Burn-induced gut mucosal homeostasis in TCR delta receptor-deficient mice

Gammadelta T lymphocytes make up approximately 50% of lymphocytes in the intestine. These cells have been shown to prime macrophages for TNF-alpha production after burn. We previously showed that neutralizing anti-TNF-alpha antibodies reduce mucosal atrophy by decreasing gut epithelial apoptosis after severe burn. We hypothesized that burn-induced mucosal turnover is diminished in T cell receptor delta gene knockout (TCR delta-/-) mice through diminished TNF-alpha activity. Forty-two wild-type and 42 TCR delta-/- mice (C57-BL6) were randomly assigned to burn and sham burn groups. The burn group underwent a 25% total body surface area (TBSA) scald burn. The proximal small intestine was harvested at 2, 12, and 48 h. To assess mucosal atrophy, mucosal height and cell numbers in the villi and crypts were determined on hematoxylin and eosin-stained tissue sections. Apoptotic gut epithelium was identified by terminal deoxyuridine nick-end labeling (TUNEL) staining, and cell proliferation was detected by immunostaining for proliferative cell nuclear antigen (PCNA). TNF-alpha mRNA expression was measured by RT-PCR. Caspase-8 activity was measured by colorimetric assay. Statistical analysis was performed with two-way analysis of variance and t testing. Significance was accepted at P < 0.05. Data are expressed as means +/- SEM. TNF-alpha mRNA expression was significantly decreased in TCR delta-/- mice at 2 h after burn. Gut epithelial apoptosis and proliferation in both wild-type and TCR delta-/- mice were significantly increased after burn, but TCR delta-/- mice had a significantly lower levels of apoptosis (P < 0.01) and proliferation (P < 0.05) when compared with wild-type mice. Burn-induced mucosal atrophy was identified in groups by decreasing villus height, crypt depth, and villus and crypt cell number (P < 0.001) compared with sham, but no difference was found between wild-type and TCR delta-/- mice. Caspase-8 activity was significantly diminished in TCR delta-/- mice compared with wild-type mice. Gammadelta T cells are associated with increased TNF-alpha expression and gut epithelial turnover in the small bowel after severe burn. However, absence of delta T cell receptor did not inhibit mucosal atrophy after severe burn. This study suggests that gut mucosal atrophy after severe burn is a multifactorial process associated with increased TNF-alpha activity.     

The relationship between microvascular endothelial function and carotid-radial pulse wave velocity in patients with mild hypertension

Carotid-radial pulse wave velocity (CRPWV) can be measured rapidly using applanation tonometry and significantly higher values have been reported among patients with risk factors for vascular disease. Forearm blood flow responses to intrabrachial infusion of acetylcholine independently predict cardiovascular morbidity among hypertensive patients. We aimed to examine the relationship between CRPWV, a potentially informative, noninvasive measure and this more established parameter of arterial health. One hundred and fifteen mildly hypertensive individuals (67% men, mean (± SD) age 54 ± 8 years, mean (± SD) blood pressure (BP) 143 ± 16/83 ± 12 mmHg) were recruited from a weekly medical outpatient clinic. Each volunteer had CRPWV measured using sequential tonometry before forearm blood flow responses to intra-arterial, endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators were assessed. There was a significant negative correlation between CRPWV and maximum forearm blood flow response to acetylcholine (r = -0.225, p = 0.016). This association remained significant in a multiple regression analysis (β = -0.213, p = 0.034). Mean arterial pressure and weight were additional independent predictors of CRPWV in this model. There was no such relationship between CRPWV and response to sodium nitroprusside (r = 0.088, p = 0.349). In patients with mild hypertension, a poor forearm blood flow response to acetylcholine independently predicted faster CRPWV, thus linking an established measure of microvascular endothelial function with a noninvasive index of conduit vessel stiffness.     

Configural analysis of the drinking man: fuzzy-set qualitative comparative analyses

The study here presents multiple configurations (i.e., causal recipes) of antecedents associating with heavy drinking using fuzzy-set qualitative comparative analysis (fsQCA). Using national survey data (United States), intermediate solutions of fsQCA analyses yield high consistency and modest coverage in identifying heavy-drinking groups.     

Breast Gangrene in an HIV-Positive Patient

Introduction

Breast gangrene has been reported as a complication following puerperal sepsis, breast surgery, nipple piercings, warfarin toxicity, etc. We report a case of primary breast gangrene in an HIV-positive individual which, to the best of our knowledge, is the first of its kind.

Case report

A 40-year-old previously healthy woman presented with fulminating left breast gangrene. She was detected to be HIV positive. Mastectomy was performed. The detailed management of the condition is discussed.

Conclusion

Severe necrotising infections may be initial manifestations of HIV infection and patients with such infections should be screened for HIV.     

The Reduced Folate Carrier (SLC19A1) c.80G>A Polymorphism is Associated with Red Cell Folate Concentrations Among Women

Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on folate and/or homocysteine levels. The present study was undertaken to assess the association between the SLC19A1 c.80G>A polymorphism and folate/homocysteine concentrations in healthy young adults from Northern Ireland.
The SLC19A1 c.80G>A polymorphism was not strongly associated with either serum folate or homocysteine concentrations in either men or women. However, in women, but not in men, this polymorphism explained 5% of the variation in red blood cell (RBC) folate levels ( P = 0.02). Relative to women with the SLC19A1 c.80GG genotype, women with the GA and AA genotypes had higher RBC folate concentrations. Consequently, compared to women with the SLC19A1 c.80GA and AA genotypes, women who are homozygous for the 80G allele may be at increased risk of having a child affected with a neural tube defect and of developing pathologies that have been associated with folate insufficiency, such as cardiovascular disease.     

The episodic random utility model unifies time trade-off and discrete choice approaches in health state valuation

Background  

To present an episodic random utility model that unifies time trade-off and discrete choice approaches in health state valuation.     

Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Objective

Indexes of brain serotonin_2A (5-HT_2A) density have never been investigated in a sample of humans with violent aggressive behaviour unbiased by medication use or current axis I psychiatric disorders. The objective of this study was to investigate prefrontal cortex 5-HT_2A binding potential (BP_ND), an index of 5-HT_2A density, in an unbiased sample of people with violent aggressive behaviour.

Methods

We used [¹⁸F] setoperone positron emission tomography to measure 5-HT_2A BP_ND in the dorsolateral prefrontal cortex (primarily sampling Brodmann area 9) in 16 participants with violent aggressive behaviour and 16 healthy control participants.

Results

In people with violent aggressive behaviours, the slope of 5-HT_2A BP_ND decline in the dorsolateral prefrontal cortex is 44% less than in healthy control participants (analysis of variance group by age interaction, p = 0.004). Prefrontal cortex 5-HT_2A BP_ND was significantly lower in participants with more severe impulsivity and aggression (multiple linear regression with age and Barratt Impulsivity Scale [BIS] as predictor variables and regional 5-HT_2A BP_ND as dependent variable; effect of BIS, dorsolateral prefrontal cortex: F_1,13 = 7.95, p = 0.014).

Conclusion

Lower prefrontal 5-HT_2A BP_ND is related to violent aggression. Lower 5-HT_2A BP_ND occurs at a younger age, when violent behaviour is more frequent, and is more prominent when impulsivity and aggression are more severe.Medical subject headings: aggression, serotonin, receptors, serotonin, 5-HT_2A, positron emission tomography, setoperone, suicide     

Vena cava tumor thrombus from renal cell carcinoma arising from adrenal vein

Renal cell carcinoma is a highly vascular tumor with the propensity to propagate along venous channels. Vena cava tumor thrombi are reported to occur in approximately 4-10 per cent of cases and requires modification of the standard radical nephrectomy. We report the first 3 cases of vena caval tumor thrombus emanating not from the renal vein, but from the adrenal vein. The recognition of this occurrence is essential in order to avert an intraoperative catastrophe.