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Biomedical subjects

M Guillaume

Publications and source records attributed to M Guillaume.

At least 19 recordsLinked to original sources
PubMed2002

A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time.

BACKGROUND: Determination of clot lysis times on whole blood, diluted whole blood, plasma or plasma fraction has been used for many years to assess the overall activity of the fibrinolytic system. We designed a completely computerised semi-automatic 8-channel device for measurement and determination of fibrin clot lysis. The lysis time is evaluated by a mathematical analysis of the lysis curve and the results are expressed in minute (range: 5 to 9999). We have used this new device for Euglobulin Clot Lysis Time (ECLT) determination, which is the most common test used in laboratories to estimate plasma fibrinolytic capacity. RESULTS: The correlation between ECLT and manual method is very tight : R = 0,99; p < 10(-6). The efficiency scores of the method are <4% in intra-assay and <7% in inter-assay. It allows to achieve the tests on hyperlipaemic samples. This new device has been easily integrated in laboratory routine and allows to achieve several ECLT every day without disturbance of laboratory workflow. CONCLUSIONS: The routine use of this new device could be useful in various situations such as assessment in atherosclerosis and arteriosclerosis associated diseases, coagulation survey of liver transplantations, cardiovascular surgery or pharmacological research.It has already provided highly promising results in preliminary studies on the relation between fibrinolysis and cardiovascular risk factors.

Adult↗
PubMed2001

Study of the retention properties of warfarin enantiomers on a beta-cyclodextrin polymeric support.

High-performance liquid chromatography was used to study the retention properties of (R)- and (S)-warfarins on a silica support coated with a beta-cyclodextrin polymer. The influence of the methanol content of the acetate buffer eluent was investigated at pH 4. The measure of the variations of retention time with temperature enables one to determine the enthalpy and the entropy of adsorption. The plot of the two thermodynamic functions shows a minimum around 30% (v/v) methanol. At low methanol contents, the decrease of the hydrophobic interactions with increasing methanol content explains the decrease of the enthalpic and entropic terms. Above 40% (v/v) methanol, the decrease of the adsorption enthalpy absolute value is due to the solvation by the organic component. From the analysis of peak shape in mass-overload conditions, the column capacity toward each enantiomer was determined. A lower capacity was found toward (S)-warfarin, the more retained enantiomer. Peak shape analysis in mass-overload conditions was used to determine the adsorption isotherm. A Langmuir-type adsorption isotherm accounts well for the experimental data.

Adsorption↗
PubMed2001

Clinical tolerance and profile of cytokine induction in healthy volunteers following the simultaneous administration of ifn-alpha and the synthetic immunomodulator murabutide.

As the therapeutic use of interferon-alpha (IFN-alpha) is limited by a dose-dependent toxicity and variable efficacy, ways of improving the therapeutic index of the cytokine are being sought. Murabutide (N-acetyl muramyl-L-alanyl-D-glutamine-O-n-butyl-ester) (ISTAC Biotechnology, Lille, France) is a safe synthetic and clinically acceptable immunomodulator that enhances the biologic activities of IFN-alpha in different experimental models. We evaluated in healthy human volunteers tolerance of the coadministration of Murabutide with increasing doses of IFN-alpha. The simultaneous administration of the two drugs was well tolerated without any increased or prohibiting toxicity, and all recipients experienced side effects that were similar to those observed after the administration of IFN-alpha alone. We also profiled the serum levels of cytokines induced following coinjection of the two drugs. We mostly detected an induction of anti-inflammatory cytokines and of human immunodeficiency virus type 1 (HIV-1)-suppressive beta-chemokines, in the absence of release of key proinflammatory cytokines. Therefore, the simultaneous administration of Murabutide and IFN-alpha is well tolerated and does not lead to increased toxicity. In addition, the selectivity in the profile of cytokines and chemokines induced following the coadministration of Murabutide and IFN-alpha points to the potential use of this combination in the treatment of inflammatory diseases and chronic viral infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2000

A double-blind, placebo-controlled study to assess tolerability, pharmacokinetics and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.

AIMS: The objective of this study was to evaluate the tolerability of a novel dual ACE-NEP inhibitor, Z13752A, after the oral administration of rising single doses in healthy volunteers. This study was also a preliminarily investigation of Z13752A pharmacodynamics (PD) and pharmacokinetics (PK). METHODS: In this randomized, placebo-controlled, sequential study, two alternating panels of eight healthy male volunteers each (six subjects receiving the active treatment + two subjects receiving placebo) were treated with increasing oral doses of Z13752A: 10, 50, 200, and 600 mg were given to panel I and 20, 100, 400 and 800 mg were given to panel II. The study was double-blind relative to placebo or active treatment, and was open with respect to the dose levels. The same volunteer received placebo only once. RESULTS: Single oral doses of Z13752A, as high as 800 mg, were well tolerated. Only six mild-to-moderate adverse events mainly headache, were reported and appeared to be of little clinical relevance. After administration of 200, 400, 600 and 800 mg of Z13752A, a nonsignificant fall in diastolic blood pressure was detected, in both the standing and supine position. After single oral doses of Z13752A, ACE inhibition appeared to be significant at all the doses tested, linearly correlated with the dose and was almost complete at doses > or = 100-200 mg. NEP inhibition was indicated by elevation of ANP and cGMP plasma concentrations in almost all subjects. In the 200-800 mg dose range, Z13752A produced a 50-100% increase of plasma cGMP levels and a 50-80% elevation in urinary cGMP concentrations. Detectable plasma levels of Z13752A were found in all the treated subjects. Z13752A was well and rapidly absorbed, with peak concentrations reached approximately 2.5 h after administration. The mean apparent elimination half-life from plasma was approximately 12 h. The pharmacokinetics of Z13752A after single oral doses were characterized by low intersubject variability and appeared to be dose-independent. CONCLUSIONS: Z13752A showed a good single dose tolerability profile at doses up to 800 mg. The pharmacokinetic data indicate that Z13752A administered orally is rapidly absorbed and available to the systemic circulation in humans. The relatively slow clearance indicates that a once-a-day dose regimen could be considered for Z13752A.

Adult↗
PubMed2000

Differences in associations of familial and nutritional factors with serum lipids between boys and girls: the Luxembourg Child Study.

BACKGROUND: Sex differences in the effects of genetic and environmental factors on circulating lipids have been examined mainly in adults, in whom the influences of sex steroid hormones are well known. OBJECTIVE: Our objective was to determine the effect of sex on genetic and environmental influences on serum lipids in prepubertal boys and girls. DESIGN: Children aged 6-8, 8-10, and 10-12 y (n = 1028) were selected at random in the Belgian province of Luxembourg, a region in Europe with a high prevalence of risk factors for cardiovascular disease and diabetes. Blood glucose and serum cholesterol, triacylglycerol, and insulin concentrations were measured, and anthropometric data and blood pressure were recorded. Familial data were obtained from standardized questionnaires. Nutritional status was obtained from a 3-d record. Participation was 70.3% of the primary cohort. RESULTS: Cholesterol, triacylglycerol, and insulin values were among the highest recorded in studies of children. In girls, cholesterol correlated positively with the energy density of intake of saturated fat (r = 0.13, P = 0.001), cholesterol (r = 0.11, P = 0.006), and protein (r = 0.12, P = 0.007) and negatively with the ratio of polyunsaturated to saturated fat intake (r = -0.14, P = 0.001) and the energy density of carbohydrate intake (r = -0.11, P = 0.019). In boys, no such relations were found. Triacylglycerol was not significantly related to nutritional factors. Consistent, independent relations were found between reported elevated cholesterol concentrations in the parental and grandparental generation and cholesterol (r = 0.101, P = 0.011) and triacylglycerol (r = 0.09, P = 0.03) in boys. No such associations were found in girls. CONCLUSION: Environmental and genetic factors may have different effects on serum cholesterol in girls and boys.

Age Distribution↗
PubMed2000

Optimal multichannel estimation of the location of a target with nonoverlapping noise.

We propose a new algorithm for estimating the location of an object in multichannel images when the noise is spatially disjointed from (nonoverlapping with) the target. This algorithm is optimal for nonoverlapping noise and for multichannel images in the maximum-likelihood sense. We consider the case in which the statistical parameters of the input scene are unknown and are estimated by observation. We assess the results for simulated images with white and Gaussian background, for a large scale of variances of the background noise, and different values of the contrast in the scene. We compare the results of this algorithm with the results obtained with two other algorithms, the optimal algorithm for monochannel nonoverlapping noise and the optimal algorithm for multichannel additive noise, and we show that in both cases improvement can be obtained. We show the efficiency of the estimation for real input scenes when the background noise is correlated clutter noise. This algorithm has the same complexity as correlation, and the improvement is obtained with no more calculation cost than with classic methods.

Journal Article↗
PubMed1999

Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch.

BACKGROUND: A new estradiol transdermal patch was developed for a once weekly application, with the aim to achieve an optimum practicability and to improve long-term compliance with estrogen replacement therapy. The pharmacokinetics of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during a 7-day application of the new patch is reported in this publication. METHODS: Unconjugated estradiol and estrone were assayed in plasma in a three-way crossover study on 18 postmenopausal women during and after a 7-day application of 3 strengths of the new patch, with daily release rates of 25, 50 and 75 micrograms of estradiol. RESULTS: During the 7-day application of the transdermal patches the concentration in plasma of unconjugated estradiol increased from less than 5 pg/ml, typical of postmenopause, to average concentrations of 26, 49 and 66 pg/ml under the patches with the release rates of 25, 50 and 75 micrograms/day of estradiol, respectively. The increases were linearly related and proportional to the strength of the patches. Upon removal of the patches, the estradiol concentrations returned to the basal postmenopausal values in 8-24 h. Retarded with regard to estradiol, there was also an increase of unconjugated estrone, from basal concentrations of 24 pg/ml to average concentrations of 39, 54 and 62 pg/ml, respectively. Estrone returned to its basal concentrations 24-48 h after removal of the patches. The estradiol/estrone ratio from the low pre-treatment values of 0.15-0.21 typical of postmenopause increased to average values of 0.51, 0.92 and respectively 1.09 during the application of the patches with the three strengths. The ratios are in the range of those of unconjugated hormones during the fertile age of women. The patches were well tolerated by the skin, with rare mild and transient reactions that disappeared spontaneously and did not cause interruption of treatment. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol found especially under the application of the two higher strengths, i.e. with release of 50 and 75 micrograms/day of estradiol. CONCLUSIONS: The effective pharmacokinetic performance over the 7-day application, combined with the good general and local tolerability and the need to apply the patches only once weekly confer to the new patches a favorable practicability for the long-term estrogen replacement therapy needed to control the most severe postmenopausal disorders.

Administration, Cutaneous↗
PubMed1999

Socioeconomic and psychosocial conditions of parents and cardiovascular risk factors in their children: the Belgian Luxembourg Child Study III.

Socioeconomic and psychosocial handicaps are often associated with disease. There is a large body of information on adults on such relationships, but data are sparse on children. In a cohort of 1028 boys and girls, selected at random from school classes in Province de Luxembourg, a mainly rural area of Belgium, these problems were analysed in age strata of 6-8, 8-10, 10-12 years. Participation rate was 71%. Information was collected from questionnaires,. Anthropometric variables, blood pressure and glucose as well as cholesterol, triglycerides and insulin were measured in the children and related to the psychosocial and socioeconomic factors, organized into rural, psychosocial, socioeconomic and alcohol/smoking clusters of observations. Rural: Duration of living in the area of the child and parents correlated with diastolic blood pressure, particularly in boys (p < 0.01). Psychosocial: Housewives (p = 0.002) and their children (p = 0.002) had higher body mass indexes (BMI) than other mothers and their children. Sons of housewives also had higher blood pressure (systolic, p = 0.0007, diastolic, p = 0.007). Socioeconomic: Socioeconomic factors of parents (profession, unemployment) played relatively minor roles. Alcohol/smoking: Alcohol consumption was related to skinfold thickness in boys (p = 0.022), but not in girls. Girls, but not boys, with smoking parents had higher BMI (p=0.014). Multiple regression analyses suggested that psychosocial factors, such as housewives as mothers of large families, may be important for associations with cardiovascular risk factors in their children. There were apparent differences in the findings between girls and boys, suggesting that boys are more vulnerable to the impacts of the factors analysed.

Adult↗
PubMed1999

Defining obesity in childhood: current practice2.

A survey of information from 26 countries was performed to examine the methods, cutoff points, and reference materials used to define obesity in childhood and adolescence. The body mass index (in kg/m2) was used frequently, as well as several other methods. Reference materials used were often based on national surveys, although reference data from other countries were sometimes used. The data presented was often insufficient to judge the representativeness of the reference material. Cutoff points varied considerably. Available data allow neither a meaningful international estimation of the prevalence of obesity nor international comparisons. Although associated with considerable problems, this situation can be improved with an international consensus which, by necessity, will be riddled with uncertainties and compromises.

Journal Article↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗