Ambulatory total extraperitoneal inguinal hernia repair: feasibility and impact on quality of life.

BACKGROUND AND OBJECTIVES: Feasibility of ambulatory laparoscopic inguinal hernia repair in developing countries is not known due to lack of dedicated outpatient centers. This study prospectively evaluated the feasibility of outpatient discharge after laparoscopic total extraperitoneal inguinal hernia repair done in combination with in-hospital services and its impact on quality of life. METHODS: Forty patients were studied who had uncomplicated inguinal hernias and fulfilled the selection criteria. Quality of life was evaluated by using the SF-12 questionnaire. RESULTS: Ninety percent of patients could be discharged as outpatients. Four patients required admission. No major complications or readmissions occurred. Physical components of quality of life deteriorated in the immediate postoperative period but improved to above preoperative levels within one month. A transient deterioration in subgroups of the mental health component was observed, which recovered to normal in less than a week. There was no significant alteration in the emotional component. There has been no recurrence at a median follow-up of 25 months. CONCLUSION: It was feasible to safely perform outpatient TEP in combination with routine in-hospital services without increasing complications or causing any adverse impact on quality of life. This was possible subject to adherence to proper selection and discharge criteria.     

Head and Neck Histoplasmosis—A Nightmare for Clinicians and Pathologists! Experience at a Tertiary Referral Cancer Centre

Histoplasmosis is a rarely reported deep mycotic infection in the Indian context. Oral or oropharyngeal manifestation can occur as an isolated symptom or as part of a disseminated process associated with immunosuppression especially with HIV and diabetes. Five cases of head and neck histoplasmosis accrued over 6 years in a tertiary referral cancer institute were reviewed. All these patients presented clinically as cancer. In three patients, the marked pseudoepitheliomatous hyperplasia led to a mistaken biopsy diagnosis of malignancy following which definitive surgical treatment was performed. The subsequent excision revealed typical features of histoplasmosis. Isolated oral presentation of histoplasmosis can mimic malignancy both clinically as well as pathologically, leading to potentially disastrous consequences. A high index of suspicion in those with overt or hidden immunosuppression and a deep wedge biopsy to demonstrate the organisms in the subepithelial tissue is recommended. This work has been presented in the “Slide seminar on Infections and Infestations” in the IAP-ID pre conference CME in APCON 2006.     

Vitamin C-induced loss of redox-dependent viability in lung microvascular endothelial cells

Recent clinical trials have shown that vitamin C, at pharmacological concentrations (milligram to approximately gram), upon infusion into circulation, modulates vasodilation and vascular tone in humans. This also results in the elevated concentrations of vitamin C in circulation in the millimolar range. Here, it was hypothesized that vitamin C at pharmacological concentrations (millimolar) would induce oxidative stress and cause loss of redox-dependent cell viability in vascular endothelial cells (ECs). To test the hypothesis, bovine lung microvascular ECs (BLMVECs) in monolayer cultures were exposed to vitamin C (0-10 mM) for different time periods (0-2 h). Electron paramagnetic resonance spectroscopy revealed the intracellular formation of ascorbate free radical in a dose- and time-dependent fashion. Vitamin C also induced formation of intracellular reactive oxygen species in a dose-dependent fashion. It was observed that vitamin C induced morphological alterations and loss of cell viability in a dose- and time-dependent fashion, as measured by light microscopy and Alamar Blue redox cell viability assay, respectively. Vitamin C analogues failed to induce such changes. Vitamin C depleted cellular GSH levels in a dose-dependent fashion, suggesting that vitamin C altered thiol-redox status in BLMVECs. Antioxidants, intracellular iron chelator, and catalase protected cells against vitamin C-induced loss of redox-dependent cell viability, confirming the role of hydrogen peroxide and iron during redox cycling of vitamin C. These results, for the first time in detail, established that vitamin C at pharmacological doses induced oxidative stress and loss of redox-dependent cell viability in microvascular ECs.     

Cytokines: the yin and yang of vitiligo pathogenesis

Introduction: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients.

Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes.

Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo.     

Viral serpin, Serp-1, inhibits endogenous angiogenesis in the chicken chorioallantoic membrane model.

BACKGROUND: Angiogenesis is a critical factor in the development of malignant tumors, in arthritic joints, and in cardiovascular disease. In cardiovascular disease, angiogenesis is recognised both as a potential therapy and as a complicating factor in atherosclerotic plaque rupture and thrombotic obstruction. Serine proteases regulate thrombosis, inflammation, and cell invasion, events that trigger various stages of angiogenesis and are in turn regulated by inhibitors, termed serpins. Serp-1 is a secreted anti-inflammatory viral serpin that profoundly inhibits early mononuclear cell invasion, and the development of atherosclerosis, transplant vasculopathy, and arthritis in a range of animal models. METHODS: The capacity of Serp-1 to alter angiogenesis was evaluated in the chicken chorioallantoic membrane (CAM) model using morphometric analysis of vascular changes and RT-PCR to explore alterations in gene expression. RESULTS: Serp-1 inhibited endogenous angiogenesis in a dose-dependent manner, with associated altered expression of laminin and vascular endothelial growth factor (VEGF). Serp-1 was ineffective in CAMs no longer in the rapid growth phase. Similar inhibition of angiogenesis was detected after inhibition of VEGF, but not after treatment with the inactivated reactive center loop mutant of Serp-1. CONCLUSIONS: The angiogenic process can be controlled using Serp-1, an anti-inflammatory agent that is effective at low concentrations with rapid reversibility, targets endothelial cells, and reduces the availability of VEGF. These properties may be especially important in cardiovascular disease, reducing plaque destabilization. It is likely that the anti-angiogenic activity of Serp-1 contributes to the observed anti-inflammatory and anti-atherogenic actions with potential importance in this therapeutic setting.     

DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients

Dysbindin gene (DTNBP1) has been associated with schizophrenia, but literature findings are inconsistent, and further analyses are required. This study is aimed to investigate if a set of DTNBP1 variations might influence clinic psychotic phenotype or treatment response in a sample of 240 Korean schizophrenic in-patients. Four variants have been selected (rs3213207; rs1011313; rs16876759; rs2619522) on the basis of previous findings of association with schizophrenia, bipolar disorder and antidepressant response. Single marker analysis gave marginal results. Haplotype analysis identified a significant association between A–A (rs3213207(A/G), rs1011313(A/G)) haplotype and lower PANSS total and positive scores at baseline (p = 0.01; 0.02) and at discharge (p = 0.008; 0.005). Covariate analysis revealed a more stable significant association between A–A haplotype and baseline scores. These results suggest a protective effect of A–A haplotype on psychotic positive symptoms at baseline.