Long-term metabolic effects of high birth weight: a critical review of the literature.

Recent studies in USA, Europe, and across the world have revealed a continuous increase of mean birth weight in the last 2 decades. Strong evidence exists from several studies indicating that individuals born with a low birth weight are more likely to present cardiometabolic complications in later life. So far, the long-term consequences of high birth weight have not been clearly defined. This review examines the role of high birth weight on the development of cardiometabolic consequences (obesity, body composition, type 2 diabetes mellitus, and cardiovascular disease) in childhood and adulthood. The majority of the studies show that high BW is associated with an increased risk for obesity. To a certain extent high birth weight affects diseases of the heart and circulatory, but does not constitutes a risk for the development of type 2 diabetes mellitus in the general population. Maternal glycemia and the subsequent fetus hyperinsulinemia appear to be the key component for increased fetal growth. With the increase in incidence of diabetes mellitus and obesity over the years, the number of high birth weight infants is likely to increase. The elucidation of the relationship between high birth weight and the cardiometabolic disorders will be particularly important.

The metabolic role of retinol binding protein 4: an update.

Retinol binding protein 4 (RBP(4)) is regarded as a novel cardiometabolic risk factor, which is secreted mainly by the hepatocytes and also by the adipose tissue. RBP(4) has been shown to induce insulin resistance, and plasma RBP(4) values are increased in type 2 diabetes mellitus, obesity, metabolic syndrome, and cardiovascular disease. Moreover, it has been found that circulating RBP(4) decreases during medical interventions that result in amelioration of the metabolic profile, such as diet, exercise, oral antidiabetic drugs, and hypolipidemic agents. However, only few of the RBP(4)-related studies have investigated whether RBP(4) constitutes a causal factor of the above-mentioned metabolic conditions. Importantly, circulating RBP(4) is influenced by some nonmetabolic conditions, such as renal failure, acute illness, injury, and liver failure. Thus, further studies investigating the metabolic roles of RBP(4) should be carefully planned, taking into account the effects of nonmetabolic conditions on circulating RBP(4).

Visfatin levels in prepubertal children born small or large for gestational age.

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.

Obesity, adipose tissue and rheumatoid arthritis: coincidence or more complex relationship?

In the last two decades we have witnessed a boost in scientific interest and knowledge of adipose tissue biology to such an extent that it was promoted to an active endocrine organ. Adipose tissue is not just related to body weight and appetite regulation. It is also implicated in obesity, a low-grade inflammatory state, as well as inflammatory conditions including rheumatoid arthritis (RA), an autoimmune disease where anti- and pro-inflammatory cytokine balance is critical. All major adipose derived products, simply termed adipokines, like leptin, adiponectin, visfatin and resistin, reportedly participate in inflammation and immunity. In this review we explore in depth the relationship between adipose tissue and RA, with focus on possible mechanisms, beyond observations about circulating or synovial levels, and special reference to future perspectives and clinical implications.

An overview of the metabolic effects of rimonabant in randomized controlled trials: potential for other cannabinoid 1 receptor blockers in obesity.

WHAT IS KNOWN AND OBJECTIVE: Rimonabant, a cannabinoid receptor blocker, has recently been used in clinical practice for weight loss and weight maintenance. Our aim was to review the results of trials of the drug in relation to weight loss and maintenance, and its impact on cardio-metabolic risk factors. METHODS: Randomized controlled trials with rimonabant were selected, through a Medline search, using the terms: rimonabant, endocannabinoid antagonist and obesity. Reports of studies on large numbers of patients and covering the topics related to this review were included. RESULTS AND DISCUSSION: In all the trials, there was a considerable reduction in body weight in subjects taking 20 mg rimonabant daily varying from 2.6 to 6.3 kg (placebo-subtracted changes). Rimonabant was also associated with haemoglobin A(1c) (HbA(1c) ) reduction. In the Rimonabant in obesity (RIO)-diabetes study, diabetic patients taking metformin or sulphonylureas showed decrease in HbA(1c) levels by 0.5-0.6 ± 0.8% when rimonabant was added, whereas in the Serenade trial patients with untreated diabetes showed a reduction in HbA(1c) of 0.8% vs. 0.3% with placebo. Similar results were obtained in diabetic patients under insulin treatment. The lipidemic profile also improved in patients taking rimonabant 20 mg daily; levels of high density lipoprotein cholesterol (HDL-c) increased significantly while levels of triglycerides (TRG) decreased in all trials, and positive effects were also observed in patients with atherogenic or untreated dyslipidaemia. In all the RIO studies, prevalence of the metabolic syndrome decreased significantly. In addition, patients treated with 20 mg rimonabant daily exhibited increase in adiponectin. The metabolic changes observed were partly independent of the weight loss and could be attributed to independent peripheral effect of rimonabant. All these beneficial metabolic effects of rimonabant could lead to progress in the prevention of cardiovascular disease. However, in all the trials the incidence of adverse events leading to discontinuation was greater in the rimonabant treated patients than placebo, mainly because of psychiatric disorders (depression and anxiety), nausea and dizziness. WHAT IS NEW AND CONCLUSION: Rimonabant is effective in reducing weight in the obese but may lead to intolerable adverse effects most notably psychiatric effects, which make it unsuitable for routine use. However, the drug provides useful proof of principle for this approach to weight loss. Novel cannabinoid type 1 receptor blockers with selectivity for peripheral receptors, may achieve similar metabolic results with decreased prevalence of psychiatric adverse effects.

Leptin and adiponectin levels in patients with ankylosing spondylitis. The effect of infliximab treatment.

BACKGROUND: Adipose tissue-derived leptin and adiponectin control hunger, energy expenditure, insulin sensitivity, endothelial function, reproduction and immunity and are thought to play a role in autoimmune diseases. However, their role in ankylosing spondylitis (AS) is not clearly defined. Tumour necrosis factor ΤNF-α is a potential modulator of adipocytokines. The effect of longterm anti-TNF-α treatment on plasma levels of leptin and adiponectin has not been assessed so far. OBJECTIVES: To assess the effect of a 6-month anti-TNF-α treatment on serum leptin and adiponectin levels in AS patients. METHODS: Thirty men with AS were included in the study. Thirty age- and weight-matched men served as controls. Clinical and biochemical parameters were assessed and serum levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. RESULTS: Mean age and disease duration of AS patients were 40.6±13.7 and 13.4±8.4 years, respectively. At baseline, AS patients exhibited significantly higher adiponectin (15.4±8.3 vs. 8.6±4.2 µg/ml, p<0.05), but no difference in leptin levels (7.2±2.9 vs. 8.9±6.4 ng/ml, p=NS). Adipocytokines did not correlate with any disease parameter. Body weight of the patients did not change significantly over the 6-month period. Serum levels of leptin and adiponectin did not change significantly after the 6-month treatment. CONCLUSIONS: Adiponectin levels were significantly higher in AS patients compared with controls. Infliximab treatment did not change serum levels of leptin and adiponectin suggesting that the anti-TNF-α treatment may not modulate significantly their levels.

The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome.

OBJECTIVE: We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS). METHODS: Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay. RESULTS: We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy. CONCLUSION: OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.

Effects of sibutramine and orlistat on mood in obese and overweight subjects: a randomised study.

BACKGROUND AND AIM: Intentional weight loss results in improvement in mood. Very few data exist regarding the effects of sibutramine on the mood of obese and overweight patients in general clinical samples. Moreover, no study has evaluated the effects of orlistat treatment on mood. The purpose of our study was to assess the effects of sibutramine and orlistat on mood in obese and overweight subjects. METHODS AND RESULTS: Sixty obese and overweight women were divided into three groups. The first group (n=20) received a low-calorie diet and sibutramine 10mg; the second group (n=20) received a low-calorie diet and orlistat 120 mg three times a day, and the third group received only the low-calorie diet. CONCLUSION: A psychiatric assessment was performed with the Hamilton Depression Rating Scale (HAMD) before and after 3 months of treatment. In all the groups a statistically significant decrease in HAMD scores was observed. However, the decrease in the sibutramine group was greater compared to that observed in the two other groups (P<0.01). These results suggest that sibutramine treatment may improve mood more than diet alone or orlistat therapy in a general clinical sample of obese patients.

Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women.

INTRODUCTION: Platelet-activating factor acetylhydrolase (PAF-AH or Lp-PLA(2)) is a Ca(2+)-independent phospholipase A(2) primarily associated in plasma with low density lipoproteins (LDL), especially with small dense LDL (sdLDL) particles. Increased plasma Lp-PLA(2) levels have been associated with increased cardiovascular risk in large clinical trials. AIM: To assess the effects of weight loss on Lp-PLA(2) activity and to examine the association of Lp-PLA(2) activity changes with the alterations of sdLDL, the primary carrier of Lp-PLA(2) in plasma. METHODS: Twenty-eight obese, non-diabetic women participated in a weight reduction program. Anthropometric parameters were assessed and parameters of glucose metabolism, lipid profile, Lp-PLA(2) activity, and LDL phenotype (using a 3% polyacrylamide gel-tube electrophoresis method), were determined at baseline and after 4months of weight loss. RESULTS: A 10% diet-induced weight loss resulted in significant improvement in most parameters of lipid and glucose metabolism. Moreover, Lp-PLA(2) activity was significantly reduced (-10.2%, p<0.01). Mean LDL particle diameter did not change after the weight loss program. The cholesterol levels of very low-density lipoprotein (VLDL) and large-buoyant LDL particles were significantly reduced, but neither the cholesterol levels of sdLDL particles nor the % proportion of the sdLDL-cholesterol over the total LDL-cholesterol were changed after the intervention program. Interestingly, the changes in Lp-PLA(2) activity were correlated with the changes of VLDL-cholesterol (r=0.39, p<0.05), but not with the changes of anthropometric or other lipid variables. CONCLUSIONS: A low-calorie diet associated with weight loss in obese women resulted in the significant reduction of the plasma levels of Lp-PLA(2), the potentially new predictor for incident atherosclerotic disease.

The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome.

BACKGROUND: Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS). OBJECTIVE: The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS. METHODS: Patients (n=89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group) for 6 months. RESULTS: Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p<0.05) together with a greater increase in LDL particle diameter (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05). CONCLUSION: Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.

Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese and overweight patients with metabolic syndrome.

BACKGROUND: Visfatin [pre-B cell colony- enhancing factor (PBEF)] is a cytokine highly expressed in visceral fat that exhibits insulin-mimetic properties. However, its role in insulin-resistant states, such as in metabolic syndrome (MetS), remains largely unknown. OBJECTIVE: To investigate the possible differences of plasma visfatin levels between obese and overweight subjects with and without MetS. DESIGN AND PATIENTS: Plasma visfatin concentrations were measured with enzyme-linked immunosorbent assay (ELISA) in 28 overweight and obese [body mass index (BMI)>28 kg/m2] subjects with Mets and 28 age- and sex-matched overweight and obese (BMI>28 kg/m2) individuals without MetS (control group). RESULTS: Patients with MetS exhibited significantly elevated waist circumference (WCR ) values, higher blood pressure readings, higher fasting glucose and triglyceride concentrations as well as lower levels of HDL cholesterol (HDL-C) compared with controls. Total and LDL cholesterol (LDL-C) concentrations did not differ significantly between the two groups. Plasma visfatin concentrations were significantly higher in subjects with MetS compared with controls [27 (16- 65) ng/ml vs 19 (10-47) ng/ml, p<0.05]. The same results were observed even after adjustment for age, sex and BMI. Plasma visfatin levels were positively correlated with age (r=0.32, p<0.05), WCR (r=0.31, p<0.05), triglyceride (r=0.59, p<0.01) and glucose (r=0.33, p<0.05) levels and were negatively correlated with HDL-C levels (r=-0.38, p<0.05). Multiple linear regression analysis revealed similar results. CONCLUSION: Plasma visfatin levels are increased in overweight and obese subjects with MetS compared with those individuals who do not fulfil the criteria for the diagnosis of MetS.

The effects of body weight status on orthostatic intolerance and predisposition to noncardiac syncope.

Orthostatic intolerance (OI) is frequently the mechanism underlying the occurrence of noncardiac syncope (NCS) and is associated with substantial risk for injury. Body weight status appears to be a modifier of orthostatic responses and possibly influences the propensity to NCS. The majority of cross-sectional studies have found that the lower the body mass index (BMI) the greater the predisposition to OI is, accompanied with both down-regulation of sympathetic nervous system activity and up-regulation of parasympathetic nervous system activity. These changes appear to occur across the whole spectrum of BMI values from underweight to obesity, while they may be associated more strongly with central body fat than total body fat. Weight loss following bariatric surgery has been consistently found to increase OI, attributed first to the effects of weight loss per se, second to the specific type of surgical procedure and third to the potential postoperative autonomic neuropathy due to vitamin deficiency. The increased OI following bariatric surgery renders this intervention not easily tolerable for the affected individuals, mandating increased fluid and salt intake, pharmacological measures or surgical adjustments to attenuate OI. All future studies investigating orthostatic responses and NCS should implement a matching of the population arms for BMI and ideally for body fat.

Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study.

BACKGROUND: Obesity is becoming increasingly common worldwide and is strongly associated with the metabolic syndrome (MetS). MetS is considered to be a cluster of risk factors that increase the risk of vascular events. OBJECTIVE: In an open-label randomised study (the FenOrli study) we assessed the effect of orlistat and fenofibrate treatment, alone or in combination on reversing the diagnosis of the MetS (primary end-point) as well as on anthropometric and metabolic parameters (secondary end-points) in overweight and obese patients with MetS but no diabetes. METHODS: Overweight and obese patients (N = 89, body mass index (BMI) > 28 kg/m2) with MetS [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria] participated in the study. Patients were prescribed a low-calorie low-fat diet and were randomly allocated to receive orlistat 120 mg three times a day (tid) (O group), micronised fenofibrate 200 mg/day (F group), or orlistat 120 mg tid plus micronised fenofibrate 200 mg/day (OF group). Body weight, BMI, waist circumference, blood pressure, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglyceride, creatinine (SCr) and uric acid (SUA) levels, as well as homeostasis model assessment (HOMA) index and liver enzyme activities were measured at baseline and after 3 months of treatment. RESULTS: Of the 89 patients enrolled, three (one in each group) dropped out during the study due to side effects. After the 3-month treatment period, 43.5% of patients in the O group, 47.6% in the F group and 50% in the OF group no longer met the MetS diagnostic criteria (primary end-point, p < 0.0001 vs. baseline in all treatment groups). No significant difference in the primary end-point was observed between the three treatment groups. Significant reductions in body weight, BMI, waist circumference, blood pressure, TC, LDL-C, non-HDL-C, triglyceride and SUA levels, as well as gamma-glutamyl transpeptidase activity and HOMA index were observed in all treatment groups. In the OF group a greater decrease in TC (-26%) and LDL-C (-30%) was observed compared with that in the O and F groups (p < 0.01) and a more pronounced reduction of triglycerides (-37%) compared with that in the O group (p < 0.05). SUA levels and alkaline phosphatase activity decreased more in the F and OF groups compared with the O group (p < 0.05). Moreover, SCr significantly increased and estimated creatinine clearance decreased in the F and OF groups but they were not significantly altered in the O group (p < 0.01 for the comparison between O and either F or OF groups). Glucose (in groups O and OF), as well as insulin levels and HOMA index (in all groups), were significantly reduced after treatment (p < 0.05 vs. baseline). CONCLUSION: The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.

A review of the metabolic effects of sibutramine.

BACKGROUND: Obesity is associated with an increased incidence of diabetes, hypertension, dyslipidaemia and coronary artery disease. Current management strategies of obesity include lifestyle management strategies of obesity include lifestyle interventions and pharmaco therapy. Sibutramine is a drug with established efficacy in weight reduction and maintenance of weight loss. It reduces food intake and attenuates the fall in reduces food intake and attenuates the fall in metabolic rate associated with weight loss. OBJECTIVE: To review the metabolic effects associated with sibutramine use. METHODS: Relevant articles were identified through a Medline search (up to December 2004). RESULTS: Weight loss with sibutramine treatment is associated with improved insulin sensitivity and a fall in glycosylated haemoglobin levels in type 2 diabetic patients. In most trials sibutramine exerted favourable effects on lipids, especially exerted favourable effects on lipids, especially on high density lipoprotein (HDL) cholesterol and triglycerides, as well as on the total:HDL cholesterol ratio. Sibutramine also lowers serum uric acid concentrations. Furthermore, this drug seems to favourably influence adipocytokines; it reduces serum leptin and resistin levels and increases adiponectin levels. Sibutramine also exerts a beneficial effect on hyper androgenaemia in obese women with polycystic ovary syndrome. Preliminary findings also suggest that weight loss following treatment with sibutramine is useful in patients with non-alcoholic fatty liver disease (NAFLD). CONCLUSION: Weight loss following sibutramine administration is associated with several favourable metabolic effects.

The effects of orlistat on metabolic parameters and other cardiovascular risk factors.

Orlistat is an antiobesity drug with a well documented efficacy in weight reduction and weight maintenance. Weight reduction with orlistat has been associated with a favourable effect on obesity-related cardiovascular risk factors. Orlistat treatment is associated with a reduction in serum insulin levels. Moreover, orlistat reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance and lowers the required dose of metformin, sulfonylureas and insulin in patients with type 2 diabetes. Furthermore, orlistat can reduce total and low density lipoprotein (LDL) cholesterol levels and improve postprandial triglyceridemia, as well as the low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDL/HDL ratio). Moreover, orlistat appears to have a favourable effect on some inflammatory markers, such as TNF-alpha and interleukin-6 and has a time-depended effect on some haemostatic factors.

Distensibility and pulse wave velocity of the thoracic aorta in patients with juvenile idiopathic arthritis: an MRI study.

OBJECTIVE: An increased incidence of cardiovascular disease has been found in rheumatic disorders. Changes in the variables of aortic elasticity in patients with juvenile idiopathic arthritis (JIA) were evaluated and their relationship to inflammation, anti-rheumatic drugs and traditional cardiovascular risk factors were investigated in this study. METHODS: Phase contrast MR was performed in 31 patients with JIA and 28 age and sex matched controls to evaluate the aortic distensibility and pulse wave velocity (PWV). Disease activity variables, plasma lipid profile, homocysteine, thyroid hormones, glucose and insulin were assessed in the patients. RESULTS: Eighteen patients had oligoarticular, 6 polyarticular and 7 systemic disease. Distensibility was lower (mean: 10.25; SD: 4.18) and PWV was higher (mean: 3.68; SD: 1.59) in the patients compared to the controls (mean: 13.4; SD: 4.99), (mean: 1.38; SD: 0.54) respectively (p < 0.01). A positive correlation between PWV and age was observed in the patients (rs = 0.47, p < 0.01) and controls (rs = 0.72, p < 0.01), and a negative correlation between distensibility and age in the patients (rs = -0.59, p < 0.01) and controls (rs = -0.63, p < 0.01). No statistically significant correlations were found between distensibility and PWV and metabolic and disease activity parameters. When distensibility and PWV were adjusted for age no significant differences were found between the three subtypes of JIA. CONCLUSION: JIA is associated with increased aortic stiffness that might suggest subclinical atherosclerosis. Early detection and follow-up by non-invasive methods may be useful in the prevention of future cardiovascular disease.

Serum uric acid levels: a useful but not absolute marker of compliance with fenofibrate treatment.

The purpose of our study was to investigate whether measurement of serum uric acid levels is a reliable method to assess adherence to fenofibrate treatment. This was a 21 week, open-label study conducted in our lipid clinic. After an 8 week dietary baseline phase, we implemented a treatment phase, during which patients received 200 mg/day micronized fenofibrate for 3 months. Serum lipid profiles, including levels of lipoprotein(a) and fibrinogen, serum uric acid, as well as muscle and liver enzymes, were measured after the dietary phase, and at the end of the 3 month treatment period. Compliance was assessed using a clinical interview. A significant decrease in serum uric acid levels was observed in the compliant, while no significant change was noticed in the non-compliant. The compliant had lower serum uric acid concentrations compared to the non-compliant (P < 0.01) after fenofibrate treatment. Furthermore, they demonstrated lower levels of triglycerides and higher high-density lipoprotein (HDL) cholesterol concentrations (P < 0.05 for both parameters). The results show that serum uric acid concentrations may be used as a useful tool to assess compliance with fenofibrate therapy.

T(2) relaxation rate of basal ganglia and cortex in patients with beta-thalassaemia major.

In thalassaemic patients, neurophysiological disturbances have been associated with high serum ferritin levels and desferrioxamine therapy. In the presence of a magnetic field, ferritin, the main iron storage protein, induces a preferential decrease of the T(2) relaxation time. The purpose of this study was to evaluate thalassaemic patients for brain iron deposition by assessing the T(2) relaxation rate (1/T(2)) of the grey matter. 41 thalassaemic patients (age range 8.5-44 years, mean 24 years) and 58 age- and sex-matched controls were included in the study. Current serum ferritin levels were obtained. The 1/T(2) values of the cortex (motor and temporal) (mean 0.0122 ms(-1), SD 0.0004), putamen (mean 0.0137 ms(-1), SD 0.0004) and caudate nucleus (mean 0.0132 ms(-1), SD 0.0003) were higher in patients compared with the controls (mean 0.0110 ms(-1), SD 0.0004; mean 0.0120 ms(-1), SD 0.0005; mean 0.0117 ms(-1), SD 0.0003, respectively) (p<0.001 for all parameters). No statistically significant differences were found in the globus pallidus. No correlation was found between 1/T(2) and serum ferritin. The higher values of 1/T(2) in the cortex, putamen and caudate nucleus of thalassaemic patients probably reflect a higher iron deposition. The lack of differences in 1/T(2) of the globus pallidus might suggest that even in thalassaemic patients iron cannot exceed a saturation level.

[Metastatic pulmonary carcinoma, revealed by Cushing syndrome, initially considered to have a pituitary origin. Course over 25 years]. / Carcinome pulmonaire métastatique, révélé par un syndrome de Cushing, initialement considéré comme d'origine hypophysaire. Evolution sur 25 ans.

It is often difficult to differentiate between Cushing's syndrome and ectopic ACTH hypersecretion which, in rare cases, may result from a carcinoid tumour. Several years may be required before development of patent Cushing's syndrome. We report the 25-year clinical course in a patient with a pulmonary carcinoid tumour. Initially, the hormone results led to the diagnosis of Cushing's syndrome and the patient was treated accordingly. Bilateral adrenectomy was performed in 1969 followed by radiotherapy of the pituitary gland in 1975 for suspected Nelson's syndrome. Actually, the carcinoid tumour, located retrocardially, had gone unnoticed until 1989. Diagnosis was suspected during a hospitalization in our unit and the patient underwent tumour exeresis and left inferior lobectomy. Despite tumour removal and demonstration of tumoural ACTH secretion, the levels of ACTH and beta-lipotrope hormone remained high suggesting lymph node and/or pulmonary metastasis. This observation emphasizes the long clinical course of carcinoid tumours despite their malignancy and the unusual response to the dexamethasone test.