Biomedical subjects

A Chandramuki

Publications and source records attributed to A Chandramuki.

At least 19 recordsLinked to original sources

PubMed2005

Neuropathology of HIV/AIDS with an overview of the Indian scene.

Neurological manifestations of HIV infection and AIDS are being recognized with a frequency that parallels the increasing number of AIDS cases. Next to sub-Saharan Africa, India has the second largest burden of HIV related pathology, essentially caused by HIV-1 clade C in both the geographic locales, in contrast to USA and Europe. But the true prevalence of HIV related neuroinfections and pathology is not available due to inadequate medical facilities, social stigma and ignorance that lead to underdiagnosis. Neurotuberculosis, followed by cryptococcosis and toxoplasmosis in various combinations are the major neuropathologies reflecting the endemicity and manifesting clinically by reactivation of latent infection. Discordance in the clinical prevalence of various infections, when compared to pathological studies highlight similarities in clinical, radiological modalities of diagnosis and inherent problems in establishing definitive diagnosis. Viral infections appear to be relatively rare. Inspite of heavy burden of HIV/AIDS, HIV associated neoplasia is infrequent, including primary CNS lymphomas. HIV encephalitis and HIV associated dementia are considered infrequent, though systematic studies have just been initiated in various centres. Peripheral neuropathy characteristically manifests with vasculitic neuropathy while diffuse infiltrative lymphocytosis syndrome (DILS) involving nerves has not been reported from India. Spinal cord pathology including vacuolar myelopathy is rare, even in asymptomatic cases. Till now the AIDS cases in India were drug naive but a new cohort of cases following initiation of HAART therapy as a national policy is soon emerging, altering the biology and evolution of HIV/AIDS in India. Lacunae in the epidemiology, diagnosis and study of biology of HIV/AIDS are outlined for future research.

Antiretroviral Therapy, Highly Active↗

PubMed2003

T helper responses to Japanese encephalitis virus infection are dependent on the route of inoculation and the strain of mouse used.

T helper cytokine and IgG subtype responses were studied in three strains of mice (C57BL/6J, Swiss albino, BALB/c; n=90 per strain) immunized with live Japanese encephalitis virus (JEV) by intraperitoneal (IP), subcutaneous (SC) and peroral (PO) routes. Lymphocytes obtained from the spleens of immunized and control mice were stimulated in vitro with JEV for 48 h and the supernatants were assayed for the presence of the cytokines IL-4 and IFN-gamma. JEV-specific IgG isotypes were also measured in the sera of immunized mice. T helper cytokine responses in mice immunized with JEV were found to be strain- and route-specific in the three species tested. Moreover, they were also dependent on the type of immunogen used (live vs killed virus), as well as the number of doses administered. C57BL/6J and BALB/c mice were more uniform in their T helper responses compared with the outbred Swiss albino mice and induced a good Th1 response (P<0.001). Among the three routes evaluated, the IP and SC routes consistently elicited a Th1 response compared with the PO route (P<0.001), where an initial Th2-type response reverted to a Th1 response after repeated immunization. Live JEV induced a Th1 response while the commercial killed vaccine induced a predominant Th2 profile.

Administration, Oral↗

PubMed2000

HIV antibody profiles in serum and CSF of patients with neurological disease can serve as predictors of outcome.

The serum and CSF antibody profiles were investigated in 100 patients with HIV in relation to the type and severity of neurological disease. Among them, 87 were positive for anti-HIV antibodies in the CSF. In 30 of 87 patients detailed analysis by western blot could be performed. In 20 of 30 the profiles were dissimilar, with more of bands being found in the serum than in the CSF. The correlation of western blot profiles to the clinical outcome indicated that the number of anti-HIV antibody bands as well as the index in the CSF of fatal cases were significantly less compared with non-fatal cases (p=0.019 and p=0.039 respectively).

Adolescent↗

PubMed2000

Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96).

One hundred patients (95 males, 5 females, mean age at presentation 31.6 +/- 9.4 yr) with various neurological disorders associated with HIV infection during 1989-1996 were evaluated at NIMHANS, Bangalore. Eighty patients belonged to group I associated with opportunistic neuroinfections and 20 to group II--non infectious neurological disorders. Cryptococcal meningitis either alone (n = 31) or associated with tuberculous meningitis (n = 6) was the most common (46.3%) followed by neurotuberculosis either alone (n = 24) or with cerebral toxoplasmosis (n = 4) accounting for 35 per cent. Other opportunistic neuroinfections included cerebral toxoplasmosis, herpes zoster, fulminant pyogenic meningitis and neurosyphilis. Clinical characteristics, diagnostic clues, their laboratory and radiological profiles and problems encountered in diagnosis and management of these opportunistic infections are highlighted. In group II (19 males and one female; mean age of 32.6 +/- 9.4 yr), two patients had cortical dementia, three acute brain stem involvement, two epilepsy and one had features suggestive of progressive multifocal leukoencephalopathy. Two patients of group I during follow up developed cortical dementia. Six had peripheral nervous system involvement similar to Guillain-Barre syndrome. Sixty six patients (63 of group I and 3 of group II) progressed to AIDS, 33 patients from group I and one patient from group II succumbed to the disease. With the rapid increase in the incidence of HIV/AIDS and an increase in the neurological manifestations of HIV/AIDS it is important to recognise the magnitude of the problem for health planning in India.

AIDS-Related Opportunistic Infections↗

PubMed1999

Oral immunisation of mice with live Japanese encephalitis virus induces a protective immune response.

This study was undertaken to evaluate the efficacy of oral immunisation of mice with live Japanese encephalitis virus (JEV). Swiss albino mice were immunised with JEV by the peroral (p.o.), intraperitoneal (i.p.) and the subcutaneous (s.c.) routes on days 0, 7 and 14 using either mouse brain derived immunogen (MBDI) or cell culture derived immunogen (CCDI). Oral immunisation of mice evoked high anti-JEV antibody titres by ELISA (Geometric mean titres of 5065 with CCDI and 8854 with MBDI). Moreover, the orally immunised mice showed 76.7% protection with MBDI and 70% with CCDI against intracerebral challenge with a lethal dose of JEV. This study demonstrates for the first time that oral immunisation of mice with live JEV generates a brisk, protective immune response. The results of this study suggest that oral immunisation with JEV holds promise for the future.

Administration, Oral↗

PubMed1997

Cerebrospinal fluid viral antibodies in obsessive-compulsive disorder in an Indian population.

Immunoglobulin G viral antibodies for herpes simplex virus type 1, varicella zoster virus, cytomegalovirus, measles, and mumps were studied in 76 subjects with obsessive-compulsive disorder and compared with a control population. There was a significantly higher titer for herpes simplex virus type 1 antibodies. Sera: cerebrospinal fluid ratios were suggestive of intrathecal synthesis.

Adolescent↗

PubMed1997

Co-existence of cerebral cysticercosis with Japanese encephalitis: a prognostic modulator.

In this study, we investigated the frequency of co-existence of cerebral cysticercosis (CC) in Japanese encephalitis (JE) cases with special emphasis on its role in predicting the final clinical outcome. Amongst the 163 confirmed cases of JE, 37.42% (61/163) had co-existent CC. This was confirmed by antibody detection in the CSF of 45 cases, CT scan of the brain in 6 cases and at autopsy in 3 cases. In 2 cases confirmation was possible by CT scan as well as at autopsy, in 4, CSF antibody levels and CT scan were suggestive of CC while in 1, CSF antibodies and autopsy were suggestive of CC The co-occurrence of Cysticercus cellulosae in the brain emerged as a prognosticator of poor outcome in JE cases (P < 0.03).

Adolescent↗

PubMed1997

Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients.

To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (> 15 pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (> 500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection.

Adolescent↗

PubMed1996

Identification of antibody responses to Mycobacterium tuberculosis antigens in the CSF of tuberculous meningitis patients by Western blotting.

One of the adjunctive modes of diagnosing tuberculous meningitis (TBM) is to detect immune responses in the cerebrospinal fluid (CSF) to the Mycobacterium tuberculosis antigen. Up to 70% of clinical TBM reveal the presence of antimycobacterial antibody by the enzyme-linked immunosorbant assay. Defining the specificity of this immune response by Western blotting on separated M. tuberculosis antigen has been attempted in this study. Only antimycobacterial antibody-positive TBM cases were included in the study. An analysis of 30 such TBM cases showed a major immune reactivity to the 30- to 40-kDa region (93%) while a lower degree of immune reactivity was seen to the 14-kDa region (87%) and to the 18- to 25-kDa region (60%). Grossly the antibody reactivity on Western blot correlated with the ELISA results. Assessment of antimycobacterial antibody in the neurologic control CSF samples of pyogenic meningitis [n = 10], cryptococcal meningitis [6], neurocysticercosis [28], neurosyphilis [8], viral meningoencephalitis [8], carcinomatous meningitis [8], iatrogenic meningitis [6], and nonneurological control CSF samples from patients undergoing spinal anesthesia [20] revealed the presence of antibody in the CSF of 2 of the 10 pyogenic meningitis and 5 of the 28 neurocysticercosis cases. A Western blot analysis of these 7 cases revealed immune reactivity to 30- to 40-kDa regions only in 2 cases (1 of pyogenic and 1 of neurocysticercosis). The remaining 5 CSF samples did not reveal any immune reactivity on Western blotting, although ELISA demonstrated antimycobacterial antibodies. The antibody response to M. tuberculosis lipoarabinomannan and 38-kDa antigen by ELISA revealed 70.58 and 41.17% positivity, respectively. Thus this study has demonstrated that, by Western blotting, the major immune response is to the 30- to 40-kDa region, namely, lipoarabinomannan. Further, this finding will be useful for specific immunodiagnosis of the TBM.

Antibodies, Bacterial↗

PubMed1996

Significance of mycobacterial immune complexes (IgG) in the diagnosis of tuberculous meningitis.

SETTING: Tuberculous meningitis (TBM) has high mortality, especially in children. Early accurate diagnosis and adequate treatment would reduce this mortality. Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF) culture positivity for Mycobacterium tuberculosis and weak clinical correlation with conventional immunoassays. OBJECTIVE: To evaluate significance of mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the diagnosis of TBM. METHOD: CSF from TBM patients and various types of other neurological (both infectious and non-infectious) and non-neurological cases was studied for the presence of IgG and anti-mycobacterial antibodies using antigen capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble extract), respectively. RESULTS: IgG in CSF could be detected in 33 of 55 (60%) and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG, anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious (49), non-infectious neurological cases (30) and non-neurological controls (32) showed the presence of IgG or anti-mycobacterial antibodies. CONCLUSION: Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a large proportion of TBM cases.

Antibodies, Bacterial↗

PubMed1996

Cryptococcal infections of the central nervous system: an analysis of predisposing factors, laboratory findings and outcome in patients from South India with special reference to HIV infection.

The incidence of cryptococcosis in patients with AIDS is significant. Predisposing factors, laboratory findings and outcome were assessed in 60 patients with cryptococcal infections of the central nervous system over a 17.5-year period (Jan. 1978-June 1995). Predisposing factors for cryptococcal infection were identified in 36 patients, with HIV infection being the commonest (18). Cryptococcal cultures were positive in all patients. India ink staining was positive in 48 patients and cryptococcal antigen was detected in 35 of 36 patients tested. Comparison of clinical and laboratory parameters between HIV-positive and HIV-negative patients showed that CSF cell response was poorer, culture of cryptococci from non-neural sites was more frequent and mortality was higher in the HIV-positive group. Although not statistically significant, concurrent systemic infections, especially tuberculosis, were more frequent in the HIV-positive group.

AIDS-Related Opportunistic Infections↗

PubMed1996

Immunohistochemical study of the expression of human groEL-stress protein in human nervous tissue.

Monoclonal antibody (ML-30) directed against 65 kDa stress protein of mycobacteria, is shown to identify human cellular protein homologous with the groEL heat shock protein in many prokaryotes. Immunohistochemical survey of nervous tissue, both central and peripheral, from patients dying of various inflammatory, degenerative and neoplastic conditions and from experimental animals, using this antibody showed punctate granular staining of the cells to a variable degree. The astrocytes showed strong immunolabelling. The normal neurons and oligodendroglia stained variably, while abnormal neurons were darkly labelled. Ependymal cells showed apical granular positivity. The ubiquitinated inclusion bodies in amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease were not recognised by the ML-30 antibody. In diseased and stressed nervous tissue from experimental animals, the expression of the ML-30 recognisable stress protein was variable. The epitope recognised by ML-30 was found stable in postmortem tissues collected up to 36 h after death and processed for paraffin sectioning, after fixation in formalin for many years. Enhanced expression of the human groEL stress protein homologue in mammalian nervous tissue following various forms of stress may play a role in modulating the extent of tissue damage by autoimmune mechanism because of its high immunogenic nature and constitutive presence in the cells.

Animals↗

PubMed1995

Japanese encephalitis virus antigen in the human brain and its topographic distribution.

This study reports the pathological findings and the distribution of viral antigen in the brains of 13 confirmed and autopsied cases of Japanese encephalitis (JE) in correlation with other virus-specific immunological parameters measured in the cerebrospinal fluid (CSF) antemortem. Japanese encephalitis virus (JEV)-specific antibodies were detected in the CSF of 10 of 13 patients, JEV antigen was detected in the CSF of 7 of 13 and JEV-specific immune complexes were detected in the CSF of 3 of 11 patients. Viral antigen was localised immunocytochemically in the brain tissue of 11 of 13 cases, indicating, that viral antigen could not be cleared from the tissues by the antibody. The topographic distribution of the tissue-associated antigen in the thalamus, hippocampus, substantia nigra and medulla oblongata explain the evolution of post JE sequelae.

Antigens↗

PubMed1995

Diagnosis of tuberculous meningitis: a comparative analysis of 3 immunoassays, an immune complex assay and the polymerase chain reaction.

OBJECTIVE: To compare 3 immunoassays, an immune complex assay, and an application of the polymerase chain reaction (PCR) for the diagnosis of tuberculous meningitis (TBM). MATERIAL: Cerebrospinal fluid (CSF) from 33 patients with TBM and from 34 control patients with infectious and non-infectious CNS diseases was analysed. RESULTS: The antibody immunoassays were either nonspecific or insensitive. However, detection of mycobacterial IgG immune complexes correlated strongly with infection, as they were detected in the CSF from 64% of the patients with TBM compared to only 3 (9%) of the control samples. PCR analysis, using Mycobacterium tuberculosis-specific oligonucleotide primers, also strongly correlated with infection, as DNA was amplified from 54% of the samples from patients with TBM, but from only 2 (6%) of the control samples. Both 'false positive' samples were also positive in the immune complex assay and came from 2 patients with otogenic brain abscesses. It is conceivable that these patients suffered from otogenic tuberculosis with secondary non-mycobacterial meningitis. When combining the immune complex assay with DNA-detection by PCR, 100% of the culture positive and 74% of culture negative samples were found to be positive, while maintaining a high specificity. CONCLUSION: Parallel analysis to detect mycobacterial immune complexes and M. tuberculosis-specific DNA by PCR from the CSF of patients may offer a sensitive and specific tool for the diagnosis of TBM.

Adolescent↗

PubMed1995

Assessment of a possible imbalance between tumor necrosis factor (TNF) and soluble TNF receptor forms in tuberculous infection of the central nervous system.

Distributions of tumor necrosis factor (TNF) and its soluble receptor forms, R55-BP and R75-BP, were analyzed in the cerebrospinal fluid of patients with severe acute or chronic central nervous system infections. Tuberculous infections were associated with high ratios of R55-BP and R75-BP to TNF, 27.2 and 28.0, respectively, suggesting a small biologically active fraction of TNF. The opposite was found in subjects with acute bacterial meningitis. They had large fractions of biologically active TNF and thus low ratios of R55-BP and R75-BP to TNF, 3.7 and 4.0, respectively. It is hypothesized that chronic infectious diseases, such as tuberculous infections, may be associated with inadequate production of TNF and a concomitant relative increase of soluble TNF receptors, which may prolong the disease.

Acute Disease↗

PubMed1995

Proliferative response of human peripheral blood mononuclear cells to Japanese encephalitis virus.

Cell-mediated immune response to Japanese encephalitis virus (JEV) and its purified envelope (E) protein was measured in 45 laboratory confirmed JE patients using a proliferation assay of peripheral blood mononuclear cells (PBMC). In parallel, JEV-specific IgM antibodies were measured by ELISA. No correlation was observed between the antibody response and results of the lymphocyte proliferation assay. Only 11 of the 42 patients positive in the antibody test were positive in the proliferation assay, and PBMC from 14/45 (31%) patients did not respond to either phytohemagglutinin and to JEV and/or its purified E protein antigen. No correlation was observed between the cell-mediated immune response and the final clinical outcome (fatality vs. recovery).

Adolescent↗

PubMed1995

Assessment of suitability & ease of performance of seven commercial assay systems for the detection of antibodies to HIV-1.

In this study, we have evaluated the suitability and ease of performance of seven HIV assays namely: Vironostika anti-HIV Uni-Form; Vironostika HIV MIXT; Elavia MIXT; Genelavia MIXT; Serodia-HIV; Immunocomb Bi-spot; and Test pack HIV-1 and 2 Abbott, for use in Indian laboratories. A panel of 41 blind coded Western blot confirmed sera were used for this purpose. Rapid assays like Immunocomb Bi-Spot, Serodia HIV and Test pack HIV-1/HIV-2 Abbott were found to be more suitable and easy to perform as compared to the ELISAs. Sensitivity of all the assays was excellent (100%). Specificity of Serodia HIV, Immunocomb Bi-spot, Test pack HIV-1 and 2 Abbott and Elavia MIXT were excellent (100%), while that of Vironostika MIXT and Vironostika anti-HIV Uni-Form was poor. Positive predictive value of the assays ranged from 64.5 to 100 per cent. Negative predictive value of six of the assays was 100 per cent and that of Vironostika anti-HIV Uni-Form was very poor.

Adult↗

PubMed1995

Pathological lesions in HIV positive patients.

Pathomorphological features of 10 HIV positive individuals studied at autopsy and biopsy are described. Nine patients had evidence of neuro-AIDS and eight of them succumbed to various opportunistic infections. One surviving patient underwent a diagnostic lymph node biopsy which revealed tuberculous lymphadenopathy. Cryptococcal meningitis was the commonest CNS opportunistic infection, seen in five cases, with disseminated systemic cryptococcosis in two. The other opportunistic infections included toxoplasma encephalitis in two, with acanthamoeba infection in one patient. Pulmonary tuberculosis was noted in three patients while other bacterial infections such as meningococcal meningitis, pseudomonas septicaemia were observed in three and pneumocystis carinii pneumonia in one. One seropositive individual was clinically asymptomatic but succumbed to a road traffic accident. The brain in this case showed features of HIV associated early leucoencephalopathy. Bacterial infections caused by organisms other than Mycobacterium tuberculosis associated with AIDS are often underdiagnosed and should be considered, especially in developing countries. In cases of cryptococcal and tuberculous meningitis or multiple parasitic infections, the patients should be screened for associated HIV infection.

AIDS-Related Opportunistic Infections↗