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Biomedical subjects

R S Misra

Publications and source records attributed to R S Misra.

At least 19 recordsLinked to original sources

Trend of antimicrobial resistance in Neisseria gonorrhoeae at New Delhi, India.

We aim to monitor the trends of antimicrobial resistance in Neisseria gonorrhoeae and to compare the results of antimicrobial sensitivity by disc diffusion and minimum inhibitory concentration (MIC). Two hundred and eleven confirmed strains of N. gonorrhoeae were subjected to antimicrobial sensitivity testing by disc diffusion using penicillin, tetracycline, ciprofloxacin and ceftriaxone from 1995 to June 1999. Penicillinase-producing Neisseria gonorrhoeae (PPNG) were detected by lodometric method. Minimum inhibitory concentration was determined by E test. A low level of penicillin resistance and PPNG detected in 1996 was maintained over the years. Significant increasing trend of tetracycline and ciprofloxacin resistance with high MIC i.e. 2-96 microg/ml and 1-32 microg/ml respectively were found. Ceftriaxone was found to be the drug of choice, being 100% sensitive. Comparison of resistance pattern by the 2 tests showed satisfactory agreement. Emergence of penicillin, quinolone and tetracyline resistance in N. gonorrhoeae isolates from a major STD centre at New Delhi indicates the need for increased awareness, prudent use of antimicrobials, and evaluation of new antimicrobials for the treatment of gonorrhoea.

Ceftriaxone↗

Disabilities in multibacillary leprosy following multidrug therapy with and without immunotherapy with Mycobacterium w antileprosy vaccine.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary leprosy patients supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine/placebo was given at 3-month intervals up to a maximum of 8 doses in the initial 2 years. The overall incidence of type 1 and type 2 reactions and neuritis during treatment and follow up was nearly equal in the patients in the vaccine and placebo groups; the differences were not statistically significant. The occurrence of disabilities, such as anesthesia, trophic ulcers, claw hand and grade 3 deformities, were not different statistically in the vaccine and placebo groups, an observation valid both for deformities present at induction and for those which developed during the course of therapy and surveillance. A statistically significant difference was observed in the recovery of newly developed trophic ulcers; recovery was quicker in the vaccine group. The recovery rate for motor deformities was marginally higher in the vaccine group, although not significant (p = 0.068) statistically. There was a statistically significant reduction in the incidence of grade 3 deformities following MDT with and without immunotherapy. To conclude, the addition of vaccine to MDT did not precipitate neuritis or deformities over and above that encountered with MDT alone, although it did accelerate bacteriological clearance, histopathological upgrading, conversion to lepromin positivity, and clinical improvement.

Anti-Inflammatory Agents, Non-Steroidal↗

Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary (LL, BL and BB) leprosy patients. The vaccinees were supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine was given at 3-month intervals up to a maximum of 8 doses. The lepromin response evaluated in terms of percentage of subjects converting to positivity status, measurement in millimeters, and duration of lepromin positivity sustained, reflected a statistically significant better outcome in the vaccine group patients (especially LL and BL leprosy) in comparison to those in the placebo group. The data indicate that lepromin-positivity status seems to have an impact on accelerating the bacteriological clearance, as is evident by the statistically significant accelerated decline in the BI of those patients who converted to lepromin positivity as compared to those remaining lepromin negative throughout therapy and post-therapy follow up. To conclude, the addition of the Mycobacterium w vaccine to standard MDT induces a lepromin response of a statistically significant higher magnitude than that observed with MDT alone.

Bacterial Vaccines↗

Lepromatous leprosy patients show T helper 1-like cytokine profile with differential expression of interleukin-10 during type 1 and 2 reactions.

Some leprosy patients suffer from clinical episodes associated with tissue damage which are designated as Type 1 (reversal reaction) when localized to the lesions and Type 2 (erythema nodosum leprosum, ENL) when accompanied by systemic involvement. We had reported earlier that stable, non-reaction lepromatous leprosy subjects show T helper 2 (Th2)- and Th0- but not Th1-like responses in the peripheral blood. To further understand the development of Th-like responses during disease, 32 lepromatous patients undergoing reactions were studied using cytokine-specific reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in peripheral blood and some skin biopsies. Of interest was the evidence of a Th1-like response with presence of interferon-gamma (IFN-gamma) and absence of interleukin-4 (IL-4) mRNA in the peripheral blood mononuclear cells (PBMC) of 85 and 64% of Type 1 and 2 reaction patients, respectively, and in all reaction sites. Whereas a Th0- was seen in some, a Th2-like response was absent. IL-12p40 mRNA was seen in 21/25 ENL and all Type 1 reaction subjects irrespective of the Th phenotype. IL-12p40 and IFN-gamma were detectable in unstimulated PBMC suggesting an in vivo priming during reactions. IL-10 was mainly associated with adherent cells and showed a differential expression in the two reactions. It was present in the PBMC of ENL but not in reversal reaction patients. Moreover, it was not detectable in the skin lesions of either type of reactions. A Th1-like cytokine profile was associated with immunopathology and persisted up to 6-7 months after the onset of reactions.

Acute Disease↗

A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin, and cotrimoxazole.

BACKGROUND AND OBJECTIVES: Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India. With reports of increasing resistance to the drug, this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500 mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim 160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. STUDY DESIGN: Forty-six patients with a clinical diagnosis of chancroid were randomly divided into 3 groups. Sixteen patients received ciprofloxacin, whereas 15 each received erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed day 21. Clinical response was noted in terms of cure, improvement, or failure. RESULTS: Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was observed in 6.7% cases in both groups. There were no failures with either ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was observed with 53.3% cure rates and a high failure rate of 46.7%. CONCLUSION: Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin is better in terms of dosage schedule, duration of treatment, and low cost. Cotrimoxazole should be discontinued as drug of choice because of high failure rates.

Adult↗

Benign lichenoid keratosis due to constant pressure.

Two well-circumscribed keratotic plaques in an elderly man, one each on symmetrically identical locations over the sides of the buttocks, are described. Clinical and histopathological features supported the diagnosis of benign lichenoid keratosis, which had probably resulted from constant pressure over the site and regressed when this factor was eliminated.

Aged↗

Chromoblastomycosis in India.

BACKGROUND: Chromoblastomycosis is reported for the first time from the states of Jammu-Kashmir and Bihar along with two additional cases from the states of Assam and Uttar Pradesh. The work carried cut on this disease in the Indian subcontinent is reviewed. METHODS: Relevant mycologic investigations, including direct microscopy, histopathology, and culture, were carried out to study the four cases. Treatment was given to two patients. RESULTS: The duration of the lesions varied from 5 to 32 years. In one case the lesion was a large erythematous plaque on the buttocks extending to the backs of the thighs, and in the others they were hypertrophic lesions on the extremities. Histopathologic study of specimens carried out in three patients revealed the causative organisms. On culture, Cladosporium carrionii was isolated in one and Fonsecaea species in the other three. The lesions in one patient were surgically excised and another patient responded well to a combined regimen of amphotericin B and 5-fluorocytosine. CONCLUSIONS: Although chromoblastomycosis is widely distributed in India, many patients remain undiagnosed due to a lack of proper facilities. Treatment is difficult and most patients are not able to afford the drugs prescribed for this condition.

Adult↗

Domiciliary health counselling in patients with sexually transmitted diseases.

To improve treatment compliance, follow-up and attendance of STD patients and their contacts, a programme, based on domiciliary visits was attempted. The programme was limited to male defaulters not responding to written and telephone calls. House visits to 79 out of 169 defaulters were made. Approximately half the number of houses were found locked. Fourteen defaulting patients reported for completion of their treatment and follow-up. Of these 11 were directly interviewed. None of the 14 patients agreed to disclose the addresses of their extramarital partners. During the study period 51 female sex contacts reported for treatment as compared to 27 in the control group. Though the numbers were small the study revealed that direct contact with the patient yielded the best results. It is suggested that to make the system cost-effective the health workers should spend time with STD patients in the clinic to mark out the correct location and time for meeting the patient either in the work place or at home in case of a follow-up.

Aftercare↗

Sero surveillance of HIV infection in high risk groups and in suspected AIDS cases in a New Delhi hospital.

A total of 17,824 sera were screened for the presence of HIV 1 + 2 antibodies by Enzyme Immuno Assay (EIA) to determine (i) seroprevalence of HIV infection in hospital high risk groups (ii) time trend of HIV seroprevalence in STD clinic attendees (both STD patients and non STD patients), over a period of six years, (iii) relationship of the STD's with HIV seropositivity (iv) clinical profile and epidemiological characteristics of the AIDS cases. A progressive increase in the HIV seropositive STD patients showing a five fold rise over six years was seen. Most gave history of multipartner sex especially with female CSW's. The most common STD associated with HIV seropositivity was Syphilis followed by Chancroid and Gonorrhoea. All had HIV-1 infection. The AIDS cases (20) presented mainly with tuberculosis, both pulmonary and extrapulmonary. The mode of infection, both in the HIV seropositive and AIDS cases, was mainly heterosexual relationship followed by blood transfusion. In a few cases, infection was perinatally transmitted. In the limited number of HIV positive contacts studied, seven were confirmed as Western Blot positive. HIV infection, although a later introduction in Delhi compared to the coastal cities, has shown a clear increasing trend in the STD patients.

Adolescent↗

Monocyte derived IL 10 and PGE2 are associated with the absence of Th 1 cells and in vitro T cell suppression in lepromatous leprosy.

Our previous studies had shown that the clinicopathological spectrum in leprosy was associated with discrete T cell subsets in circulation, with tuberculoid patients having antigen-induced Th 1, whereas lepromatous leprosy patients with antigen-specific T cell anergy possessed Th 2 cells. The present study shows that infected monocytes from lepromatous but not tuberculoid leprosy patients released soluble factors (MoF(s)) containing IL-10 and PGE2 which inhibited M. leprae induced in vitro lymphoproliferation of previously sensitised healthy or tuberculoid leprosy subjects. A strong negative correlation was observed between adherent cell derived IL-10 and IL-2 at the level of both the product and cytokine mRNA. Moreover, anti-IL-10 antibodies and indomethacin partially reversed the suppressor effects of MoF(s). Taken together these studies indicate that infected monocytes contribute to the development of T cell anergy by releasing factors that affect regulatory cytokines and T cell subset differentiation in lepromatous leprosy.

Antibodies↗

Addition of immunotherapy with Mycobacterium w vaccine to multi-drug therapy benefits multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w, was given in addition to standard chemotherapy (multidrug therapy (MDT)) to 93 multibacillary (MB) leprosy patients. One hundred and seven patients with similar types of disease served as controls and received MDT + placebo injections. The study was a double-blind randomised trial. On opening the codes, results obtained were in concordance with those in a single-blind trial which has been extensively reported. Bacteriological clearances were significantly more rapid in vaccinated patients (p < 0.03). Thirty-five LL or BL patients with a high bacterial index (BI) of 6 were completely cleared of acid-fast bacilli (AFB) after eight doses of vaccine. Only 8 patients in the control group became bacteriologically negative in the same time period. They all had BIs < 4. Associated with decreasing BI was accelerated clinical regression of lesions after vaccination and lepromin conversion rates of 100% for BB, 71% for BL and 70% for LL. A significant number of immunised patients showed histological improvement (p < 0.004). Thirty-six showed a complete disappearance of dermal granulomas and a picture of non-specific infiltration. The vaccine did not precipitate neuritis or deformities; episodes were noted in vaccinated patients as were incidences of Type 2 reaction. The overall improvement was reflected by a shorter duration of treatment and faster release of vaccinated patients.

Bacterial Vaccines↗

Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae.

Cytokine profiles of circulating mononuclear cells were studied with the aim of delineating T-cell subsets in leprosy patients with active disease. Using reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokine mRNA and enzyme-linked immunoassay (ELISA) for the secreted products, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied. Three antigens, native Mycobacterium leprae, a recombinant antigen LSR/A15 of M. leprae and peptide 624 spanning 58-77 amino acids of the latter, were used to induce cytokine expression and release. Half of the subjects, irrespective of the clinical type or antigen used, showed a mixed T-helper type 0 (Th0)-like cytokine pattern, with evidence of the concomitant presence of IFN-gamma and IL-4. The remainder showed a polarized pattern based on the type of leprosy. Lepromatous patients with disseminated disease had Th2-type cytokines, with IL-4 but not IFN-gamma. In contrast, tuberculoid leprosy patients with localized disease showed a Th1-like profile, with the presence of IFN-gamma but not IL-4. Of interest was the stability of the Th phenotype for M. leprae-related antigens. Both the recombinant and the peptide antigens induced the same phenotype as the natural M. leprae bacillus in all except four of 45 leprosy patients.

Antigens, Bacterial↗

Clinical utility of LSR/A15 gene for Mycobacterium leprae detection in leprosy tissues using the polymerase chain reaction.

Skin biopsy and slit-skin smears from 46 leprosy patients and 4 nonleprosy patients were tested for the presence of Mycobacterium leprae by the polymerase chain reaction (PCR) using primers based on the sequence of the LSR/15 kD gene. The PCR was found to be specific and sensitive, with a detection level of 10 and 100 bacilli. PCR using skin biopsies gave a higher detection rate than did slit-skin smears, probably due to the higher density of bacilli in a 4-mm punch biopsy. Dot blot hybridization with radioactive probes was 10-fold more sensitive than the ethidium bromide staining. Eight patients who did not show acid-fast bacilli in tissues by the conventional methods were shown to have PCR-amplified M. leprae DNA. False-negative results were obtained in 3 cases even though formal evidence for tissue inhibitors was absent.

Base Sequence↗