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.

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non-specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

Nine cases of plasma cell tumors were diagnosed by fine-needle aspiration cytology, the sites of aspiration being soft-tissue swellings in five cases, lymph nodes in three cases, and both soft-tissue swelling and lymph node in one case. The age of the patients ranged from 33 to 74 yrs, with a median of 52 yrs. Only three of these nine cases were clinically diagnosed as multiple myeloma. Unequivocal demonstration of myeloma cells was possible in eight cases. The smear in ninth case showed mostly undifferentiated blast cells with a few cells showing plasmacytoid differentiation. Giant myeloma cells with monstrous segmented nuclei were encountered in two cases. M-component could be demonstrated in serum and/or urine samples in all seven cases in which it was sought.

Increasing numbers of children affected by HIV are being recognised in northern India. The present study aimed to evaluate the clinical profile of 516 children affected by HIV at the Pediatric Allergy and Immunology Unit, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India, during the period January 1994 to May 2008. In total, 454 children (327 boys and 127 girls) infected by HIV were analysed. The median age at presentation was 54 months. Of these children, 401 (88.3%) acquired the infection vertically and 26 (5.7%) acquired it through transfusion of blood/blood products. Moreover, 156 children (34.4%) were asymptomatic at presentation to hospital. Common clinical features included fever (36.6%), respiratory infections (31.7%), lymphadenopathy (30.0%), hepatosplenomegaly (21.8%) and diarrhoea (18.1%); 299 children (65.9%) were malnourished. Triple drug antiretroviral therapy was initiated in 205 children. Children receiving such therapy showed significant improvement in clinical and immunological parameters. Furthermore, follow-up rates improved markedly following free supply of the drug. Therapy was very well tolerated. To conclude, physicians looking after children need to be familiar with the varying clinical presentation of HIV infection. To the best of our knowledge, this is the largest paediatric series on HIV infection from a single centre from any developing country.

Summary In order to identify a specific recombinant antigen oi Leishmania donovani with potential use for diagnosis, a cDNA library was constructed in lambda ZAP II expression vector. On screening the cDNA library using pooled sera from Indian patients with kala azar, 20 antibody reactive clones were identified. These were subcloned into pBluescript phagemid by an in vivo excision procedure. The molecular weights of the expressed recombinant proteins varied from 15 to 70 kDa and the cDNA insert sizes varied from 0.5 kb to the largest size of approximately 2.0 kb which was designated as the E2b clone. The nucleotide sequencing revealed that 50% of the clones had sequence homology to the heat shock protein gene of L. donovani. The serological studies conducted with the kala azar positive sera and sera from healthy laboratory workers using the recombinant protein from the E2b clone and having sequence homology to Ldhsp 70. indicated that although all the kala azar sera were positive. 12 of 20 healthy individuals also showed antibodies against the recombinant hsp70. indicating that this antigen is not suitable for serological diagnosis of kala azar.