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Biomedical subjects

M Guillaume

Publications and source records attributed to M Guillaume.

At least 19 recordsLinked to original sources

[Subcutaneous abcesses due to Mycobacterium avium due to a reconstitution syndrome in AIDS patients].

Clinical presentations of opportunistic infections in AIDS patients have dramatically changed since the introduction of HAART. The immune reconstitution syndrome (IRS) is typical of this change. The authors discuss the case of an AIDS female patient presenting with subcutaneous abcesses and abdominal lymph node enlargement due to Mycobacterium avium and occurring 10 weeks after initiation of HAART. This was related to the exacerbation of immune response against the bacteria that had previously infected the patient. Many cases of IRS involving M. avium have now been described, but cutaneous localisations remain infrequent. The treatment consists in HAART continuation associated with anti mycobacterial antibiotics and possibly anti inflammatory drugs.

AIDS-Related Opportunistic Infections↗

[Pathophysiology of Behcet's disease].

SUBJECT: Pathophysiology of Behçet's disease (BD) is complex. Recent experimental data shed new light on the mechanisms leading to organ lesions. MAIN ISSUES: Neutrophils and cytotoxic lymphocytes are now recognized as key effector cells in BD. Genetic susceptibility, environmental factors (virus and/or bacterial infections), inflammatory response abnormalities (heat shock proteins, dysregulated NO production) and abnormal immune response play also a major role in BD pathogeny. PERSPECTIVES: Better understanding of the BD pathophysiology will allow the development of new therapies more specific of BD.

Behcet Syndrome↗

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women.

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.

Aged↗

Operating characteristics of the Finapress system to predict elevated left ventricular filling pressure.

BACKGROUND: Dyspnea is a common symptom and can be caused by many different conditions. The detection of congestive heart failure (CHF) is sometimes difficult. HYPOTHESIS: The pulse amplitude ratio (PAR) measured by the Finapress procedure during a Valsalva maneuver can detect elevated left ventricular end-diastolic pressure (LVEDP) accurately over a wide range of values. METHODS: Comparison of the estimated LVEDP by PAR with the invasively measured LVEDP before and after ventriculography during coronography was made in 101 consecutive stable patients referred for chest pain and/or chronic dyspnea. RESULTS: A significant correlation was found between the catheter-measured LVEDP (range 3-40 mmHg) and the PAR (R2 = 0.70, p < 0.001). The receiver operator characteristics (ROC) of the PAR to detect an LVEDP > 15 mmHg can be considered to be excellent, with an area under the ROC curve achieving 0.92 (95% confidence interval [CI] 0.87-0.96; p < 0.001). A PAR of > 0.675 predicted the presence of an LVEDP > 15 mmHg with a sensitivity of 0.865 (95% CI 0.780-0.926) and a specificity of 0.847 (95% CI 0.730-0.928). The positive and negative LRs were 5.70 and 0.16, respectively. CONCLUSIONS: The observed likelihood ratios confirm that the PAR determined by the Finapress procedure may be a useful bedside diagnostic tool in patients with cardiac conditions.

Adult↗

Lumiracoxib does not affect the ex vivo antiplatelet aggregation activity of low-dose aspirin in healthy subjects.

This randomized, double-blind, placebo-controlled study evaluated the pharmacodynamic effects of concomitant low-dose aspirin and lumiracoxib in healthy subjects. Participants received lumiracoxib 400 mg once daily (n = 14) or placebo (n = 14) for 11 days, with concomitant low-dose aspirin (75 mg once daily) from days 5 to 11. Ex vivo pharmacodynamic assessments included assays of platelet aggregation and urinary thromboxane and prostacyclin metabolite profile. Arachidonic acid-stimulated platelet aggregation was reduced from 76.3% on day 4 to 4.8% on day 11 in the placebo group and from 75.8% on day 4 to 5.1% on day 11 in the lumiracoxib group. Collagen-induced platelet aggregation was reduced from 77.5% on day 4 to 52.8% on day 11 in the placebo group and from 79.5% on day 4 to 55.9% on day 11 in the lumiracoxib group. Urinary thromboxane and prostacyclin were unaffected by lumiracoxib. In conclusion, concomitant lumiracoxib did not interfere with the cyclooxygenase-1-mediated antiplatelet effects of low-dose aspirin.

Adolescent↗

Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation.

The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxidation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted by endothelial cells, circulating LDL and MPO in close interaction, constitutes a synergic mechanism for the genesis of Mox-LDL.

Cell Membrane↗

Surgical repair for aortic valve fibro-elastoma: a case report.

Valvular cardiac tumours are rare but account for a high prevalence of stroke or sudden death. We report a case of an incidental finding on echocardiographic screening of a 65-year-old man. He was admitted to the emergency department for an episode of sinus bradycardia due to B-blocker overdose. Diagnosis of fibro-elastoma was rapidly suspected and the patient underwent surgery in order to prevent embolization. Epidemiology, diagnosis and treatment are discussed.

Aged↗

Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers.

The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated. Ten forearm blisters were formed (n = 12) 12 h prior to the last dose. Concentrations of ertapenem in blister fluid exceeded 4 micro g/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval. The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗