Histologic and Manometric Studies on the Esophagus Following Endoscopic Sclerotherapy

Objective The aim of this work was to study the histologic and manometric changes in the distal esophagus beyond 2 years following endoscopic sclerotherapy (EST) and/or surgical intervention, and to try to understand the etiological factors associated with these changes. Patients and interventions Forty patients, with an average age of 61.5 years, were studied for 2–12 years following sclerotherapy and/or surgical intervention. The causes of liver disease were alcoholic cirrhosis (78.6%), primary biliary cirrhosis (14.3%), and chronic aggressive hepatitis (7.1%). A predominant number of cases (65%) had a mesocaval interposition shunt due to the failure of EST, 32.5% EST alone, and 2.5% esophageal devascularization. All patients had esophageal manometry following mucosal biopsies taken in duplicate endoscopically from three levels of the distal esophagus. Results In the EST and shunt groups, 88.5% had manometric abnormalities, esophagitis, and chronic inflammatory changes. In the EST group, all but two patients had manometric abnormalities and chronic inflammatory changes. Analysis of the patient groups on the basis of the number of EST sessions and the amount of sclerosant injected showed that both histologic changes and dysmotility were more profound in those treated over five times with EST. The differences were significant. Conclusion It appears that EST causes persistent manometric abnormalities and chronic inflammatory changes in the distal esophagus, the severity of which seems to vary directly with the frequency of sclerotherapy and not amount of sclerosant injected.     

Membranous nephropathy with light chain restricted deposits

The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M‐type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow‐up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow‐up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non‐malignant associated MN with monoclonal deposits on IF.     

Imaging features of central nervous system fungal infections

Fungal infections of the central nervous system (CNS) are rare in the general population and are invariably secondary to primary focus elsewhere, usually in the lung or intestine. Except for people with longstanding diabetes, they are most frequently encountered in immunocompromised patients such as those with acquired immunodeficiency syndrome or after organ transplantation. Due to the lack of inflammatory response, neuroradiological findings are often nonspecific and are frequently mistaken for tuberculous meningitis, pyogenic abscess or brain tumor. Intracranial fungal infections are being identified more frequently due to the increased incidence of AIDS patients, better radiological investigations, more sensitive microbiological techniques and better critical care of moribund patients. Although almost any fungus may cause encephalitis, cryptococcal meningoencephalitis is most frequently seen, followed by aspergillosis and candidiasis. The biology, epidemiology and imaging features of the common fungal infections of the CNS will be reviewed. The radiographic appearance alone is often not specific, but the combination of the appropriate clinical setting along with computed tomography or magnetic resonance may help to suggest the correct diagnosis.     

Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions

Background: Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA-IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). Results: Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 ± 41.8 vs. 118 ± 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 ± 26.8 vs 74.3 ± 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. Conclusions: Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.     

Determination of stature from cephalo-facial dimensions in a North Indian population

A forensic medicine specialist, while a conducting medico-legal autopsy, is often asked to opine about the identity of the deceased in unknown fragmentary and dismembered remains. Determination of stature is an important aspect in establishing identity in such cases. Sometimes, cephalo-facial remains are brought for postmortem and forensic examination. The aim of the present study was to estimate the stature from cephalo-facial dimensions in a sample of 252 Koli male adolescents from North India. As a part of Indian caste system, Kolis are an endogamous group of North India. Along with stature, sixteen cephalo-facial measurements were taken on each subject. The findings suggest that all the cephalo-facial measurements are significantly correlated with stature (P<0.001, P<0.01); the measurements of the cephalic region have strong correlation with stature than those of the facial region. This was also supported by the regression analysis, which shows that the cephalic measurements give better prediction of stature. Reliability of the regression formulae was checked by comparing the estimated and actual stature within the same sample (genetically homogeneous population, n=252) and in another sample taken from a mixed population of North India (genetically heterogeneous population, n=90).     

Reassessing cultural evaluations in geriatrics: insights from cultural psychiatry

Current cultural competency models in geriatrics represent positive developments but may focus disproportionately on group-level information without attending to intracultural, individual variations. This article reviews these limitations and introduces the cultural formulation from psychiatry as a more-thorough assessment strategy. By focusing on the patient's relationships with cultural identity, illness explanations, social networks, and the physician, a cultural formulation designed for geriatrics may help clinicians plan treatment and follow-up in a more-comprehensive and -patient-centered way. Detailed case studies illustrate its potential applications within geriatrics.     

Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity

Withania somnifera, commonly called Ashwagandha in the Indian traditional system of medicine has been reported for several pharmacological activities. This study demonstrates, for the first time, the potential role of the chemically standardized leaf extract of W. somnifera (WSL) and it's identified component in activating immune system. WSL enhanced Th1 cytokine IFN-γ expression in Con A primed splenocytes in vitro. When given orally for 2 weeks to BALB/c mice immunized with emulsion of OVA in Freund's adjuvant (OVA-FCA), it caused dose-dependent proliferation of T cells and improved their ability to secrete IL-2 and IFN-γ, but moderately down-regulated Th2 cytokine IL-4. Flow cytometric analysis of lymphocyte surface markers of T cells CD3⁺, CD4⁺ and CD8⁺, and B cells CD19⁺ indicated prominent enhancement in proliferation and differentiation of lymphocytes. Further, the effect of WSL in immunized mice elicited up-regulation of β-integrins LFA (CD11a) and Mac-1 (CD11b) in splenocytes. Co-stimulatory molecules CD80 and CD86 that are important secondary signals for the activation of immune system elicited remarkable enhanced expression when observed in spleen-derived macrophages isolated from WSL treated mice. Chemical standardization of WSL suggested that the withanolide 2,3 dihydro-3-sulphonile withanone is a major constituent of WSL responsible for skewing to Th1 immune polarization by stimulating the expression of IFN-γ and B cell switch over to secrete IgG2a while simultaneously enhancing the expression of co-stimulatory molecules and integrins. These studies demonstrate the possible usefulness of WSL and its major constituent WSL-2 as Th1 immune adjuvants for chronic infectious ailments where patients suffer from weakened Th1 immunity.