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Biomedical subjects

E Bruckert

Publications and source records attributed to E Bruckert.

At least 19 recordsLinked to original sources
PubMed2004

[The interest of cholesterol levels in young children. Study in a population of 4,697 children aged 4].

INTRODUCTION: There is a need to dispose of normal cholesterol levels in young children. In view of the paucity of such data in France, we analysed the results of screening conducted in children. METHOD: We analysed the cholesterol levels of 4697 children, with a mean age of 4.3 years, attending a medical check-up in a Child Health Unit in a National Health Scheme centre in Paris. All the children were recruited consecutively during the year 2002. RESULTS: The mean cholesterol level was of 4.4 mmol/L +/- 0.75. We detected a slight gender-related variation (the mean in girls and boys were of 4.5 +/- 0.76 and 4.4 +/- 0.74 respectively). The 95 percentile in girls and boys were 5.7 and 5.6 mmol/L, respectively. DISCUSSION: For the first time in France, we now have access to data on normal cholesterol levels in a large cohort of 4 year-old children. Screening for hypercholesterolaemia in children provides the opportunity to discuss dietary counselling.

Child, Preschool↗
PubMed2004

Adrenal insufficiency after adrenal hemorrhage.

Acute adrenal hemorrhage (AAH) is an extremely rare disorder, especially in adults, and may be difficult to diagnose because of its nonspecific presentation. We report a case of AAH following a sepsis, resulting in persistant adrenal insufficiency contrasting with the radiologic normalisation of the adrenals on computed tomography (CT) scan imaging.

Acute Disease↗
PubMed2004

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP.

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.

Biomarkers↗
PubMed2004

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women.

OBJECTIVE: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.

Acute-Phase Proteins↗
PubMed2003

[The growth hormone/insulin-like growth factor axis. What is its role in the atherosclerotic process?].

UNLABELLED: GROWTH HORMONE AND ATHEROSCLEROSIS: Adult-onset growth hormone (GH) deficiency is associated with an increase in cardiovascular morbidity and mortality. MECHANISMS: Other than classical risk factors, such as dyslipidemia, a direct interaction between the activity of the GH/IGF-1 axis and the endothelium also plays a part. It is possible that the modulating effect of IGF-1 on nitric oxide (NO) synthesis is also important, together with the anabolic effect on the myocardiocytes. Substitution of recombinant GH induces rapid reduction in the atherosclerotic plaques, suggesting a direct effect of the GH/IGF axis on the atherosclerotic process. In addition to the acquired GH deficiency, as in non-substituted patients following hypophysectomy, attention has recently been focused on the relative GH deficiency as is seen in obesity and in the course of ageing. PERSPECTIVES FOR CARDIOVASCULAR ENDOCRINOLOGY: Therapeutic intervention in the GH/IGF axis might influence the atherosclerotic process. Study of the GH/IGF axis activity and of its correlation with atherosclerosis opens new perspectives in the understanding of the role of this axis in cardiovascular diseases.

Age of Onset↗
PubMed2002

APOE: a potential marker of disease progression in ALS.

Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).

Adult↗
PubMed2002

Pituitary carcinoma: report of an exceptional case and review of the literature.

Pituitary carcinomas are exceptional tumors and constitute 0.1 to 0.2% of pituitary tumors. Their definition includes well-established criteria but distant metastasis is the hallmark required for diagnosis. We report the fourth case of gonadotropic pituitary carcinoma described in the literature. This case illustrates the dramatic outcome of these tumors. The most interesting feature of our case was the loss of differentiation with time, established by retrospective analysis of the primary tumor surgically treated 15 years earlier. Most of the previously reported cases exhibited a majority of adrenocoticotropin and non-functioning pituitary tumors. However, the frequency of non-functioning tumors seems smaller than previously believed. In the discussion, we stress the need to detect these very aggressive tumors as early as possible and identify treatments to improve the dramatic course of these carcinomas.

Carcinoma↗
PubMed2002

A constellation of cardiovascular risk factors is associated with hepatic enzyme elevation in hyperlipidemic patients.

Abnormal circulating levels of hepatic enzymes are frequently found in subjects displaying hyperlipidemia or obesity or both. At present, there is a paucity of information on the principal cardiovascular risk factors that are associated with elevated plasma levels of hepatic enzyme activity in hyperlipidemic patients. We analyzed the potential relationships between serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) and cardiovascular and metabolic risk factors in a cohort of 8,501 men and women referred to our outpatient clinic for hyperlipidemia by their general practitioner. In this cohort, 27.6% of patients displayed serum levels of ALT above the upper limit of normal values. Both men and women who exhibited ALT levels superior to the upper limit of the normal range had elevated systolic (SBP) and diastolic blood pressure (DBP), body mass index (BMI), alcohol intake, and serum levels of blood glucose, uric acid, total cholesterol, and triglycerides (P <.0035 for all parameters). In a multivariate analysis, BMI, uric acid, and blood glucose remained significantly associated with ALT levels in men and women. We conclude that cardiovascular and metabolic features characterizing the plurimetabolic syndrome, including serum uric acid levels, are associated with significant elevation of hepatic enzyme activities. Because these abnormalities may not only be reversible but also associated with a poor prognosis, further studies are needed to identify those dyslipidemic patients who are at risk for the development of severe hepatic tissue damage.

Adult↗
PubMed2002

A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length.

Our study aims to provide a comprehensive view of the endocrine features in Kennedy's disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent. Gynecomastia was postpubertal but appeared before muscular weakness in most cases. Thirteen patients had alteration of testicular exocrine function. Hormonal profile of partial androgen resistance was present in 86% of the patients, with an elevated testosterone level in 68%. Androgen insensitivity seems to appear later in life in KD, similar to the development of neurological signs. Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity. This is supported by numerous in vitro data correlating variations in the CAG tract with androgen receptor activity; the longer the CAG repeats, the weaker the receptor transactivation. Ours is the first study to show such a clear and prominent pattern of androgen insensitivity in KD. In clinical practice, KD patients are often misdiagnosed as having amyotrophic lateral sclerosis. Careful examination of the endocrine component could avoid such a deleterious misdiagnosis.

Adult↗
PubMed2001

Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.

Sitosterolemia is a rare autosomal recessive disorder characterized by (a) intestinal hyperabsorption of all sterols, including cholesterol and plant and shellfish sterols, and (b) impaired ability to excrete sterols into bile. Patients with this disease have expanded body pools of cholesterol and very elevated plasma plant-sterol species and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In previous studies, we have mapped the STSL locus to human chromosome 2p21. Recently, we reported that a novel member of the ABC-transporter family, named "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be identified. We identified another ABC transporter, located <400 bp upstream of sterolin-1, in the opposite orientation. Mutational analyses revealed that this highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated in the remaining pedigrees. Thus, two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are indispensable for the regulation of sterol absorption and excretion. Identification of sterolin-1 and sterolin-2 as critical players in the regulation of dietary-sterol absorption and excretion identifies a new pathway of sterol transport.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

[Hyperlipidemias: new data and new concepts].

STATINS: Strategy for management of patients displaying hyperlipidemia has changed since the the first statin has been launched in France more than ten years ago. Following the first primary and secondary prevention studies conducted with hyperlipidemic subjects, results have been extended to patients with cholesterol levels within normal range both in primary (AFCAPS/TexCAPS) and secondary (CARE) prevention. Drug therapy has been simplified with targets tailored to the patient's risk. OPEN QUESTIONS: Despite these important results from intervention studies with statins, other crucial questions remain. Among these questions the first one concerns the possibility that cardiovascular benefits demonstrated with statins are also partly due to other (pleiotropic) effects. This was first hypothesised when statins were proven to be efficacious after short term treatments (one year in the regression studies). The second question is whether we can extend the benefit observed in populations included in published trials to primary prevention of stroke and to the groups less well represented in previous trials including women, elderly patients. The current trends and economic strains of every health care systems have focused on evidence-based medicine and cost-efficacy studies. ROLE OF TRIGLYCERIDES: Beyond LDL-cholesterol there is clear emergence of a role of triglyceride in cardiovascular disease as well as new data on pathophysiology of the so-called reverse cholesterol transport. Recent trials including patients with hypertriglyceridemia as well as a decline of the benefit observed in hypertriglyceridemic patients strongly suggest that the use of statins may have its own limitation. IMPORTANCE OF DIET: Finally, translating results of recent trials in clinical practice remains a challenge for treating physicians who face poor compliance and difficulties in implementing diet in patients.

Acute Disease↗
PubMed2001

Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia.

BACKGROUND: Hyperhomocysteinemia is a risk factor for cardiovascular disease. Elevation in homocysteine levels has recently been demonstrated during lipid lowering treatment with fibrates. We compared the effect of a statin and a fibrate (atorvastatin and fenofibrate) on plasma levels of homocysteine and other thiol compounds in hyperlipidemic patients. METHOD AND RESULTS: The study was of open randomized, parallel design with a preliminary screening phase, and a 6 week placebo period. After the placebo period, patients were allocated randomly to atorvastatin or fenofibrate for a 6 month period. Plasma thiols were assayed by high pressure liquid chromatography with fluorescence detection. There were 29 patients in the fenofibrate group and 24 in the atorvastatin group. Fenofibrate induced a significant increase in both homocysteine and cysteine plasma levels (+35.8 and +18%, respectively, P<0.0001); by contrast, cysteinylglycine remained stable. There were no significant changes in any thiol compounds in the atorvastatin group. Both treatments induced a significant decrease in uric acid, although fenofibrate was noticeably more effective than atorvastatin (-22.8 and -6.4%, respectively). Fenofibrate induced a non-significant increase in creatinine (12%) while atorvastatin reduced it (4.7%, NS). CONCLUSION: Our study confirms that the induction of elevations in plasma homocysteine and cysteine levels are a distinct feature of the pleiotropic effects of fibrates. Further studies are needed not only to investigate the potential deleterious effects of this modification, but also to define the specific mechanism which underlies such fibrate-mediated action.

Atorvastatin↗
PubMed2001

Smaller LDL particle size in women with polycystic ovary syndrome compared to controls.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically. RESULTS: LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables. CONCLUSIONS: Our results suggest that androgen excess and mild insulin-resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.

Adult↗