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M Lambert

Publications and source records attributed to M Lambert.

At least 55 records · Page 3Linked to original sources
PubMed2004

Lack of gender effect on the pharmacokinetics and pharmacodynamics of dexamethasone in the camel after intravenous administration.

The pharmacokinetics and pharmacodynamics of dexamethasone were studied in six male and six female camels after a single intravenous dose (0.05 mgkg(-1) body weight) of dexamethasone. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for female and male camels, respectively (mean+/-SEM) were as follows: terminal elimination half-lives were 8.02+/-1.15 and 7.33+/-0.80 h, total body clearances were 95.5+/-16.0 and 124.5+/-11.9 ml h(-1) per kg, volumes of distribution at steady state were 0.72+/-0.08 and 0.87+/-0.14 litre kg(-1), and the volumes of the central compartment were 0.12+/-0.02 and 0.17+/-0.02 litre kg(-1). There was no significant difference in any pharmacokinetic parameter between female and male camels. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol, circulating lymphocytes and neutrophils numbers and were analysed using indirect pharmacokinetic/pharmacodynamic models. The estimated IC50 of dexamethasone for cortisol and lymphocytes for female and male camels were 3.74+/-0.99 and 2.28+/-1.09 and 2.63+/-0.71 and 2.41+/-0.79 ng ml(-1), respectively. The EC50 for neutrophils for female and male camels were 24.5+/-5.83 and 20.2+/-3.82 ng ml(-1), respectively. There was no significant difference in any pharmacodynamic parameter between female and male camels. Dexamethasone in urine could be detected for 4-5 days by enzyme-linked immunosorbent assay and for 3-4 days by liquid chromatography/mass spectrometry after an intravenous dose of 0.05 mg kg(-1) body weight.

Animals↗
PubMed2004

Pharmacokinetics and pharmacodynamics of dexamethasone after intravenous administration in camels: effect of dose.

The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg body weight. Dexamethasone showed dose-independent pharmacokinetics. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for the lowest intravenous dose (mean+/-SD) were as follows: terminal elimination half-life 8.17 +/- 1.79 h; total body clearance 100.7 +/- 52.1 (ml/h)/kg; volume of distribution at steady state 0.95 +/- 0.23 L/kg; and volume of the central compartment 0.22 +/- 0.07 L/kg. The extent of plasma protein binding was linear over the concentration range 5-100 ng/ml and averaged 75% +/- 2%. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol concentrations, numbers of circulating lymphocytes and neutrophils and plasma glucose concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic models. The cumulative systemic effect increased with dose for markers of pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and lymphocytes for the lowest dose were 3.74 +/- 2.44 and 5.58 +/- 8.37 ng/ml, respectively and the EC50 values for neutrophils and glucose were 45.8 +/- 36.9 and 1.17 +/- 0.71 ng/ml, respectively.

Animals↗
PubMed2004

Insulin resistance syndrome in a representative sample of children and adolescents from Quebec, Canada.

OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS: In all age-sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION: IRS is highly prevalent in youth, even among children as young as age 9 y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.

Adolescent↗
PubMed2004

The Delta>15 Kb deletion French Canadian founder mutation in familial hypercholesterolemia: rapid polymerase chain reaction-based diagnostic assay and prevalence in Quebec.

Approximately one in 500 individuals in Western population has autosomal dominant familial hypercholesterolemia due to mutations in the low-density lipoprotein receptor (LDLR) gene. Screening for these mutations is hampered by their large number, except in founder populations. We identified the breakpoint of the >15 kb deletion involving the LDLR gene promoter and exon 1, responsible for more than 60% of French Canadian hypercholesterolemia cases, as well as the breakpoint of the 5 kb deletion of exons 2 and 3 that accounts for an additional 5% of cases. Both deletions appear to be because of homologous recombination by unequal crossing-over between the left arms of Alu repeats. Using RepeatMasker, we determined that 55% of the LDLR gene is composed of Alu elements; thus, it is not surprising that most LDLR rearrangements involve at least one Alu. Furthermore, we developed a rapid polymerase chain reaction-based assay for the French Canadian-1 (>15 kb) and French Canadian-5 (5 kb) hypercholesterolemia alleles. Screening a representative population sample of 943 French Canadian youths whose LDL cholesterol levels were above the 50th percentile allowed us to estimate the prevalence of the >15 kb allele as 0.11% (95% confidence interval, 0.03-0.38).

Base Sequence↗
PubMed2004

Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical significance in a series of 74 patients.

The aim of this study is to determine prevalence, clinical significance of antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), anti-beta2GP1 and lupus anticoagulant (LA) in a cohort of 74 patients with primary Sjögren's syndrome (pSS) according to revised European criteria. aPL were found in 25 (34%) patients; IgG in 23 (12 had low titres, six moderate titres and five high titres) and IgM in five (three and two had respectively moderate and high titres). Eight (11%) patients were found to have LA; anti-beta2GP1 antibodies were detected only in three (4%) patients. Only two patients with LA, aPL and beta2GP1 had recurrent venous thrombosis. One patient with moderate titres of aPL exhibited recurrent spontaneous foetal losses. Peripheral neuropathies without cryoglobulinemia were more frequent in the aPL group. Other systemic involvements of pSS were the same in both groups with or without aPL. Patients with aPL have more concurrent immunological diseases such as thyroiditis and primary biliary cirrhosis and a higher prevalence of hypergammaglobulinemia (P < 0.05). Even if aPL prevalence reached 30% in pSS, titres were usually low, with a close correlation with hypergammaglobulinemia but not with antiphospholipid syndrome, which is related to positivity of both LA and aPL.

Adult↗
PubMed2003

Both insulin resistance and diabetes in Psammomys obesus upregulate the hepatic machinery involved in intracellular VLDL assembly.

OBJECTIVE: In the current study, we examined the mechanisms that regulate hepatic apolipoprotein B (apoB)-containing lipoprotein secretion in Psammomys obesus, a good animal model for the investigation of insulin resistance and diabetes. METHODS AND RESULTS: When fed chow ad libitum, 22% maintained normoglycemia and normoinsulinemia (group A), 33% exhibited normoglycemia and appreciable hyperinsulinemia (group B), and 45% developed overt diabetes (group C). Body weight gain, plasma free fatty acid elevation, hypertriglyceridemia, and hypercholesterolemia characterized groups B and C. Triton WR-1339 injection, at fasting, resulted in higher plasma VLDL-triglyceride and VLDL-apoB accumulation in groups B and C, suggesting increased VLDL production by the liver. Pulse-chase labeling experiments in cultured hepatocytes with [35S]methionine revealed reduced intracellular degradation and enhanced secretion of newly synthesized apoB in groups B and C. Concomitant with the raised triglyceride and cholesterol contents in the livers of groups B and C, there was an increase in lipogenesis and in the activity of microsomal triglyceride transfer protein, monoacylglycerol acyltransferase, and diacylglycerol transferase. Pretreatment of hepatocytes with proteasomal inhibitors eliminated the differences in apoB secretion among groups A, B, and C. CONCLUSIONS: Our data indicate that both insulin resistance and diabetes triggered the intracellular machinery involved in VLDL assembly and secretion.

Acetylcysteine↗
PubMed2003

Hyperlipidemic profiles during remission in childhood idiopathic nephrotic syndrome.

Hyperlipidemia, an important characteristic of idiopathic nephrotic syndrome in children (NS), is usually observed during the active phase of the disease and disappears with the resolution of the proteinuria. However, persisting lipid anomalies during remission have been reported in a few studies and raise the question of the later development of atherosclerosis. Plasma lipid profiles in 25 children with NS at remission, with or without active prednisone treatment, were compared with those of an age-matched population. The results indicate that plasma total and LDL-cholesterol levels were above the 95(th) percentile for age and sex in 12 of the 25 patients (48%) with 7 of them having apolipoprotein B and triglyceride concentrations above the 95(th) percentile. Moreover, frequently relapsing children were more likely to have abnormal lipid profile during the remission. We conclude that close monitoring of lipid levels during the remission of the NS especially in those with frequent relapses, is necessary to select the high-risk patients.

Adolescent↗
PubMed2003

[Antiphospholipid antibodies in HELLP syndrome: clinical and biological study in 68 women].

PURPOSE: Pregnancy complicated by the HELLP syndrome and antiphospholipid syndrome have rarely been reported. We report a study on anticardiolipin antibodies in HELLP syndrome. METHODS: Between March 1996 and September 1999, anticardiolipin antibodies were checked in all women with HELLP syndrome hospitalised in a maternity of the North of France. The women with positive anticardiolipin antibodies were seen month later in a internal medicine department. RESULTS: In the period 68 women with HELLP syndrome were checked for anticardiolipin antibodies. Apl were present in 9 patients (Incidence 42.8/1000 HELLP Year). They persisted after the accident only in 3 patients. Antiphospholipid syndrome was diagnosed in 2 patients, prevalence between the HELLP syndrome for the 42 month period was 0.03. CONCLUSIONS: HELLP syndrome may be a manifestation linked to the antiphospholipid syndrome and may revealed it.

Adult↗
PubMed2003

[Patient compliance with drug therapy in temporal arteritis].

OBJECTIVE: To evaluate patient compliance with drug therapy in temporal arteritis and to determine the characteristics of compliant or non-compliant patients. METHODS: Inpatients and outpatients from an Internal Medicine Unit were interviewed. Compliance with drug dosage and administration time was assessed with a questionnaire for the following drugs: glucocorticoids, calcium, vitamin D, diphosphonates (prevention of glucocorticoid-induced osteoporosis). RESULTS: Forty-nine patients were interviewed (61% female, mean age = 73.7 years). Glucocorticoids were prescribed to 96% of the patients, calcium and vitamin D to 86% and diphosphonates to 49%. Compliance with drug therapy was 87%, 60%, 68% and 51%, respectively, for all treatments. It was independent from the disease duration. Male were more compliant than female (P = 0.012). CONCLUSION: Half of the patients with temporal arteritis are non-compliant with drug therapy. The questionnaire is simple. It can be used in everyday clinical practice to study and improve patient compliance.

Aged↗
PubMed2003

Hyperadiponectinaemia in anorexia nervosa.

OBJECTIVE: Adiponectin (ApN) is a fat-derived hormone that enhances insulin sensitivity, controls body weight, prevents atherosclerosis and negatively regulates haematopoiesis and immune functions. In contrast to many proteins secreted by adipose tissue, the circulating level of ApN falls in obesity and insulin resistance states. The influence of starvation-induced depletion of fat stores on ApN concentrations is yet unknown. We therefore investigated plasma ApN in anorexia nervosa (AN). PATIENTS AND DESIGN: We measured plasma ApN in 26 female anorectic patients and examined its relationships to several anthropometric or metabolic parameters. Twenty-four age-matched healthy female controls (C) were also studied. RESULTS: Body mass index (BMI) and fat mass were markedly decreased in AN. However, plasma ApN levels were 30% higher in anorectic than in control subjects (P < 0.01), while a reverse pattern was observed for leptin concentrations. When normalized for fatness, ApN values almost doubled in AN. ApN levels were negatively correlated with BMI and fat mass (P < 0.05 in the combined population, AN + C). Insulin sensitivity tended to be 40% higher in AN (n = 7) than in C (n = 12) subjects, and plasma ApN levels were positively correlated with insulin sensitivity (P < 0.05 in AN + C subgroups). Total and low density lipoprotein (LDL)-cholesterol were higher, or tended to be higher, in AN, but there were no correlations between plasma ApN and plasma lipids. By contrast, ApN was related to the lipid profile, in a manner consistent with its antiatherogenic role, in healthy controls [i.e. negatively correlated with triglycerides, total and LDL-cholesterol and total/high density lipoprotein (HDL) cholesterol; P < 0.05 or less for each parameter]. In a multiple regression analysis, BMI and insulin sensitivity in AN were independent determinants for ApN levels, explaining up to approximately 80% of the variance in this measure. CONCLUSIONS: Plasma adiponectin levels are increased in anorexia nervosa. This may, at least in part, be due to the lack of negative feedback exerted by fat mass on adiponectin production and/or to enhanced insulin sensitivity. We speculate that hyperadiponectinaemia could, in turn, contribute to maintain a state of enhanced insulin sensitivity and possibly exacerbate haematological and infectious complications of anorexia nervosa.

Adiponectin↗
PubMed2003

EMG amplitude in maximal and submaximal exercise is dependent on signal capture rate.

This study analysed the effect of different electromyographic (EMG) capture rates during maximal voluntary contraction, submaximal and maximal dynamic cycling activity on EMG amplitude and signal characteristics. Ten healthy subjects participated in this study. Peak power output (PPO) and maximal isometric force output (MVC) were measured, followed by a progressive cycle ride on a cycle ergometer. Electromyographic (EMG) data were simultaneously captured during the MVC and cycling activities at frequencies of 32, 64, 128, 256, 512, 1024 and 1984 Hz. Significant differences in amplitude were found (p < 0.01) between MVC, submaximal (SUB) and maximal cycling activities (PWATT) for all capture rates. Asymptote values for IEMG amplitude occurred at EMG capture rates of 1604 +/- 235.6 Hz during MVC, 503.1 +/- 236.2 Hz during PWATT and 326.2 +/- 105.4 Hz during SUB cycling activity and were significantly different (p < 0.01). No significant differences were found for force/EMG ratios between PWATT and MVC at 1984 Hz capture rates (3.8 +/- 1.7 N/V vs 2.5 +/- 0.9 N/V) while significant differences occurred at 32 Hz capture rate (6.2 +/- 3.8 vs 16.0 +/- 8.0; p < 0.01). Low correlations were found between EMG activity captured at 1984 Hz during PWATT and lean thigh volume (r = 0.36) and MVC (r = 0.32). Asymptote values found on this study suggest that data captured below 326 Hz for SUB, 503 Hz for PWATT and 1604 Hz for MVC are not reliable. Therefore apparatus capturing EMG data at low frequencies from these values cannot be used for quantitative data analyses.

Adult↗
PubMed2003

Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin.

Adipose tissue secretes a large number of physiologically active peptides that often share structural properties with cytokines, and are therefore collectively referred to as "adipocytokines". Some of these are almost exclusively secreted by adipose tissue. Leptin, adiponectin and resistin are specific fat-derived hormones that affect fuel homeostasis and insulin action, and may also be involved in hematopoiesis and immune functions. Anorexia nervosa is characterized by chronic self-starvation and severe weight loss, mainly at the expense of adipose tissue. Starvation-induced depletion of fat stores is accompanied by alterations of circulating adipocytokines. Plasma leptin and likely resistin levels are decreased in anorectic patients, while plasma adiponectin levels are increased. These alterations may have potential repercussions in the pathophysiology of anorexia nervosa. Thus, low leptin and high adiponectin may separately or in concert contribute to altered hematopoiesis and immunity, enhanced insulin sensitivity, neuroendocrine disturbances or osteopenia in anorexia nervosa.

Adipocytes↗
PubMed2003

Subjective well-being and initial dysphoric reaction under antipsychotic drugs - concepts, measurement and clinical relevance.

Since the introduction of neuroleptics in 1952, many studies have examined objective aspects of efficacy and tolerability. Despite the fact that neuroleptic treatment should also improve the patient's subjective experiences, this outcome criterion has been neglected in the past. This is unfortunate, as subjective well-being with treatment appears to be strongly related to patients' readiness to take their medication. The few existing studies differ in methodology and are difficult to compare due to a number of weaknesses, including varying underlying concepts, used assessment scales, or small sample sizes. Negative subjective well-being may manifest itself throughout the entire neuroleptic treatment, even as early as in the first 48 hours after neuroleptic treatment starts (initial dysphoric reaction, IDR). The aetiology of reduced subjective well-being or IDR is not fully explained; neuroleptic side effects, especially affective, cognitive and motor adverse events, differential effects of varying psychopathology or biopsychosocial are factors in discussion. The clinical impression is characterised by symptoms as dysphoria/anhedonia, reduced vitality, and emotional indifference, which could have a negative impact on relevant clinical factors such as response or medication adherence, and therefore on outcome. With regard to pharmacological treatment, evidence suggests that atypical antipsychotics induce less negative subjective effects than conventional neuroleptics, and that various new-generation antipsychotics could be evaluated differently by patients. This article reviews existing literature in order to approach relevant questions for pharmacotherapy.

Antipsychotic Agents↗
PubMed2003

Elevated serum heat-shock protein 70 levels in patients with acute infection: use of an optimized enzyme-linked immunosorbent assay.

Heat-shock proteins (Hsps) are highly conserved throughout evolution and evoke great interest both in basic biology and in medicine. They are expressed in small quantities under normal conditions, and their expression can be strongly induced by several stressors. Although their action is basically intracellular, it is now obvious that these proteins can be released into the extracellular environment from viable cells. In this study, the human Hsp 70 serum concentrations were determined using an optimized, cost-effective enzyme-linked immunosorbent assay (ELISA). The average intra-assay variation was 6%, whereas the average interassay variation was 9%. The sensitivity of the assay was 10 ng/ml, and spiking experiments showed recoveries between 101 and 109%. As an application of the technique, we have investigated the serum levels of human Hsp 70 in patients with infection and in healthy subjects. Our data show significantly higher levels of Hsp 70 (P = 0.003) in patients compared to control subjects. Positive correlations were noticed between the serum levels of Hsp 70 and various markers of inflammation (IL-6; r = 0.579, P = 0.009, TNF-alpha; r = 0.552, P = 0.012, IL-10; r = 0.361, P = 0.002). We conclude that Hsp 70 is involved in inflammation of infectious origin. The interindividual variation in the serum concentration of Hsp 70 precludes the use of serum Hsp 70 levels to distinguish patients from healthy subjects.

Acute Disease↗