. In girls, no contribution or weaker contributions of physical inactivity were found. This suggests that contributory factors leading to obesity might be different in girls and boys.

Belgium↗

Pharmacokinetics of estradiol and of estrone during application of three strengths of an estradiol transdermal patch with active matrix.

The pharmacokinetic pattern of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during and after application of three strengths of a new transdermal estradiol patch (Dermestril) with active matrix was investigated in a cross-over study in 24 women in natural or surgical menopause. Free estradiol and estrone were assayed by GC-MS on plasma samples obtained during a 4-day application on the upper buttocks of the patches with 3 strengths and release rates of 25, 50 and 100 micrograms/day estradiol. The estradiol concentrations in plasma increased from 0-10 pg/ml typical of menopause to average concentrations of 23, 40 and 79 pg/ml during the application of the new estradiol transdermal patches with the three strengths. The concentrations of estradiol are in the range of those during the early follicular phase in women in fertile age. The increases were linearly related with the strength of the patches. Upon removal of the patches the estradiol concentrations returned to the basal low values in 8-24 h. Retarded with regard to estradiol, there was also an increase of estrone, from basal average concentrations of 22-32 pg/ml up to 31, 39 and 60 pg/ml. The increase of estrone was less pronounced than that of estradiol. Also estrone returned to its basal concentrations 24 h after removal of the patches. The estradiol/ estrone ratio from very low values typical of postmenopause increased to values of about 1, i.e. in the range of those found during the fertile age of woman. The adhesion of the patches was satisfying, provided that direct rough frictions were avoided. The patches were locally well tolerated, with rare mild and transient irritating effects on the skin. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol (headache, mastodynia and pelvic heaviness) which in the practical use can be easily avoided by the application of patches of lower strength.

Administration, Cutaneous↗

Cardiovascular risk factors in children from the Belgian province of Luxembourg. The Belgian Luxembourg Child Study.

The Province of Luxembourg is an area in Belgium with a high prevalence of risk factors for cardiovascular disease and non-insulin-dependent diabetes mellitus among adults. In the present study, children in the age groups 6-8, 8-10, and 10-12 years were selected at random from school classes (n = 1,028), with a participation rate of 70.3%. Anthropometric factors, blood pressure, and fasting blood glucose, plasma cholesterol, triglyceride, and insulin levels were measured in 1992. All anthropometric and metabolic variables increased with age, except for waist: hip circumference ratio in boys and cholesterol in girls. In the oldest group, girls who had passed menarche were taller and heavier and had greater skinfold, body mass index, insulin, and systolic blood pressure values but lower total cholesterol levels and waist: hip ratios than girls who had not passed menarche. Boys had lower skinfolds and higher waist: hip ratios than girls in all age groups, and were significantly shorter and lighter in the oldest age group. There was no difference in body mass index between the two sexes. Girls had higher triglyceride and insulin levels in the 10- to 12-year age group, lower blood glucose values in the 8-10 and 10-12 age groups, and lower diastolic blood pressures in the 8-10 age group. Obesity, blood glucose, triglycerides, insulin, and blood pressure were highly interrelated. Cholesterol, triglycerides, insulin, and blood pressure values were all among the highest of values previously reported in other studies. The deciles of body mass index above 50 appeared to be particularly elevated, suggesting that obesity, when present, was pronounced in this population of children. These findings suggest an accumulation of genetic susceptibility to cardiovascular disease and non-insulin-dependent diabetes mellitus in this stable, ethnically homogeneous, and rather isolated part of continental Europe.

Anthropometry↗

Evaluation of tolerability and antibody response after recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and a single dose of recombinant hepatitis B vaccine.

Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) has been shown to augment antigen presentation by macrophages and dendritic cells in vitro, and to increase antibody responses to injected antigens in experimental animals. To evaluate the usefulness of rhGM-CSF as a vaccine adjuvant, 108 healthy volunteers were randomly assigned to receive an injection of rhGM-CSF (n = 81) or placebo (control group; n = 27), followed by an injection with recombinant hepatitis B vaccine into the same site. During the study period of 28 days, protective antibody titers to hepatitis surface antigen (anti-HBs10 mIU ml-1) were observed in 11 of 81 subjects receiving rhGM-CSF, but in none of the controls (P = 0.035). Injections were well tolerated. A single i.m. or s.c. injection of 20-40 micrograms of rhGM-CSF significantly enhances antibody responses when given at the same site as recombinant hepatitis B vaccination.

Adjuvants, Immunologic↗

Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients.

OBJECTIVE: To evaluate the effect of tracheal gas insufflation (TGI) in spontaneously breathing, intubated patients with chronic obstructive pulmonary disease (COPD) undergoing weaning from the mechanical ventilation. DESIGN: A prospective study in humans. SETTING: Polyvalent intensive care unit (14-bed ICU) in a 700-bed general university hospital. PATIENTS: Twelve patients with chronic obstructive pulmonary disease (COPD) who required intubation and mechanical ventilation were studied. All patients met standard criteria for weaning from mechanical ventilation. Seven patients (group 1) had been transorally intubated during episodes of acute respiratory failure. Five patients, all men (group 2), had previously undergone tracheostomy and had a transtracheal tube in place. INTERVENTIONS: Intratracheal, humidified, O2-mixture insufflation (TGI) was given via a catheter placed in distal or proximal position. Gas delivered through the intratracheal catheter was blended to match the fractional of inspired gas through the endotracheal tube. Continuous flows of 3 and 6 l/min in randomized order were used in each catheter position. Prior to data collection at each stage, an equilibration period of at least 30 min was observed, and thereafter blood gases were analyzed every 5 min. A new steady state was assumed to have been established when values of both PaCO2 and V CO2 changed by less than 5% between adjacent measurements. The last values of blood gases were taken as representative. The new steady state was confirmed within 35-50 min. Baseline measurements with zero Vcath were made at the beginning and end of the experiment. RESULTS: This study shows that VT, MV, PaCO2, and VD/VT are reduced in a flow-dependent manner when gas is delivered through an oral-tracheal tube (group 1). The distal catheter position was more effective than the proximal one. In contrast, when gas was delivered through tracheostomy (group 2), TGI was ineffective in the proximal position and less effective than in group 1 in distal position. CONCLUSION: Under the experimental conditions, tracheal gas insufflation decreased dead space, increased alveolar ventilation and possibly reduced work of breathing. From the preliminary data reported here, we believe that TGI may help patients experiencing difficulty during weaning.

Acute Disease↗

Effects of felbamate on the pharmacokinetics of phenobarbital.

The effects of felbamate on the pharmacokinetics of phenobarbital and one of its main metabolites, parahydroxyphenobarbital, were assessed in a parallel-group, placebo-controlled, double-blind study, in 24 healthy volunteers. Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased phenobarbital values for area under the plasma concentration-time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S-mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that phenobarbital hydroxylation is mediated in part by this isozyme.

Adult↗

Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

Adult↗

Familial trends of obesity through three generations: the Belgian-Luxembourg child study.

Province de Luxembourg in Belgium is an area with clustering of obesity as well as other risk factors for cardiovascular diseases and non-insulin dependent diabetes mellitus. In this study, obesity was studied in a total of 1028 boys and girls in age-strata 6-8, 8-10, 10-12 years, selected at random from school classes. Participation rate was about 70%. Non-participants did not differ from participants in comparisons of school records of height and weight. Furthermore, information on birth weight, parents' height and weight was collected, as well as reported problems of obesity in grandparents. The results show a high prevalence of pronounced obesity in these children. BMIs were strongly correlated between the children and both parents. Furthermore, grandparents' obesity problems were related to the BMI of parents, and also to obesity indices in the children. Birth weights were related to current BMI of the children (in girls only for the youngest age-group), and to their mothers' BMI. It was concluded that obesity is prevalent in this area and can be traced through three generations, and seems to be discoverable already at birth. Energy intake is high and physical activity level is low in these children. However, statistical analyses suggest that familial factors exert a greater impact than environmental factors on the BMI of the children. These results, as well as the wide-spread, consistent familial clustering of obesity, traceable already at birth, suggest influence of strong genetic traits for obesity in this population.

Adolescent↗

Synthesis and biodistribution of [5-131I]iodotropapride: a potential D2 dopamine receptor imaging agent.

[5-131I]Iodotropapride is a benzamidic compound which displays high affinity and selectivity for dopaminergic receptors. It was prepared from the corresponding brominated compound by a nucleophilic substitution with [131I]iodine (t1/2 = 8.02 days, E gamma = 364 keV) based on the use of Cu(I) as catalyst and high specific activity of [131I]NaI. After i.v. injection in rats the tracer crosses the blood-brain barrier (0.42 +/- 0.06% of injected dose in the total brain) and demonstrates a high affinity binding to the striatum. The striatum-to-cerebellum ratio increases with time and reaches values of 9 and 22 at 30 and 120 min after injection, respectively. This specific uptake in the striatum is saturable and can be blocked by pretreatment with different D2 antagonists. When labeled with 123I (t1/2 = 13 h, E1 = 159 keV), the corresponding [123I]iodotropapride may be useful for the investigation of the D2 dopamine receptors in humans with single photon emission computer tomography (SPECT).

Animals↗

Myocardial kinetics of potassium-38 in humans and comparison with copper-62-PTSM.

UNLABELLED: The aim of this study was to define the kinetics of 38K and its suitability to evaluate myocardial blood flow at rest and during pharmacological vasodilation in normal subjects. Potassium-38's kinetic characteristics were also compared to those of a 62Cu-pyruvaldehyde bis(n4-methyl-thio-semicarbazone) copper (II) (PTSM) flow tracer. METHODS: Potassium-38 and 62Cu-PTSM were injected at rest and after pharmacological vasodilation in six healthy volunteers. Dynamic PET acquisition was performed over 20 min and myocardial tracer retention calculated. Homogeneity of regional myocardial tracer distribution was also evaluated. RESULTS: High image quality of the heart was observed at rest and after dipyridamole with both tracers. Potassium-38 demonstrated prolonged myocardial retention with minimal lung and liver accumulation. In contrast to 38K, 62Cu-PTSM demonstrated high liver uptake which may hinder observation of the inferior wall of the myocardium. Copper-62-PTSM dipyridamole-to-rest retention ratio was 1.49. CONCLUSIONS: Potassium-38 and 62Cu-PTSM display suitable kinetics for the qualitative evaluation of blood flow and flow reserve in the human heart. Compared to 62Cu-PTSM, potassium-38, which does not show high liver uptake, may more accurately estimate blood flow in the inferior wall of the heart. However, accurate quantification of myocardial blood flow using 38K or 62Cu-PTSM retention appears to be limited to decreasing retention fraction at hyperhemic states.

Adult↗

Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract.

Horse chestnut extract (HCE), containing 70% escin, is the main active component of Veinotonyl 75. The aim of this work was to investigate pharmacological properties attempting to elucidate the efficacy of HCE in chronic venous insufficiency. Veinotonic and lymphagogue properties: HCE dose dependently contracts the canine saphenous isolated vein (cumulative doses 5 x 10(-8) to 5 x 10(-4) g/ml). Its action lasts more than 5 h. In the perfused canine saphenous vein, HCE (25-50 mg in bolus) increases the venous pressure of the normal vein and the pathological vein stenosed 8 days before, and the contractile response to noradrenaline is significantly potentiated. Moreover, during the perfusion in inverse direction of the blood stream, a clear contracting effect on the valves is also obtained with HCE. In the anaesthetized dog, HCE in situ improves the femoral vein compliance and opposes the venous distension obtained during clamping in a carotido-femoral perfusion with constant flow. In other respects, HCE significantly increases femoral venous pressure and flow, together with thoracic lymphatic flow, while respecting the arterial parameters (2.5 and 5 mg/kg i.v.). Vasculotropic action: HCE dose dependently diminishes the cutaneous capillary hyperpermeability induced either by injections of phlogistic agents as histamine and serotonin in the rat (100 to 400 mg/kg p.o.), or by an irritative agent (chloroform) application in the rabbit (50 to 300 mg/kg p.o. and 2.5 to 5 mg/kg i.v.). It significantly increases the vascular resistance in the guinea pig fed a scorbutigenic diet as measured by the petechia method (50 to 400 mg/kg p.o.). Antiedema and antiinflammatory properties: HCE decreases the formation of edemas induced in the rat's hind paw, one of lymphatic origin, the other of inflammatory origin (200 to 400 mg/kg p.o.). In an experimental model of pleurisy in the rat HCE suppresses plasmatic extravasation and leucocytes emigration into the pleural cavity (200 to 400 mg/kg p.o.; 1 to 10 mg/kg i.v.). It decreases the connective tissue formation in the subchronic model of inflammatory granuloma in the rat (400 mg/kg p.o. and 5-10 mg/kg s.c.). Antiradical mechanism of action both in vitro and in vivo: HCE dose dependently inhibits both enzymatic and non-enzymatic in vitro lipid peroxidation (5 x 10(-6) to 5 x 10(-4) g/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography.

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 +/- 4) to exercise (47 +/- 13 clearance units; p less than 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 +/- 6) to exercise (33 less than or equal to 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 +/- 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 +/- 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Aged↗