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Selected AbstractsImpaired aortic elastic properties in patients with systemic sarcoidosisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2008I. Moyssakis Abstract Background, Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar. Materials and methods, A total of 83 consecutive patients (26 male/57 female, mean age 51·1 ± 13·3 years) with Sar, without cardiac symptoms, were included. All patients underwent echocardiographic and respiratory evaluation including lung function tests. Additionally, 83 age- and sex-matched healthy subjects served as controls. AoD was determined non-invasively by ultrasonography. Results, AoD was lower in the Sar compared to the control group (2·29 ± 0·26 vs. 2·45 ± 0·20 ·10,6 cm2· dyn,1, P < 0·01), while left ventricular mass (LVM) was higher in the Sar group (221·3 ± 50·2 vs. 195·6 ± 31·3 g, P = 0·007). Furthermore, myocardial performance of both ventricles was impaired in the Sar group. Multivariate linear regression analysis in the total sample population demonstrated a significant and independent inverse relationship between AoD and the presence of Sar (P < 0·001). The same analysis in the Sar patients showed that AoD was associated significantly and independently with the stage of Sar, age, systolic blood pressure, LVM and myocardial performance of both ventricles. No significant relationship was found between AoD and disease duration, pulmonary artery pressure or lung function tests. Conclusions, Presence and severity of Sar are associated with reduced aortic distensibility, irrespective of the disease duration, pulmonary artery pressure and lung function. In addition, patients with Sar have increased LVM and impaired myocardial performance. [source] Pleiotropic effects on subclasses of HDL, adiposity, and glucose metabolism in adult Alaskan EskimosAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2010M. Elizabeth Tejero The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 ± 0.11 for LDL2 (intermediate) and 0.89 ± 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Prevalence of Interatrial Block in Healthy School-Aged Children: Definition by P-Wave Duration or Morphological AnalysisANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010F.E.S.C., Polychronis Dilaveris M.D. Background: P waves ,110 ms in adults and ,90 ms in children are considered abnormal, signifying interatrial block, particularly in the first case. Methods: To evaluate the prevalence of interatrial block in healthy school-aged children, we obtained 12-lead digital ECGs (Cardioperfect 1.1, CardioControl NV, Delft, The Netherlands) of 664 healthy children (349 males/315 females, age range 6,14 years old). P-wave analysis indices [mean, maximum and minimum (in the 12 leads) P-wave duration, P-wave dispersion, P-wave morphology in the derived orthogonal (X, Y, Z) leads, as well the amplitude of the maximum spatial P-wave vector] were calculated in all study participants. Results: P-wave descriptor values were: mean P-wave duration 84.9 ± 9.5 ms, maximum P-wave duration 99.0 ± 9.8 ms, P dispersion 32.2 ± 12.5 ms, spatial P amplitude 182.7 ± 69.0 ,V. P-wave morphology distribution in the orthogonal leads were: Type I 478 (72.0%), Type II 178 (26.8%), Type III 1 (0.2%), indeterminate 7 (1%). Maximum P-wave duration was positively correlated to age (P < 0.001) and did not differ between sexes (P = 0.339). Using the 90-ms value as cutoff for P-wave duration, 502 (75.6%) children would be classified as having maximum P-wave duration above reference range. The 95th and the 99th percentiles were in the overall population 117 ms and 125 ms, respectively. P-wave morphology type was not in any way correlated to P-wave duration (P = 0.715). Conclusions: Abnormal P-wave morphology signifying the presence of interatrial block is very rare in a healthy pediatric population, while widened P waves are quite common, although currently classified as abnormal. Ann Noninvasive Electrocardiol 2010;15(1):17,25 [source] Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillanceCLINICAL ENDOCRINOLOGY, Issue 5 2005A. Brew Atkinson Summary Objective, There have been a few reports on long-term remission rates after apparent early remission following pituitary surgery in the management of Cushing's disease. An undetectable postoperative serum cortisol has been regarded as the result most likely to predict long-term remission. Our objective was to assess the relapse rates in patients who underwent transsphenoidal surgery in order to determine whether undetectable cortisol following surgery was predictive of long-term remission and whether it was possible to have long-term remission when early morning cortisol was measurable but not grossly elevated. Endocrinological factors associated with late relapse were also studied. Patients, We reviewed the long-term outcome in 63 patients who had pituitary surgery for the treatment of Cushing's disease between 1979 and 2000. Measurements, Case notes were reviewed and the current clinical and biochemical status assessed. Our usual practice was that early after the operation, an 08:00 h serum cortisol was measured 24 h after the last dose of hydrocortisone. This was followed by a formal low-dose dexamethasone suppression test. Current clinical status and recent 24-h urinary free cortisol values were used as an index of activity of the Cushing's disease. If there was evidence suggesting relapse, a low-dose dexamethasone suppression test was performed. In many patients, sequential collections of early morning urine specimens for urinary cortisol to creatinine ratio were also performed in an attempt to diagnose cyclical and intermittent forms of recurrent hypercortisolism. We did this if there was conflicting endocrine data, or if patients were slow to lose abnormal clinical features. Results, Mean age at diagnosis was 40·3 years (range 14,70 years). Mean follow-up up time was 9·6 years (range 1,21 years). Forty-five patients (9 males/36 females) achieved apparent remission immediately after surgery and were subsequently studied long term. Of these 45 patients, four have subsequently died while in remission from hypercortisolism. Ten of the remaining 41 patients have relapsed. Of those 10, six demonstrated definite cyclical cortisol secretion. Two of the 10 had undetectable basal serum cortisol levels in the immediate postoperative period. Thirty-one patients are still alive and in remission. Fourteen (45%) of the 31 who remained in remission had detectable serum cortisol levels (> 50 nmol/l) immediately postoperatively, and remain in remission after a mean of 8·8 years. Our relapse rate was therefore 10/45 (22%), after a mean follow-up time of 9·6 years, with mean time to relapse 5·3 years. Conclusions, The overall remission rate of 56% (35/63) at 9·6 years follow-up is disappointing and merits some re-appraisal of the widely accepted principle that pituitary surgery must be the initial treatment of choice in pituitary-dependent Cushing's syndrome. Following pituitary surgery, careful ongoing expert endocrine assessment is mandatory as the incidence of relapse increases with time and also with increasing rigour of the endocrine evaluation. A significant number of our patients were shown to have relapsed with a cyclical form of hypercortisolism. [source] Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitisLIVER INTERNATIONAL, Issue 6 2010Lars P. Bechmann Abstract Background & aims: Hepatocyte apoptosis is a key event in non-alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82±1.41; age: 45±10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis-related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. Results: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: × 11.56; FATP-5: × 1.33; CD95/Fas: × 3.18; NOXA: × 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72±2.32 mg/dl vs. patients: 23.03±1.24 mg/dl) and M30 levels (control: 83.12±7.46 U/L vs. patients: 212.61±22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. Conclusions: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis. [source] Sex differences in grey seal diet reflect seasonal variation in foraging behaviour and reproductive expenditure: evidence from quantitative fatty acid signature analysisJOURNAL OF ANIMAL ECOLOGY, Issue 3 2007CARRIE A. BECK Summary 1Intraspecific variation in diet can be an important component of a species niche breadth. We tested the hypothesis that sex differences in seasonal foraging behaviour and energy storage of sexually size dimorphic grey seals Halichoerus grypus (Fabrisius 1971) are reflected in differences in the diet and niche breadth. Diet composition was estimated for 496 adult (226 males, 270 females) and 91 juvenile (46 males/45 females; all 6 months old) grey seals sampled between 1993 and 2000 using quantitative fatty acid signature analysis. Niche breadth and overlap were estimated using the Shannon,Weaver diversity index (H,) and the Morisita,Horn index (CH), respectively. 2Sand lance Ammodytes dubius (Reinhardt 1837) and redfish Sebastes sp. (Cuvier 1829) accounted for a high proportion of the diet in both sexes and age groups. However, the diets of adult males were significantly more diverse across all seasons (H,: males 0·36 ± 0·007 vs. females 0·28 ± 0·007) and less energy dense in spring (male 5·3 ± 0·07 kJ g,1 vs. females 5·6 ± 0·09 kJ g,1) than those of adult females. 3Season and sex explained most of the observed variation in adult diets, but there were significant sex,season interactions. These differences were most evident during the post-breeding (spring) foraging period when energy acquisition is important to female recovery of nutrient stores needed to support pregnancy. Females selected fewer and higher quality prey species in spring than males. 4There were no sex differences in the diets of juvenile grey seals. Although many of the species overlapped with those eaten by adults, juvenile niche breadth (H,: 0·41 ± 0·014, n = 91) was significantly broader than that of adults (H,: 0·30 ± 0·011, n = 115). Juvenile diets were also of lower energy density (5·3 ± 0·04 kJ g,1) than those of adults (5·6 ± 0·09 kJ g,1), suggesting less selectivity in these young and relatively naïve predators. 5Sex-specific seasonal changes in diet correspond to seasonal changes in diving behaviour and rate of body energy accumulation of adult males and females. Sex-specific reproductive requirements appear to be a primary factor generating the intraspecific variation in the seasonal foraging ecology of this large marine carnivore. However, sex differences in the breadth and energy content of diets also suggest the influence of body-size dimorphism as a factor shaping the diet of this species. [source] Plasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjectsDIABETES OBESITY & METABOLISM, Issue 6 2005M. K. Heliövaara Aim:, It has been shown that atherosclerosis is an inflammatory disease. Recent data suggest that inflammation precedes type 2 diabetes. Hence, we wanted to study the interrelationship between IL-6, insulin sensitivity, lipids and numerous acute-phase proteins. Methods:, Twenty-one healthy individuals [16 males/5 females, age 27.9 ± 1.8 years, body mass index (BMI) 24.1 ± 0.8 kg/m2] participated in the study. Each patient went through a 4-h hyperinsulinaemic (40 mU/m2/min) euglycaemic clamp and 4-h saline infusion. Blood samples were taken before and at the end of the infusions. Results:, Plasma interleukin (IL)-6 concentration correlated inversely with insulin sensitivity (M -value) (r = ,0.49, p < 0.05). Moreover, the plasma levels of IL-6 associated with c-peptide (r = 0.49, p < 0.05), fat% (r = 0.43, p < 0.05) and diastolic blood pressure (r = 0.46, p < 0.05). ,-1-acid glycoprotein was related to HbA1c (r = 0.47, p < 0.05), insulin (r = 0.55, p < 0.01), diastolic blood pressure (r = 0.58, p < 0.01), systolic blood pressure (r = 0.58, p < 0.01) and triglycerides (r = 0.58, p < 0.01). Haptoglobin was correlated with insulin (r = 0.46, p < 0.05), total cholesterol (r = 0.61, p < 0.01), BMI (r = 0.58, p < 0.01), fat% (r = 0.63, p < 0.01) and lipid oxidation during clamp (r = 0.43, p < 0.05). Diastolic blood pressure decreased during the clamp (from 78.3 ± 1.9 to 72.1 ± 2.0 mmHg, p = 0.001). Insulin infusion did not affect the serum levels of most acute-phase proteins. Conclusions:, Our study suggests that low grade inflammation, as reflected by IL-6, A1GP and haptoglobin contributes to the regulation of insulin sensitivity, lipid metabolism and blood pressure in normal human physiology. 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