Changing perspectives in Japanese encephalitis in India

Japanese encephalitis is a serious public health problem with significant mortality in children and old people. It occurs throughout much of Asia (43 000 cases worldwide per year). In recent years it has caused many epidemics in different parts of the country. In view of the high mortality and severe sequelae which often leaves behind highly dependent and disabled survivors, the disease is assuming great importance. A review of the pathogenesis, epidemiology, management and prevention together with changing perspectives in all these areas is presented.     

Chronic Granulomatous Disease: Two Decades of Experience From a Tertiary Care Centre in North West India

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57 %) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.     

Vitamin E Supplementation,Superoxide Dismutase Status,and Outcome of Scaling and Root Planing in Patients With Chronic Periodontitis: A Randomized Clinical Trial

Background: This study investigates the levels of superoxide dismutase (SOD) activity in serum and saliva of patients with chronic periodontitis (CP). In addition, the outcome of scaling and root planing (SRP) with and without vitamin E supplementation is evaluated in terms of changes in periodontal parameters and SOD activity in patients with CP. Methods: Serum and salivary SOD activity in 38 patients with CP were compared with those of 22 systemically and periodontally healthy individuals (control group). At periodontal examination, serum and saliva samples were obtained. Patients with CP were randomly divided into treatment groups 1 (TG‐1) and 2 (TG‐2). SRP was performed for both groups, and TG‐2 also received 200 mg (300 IU) vitamin E every other day. Periodontal parameters and SOD activity were evaluated after 3 months. SOD activity was determined using an SOD assay and enzyme‐linked immunosorbent assay reader at 450 nm. Results: SOD activity in both serum (P <0.05) and saliva (P <0.001) was lower in patients with CP compared with controls. After 3 months of follow‐up, SOD activity improved in both treatment groups; however, the improvement in TG‐2 was higher than in TG‐1, along with more improvement in periodontal parameters. Serum SOD levels in TG‐2 increased even above the level of the control group. Conclusions: Systemic and local SOD levels are lowered in CP. Adjunctive vitamin E supplementation improves periodontal healing as well as antioxidant defense.     

Malignant transformation in mature cystic teratoma of the ovary: report of five cases and review of the literature

The incidence of malignant transformation in mature cystic teratoma (MCT) of the ovary is less than 2% as reported in gynaecological and pathological literature. Here we present a series of five patients, who developed malignant transformation in MCT of the ovary, over a 6-year period (1999–2004). The morphological and clinico-pathological features of malignant transformation in MCT of the ovary are discussed.     

Immune biology of macaque lymphocyte populations during mycobacterial infection

Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette-Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and gammadelta T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and gammadelta T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of gammadelta T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and gammadelta T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded alphabeta and gammadelta T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and gammadelta T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates.     

The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelial derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are underway to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers, and are now underway to assess the safety and efficacy of Poly SFH-P as a clinically useful red cell substitute in the treatment of acute blood loss in the setting of trauma and surgery.     

In vivo effects of anti-leprosy drugs on the rat peritoneal macrophages and lymphocyte subpopulations.

The present study describes the in vivo effects of anti-leprosy drugs on rat peritoneal macrophages and T-cell homeostasis. It was observed that BCG-elicited rat peritoneal macrophages produced more H2O2 and expressed more Ia antigen on their cell surfaces compared with resident peritoneal macrophages. Furthermore, elicited macrophages isolated from rats administered multidrug therapy (MDT), consisting of dapsone, clofazimine and rifampicin in high dose (10 x MDT) released more O2-. On the contrary, there was a significant decrease in the Ia antigen expression on these macrophages. Anti-leprosy drug treatment in high dose (10 x MDT) decreased the total number of blood T-helper (W3/25+) cells and increased the total number of blood T-suppressor (OX-8+) cells which resulted in a significant decrease in a W3/25: OX-8 ratio. Electron microscopy of elicited macrophages isolated from 10 x MDT treated rats showed development of many filipodia compared with control macrophages. These data show that 10 x MDT treatment in rats for 1 month alters the homeostasis of blood T-cell subpopulations which perhaps decreases the Ia expression on macrophages. However, the increase in O2- production and the appearance of filipodia on the macrophages is due to a direct effect of drugs on the macrophages. MDT treatment for 1 month in a therapeutic dose has no effect on the above-mentioned parameters.