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Context: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare., Objective: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series., Design: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS., Results: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds., Conclusion: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition., (Copyright © 2017 Endocrine Society)

Background: In 2013, new regulations for the prevention of sharps injuries were introduced in the UK. All health care employers are required to provide the safest possible working environment by preventing or controlling the risk of sharps injuries., Aims: To analyse data on significant occupational sharps injuries among health care workers in England, Wales and Northern Ireland before the introduction of the 2013 regulations and to assess bloodborne virus seroconversions among health care workers sustaining a blood or body fluid exposure., Methods: Analysis of 10 years of information on percutaneous and mucocutaneous exposures to blood or other body fluids from source patients infected with a bloodborne virus, collected in England, Wales and Northern Ireland through routine surveillance of health care workers reported for the period 2002-11., Results: A total of 2947 sharps injuries involving a source patient infected with a bloodborne virus were reported by health care workers. Significant sharps injuries were 67% higher in 2011 compared with 2002. Sharps injuries involving an HIV-, hepatitis B virus- or hepatitis C virus (HCV)-infected source patient increased by 107, 69 and 60%, respectively, between 2002 and 2011. During the study period, 14 health care workers acquired HCV following a sharps injury., Conclusions: Our data show that during a 10-year period prior to the introduction of new regulations in 2013, health care workers were at risk of occupationally acquired bloodborne virus infection. To prevent sharps injuries, health care service employers should adopt safety-engineered devices, institute safe systems of work and promote adherence to standard infection control procedures., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Congenital disorders of glycosylation comprise a group of genetic defects with a high frequency of intellectual disability, caused by deficient glycosylation of proteins and lipids. The molecular basis of the majority of the congenital disorders of glycosylation type I subtypes, localized in the cytosol and endoplasmic reticulum, has been solved. However, elucidation of causative genes for defective Golgi glycosylation (congenital disorders of glycosylation type II) remains challenging because of a lack of sufficiently specific diagnostic serum methods. In a single patient with intellectual disability, whole-exome sequencing revealed MAN1B1 as congenital disorder of glycosylation type II candidate gene. A novel mass spectrometry method was applied for high-resolution glycoprofiling of intact plasma transferrin. A highly characteristic glycosylation signature was observed with hybrid type N-glycans, in agreement with deficient mannosidase activity. The speed and robustness of the method allowed subsequent screening in a cohort of 100 patients with congenital disorder of glycosylation type II, which revealed the characteristic glycosylation profile of MAN1B1-congenital disorder of glycosylation in 11 additional patients. Abnormal hybrid type N-glycans were also observed in the glycoprofiles of total serum proteins, of enriched immunoglobulins and of alpha1-antitrypsin in variable amounts. Sanger sequencing revealed MAN1B1 mutations in all patients, including severe truncating mutations and amino acid substitutions in the alpha-mannosidase catalytic site. Clinically, this group of patients was characterized by intellectual disability and delayed motor and speech development. In addition, variable dysmorphic features were noted, with truncal obesity and macrocephaly in ∼65% of patients. In summary, MAN1B1 deficiency appeared to be a frequent cause in our cohort of patients with unsolved congenital disorder of glycosylation type II. Our method for analysis of intact transferrin provides a rapid test to detect MAN1B1-deficient patients within congenital disorder of glycosylation type II cohorts and can be used as efficient diagnostic method to identify MAN1B1-deficient patients in intellectual disability cohorts. In addition, it provides a functional confirmation of MAN1B1 mutations as identified by next-generation sequencing in individuals with intellectual disability.

Objectives: Off-pump coronary artery bypass (OPCAB) surgery is a technically more demanding strategy of myocardial revascularization compared with the standard on-pump technique. Thoracic epidural anaesthesia, by reducing sympathetic stress, may ameliorate the haemodynamic changes occurring during OPCAB surgery. The aim of this randomized controlled trial was to evaluate the impact of thoracic epidural anaesthesia on intraoperative haemodynamics in patients undergoing OPCAB surgery., Methods: Two hundred and twenty-six patients were randomized to either general anaesthesia plus epidural (GAE) (n = 109) or general anaesthesia (GA) only (n = 117). Mean arterial blood pressure (MAP), heart rate (HR) and central venous pressure (CVP) were measured before sternotomy and subsequently after positioning the heart for each distal anastomosis., Results: Both groups were well balanced with respect to baseline characteristics and received a standardized anaesthesia. The MAP decreased in both groups with no significant difference (mean difference (GAE minus GA) -1.11, 95% CI -3.06 to 0.84, P = 0.26). The HR increased in both groups after sternotomy but was significantly less in the GAE group (mean difference (GAE minus GA) -4.29, 95% CI -7.10 to -1.48, P = 0.003). The CVP also increased in both groups after sternotomy, but the difference between the groups varied over time (P = 0.05). A difference was observed at the third anastomosis when the heart was in position for the revascularization of the circumflex artery (mean difference (GAE minus GA) +2.09, 95% CI 0.21-3.96, P = 0.03), but not at other time points. The incidence of new arrhythmias was also significantly lower in the GAE compared with the GA group (OR = 0.41, 95% CI 0.22-0.78, P = 0.01)., Conclusion: Thoracic epidural with general anaesthesia minimizes the intraoperative haemodynamic changes that occur during heart positioning and stabilization for distal coronary anastomosis in OPCAB surgery.

Background: We examined the role of socio-economic status (SES) and marital status in premature mortality among working-age Russian males. Life expectancy among this group dropped sharply following the collapse of the Soviet Union and has yet to recover despite the relative economic and political stability of the last decade., Methods: We employed individual-level data from a large-scale, population-based, case-control study (n = 3500). Adjusting for age group, hazardous drinking and smoking status, we estimated mortality odds ratios to determine the impact of SES and marital status on premature mortality due to all, alcohol- and non-alcohol-related causes of death., Results: Results revealed clear protective effects of SES and marital status against premature mortality. Although the effects for marital status were significant across alcohol- and non-alcohol-related causes of death, the effects of SES were largely limited to non-alcohol-related causes of death. When heavy drinkers were excluded from the analysis, however, SES was found to protect against premature mortality for alcohol-related causes., Conclusion: While hazardous drinking is known to be a leading cause of premature mortality among working-age Russian males, it is unwise to ignore other factors. Given the substantial social and economic impacts in Russia of the dissolution of the Soviet Union, it is important to examine the health effects of SES and marital status and other social forces in the nation. Our results reveal that while Russia has a very different past in terms of medicine, public health and economic institutions, it currently faces public health threats that follow similar patterns to those found in Western nations.

Recombinant human inhibin A was isolated from recombinant mammalian cell line culture media. Two forms of inhibin were identified with Mr of 34 and 31 Kd composed of subunits (alpha, beta) of 24 and 15 Kd and 21 and 15 Kd respectively. Both forms are bioactive in an inhibin in vitro bioassay and immunoactive with potencies comparable to or higher than purified bovine inhibin. Amino acid analyses and NH2-terminal sequences of each of the subunits are consistent with those predicted from their cDNA structures. The inhibin alpha- but not beta-subunit is glycosylated based on its binding to the lectins concanavalin A and wheat germ lectin. The difference in molecular weight of 31 and 34 Kd inhibin is attributed to variation in glycosylation of the alpha-subunit. The 31+34 Kd inhibin is heterogeneous on isoelectric focusing gels consisting of four isoforms in the pH range 6.2-7.6. Inhibition also exhibits in vivo biological activity by suppressing serum FSH but not LH in castrate male rats. These physicochemical and biological characteristics of recombinant human inhibin are similar to those described for native inhibin isolated from a variety of other species.