Serum leptin concentrations during severe protein-energy malnutrition: correlation with growth parameters and endocrine function

Circulating leptin, insulin, insulin-like growth factor-I (IGF-I), cortisol, and albumin concentrations and the growth hormone (GH) response to provocation were measured in 30 children with severe protein-energy malnutrition (PEM), 20 with marasmus and 10 with kwashiorkor, as well as 10 age-matched normal children (body mass index [BMI] >50th and <90th percentile for age and sex) and 10 prepubertal obese children (BMI >95th percentile for age and sex). Patients with PEM had a significantly lower BMI, midarm circumference (MAC), and skinfold thickness (SFT) compared with the age-matched control group. Basal cortisol and GH concentrations were significantly higher in the malnourished groups versus controls. Leptin and IGF-I were significantly lower in the marasmic and kwashiorkor groups versus normal children. Fasting insulin levels were significantly decreased in the kwashiorkor group compared with marasmic and normal children. The BMI correlated significantly with leptin (r = .77, P < .001), basal insulin (r = .61, P < .001), and IGF-I (r = .77, P < .001) and negatively with basal GH (r = -.52, P < .001). These findings suggest that during prolonged nutritional deprivation, the decreased energy intake, diminished subcutaneous fat mass, and declining insulin (and possibly IGF-I) concentration suppress leptin production. In support of this view, serum leptin levels were positively correlated with triceps, scapular, and abdominal SFT (r = .763, .75, and .744, respectively, P < .0001) in all of the children. Moreover, basal insulin and circulating IGF-I were correlated significantly with leptin concentrations (r = .47 and .62, respectively, P < .001). Basal levels of cortisol and GH were significantly elevated in the 2 groups with severe PEM. It is suggested that low leptin levels can stimulate the hypothalamic-pituitary-adrenal (HPA) axis and possibly the hypothalamic-pituitary-GH axis to maintain the high cortisol and GH levels necessary for effective lipolysis to ensure a fuel (fatty acids) supply for the metabolism of brain and peripheral tissue during nutritional deprivation. In summary, during prolonged PEM, the decreased synthesis of IGF-I and the low level of insulin and/or its diminished effect due to an insulin-resistant status in the presence of high circulating GH and cortisol levels ensure substrate diversion away from growth toward metabolic homeostasis. Leptin appears to be an important signal in the process of metabolic/endocrine adaptation to prolonged nutritional deprivation.     

Vascular manifestations of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a well-known acute and/or chronic multisystem disease of complex autoimmune nature, having predilection for cardiovascular system. While its cardiac manifestations have been adequately studied, there is paucity of information on its vascular manifestations. Accordingly, we studied the incidence of vascular manifestations in 50 consecutive SLE patients seen at our institutions and in private practice during the past 12 years. Systemic hypertension (44%) was the most common vascular manifestation followed by vasculitis (30%), Raynaud's phenomenon (26%), telangiectasis (20%), premature coronary atherosclerosis (6%), digital ulceration (6%), thrombophlebitis (6%), pulmonary hypertension (4%) and portal hypertension (4%). Diffuse systemic vasculitis similar to polyarteritis nodosa was rare (2%). Often more than one lesion was found in the same patient. The clinical diagnosis of these vascular manifestations in the context of the primary disease (SLE) usually does not pose any difficulty except when they antedate it. We also studied the pathology and pathogenesis of some of these vascular lesions in both autopsy and biopsy specimens by both light microscopy and immunofluorescent techniques. Our results as well as those of others who also studied these lesions indicate that immune complex deposition and subsequent complement activation play an important role in the pathogenesis of vasculitis, coronary arteritis and premature coronary atherosclerosis. Corticosteroids and vasodilators remain the drugs of choice for the management of the majority of the symptoms arising from the vascular lesions of SLE.     

Circumferential quantitative analysis of planar 201T1 myocardial scintigraphy in the diagnosis of coronary artery disease

Methodology for the computer analysis of 201T1 myocardial perfusion images has been developed by several laboratories. Substantial evidence of the advantage of this approach over visual inspection alone has been reported. The currently available computer analyses use different algorithms to analyze 201T1 kinetics in the myocardium. The authors evaluated and compared two widely used software programs, Medical Data System (MDS): a mean-count profile, and the Cedars Sinai (CS): a maximal-count profile, of planar 201T1 scintigraphy for their ability to detect coronary artery disease (CAD).     

VE1 immunohistochemistry is an adjunct tool for detection of BRAF V600E mutation: Validation in thyroid cancer patients

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy among other endocrine tumors, and BRAF ^V600E is a frequent genetic mutation occurring in the disease. Although different molecular techniques, most importantly sequencing has been widely recognized as a gold standard but molecular diagnosis remains an expensive, laborious, and time‐intensive process. Recently, immunohistochemistry (IHC) with anti‐BRAF V600E (VE1) antibody has increased practical utility and implemented clinically for the detection of BRAF ^V600E mutation. Therefore, the study aimed to evaluate diagnostic accuracy of VE1 IHC for detecting the BRAF ^V600E mutation frequency and clinical implementation in diagnostic laboratories. In this study, 72 formalin fixed paraffin‐embedded tissues (FFPE) were used to determine the BRAF ^V600E mutation status using IHC and Sanger sequencing. The mutation was found in 29% and 28% cases using IHC and Sanger sequencing, respectively. Furthermore, the results showed 100% sensitivity, 98.07% specificity, 95.2% positive predictive value, and 100% negative predictive value. Notably, significant associations were found between BRAF ^V600E status and tumor stage, tumor focality, and extrathyroidal extensions, respectively. VE1 IHC was found to be a highly sensitive, specific, and diagnostically accurate method in this cohort. Therefore, BRAF ^V600E detection through IHC has been considered as the best tailored technique for routine pathology laboratories.     

Fractography and oxidative analysis of gamma inert sterilized posterior-stabilized tibial insert post fractures: Report of two cases

BackgroundHighly crosslinked ultra-high molecular weight polyethylene (UHMWPE) has shown success in reducing wear in hip arthroplasty but there remains skepticism about its use in Total Knee Replacement (TKR) inserts that are known to experience fatigue loading and higher local cyclic contact stresses.MethodsTwo Legacy Posterior-Stabilized (LPS) Zimmer NexGen tibial implants sterilized by gamma irradiation in an inert environment with posts that fractured in vivo were analyzed. Failure mechanisms were determined using optical and scanning electron microscopy along with oxidative analysis via Fourier Transform Infra-Red (FTIR) spectroscopy.ResultsMicrographs of one retrieval revealed fatigue crack initiation on opposite sides of the post and quasi-brittle micromechanisms of crack propagation. FTIR of this retrieval revealed no oxidation. The fracture surface image of the second retrieval indicated a brittle fracture process and FTIR revealed oxidation in the explant.ConclusionsThese two cases suggest that crosslinking of UHMWPE as a manufacturing process or sterilization method in conjunction with designs that incorporate high stress concentrations, such as the tibial post, may reduce material strength. Moreover, free radicals generated from ionizing radiation can render the polymer susceptible to oxidative embrittlement.Clinical relevanceOur findings suggest that tibial post fractures may be the results of in vivo oxidation and low level crosslinking. These and previous reports of fractured crosslinked UHMWPE devices implores caution when used with high stress concentrations, particularly when considering the potential for in vivo oxidation in TKR.