Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

Studies on the pathological effects of feeding betel-nut meal in albino rats.

The pathological effects of betel-nut meal consumption in weaned albino rats were studied for a period of 4 weeks. In higher concentrations (60-100%), toxic effects were observed. The rats showed severe diarrhoea and died within 1-3 weeks depending upon the amount of betel-nut meal consumed. In lower concentrations (5-10%), no grossly detectable pathological changes were observed in any one of the experimental rats. With the increase in the concentration of betel-nut meal in the experimental diets, the pathological changes were intensified gradually. The pathological changes observed in the rats fed with experimental diets containing more than 15% betel-nut meal were necrosis of the buccal and intestinal mucosa, splenomegaly, fatty changes in the liver and stunted skeletal growth. Catarrhal enteritis was observed in the rats fed with 15% betel-nut meal and haemorrhagic gastroenteritis was observed when the concentration of the betel-nut meal was raised above 15%.     

Fine-needle aspiration biopsy in diagnosis of follicular lymphoma: cytomorphologic and immunohistochemical analysis

Follicular lymphoma is a relatively uncommon type of non-Hodgkin's lymphoma (NHL) thought to derive from follicular center cells. There are limitations to fine-needle aspiration in the diagnosis of follicular NHL, and very few studies are available on it. We describe here the cytomorphologic features of eight biopsy-proven cases of follicular NHLs and five biopsy-proven cases of intermediate-grade NHLs. Five cases of reactive lymphoid hyperplasia (RLH) diagnosed on cytology were also studied cytomorphologically. Image morphometry was done in follicular and intermediate-grade NHLs, immunocytochemistry was done in follicular and intermediate-grade NHLs, and immunocytochemistry for bcl-2 expression was studied in five cases of follicular NHLs. The aspirate smears of follicular NHL showed the presence of higher grades, many to abundant (++ to +++) monomorphic lymphoid aggregates, with an increased number of mast cells. Lymphohistiocytic tangles and tingeable body macrophages were not observed in any of the cases. Cytomorphologically, all the cases of intermediate-grade NHL showed a predominantly monomorphic population of lymphoid cells with absent or few grades (+) of lymphoid aggregates. Image morphometric data analysis of each cell parameter for follicular and intermediate-grade NHLs were found to be statistically insignificant (P > 0.05) and hence of little help in diagnosis of follicular vs. low-grade NHLs. Immunocytochemistry for bcl-2 expression in follicular NHL showed variable results, ranging from 0-90% (expressed as bcl-2 index). Certain characteristic cytomorphological features such as the presence of monomorphic lymphoid cell aggregates and an increased number of mast cells are soft indicators for the diagnosis of follicular NHL on aspiration smears. Immunocytochemistry for bcl-2 expression may be of help in cases with clinical and cytological suspicion of lymphoma. Image morphometry has a small role in this regard.     

Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?

PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.     

Brief Clinical Report: Serum Tumor Necrosis Factor for Monitoring Response of Hepatic Veno-occlusive Disease to Pentoxiphyllin-A Case Report

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.     

Two-month glucocorticoid treatment increases proliferation in the stomach and large intestine of rats

BACKGROUND/AIMS: It has been shown that acute or short-term treatments with glucocorticoids lead to a marked decrease in proliferation in the stomach and large intestine. The effects of more prolonged glucocorticoid treatment on cell renewal in these organs are not known. The present work was therefore undertaken to examine the proliferative activity in the stomach and colon during 2 months of glucocorticoid treatment in comparison with shorter treatments. METHODS: Rats were treated with either the glucocorticoid triamcinolone acetonide or vehicle for 63, 33 or 3 days. Proliferation was assessed in the glandular epithelium of the fundal part of the stomach and in the epithelium of the colonic crypts using three criteria: the mitotic index; the bromodeoxyuridine labelling index, and the proliferating cell nuclear antigen-labelling index (percentage of mitotic or labelled cells). RESULTS: Treatment with glucocorticoid for 63 days resulted in a very significant increase in all proliferative parameters tested in the gastric mucosa and the colonic crypts. On the contrary, treatments with glucocorticoid for 3 or 33 days had a marked inhibitory influence on proliferation in these tissues. CONCLUSION: As opposed to treatments for 3 or 33 days, glucocorticoid treatment for 2 months leads to an increase in the number of cycling cells in the gastric and colonic mucosae.     

Myeloid Mixed Lineage Kinase 3 Contributes to Chronic Ethanol-Induced Inflammation and Hepatocyte Injury in Mice

Proinflammatory activity of hepatic macrophages plays a key role during progression of alcoholic liver disease (ALD). Since mixed lineage kinase 3 (MLK3)-dependent phosphorylation of JNK is involved in the activation of macrophages, we tested the hypothesis that myeloid MLK3 contributes to chronic ethanol-induced inflammatory responses in liver, leading to hepatocyte injury and cell death. Primary cultures of Kupffer cells, as well in vivo chronic ethanol feeding, were used to interrogate the role of MLK3 in the progression of liver injury. Phosphorylation of MLK3 was increased in primary cultures of Kupffer cells isolated from ethanol-fed rats compared to cells from pair-fed rats. Kupffer cells from ethanol-fed rats were more sensitive to LPS-stimulated cytokine production; this sensitization was normalized by pharmacological inhibition of MLK3. Chronic ethanol feeding to mice increased MLK3 phosphorylation robustly in F4/80⁺ Kupffer cells, as well as in isolated nonparenchymal cells. MLK3^−/− mice were protected from chronic ethanol-induced phosphorylation of MLK3 and JNK, as well as multiple indicators of liver injury, including increased ALT/AST, inflammatory cytokines, and induction of RIP3. However, ethanol-induced steatosis and hepatocyte apoptosis were not affected by MLK3. Finally, chimeric mice lacking MLK3 only in myeloid cells were also protected from chronic ethanol-induced phosphorylation of JNK, expression of inflammatory cytokines, and increased ALT/AST. MLK3 expression in myeloid cells contributes to phosphorylation of JNK, increased cytokine production, and hepatocyte injury in response to chronic ethanol. Our data suggest that myeloid MLK3 could be targeted for developing potential therapeutic strategies to suppress liver injury in ALD patients.Key words: Alcoholic liver disease (ALD), Kupffer cells, Necroptosis, Toll-like receptor 4 (TLR4), Cytokines