Development and steroidogenic activity of preantral follicles in the neonatal rat ovary

The neonatal rat ovary is completely devoid of antral follicles until the twelfth day of age. During this period the ovary becomes steroidogenically active and responsive to gonadotrophins. The aim of this study was to correlate the onset of ovarian androgen and oestrogen production in vitro with the first appearance of distinct granulosa and theca cells. Although ovarian aromatase activity increased significantly on day 7 of age, ovarian oestrogen production was limited by low progesterone and testosterone production until day 12 of age. Increased aromatase activity on day 7 and androgen production on day 12 were coincident with the first appearance of granulosa and theca cells respectively. These functional and morphological changes were not associated with significant alterations in ovarian weight or concentrations of LH or FSH in serum.     

Physician demographics and the risk of medical malpractice.

PURPOSE: This study was undertaken to clarify which, if any, physician demographic characteristics are associated with an increased rate of medical malpractice claims. METHODS: We analyzed the malpractice experience of 9,250 physicians insured for at least 2 years from 1977 to 1987 in the state of New Jersey. After adjusting for years at risk, physician claims per year was categorized into low, medium, and high. RESULTS: Male physicians were three times as likely to be in the high-claims group as female physicians, even after adjusting for other demographic variables (relative risk, 3.1; 99% confidence interval, 2.2 to 4.4). Specialty was strongly associated with claims rate, with neurosurgery, orthopedics, and obstetrics/gynecology having 7 to 12 times the number of claims per year as psychiatry, the specialty with the fewest claims. The rate of claims varied with age (p < 0.001) and peaked at approximately age 40. No association was evident between claims rate and a physician's site of training or type of degree. CONCLUSION: Male physicians are three times as likely to be in a high-claims category as female physicians. We suspect that the most likely explanation for this finding is that women interact more effectively with patients. Understanding the reasons for the variation in claim rates between physicians may lead to the development of methods to reduce the overall rate of malpractice claims.     

Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging

Aims/hypothesis

The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM. We used the VMAT2 tracer [¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine to quantify BCM in humans with impaired glucose tolerance (prediabetes) or type 2 diabetes, and in healthy obese volunteers (HOV).

Methods

Dynamic positron emission tomography (PET) data were obtained for 4 h with metabolite-corrected arterial blood measurement in 16 HOV, five prediabetic and 17 type 2 diabetic participants. Eleven participants (six HOV and five with type 2 diabetes) underwent two abdominal PET/computed tomography (CT) scans for the assessment of test–retest variability. Standardised uptake value ratio (SUVR) was calculated in pancreatic subregions (head, body and tail), with the spleen as a reference region to determine non-specific tracer uptake at 3–4 h. The outcome measure SUVR minus 1 (SUVR-1) accounts for non-specific tracer uptake. Functional beta cell capacity was assessed by C-peptide release following standard (arginine stimulus test [AST]) and acute insulin response to the glucose-enhanced AST (AIRargMAX). Pearson correlation analysis was performed between the binding variables and the C-peptide AUC post-AST and post-AIRargMAX.

Results

Absolute test–retest variability (aTRV) was ≤15% for all regions. Variability and overlap of SUVR-1 was measured in all groups; HOV and participants with prediabetes and with type 2 diabetes. SUVR-1 showed significant positive correlations with AIRargMAX (all groups) in all pancreas subregions (whole pancreas p?=?0.009 and pancreas head p?=?0.009; body p?=?0.019 and tail p?=?0.023). SUVR-1 inversely correlated with HbA_1c (all groups) in the whole pancreas (p?=?0.033) and pancreas head (p?=?0.008). SUVR-1 also inversely correlated with years since diagnosis of type 2 diabetes in the pancreas head (p?=?0.049) and pancreas tail (p?=?0.035).

Conclusions/interpretation

The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.

     

Serum high density lipoprotein subclasses, testosterone and sex-hormone-binding globulin in Trinidadian men of African and Indian descent

Serum high-density lipoprotein (HDL) cholesterol, testosterone and sex-hormone-binding globulin (SHBG) were measured in 300 men, aged 35-64 years, of African and Indian descent who represented a 40% sample of participants in a community survey of coronary heart disease in Trinidad. Free testosterone was calculated from total testosterone and SHBG. In 113 men, HDL2 and HDL3 cholesterol were measured by a precipitation technique. Indian men had a significantly lower HDL-cholesterol concentration than African men (P = 0.003), which is known to be due to a reduction in the HDL3 fraction (demonstrable only in younger men in the subsample drawn for this study). Testosterone did not differ with ethnic group, but SHBG was reduced in Indians (P = 0.03). After allowance for age, ethnic group, alcohol consumption and smoking habit, HDL cholesterol was associated positively with SHBG (P = 0.025) but was not related significantly to either total testosterone or its free and bound components. Serum HDL2 cholesterol was associated positively and independently with SHBG (P = 0.001) and total and bound testosterone (P = 0.002), whereas HDL3 cholesterol showed no significant associations with these factors. Neither SHBG or testosterone afforded an explanation for the relatively low HDL and HDL3 cholesterol concentrations in Indian men.     

MHV68 Latency Modulates the Host Immune Response to Influenza A Virus

Murine gammaherpesvirus 68 (MHV68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. Like other herpesviruses, MHV68 causes acute infection and establishes life-long latency in the host. Recently, it has been shown that mice latently infected with MHV68 have resistance to unrelated pathogens in secondary infection models. We therefore hypothesized that latent MHV68 infection could modulate the host response to influenza A virus. To test this hypothesis, mice were infected intranasally with influenza virus following the establishment of MHV68 latency. Mice latently infected with MHV68 showed significantly higher survival to influenza A virus infection than did PBS mock-infected mice. Latent MHV68 infection led to lower influenza viral loads and decreased inflammatory pathology in the lungs. Alveolar macrophages of mice latently infected with MHV68 showed activated status, and adoptive transfer of those activated macrophages into mice followed the infection with influenza A virus had significantly greater survival rates than control mice, suggesting that activated alveolar macrophages are a key mechanistic component in protection from secondary infections.