The absence of JC virus antigens in Indian children with medulloblastomas.

BACKGROUND: The human polyoma virus, also known as the JC virus (JCV), replicates predominantly in the oligodendrocytes, the myelin producing cells in the central nervous system and results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) especially in immunosuppressed patients with AIDS. Several investigators have also documented the presence of the viral genome and early and late antigens in a variety of brain tumors particularly in medulloblastomas, gliomas and ependymomas. Reports also indicate the presence of JCV in patients with colon cancer. The T antigen of JCV has been postulated to have oncogenic potential as substantiated by animal experiments. Although JCV infects 80% of the population, there are scant epidemiological studies regarding JCV from India. There are also reports of the low prevalence of PML in patients with AIDS from India and Africa. AIM: This study was undertaken to investigate if Indian children with medulloblastomas also show evidence of JCV. METHODS: Twenty-two consecutive cases of medulloblastomas were investigated for the presence of T antigen and agnoprotein of JCV in biopsy specimens by immunohistochemistry. Antibodies to the agnoprotein antigen raised in rabbits and a monoclonal antibody against SV40 T antigen raised in mice that cross-reacts with JCV T antigen were used. RESULTS: Out of 22 patients, 4 had desmoplastic tumors while the rest had classical tumors. All children were below the age of 10. Results indicate that while PML tissues showed consistent immunostaining both with antibody to T antigen and agnoprotein antibody, none of the tumors showed any positive staining for JC viral antigens. CONCLUSION: JCV antigens could not be detected by immunohistochemistry in the tumor tissues of Indian children with medulloblastomas.

Time trends of paediatric HIV infection in North India.

Paediatric HIV infection continues to pose a serious threat in the developing world. While in the developed world, mother to child transmission has been reduced to less than 3%, in India no regular zidovudine (azidothymidine) intervention programmes operate. Some 20 million babies are born each year and the number of infected babies could be >50,000 per year. The present study was designed to assess the change, if any, in the time trends of HIV infection in children over the last 15 years as observed at the surveillance centre attached to Nehru Hospital, Chandigarh. All patients reporting to the surveillance centre at the PGIME&R, Chandigarh were subjected to a detailed history and screened for HIV by the three tests protocol recommended by the WHO. In babies under 18 months of age, viral load assay or DNA analysis was done to confirm infection. Timetrends were ascertained over a 15-year period to assess the impact of information, education and communication programme launched by National AIDS Control Organisation. Data indicates that the total number of HIV positive cases increased 10-fold over the last 10 years. During 1991, 41 cases were recorded; the number increased to 439 in year 2001, and 574 in 2004 (r=0.98). A similar trend was observed in the paediatric age group. During the initial 5 years ie, 1987 to 1992 only 7 paediatric cases were documented positive while the number increased to 45 in the year 2001 to 64 in the year 2004 with a cumulative figure of 323 children. Linear regression analysis showed a highly significant trend (r=0.94). Out of the 323 cases, 44.6% were symptomatic. Maximum number of babies were observed in the age group of 3-5 years. Thirty-nine patients (12%) had acquired the infection through blood. Thus the information, education and communication programme has had very little impact on the HIV epidemic and it calls for urgent antiretroviral intervention in antenatal mothers to control the emerging paediatric HIV epidemic.

Poor responses to recombinant HBV vaccination in patients with HIV infection.

The study was conducted with an aim to assess the efficacy of recombinant HBV vaccination in untreated HBV seronegative HIV/AIDS subjects as compared to normal controls. The second objective was to identify differences in CD4 and CD8 T cell numbers/kinetics/functions and levels of TH2 cytokines (IL4 and IL10) in different groups during the three-dose vaccination regimen. 40 HIV/AIDS patients were subdivided into groups 1A where patients had a high CD4 (> 200/mm3) count and IB where patients had a low CD4 (< 200/mm3) count. Twenty normal healthy control subjects were also recruited in the study (group II). Patients received 40 micro and controls received 20 micro of recombinant HBV vaccine in each dose. All subjects received 3 doses of the vaccine. Detection of CD4 and CD8 cells was done by flowcytometry. TH2 type of cytokines IL4 and IL10 were estimated in the culture supernatant of PHA stimulated leukocyte rich plasma by sandwich ELISA. Anti-HBs levels were estimated in the serum by ELISA. Anti-HBs response was severely compromised in patients as compared to controls. Groups II, 1A and 1B showed titers of 16906 +/- 21303, 8834 +/- 14136 and 462 +/- 814 m/U/m/ respectively. Both CD4 and CD8 cells increased significantly after vaccination in all the groups irrespective of the disease status. On the other hand, IL4/IL10 responses to PHA stimulation in the HIV-positive groups were much lower than in controls (P< 0.1). Despite a double dose of vaccine in patients, the antibody response was significantly lower which correlated with a lower CD4 count. Cytokines IL4 and IL10 which regulate antibody response, were also lower in-patients and this together with a low CD4 count possibly accounted for the low anti-HBs levels. All patients with high CD4 lymphocyte count were responders while only 47% of patients with low CD4 lymphocyte count responded to immunization. Patients with a CD4 count of less than 50 failed to respond. Thus early immunization is advocated in all HIV patients at a stage when they are still capable of mounting an adequate immune response.

Clinico-cytopathological spectrum of hepatocellular carcinoma, its correlation with serum alpha-fetoprotein level, and hepatitis B and C viral markers.

Fine-needle aspirationbiopsy (FNAB) is now widely accepted as a diagnostic modality for the treatment of hepatocellular carcinoma (HCC). The most common diagnostic problem in HCC is distinguishing it from a metastatic carcinoma. The literature from India on HCC is scanty. Hence, we studied the cytomorphological features of HCC and metastatic carcinoma. The study included 37 cases of space-occupying lesions (SOLs) of the liver as demonstrated by ultrasound or computed tomography (CT) scan. Cytomorphological features of these SOLs were analyzed in all subsequent to FNAB. Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-HCV) and alpha-fetoprotein (AFP) were determined in all the cases by enzyme-linked immunosorbent assay (ELISA). The cytopathological diagnosis was HCC in 22 and metastatic carcinoma of the liver in 15. The individual cytomorphological features and which helped to make a definite diagnosis of HCC were: a high nuclear cytoplasmic ratio (81.8%), predominantly trabecular pattern (63.6%) and atypical naked nuclei (100%). Other features were prominent multiple nucleoli (63.3%), hyperchromasia (100%) and moderate anisonucleosis (59%). AFP was elevated in 81.8% of the cases with a mean of 634.8+812.7 ng/ml. HBsAg by ELISA was found to be positive in 72.7% of cases while only 1 case (4.5%) was positive for anti-HCV. In 1 case (4.5%), there was dual infection due to hepatitis B virus (HBV) and HCV. No viral cause was found in 18.3% of cases.