Transmesenteric hernia: A rare cause of bowel ischaemia in adults

INTRODUCTIONTransmesenteric herniae are a rare cause of bowel ischaemia in adults with few reported cases in published literature.PRESENTATION OF CASEWe report a rare case of a 26-year-old female with spontaneous transmesenteric hernia of jejunum and proximal ileum due to a congenital mesenteric defect resulting in bowel gangrene, presenting initially with no haemodynamic or biochemical abnormalities. The hernia was reduced, small bowel resected and primary side to side anastomosis performed, following which the patient made a good recovery and was discharged 5 days later.DISCUSSIONThe insidious onset of transmesenteric herniae and lack of specific radiological or laboratory investigations reaffirms the importance of surgeons maintaining a high index of suspicion for this critical surgical emergency.CONCLUSIONClose monitoring of the patient's general condition in cases of non-specific abdominal pain is essential to identify the rare deteriorating patient for early surgical intervention and optimal outcome.     

In schizophrenia,non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy

Around one third of schizophrenia patients are non-responders to antipsychotic therapy. The present study aimed to delineate the pathway-phenotypes of non-remitters (NRTT) and partial remitters (PRTT) to treatment with antipsychotics as defined using the Global Clinical Impression scales. We recruited 60 NRTT, 50 PRTT and 43 healthy controls and measured schizophrenia symptoms, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and μ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Soft independent modeling of class analogy (SIMCA) showed that NRTT and PRTT are significantly discriminated with a cross-validated accuracy of 94.7% and are qualitatively distinct classes using symptomatome, and neuro-immune-opioid-cognitome (NIOC) features as modeling variables. Moreover, a NIOC pathway phenotype discriminated PRTT from healthy controls with an accuracy of 100% indicating that PRTT and controls are two qualitative distinct classes. Using NIOC features as discriminatory variables in SIMCA showed that all PRTT were rejected as belonging to the normal control class and authenticated as belonging to their target class. In conclusion, a non-response to treatment can best be profiled using a SIMCA model constructed using symptomatome and NIOC features. A partial response should be delineated using SIMCA by authenticating patients as controls or PRTT instead of using scale-derived cut-off values or a number of scale items being rated mild or better. The results show that PRTT is characterized by an active NIOC pathway phenotype and that both NRTT and PRTT should be treated by targeting neuro-immune and opioid pathways.

     

Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia

Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.     

Curcumin has a palliative action on gentamicin-induced nephrotoxicity in rats

Generation of free radicals in kidney cortex plays an important role in the pathogenesis of gentamicin (GM) nephrotoxicity, and curcumin, the yellow curry pigment isolated from turmeric, has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of curcumin on GM nephrotoxicity. Curcumin was given to rats at an oral dose of 200 mg/kg/day for 10 days, and in some of these rats GM was also injected intramuscularly at a dose of 80 mg/kg/day during the last 6 days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, and reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex. The concentration of GM in renal cortex was measured microbiologically. GM significantly increased the concentrations of urea and creatinine (P < 0.05) by about 111 and 97%, respectively. GM treatment reduced cortical GSH concentration by about 31% (P < 0.05), and the activity of SOD by about 27% (P < 0.05). Curcumin significantly mitigated these effects. Sections from saline and curcumin-treated rats showed apparently normal proximal tubules. However, kidneys of GM-treated rats had a moderate degree of necrosis. The degree of necrosis appeared lessened when GM was given simultaneously with curcumin. The concentration of GM in the renal cortex of the rats given GM + curcumin was significantly (P < 0.05) lower than that found in rats treated with GM alone by about 39%. The results suggested that curcumin had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further studies, curcumin may potentially be useful as a nephroprotectant agent.     

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

AIM To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy.METHODS A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensinconverting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance(HOMA-IR).RESULTS Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis(F0-F) = 179, moderate fibrosis(F2) = 64, and advanced fibrosis(F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage(P 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤-0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis.CONCLUSION Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.     

Thoracic Epidural Anesthesia Attenuates Hemorrhage-induced Impairment of Intestinal Perfusion in Rats

Background: During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats.

Methods: In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry.

Results: During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15]vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7]vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa.