Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus

Moderate alcohol intake has been associated with increased life expectancy due to reduced mortality from cardiovascular disease. We prospectively examined the effects of alcohol consumption on mortality in Type 2 diabetic patients in Switzerland

Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease

<p/> <p>Background</p> <p>As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.</p> <p>Methods</p> <p>A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.</p> <p>Results</p> <p>At baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.</p> <p>Conclusion</p> <p>Immediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.</p

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Granular cell tumors of the urinary bladder

BACKGROUND: Granular cell tumors (GCTs) are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. MATERIALS AND METHODS: We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. RESULTS: Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100) and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13), neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin) and sarcoma (desmin, vimentin) markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. CONCLUSION: We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively

Monitoring Procalcitonin in Febrile Neutropenia: What Is Its Utility for Initial Diagnosis of Infection and Reassessment in Persistent Fever?

Background: Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever.Methods: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%).Results: At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p&lt;0.001). PCT &gt;500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was &gt;500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak &gt;500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT &lt;500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively.Conclusion: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycose

Metabolic Impact of Adult-Onset, Isolated, Growth Hormone Deficiency (AOiGHD) Due to Destruction of Pituitary Somatotropes

Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre+/−,iDTR+/− offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre−/−,iDTR+/− mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe