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Biomedical subjects

E Bruckert

Publications and source records attributed to E Bruckert.

At least 19 recordsLinked to original sources

Screening for liver disease using non-invasive biomarkers (FibroTest, SteatoTest and NashTest) in patients with hyperlipidaemia.

BACKGROUND: Mortality related to complications of cirrhosis is increasing in patients with insulin-resistance factors. Hyperlipidaemic patients have multiple risk factors of insulin resistance. It is impossible to perform liver biopsy in such a large number of hyperlipidaemic patients to identify patients with advanced liver fibrosis or with steatohepatitis (non-alcoholic steatohepatitis, NASH). AIMS: To use the non-invasive biomarkers, FibroTest (FT), SteatoTest and NashTest, and to assess the prevalence of advanced liver disease in a large population of hyperlipidaemic patients. METHODS: A consecutive cohort of hyperlipidaemic patients was followed prospectively in a lipid centre and the sera were analysed retrospectively. RESULTS: A total of 2834 subjects were included: 1909 hyperlipidaemic patients and 925 blood donors (BD). Advanced fibrosis was identified by FT in 53/1909 (2.8%) hyperlipidaemic patients vs. 0/925 BD (0%) (P < 0.0001); advanced steatosis in 569/1893 hyperlipidaemic patients (30.1%) vs. 8/164 (4.9%) BD (P < 0.0001) and NASH in 132/1893 (7%) vs. 0/164 (0%), respectively (P < 0.0001). There was a highly significant and linear association between the number of metabolic syndrome factors and liver disease prevalence - the highest being for type 2 diabetics: advanced steatosis 66%, NASH 24% and advanced fibrosis 6%. CONCLUSIONS The prevalence of fibrosis, steatosis and NASH in hyperlipidaemic patients appears to be high (3%, 30% and 7%, respectively). Biomarkers could be useful for screening of advanced fibrosis and NASH in patients with several metabolic syndrome factors, to prevent liver mortality.

Biomarkers↗

Hypertriglyceridemic waist and 7.5-year prospective risk of cardiovascular disease in asymptomatic middle-aged men.

BACKGROUND: Few studies suggest that the combined increase in plasma triglycerides (TG) and in waist circumference (WC), termed 'hypertriglyceridemic waist' (HTGW), is an interesting marker of risk for cardiovascular disease (CVD). OBJECTIVE: Using cutoffs used for defining HTGW, we examined the prospective association of HTGW with CVD risk in a French cohort of men. DESIGN: Men were participants in the SU.VI.MAX study, an intervention trial testing the impact of an antioxidant supplementation on chronic diseases. Data were collected in 1994-1996 in 3430 men followed up for 7.5 years. Cutoffs used for defining HTGW were WC > or =90 cm and TG > or =2 mmol/l. We assessed the relative risk (RR) (95% confidence interval (CI)) of CVD in groups defined according to both WC and TG levels. RESULTS: In this population, 41.2% of the subjects were classified as low WC/low TG, 43.2% as high WC/low TG, 3.5% as low WC/high TG and 12.1% as HTGW. During follow-up, 122 subjects had a CVD event. In this group, HTGW prevalence was 26.2%. After adjustment for age, RR (95% CI) for CVD for the HTGW group showed the highest association with CVD risk: 2.13 (1.21-3.76), using low WC/ low TG as the reference group. CONCLUSION: HTGW was associated with the risk of CVD after 7.5 years of follow-up in a low-risk middle-aged men population. This marker may be used as a useful clinical tool to screen for men at risk of CVD.

Antioxidants↗

[Patient education and patient at risk. A new approach in cardiology].

For more than 10 years, preventive cardiology has obtained many positive results. Cardiologists can alter the prognosis of cardiovascular disease in primary and secondary prevention. In primary prevention or during the chronic phases of coronary artery disease, prevention is mainly based on drugs. However, prevention can be achieved only if patients have a good understanding of their disease, fair relationships with their physicians and a strict compliance with their treatments. Patient education is useful for the patient in order to control cardiovascular risk. In France, the PEGASE program evaluates the efficacy of an educational program in high risk patients. The final objective of this program is to spread this educational program for high risk patients to cardiologists all over the country.

Cardiovascular Agents↗

Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss.

OBJECTIVE: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)gamma2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. METHODS: Twenty-three non-diabetic obese subjects with normal (NGT, n = 11) or impaired glucose tolerance (IGT, n = 12) (age, 47 +/- 3 years; body mass index, 39.3 +/- 1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. RESULTS: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P = 0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARgamma2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARgamma2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. CONCLUSION: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.

Adipose Tissue↗

[Treatment of obstructive aortic atheroma in homozygotic familial hypercholesterolemia].

The object of this report is to describe the surgical treatment of a rare clinical form of homozygotic familial hypercholesterolaemia (HFH) associating valvular and supravalvular stenosis with coronary ostial stenosis. Three patients, two male and one female, aged 15, 23 and 41 respectively, suffering from HFH diagnosed in early childhood, presented with obstacles to left ventricular ejection and myocardial ischaemia due to coronary ostial stenosis. Surgery consisted of corrections in a single procedure of all abnormalities by aortic valve replacement, ascending aortic replacement and widening of the coronary artery ostia which were reimplanted on the aortic tube. The postoperative course of all three patients was favourable. Postoperative echocardiography showed the normal position of the valvular prosthesis, normalisation of the left ventricular ejection fraction with no significant residual obstruction. Angioscan of the coronary arteries showed a good result of coronary ostial widening. The authors conclude that HFH is a rare condition and that disease of the ascending aorta is common in this variety with involvement of the aortic valve, the ascending aorta and the coronary ostia. The surgical procedure described by the authors allows correction of all the abnormalities with the hope of a good long-term result.

Adolescent↗

[Role of LDL in cardiovascular diseases. New data and new recommendations].

The management of hypercholesterolemia has rapidly progressed with the large clinical trials mainly on statins. Over the past 15 years, it has been demonstrated that the principle target was LDL-cholesterol and that treatment with statins decreased cardiovascular morbidity and global mortality. The studies have progressively targeted patients with increasingly lower cholesterol levels but always at high risk. Recent data are in favour of the so-called "aggressive" strategy aimed at reducing cholesterol to very low levels. The emergence of new therapies with stronger statins and the concept of combining lipid-lowering treatments has improved the chances of reaching this aim. Prompted by this progress, the transposition of this aggressive strategy to clinical practice is confronted with many problems, which stem from practitioners' and patients' reticence and fears (raising the question of compliance to treatment) and, more generally, the problem of cost. In this perspective, therapeutic education is one of the tools that would promote compliance. New treatments in the field of HDL would further support the progress made in such prevention.

Anticholesteremic Agents↗

Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism.

OBJECTIVE: We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies. MATERIALS AND METHODS: We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I). RESULTS: Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy. CONCLUSIONS: We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.

Adult↗

Blood lipid and lipoprotein levels: relationships with educational level and region of residence in the French SU.VI.MAX study.

BACKGROUND: Blood lipid profile of French men and women obtained from the general population is not well known. Furthermore, the association between these lipids, as a function of other potential risk factors for cardiovascular disease, and sociodemographic factors such as age, educational level, and region of residence is not well studied in large samples in Europe. METHODS: Data on French healthy volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years for women (n = 7876) were obtained from the "Supplementation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline blood samples were collected in 1994-1995 and analyzed for cholesterol, triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed separately for men and women as a function of age, educational level, and area of residence. RESULTS: Overall, blood lipid levels for men and women did not differ significantly from those reported in other Western industrialized countries. Except for triglyceride in men, all blood lipids were statistically different among ages. In women, cholesterol, apo-A1, and apo-B showed a significant decrease with educational level. Statistical differences were found in both genders between blood lipids and lipoproteins among regions of residence. CONCLUSIONS: Even if differences between region of residence were found in blood lipid levels, this cannot explain the North-East to South gradient in the prevalence of cardiovascular disease in France nor differences between France and other industrialized Western countries.

Adult↗

[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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗