PubMed Health⌕ Search

Biomedical subjects

R Prabhakar

Publications and source records attributed to R Prabhakar.

At least 37 records · Page 2Linked to original sources
PubMed1998

Influence of HLA-DR2 phenotype on humoral immunity & lymphocyte response to Mycobacterium tuberculosis culture filtrate antigens in pulmonary tuberculosis.

Association of HLA-DR2 genes/gene products has been shown with pulmonary tuberculosis (PTB) patients in India. In the present study, the influence of HLA-DR2 and non-DR2 genes/gene products on immunity to tuberculosis has been studied. Plasma samples of -DR2 positive patients (active and inactive TB) showed a higher antibody titre to Mycobacterium tuberculosis culture filtrate antigens than non-DR2 (-DR2 negative) patients. Immunoblot analysis revealed a trend towards an increased percentage of DR2 positive patients recognizing 38, 32/34 and 30/31 kDa antigens of M. tuberculosis than DR2 negative patients. A low spontaneous lymphoproliferative response (without antigen stimulation) was seen in HLA-DR2 positive active TB patients than HLA-DR2 negative patients. However, the antigen stimulated lymphocyte response was higher in the -DR2 positive patients (active and inactive TB) when compared to non-DR2 patients. Further, an inversional correlation between antibody titre and spontaneous as well as antigen induced lymphocyte response (measured by 3H thymidine uptake and expressed as counts per minute) was seen in HLA-DR2 positive active PTB patients than non-DR2 patients. The present study suggests that HLA-DR2 genes/gene products may be associated with a regulatory role in the mechanism of disease susceptibility to tuberculosis. The genes while augmenting the humoral immune response, they suppress the spontaneous and antigen induced lymphocyte response in -DR2 positive patients with active disease.

Adult↗
PubMed1997

Restriction fragment length polymorphism of Mycobacterium tuberculosis strains from various regions of India, using direct repeat probe.

Intraspecies differentiation was studied on 68 M. tuberculosis strains obtained from 6 states of India by restriction fragment length polymorphism (RFLP) using a direct repeat probe (DR probe) hybridised with Alu I digest of DNA. Most strains showed polymorphism based patterns that comprised between 2 to 7 bands and were grouped into 26 RFLP types. Of the 11 strains tested from Amritsar, 8 were RFLP type 5; the remaining 3 were of type 11 and were exclusively confined to this region. The strains from other regions were more heterogeneous. We confirm that DR-associated RFLP can be an excellent tool for the differentiation of M. tuberculosis strains. Depending on their geographical origin, these strains can be differentiated to a large extent by DR fingerprinting.

DNA Fingerprinting↗
PubMed1997

Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report.

OBJECTIVES: To assess and compare the efficacy of a 6-month short-course chemotherapy regimen (SCC) with that of a 12-month standard regimen in the treatment of abdominal tuberculosis. DESIGN AND SUBJECTS: A total of 193 adult patients with evidence of abdominal tuberculosis were randomly allocated to one of two daily regimens: 1) a 6-month SCC regimen with rifampicin, isoniazid and pyrazinamide for 2 months followed by rifampicin with isoniazid for another 4 months (6R series) and 2) and 12-month standard regimen of ethambutol and isoniazid with streptomycin supplemented for 2 weeks (12E series). Surgery was undertaken only for patients suspected to have obstruction or perforation of the intestine. RESULTS: A total of 163 (85 6R, 78 12E) patients were available for efficacy analysis after exclusion of 30 patients for various reasons. At the end of treatment clinical status was normal in 84 (99%) in 6R patients and in 73 (94%) in 12E patients. Of these, 147 patients completed follow-up for 5 years; none had relapsed requiring treatment for abdominal tuberculosis. CONCLUSION: A 6-month SCC regimen has been found to be as effective as the standard 12-month regimen in the treatment of all forms of abdominal tuberculosis.

Adolescent↗
PubMed1997

Short-course chemotherapy in the treatment of Pott's paraplegia: report on five year follow-up.

OBJECTIVE: To assess the efficacy of 9-month short-course chemotherapy (SCC) and to study the pattern of neurological recovery in patients with Pott's paraplegia. DESIGN: Patients with recent onset of spastic paraplegia due to clinically and radiologically active spinal tuberculosis involving vertebral bodies of level D4-L1 were treated with streptomycin, rifampicin, isoniazid and ethambutol daily for the first 2 months, followed by rifampicin plus isoniazid twice weekly for the next 7 months. The study was conducted in 2 phases. In the first phase 10 patients were admitted to the open trial where all patients had undergone modified Hong Kong surgery in addition to chemotherapy. In the next phase 23 patients enrolled in the study were randomly allocated to receive either chemotherapy alone or surgery plus chemotherapy. All the patients were followed for 5 years from the start of treatment. A scoring system was devised to predict neurological recovery. RESULTS: In all, 33 patients were admitted and treated with SCC. Thirteen patients were allocated to the chemotherapy (CHEM) regimen; of these 3 patients had to be operated upon for clinical deterioration; the remaining 20 had surgery plus chemotherapy; 4 were excluded for various reasons, leaving 29 patients in the analysis. None relapsed requiring treatment. CONCLUSION: A combination of surgery (when indicated) and SCC of 9 months' duration is effective in the treatment of Pott's paraplegia. All patients had neurological recovery by the end of 9 months; 8 recovered with chemotherapy alone. Complete motor recovery was seen in 62% by the 3rd month and 90% by the 6th month.

Adolescent↗
PubMed1997

Late onset paraplegia--a sequela to Pott's disease. A report on imaging, prevention and management.

Late onset paraplegia is a neurological complication that develops after a variable period in a patient with healed tuberculous disease of the vertebrae. In this retrospective analysis clinical features, imaging in diagnosis and treatment of this condition are described among 5 cases seen over a period of 5 years. This complication occurred even after successful treatment of initial spinal lesions with rifampicin-containing regimens. Magnetic resonance imaging was useful in pinpointing the exact pathology; one case had syrinx and two cases had marked internal gibbus with cord atrophy. Of the two cases who accepted surgical treatment, one improved.

Adolescent↗
PubMed1997

Study of the feasibility of involving male student volunteers in case holding in an urban tuberculosis programme.

This paper reports the feasibility of involving unpaid National Service Scheme (NSS) male student volunteers in a city-based tuberculosis (TB) programme in supplying drugs and retrieving non-complaint TB patients. Twenty-five students were selected after assessing their attitude and were trained on TB drug delivery, home visits and motivation of non-compliant patients. Twenty-three sputum positive patients identified in a medical camp were started on an 8-month short-course chemotherapy regimen. Students supplied the drugs on a weekly basis and defaulters were visited. The treatment completion rate was 83% and defaulter retrieval was 57%. All patients had sputum smear conversion by 2 months and one relapsed during the 24-month follow-up.

Adolescent↗
PubMed1996

Influence of HLA-DR and -DO phenotypes on tuberculin reactive status in pulmonary tuberculosis patients.

SETTING: HLA and tuberculin status in pulmonary tuberculosis patients. Tuberculosis Research Centre, Indian Council of Medical Research, Madras, India. OBJECTIVE: To elucidate the role of HLA-class-II genes/gene products on tuberculin reactivity in pulmonary tuberculosis patients. DESIGN: Serological determination of HLA-DR and -DQ antigens was carried out in 62 healthy control subjects and 146 pulmonary tuberculosis patients. The tuberculin reaction pattern of pulmonary tuberculosis patients to PPD was studied and the role of HLA-DR and -DQ antigens (class-II gene products) on tuberculin reaction was analysed. RESULTS: HLA-DR and -DQ antigens did not influence high, medium and low tuberculin reaction dramatically in active pulmonary tuberculosis patients. However, a heterozygous combination of various HLA-DR antigens influenced the tuberculin reaction. CONCLUSION: The HLA-genetic make up (heterozygous combination) of the individual may influence the tuberculin reaction pattern in pulmonary tuberculosis.

Adult↗
PubMed1996

Bactericidal action of ofloxacin, sulbactam-ampicillin, rifampin, and isoniazid on logarithmic- and stationary-phase cultures of Mycobacterium tuberculosis.

The bactericidal actions of ofloxacin and sulbactam-ampicillin, alone and in combination with rifampin and isoniazid, on exponential-phase and stationary-phase cultures of a drug-susceptible isolate of Mycobacterium tuberculosis were studied in vitro. In exponential-phase cultures, all drugs were bactericidal, with the higher concentrations of ofloxacin (5 micrograms/ml) and sulbactam-ampicillin (15 micrograms of ampicillin per ml) being as bactericidal as 1 microgram of isoniazid per ml or 1 microgram of rifampin per ml. In two-drug combinations, both drugs increased the levels of activity of isoniazid and rifampin and were almost as bactericidal as isoniazid-rifampin; they also appeared to increase the level of activity of isoniazid-rifampin in three-drug combinations. In contrast, ofloxacin and sulbactam-ampicillin had little bactericidal activity against stationary-phase cultures and were less active than isoniazid or rifampin alone. Furthermore, in two-drug or three-drug combinations, they did not increase the level of activity of isoniazid, rifampin, or isoniazid-rifampin. These findings suggest that ofloxacin and sulbactam-ampicillin are likely to be most useful in the early stages of treatment and in preventing the emergence of resistance to other drugs but are unlikely to be effective as sterilizing drugs helping to kill persisting lesional bacilli.

Ampicillin↗
PubMed1996

Tuberculosis--the continuing scourge of India.

Epidemiological picture of tuberculosis in India is complex with wide variation in the annual risk of infection and prevalence of disease. The concentration of the disease among younger age groups makes tuberculosis a major socio-economic burden in India. The disability adjusted life years (DALYS) is estimated to be around 63 and 46 lakhs of years of life lost in men and women respectively. The burden is likely to increase with HIV epidemic with an increase of cases with dual infection, increase in morbidity and mortality due to tuberculosis. Management of drug resistant tuberculosis is a major hurdle in tuberculosis control and is a major step in cutting the chain of transmission to those with HIV infection, AIDS and immunodeficiency. Development of new therapeutic modalities to address this problem are also urgently required. Poor patient compliance has been the reason for failure of many control programmes. Operational research studies conducted by the TRC have resulted in elucidation of socio-behavioural aspects of patients which need further investigation for remedial measures. Studies to improve drug delivery and to measure the impact of health education and mass media on compliance are areas which need to be concentrated. Newer techniques such as DNA fingerprinting need to employed to improve knowledge of the patterns of transmission in communities. The impact of HIV infection on tuberculosis and the role of chemoprophylaxis in HIV infected individuals in high risk populations, children in close contact with newly diagnosed patients and HIV infected individuals need to be urgently explored. Improved methods for diagnosis of Mycobacterium tuberculosis infection must await considerable advance in the understanding of basic immunology, mycobacterial antigenic structure and host-parasitic interaction.

Adolescent↗
PubMed1996

Immune response & modulation of immune response induced in the guinea-pigs by Mycobacterium avium complex (MAC) & M. fortuitum complex isolates from different sources in the south Indian BCG trial area.

A total of 139 guineapigs were used to study the immune response and its modulation induced by Mycobacterium avium complex (MAC) and M. fortuitum complex strains obtained from different sources in the south Indian BCG trial area. The guineapigs were divided into groups and some were directly sensitised/immunised with different MAC strains. M. fortuitum complex strain or BCG and others were sensitised with MAC or M. fortuitum complex and then immunised with BCG. The resulting delayed type hypersensitivity (DTH) response in the different groups of guineapigs was studied by skin tests using PPD-RT23 and PPD-B, and protective response was studied by challenging the guineapigs with a south Indian low virulent strain of M. tuberculosis and enumerating the bacilli in spleen at different points of time. The 3 strains of MAC induced similar low levels of DTH to PPD-RT23 but much higher and varying levels of DTH to PPD-B. MAC strains from soil and sputum induced different levels of immune modulation during subsequent immunisation with BCG on the DTH response to PPD-RT23 and PPD-B. At 2 wk after challenge, 23.8, 81 and 90.5 per cent protection was induced by the standard strain, soil isolate and sputum isolate of MAC, respectively, while 33.3 per cent protection was induced by the M. fortuitum complex strain compared to the protection induced by BCG alone. Prior exposure to MAC or M. fortuitum complex did not have any modulatory effect on the protective immunity due to BCG at this time point. However, at 6 wk after challenge, while the guineapigs immunised with BCG were protected, modulation of the protective response resulting from BCG was observed in the guineapigs sensitised with MAC and M. fortuitum from soil.

Animals↗
PubMed1995

IS6110 restriction fragment length polymorphism typing of clinical isolates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras, south India.

SETTING: Madras, India. OBJECTIVE: To explore the utility of a standardized IS6110/PvuII deoxyribonucleic acid (DNA) fingerprinting restriction fragment length polymorphism (RFLP) typing method for distinguishing between isolates of Mycobacterium tuberculosis, and to assess the potential for distinguishing between relapse versus reinfection rates. DESIGN: To assess RFLP heterogeneity in the population, initial isolates, obtained from the sputum of tuberculous 98 patients in diagnosis and follow-up during short-course chemotherapy, were stored and compared. To assess the frequency of disparity between the RFLP type of the initial isolate and one obtained after successful completion of chemotherapy, either during relapse or as an isolated positive culture, 124 isolates comprising 62 such pairs were coded and compared both blind and after decoding. RESULTS: Although a wide variety of DNA band patterns (fingerprints) was present, the isolates from 39 (40%) of the patients showed a single copy of IS6110. Only 15 pairs of coded initial and follow-up isolates could be identified as having the same band pattern when isolates with zero or single bands were excluded. Nevertheless, after decoding, in a retrospective analysis that included all isolates, those isolates that bacteriologically defined a patient's relapse more often showed RFLP type identity with the initial isolate (19 of 30 comparisons) than did isolates that were obtained as isolated positive cultures (3 of 32 comparisons) (X2 P < 0.001). Tests of sensitivity to chemotherapeutic drugs, catalase activity and resistance to thiophene-2-carboxylic acid hydrazide were of minimal value in discriminating between isolates. CONCLUSIONS: Despite the high frequency of single- and zero-band isolates in this population, the discriminatory power of RFLP typing with IS6110 is sufficiently high to be useful for clinical and epidemiological studies.

Adolescent↗
PubMed1995

Value of bronchoalveolar lavage and gastric lavage in the diagnosis of pulmonary tuberculosis in children.

OBJECTIVE: The aim of our study was to find out if bronchoalveolar lavage (BAL) would be better than gastric lavage for the isolation of Mycobacterium tuberculosis from pediatric patients with suspected pulmonary tuberculosis. DESIGN: 50 children with suspected pulmonary tuberculosis at a mean age of 5.1 years (range 7 months to 12 years) were studied. Early morning gastric lavage was collected. Flexible bronchoscopy and bronchoalveolar lavage was performed under local anaesthesia after obtaining informed consent from the parents. The BAL fluid and gastric lavage specimens were subjected to smear examination for acid-fast bacilli (AFB) and culture for mycobacteria using established methods. RESULTS: Of the 50 cases, M. tuberculosis was grown in 6 BAL samples (12%) and 16 gastric lavage samples (32%) making a total of 17 culture proven cases (34%). Out of the 6 BAL positive cases, gastric lavage was also positive in 5 cases. CONCLUSION: We conclude that gastric lavage is better than BAL for bacteriologic confirmation of pulmonary tuberculosis in children. The overall bacteriologic yield combining both procedures was 34% while gastric lavage alone was positive in 32% of the cases.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Feasibility of involving literate tribal youths in tuberculosis case-finding in a tribal area in Tamil Nadu.

SETTING: Tribal area in South India with a population of 96,000, where the tuberculosis case-finding activity was very poor. OBJECTIVES: To investigate the feasibility of (1) involving literate (who can read and write) tribal youth volunteers for detecting cases of pulmonary tuberculosis (PT) in their respective hamlets; and (2) antituberculosis drug delivery to sputum-positive patients at their homes by village health nurses (VHNs). DESIGN: One volunteer from each of 61 hamlets was selected and trained in the detection of subjects with chest symptoms, sputum collection and transportation to the Primary Health Centre for smear examination. All smear-positive patients were treated with 2RHZ/6TH and the drugs were supplied by VHNs fortnightly at their homes. RESULTS: During a period of 1 year (1992-93), the total population screened was 9383 persons; of these 5755 were aged 15 years and above. A total of 338 symptomatic subjects were identified; 12 sputum-positive cases were detected and started on treatment. Antituberculosis drugs were supplied by VHNs to patients for the first 9 months of the study and by literate youths for the next 3 months. Spot drug checks revealed that 11 of the 12 patients were regular in drug consumption. CONCLUSION: It is feasible to train literate tribal youth volunteers within a short time to detect subjects with chest symptoms in the community and thereby cases of pulmonary tuberculosis. They can serve as an excellent model for community participation in difficult areas.

Antitubercular Agents↗
PubMed1995

Restriction fragment length polymorphism typing of clinical isolates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras, India, by use of direct-repeat probe.

Large numbers of Mycobacterium tuberculosis isolates that were obtained from patients' sputa on diagnosis and during follow-up after short-course chemotherapy in Madras, India, have either no copy or only a single copy of IS6110. This poses a limitation for DNA fingerprinting with an IS6110-based probe to determine the frequency of exogenous reinfection versus that of endogenous reactivation. In the present study, we overcame this limitation by using an alternate probe, the direct-repeat element. Comparison of pre- and posttreatment isolates by direct-repeat restriction fragment length polymorphism analysis indicated a high degree of endogenous reactivation among patients who have relapses after the successful completion of chemotherapy.

Bacterial Typing Techniques↗
PubMed1995

Repeatability of nerve thickness assessment in the clinical examination for leprosy.

The assessment of the thickness of the superficial peripheral nerve trunks to document nerve involvement is an important aspect of clinical examination in case finding for leprosy, and is usually done by trained paramedical workers (PMWs). This assessment is subject to variability and has implications on the outcome of the survey. The present study proposes to quantify this variability. In this study, 242 individuals, consisting of 50 neuritic cases, 143 nonneuritic cases of leprosy and 49 normal controls, selected from the records of the trial of BCG prophylaxis in leprosy in South India, were examined by a doctor and paramedical workers. Repeatability of nerve thickness assessment for ulnar and popliteal nerves between the medical officer (MO) and the PMWs was quantified using Kappa statistics. The Kappa values for repeatability between the MO and the PMWs ranged from 0.45 to 0.54 and 0.52 to 0.69 for ulnar and popliteal nerves, respectively. The implications of the variability in nerve assessment are discussed.

Humans↗
PubMed1995

Relapses during long-term follow up with drug-susceptible M. leprae among multibacillary leprosy patients treated with multidrug therapy regimens; case reports.

A controlled clinical trial in highly bacilliferous multibacillary leprosy patients was initiated in 1977. We report here two cases of relapse during long-term follow up of patients 15 years after the start of treatment. The patients reported here were treated with rifampin, isoniazid, clofazimine and dapsone for the first 3 months followed by clofazimine and dapsone until 84 months in one case; the other case received the same treatment but had received dapsone alone for 60-80 months. The relapses occurred 6(1/2) 7(1/2) years after therapy was discontinued.

Drug Therapy, Combination↗
PubMed1995

Characterization of mycobacterial antigens and antibodies in circulating immune complexes from pulmonary tuberculosis.

Circulating immune complexes (CICs) in serum samples from patients with pulmonary tuberculosis (bacteriologically positive [S+C+] and bacteriologically negative [S-C-]) and controls (NHC) have been measured by using C1q binding assay (C1qBA) and 3.5% polyethylene glycol precipitation and measurement of absorbance at 280 nm (PEG-OD 280). Although C1qBA did not show any difference between tuberculous and normal serum samples, PEG-OD 280 was significantly elevated in tuberculous samples. The effect of chemotherapy on CIC levels was studied. During the treatment, initially (for up to 2 months) there was a rise in CIC levels and later a fall, coinciding with bacterial clearance. Anti-purified protein derivative antibodies of class immunoglobulin G (IgG) and immunoglobulin M were measured in the serum samples and PEG precipitates. Anti-mycobacterial antibody measurement in CICs was more discriminatory between the groups than serum antibody. For characterization of the complexed antibody, the PEG precipitates were used in the Western blot and the patterns were compared. S+C+ CICs contained antibodies for a wide range of antigens ranging from 100 Kd to 10 Kd. However, none of the NHC-CICs contained antibodies for antigens < 70 Kd. Thus, when using the criterion of positivity for antibodies to antigens < 70 Kd as a marker for pulmonary tuberculosis, 24 of 24 (100%) of the S+C+ CICs were positive. Similarly, 11 of 16 (70%) of the S-C- CICs contained antibodies for antigens < 70 Kd.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗