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Biomedical subjects

R S Misra

Publications and source records attributed to R S Misra.

At least 37 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

ACTH acts directly on melanocytes to stimulate melanogenesis--an in vitro study.

A total of 108 whole skin organ cultures taken from vitiliginous skin were incubated in MEM containing ACTH. It was observed that 53.7% that is 58 showed a positive response with an increase in pigment production and enzyme activity, as observed on frozen sections stained for dopaoxidase activity. On immunohistochemical staining for locating ACTH binding, it is observed that 27.3% control skin and 72.7% ACTH treated skin show positivity. The ACTH is seen to bind with the melanocyte membrane as well as the cytoplasm. This indicates that ACTH can bind to the MSH-receptors expressed by the melanocyte. Thus, ACTH acts directly on the melanocyte to enhance melanogenesis and does not require to act via the adrenal-pituitary axis. This also indicates that the response is not associated with immune suppression by ACTH.

Adrenocorticotropic Hormone↗
PubMed1994

Localized lepromatous leprosy and its response to chemo-immunotherapy.

BACKGROUND: This is an unusual presentation of lepromatous leprosy (LL) in a young boy, 12 years of age. The study forms part of a large scale immunotherapeutic trial with Mycobacterium w (M.w) antileprosy vaccine. The trial is being conducted in two major hospitals in New Delhi, India. MATERIALS AND METHODS: This patient presented with three lesions: one on each forearm and the third on the left leg. He was classified initially as borderline tuberculoid leprosy. Slit-skin smears and histopathology from the lesions proved the diagnosis to be lepromatous leprosy with a bacterial index (BI) 6+. The initial lepromin test was negative. The patient was treated with chemo-immunotherapy (standard multidrug therapy and immunotherapy with Mycobacterium w vaccine). RESULTS: Investigations after 1 year (15 months) of multi-drug therapy and three doses of vaccine, showed a remarkable fall in the BI from 6 to 0 in the lesions, a lepromin positivity of 5 mm, and a histological upgrading from lepromatous leprosy to borderline tuberculoid. Immunologic studies at 15 months revealed a good LTT response and high levels of cytokines, specifically IL-2 and IFN-gamma. CONCLUSIONS: This report presents an LL patient with disease limited to a few sites. It stresses the importance of slit-smear and biopsy in all patients of leprosy, and it highlights the upgrading observed on administration of chemo-immunotherapy.

Bacterial Vaccines↗
PubMed1993

Combined multidrug and Mycobacterium w vaccine therapy in patients with multibacillary leprosy.

Immunotherapy with Mycobacterium w vaccine was attempted in patients with borderline-borderline, borderline lepromatous (BL), or lepromatous leprosy (LL) to determine whether immunization can hasten recovery and reduce treatment time by invigorating cell-mediated immunity. Mycobacterium w, a nonpathogenic, rapidly growing, atypical mycobacterium, shares a number of common B and T cell determinants with Mycobacterium leprae and Mycobacterium tuberculosis. Patients receiving the vaccine had rapid clinical improvement and accelerated bacteriologic clearance. After treatment with vaccine for 2 years, 13 of 31 BL and LL patients were bacteriologically negative as were 5 of 25 controls. Vaccinated patients had one of two distinct histologic features, either an upgrading in the disease spectrum or complete clearance of granuloma. Some 80% of lepromin conversions were in BL and LL patients who received vaccine versus none and 14.3% of BL and LL controls, respectively. Thirteen of 17 vaccinated LL patients were released from treatment after 2 years in contrast to 2 of 15 controls.

Bacterial Vaccines↗
PubMed1993

Treatment of paucibacillary leprosy.

BACKGROUND: When multidrug therapy was introduced a decade ago to shorten the duration of treatment, paucibacillary leprosy was advocated 6 months of treatment. The diagnosis is based mainly on clinical and histopathologic examination, negative slit-skin smear examination, and positive lepromin test. METHODS: The case records of 508 paucibacillary leprosy patients attending our urban leprosy center have been analyzed with reference to regularity of therapy, response to multidrug regimen, follow-up, and relapse. RESULTS: The incidence of paucibacillary leprosy was found to be 37%. Defaulter rate was 45%. Nine percent of the cases attended the center with deformities emphasizing the need for corrective surgery and early case detection to prevent them. CONCLUSIONS: The main problem that we faced was the optimum duration of treatment, which is as yet an unsettled question. The opinions of other workers have been given, and a slight modification in current WHO regimen has been suggested without significantly affecting the cost of therapy.

Drug Therapy, Combination↗
PubMed1993

Post-kala-azar dermal leishmaniasis: a clinical and therapeutic study.

BACKGROUND: Post-kala-azar dermal leishmaniasis is a condition peculiarly confined to the Indian subcontinent. METHODS: The clinical features and investigations in 18 patients of post-kala-azar dermal leishmaniasis were studied. RESULTS: There was a polymorphic picture from hypopigmented macules to nodules and plaques. Mucous membranes were affected in five, the lips and glans penis being the most frequent sites. Histopathologically, a rich dermal infiltrate was seen in indurated lesions and in macules; it was confined to perivascular foci in the upper dermis. Leishman-Donovan bodies were seen in 16. CONCLUSIONS: The lesions cleared in 4 to 5 months after treatment with sodium antimony gluconate intramuscularly 20 mg/kg/day up to a maximum of 1 g/day. The drug was well tolerated.

Adolescent↗
PubMed1993

Post-kala-azar dermal leishmaniasis: a light and electron microscopic study of 18 cases.

Post-kala-azar dermal leishmaniasis (PKDL) is caused by the protozoan parasite, Leishmania donovani, and is seen in patients with history of having been treated earlier for the visceral disease form, kala-azar, caused by the same organism. The findings from 18 patients with PKDL are described in this study. The skin manifestations ranged from hypopigmented macules to infiltrated plaques and nodules. Histopathologic examination revealed a cellular infiltrate of lymphocytes, plasma cells, and macrophages. The macrophages were scattered amidst the infiltrate without any localization. In hypopigmented lesions, the infiltrate was confined to the perivascular region in the superficial dermis and was composed mainly of lymphocytes and few plasma cells. In the nodular lesions, the infiltrate occupied the entire thickness of the dermis. Leishman-Donovan bodies were scarce and identified in 16 cases after a prolonged search of Weigert's iron hematoxylin-stained sections. In 2 cases, Leishman-Donovan bodies were not demonstrable. Electronmicroscopic study revealed parasitized macrophages which showed no structural evidence of activation despite the active cellular response around them. The fine structure of the parasites in the histiocytes was also well maintained. This unusual tropical dermatosis is a unique example of change in organotropism of a parasite associated with a change in the host response.

Adolescent↗
PubMed1993

Reversal reaction in multibacillary leprosy patients following MDT with and without immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w.

Immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w, was given in addition to standard multidrug therapy (MDT) to 53 multibacillary lepromin negative patients belonging to BB, BL and LL types of leprosy (vaccine group). An equal control group received MDT and injections of micronized starch as placebo. Both the vaccine and placebo were administered intradermally every 3 months. The patients were evaluated at determined intervals by clinical, bacteriological and histopathological parameters and lepromin testing. Reactional episodes were analysed with reference to incidence, onset, frequency and severity during and after release from treatment (RFT). Incidence of reversal reaction (RR) was marginally higher in the vaccine group (22.6% vaccine group vs 15% control group). All cases with a history of downgrading type 1 reaction developed RR during therapy. Most episodes occurred within the 1st year of the commencement of therapy--50% developing within 3 months. Late reversal reaction (after RFT) were observed in 3.8% of cases in both groups, and 50% of the reactors in the control group and 33% in the vaccine group had repeated reactional episodes. Incidence of neuritis associated with RR as well as isolated neuritis was similar in both groups.

Bacterial Vaccines↗
PubMed1993

Effect of recombinant interferon gamma administration on lesional monocytes/macrophages in lepromatous leprosy patients.

Hydrogen peroxide (H2O2) and superoxide anion (O2-) were estimated in lesional cells from 10 lepromatous leprosy patients injected intralesionally with recombinant interferon-gamma (rIFN-gamma). Clinically similar contralateral lesions injected with excipient served as controls. Lesional esterase-positive cells (suggestive of monocytes/macrophages) from rIFN-gamma-injected sites of many subjects showed net increments in the H2O2 and O2 levels compared to controls. When these cells were exposed to Mycobacterium leprae in vitro, there was a down-regulation of O2- in 4 of 5 subjects. Such inhibition was not observed in rIFN-gamma-injected sites. From the present studies it was not possible to determine whether the above effects of rIFN-gamma were primarily on lesional mature macrophages or on newly migrated young monocytes. Erythema and induration were observed at the cytokine-injected site but not at the control site between 24 and 72 hr. A monthly slit-skin smear examination of the former site showed a bacterial index (BI) reduction compared to the controls in 4 of 10 patients, this reduction occurring as early as 4 to 8 weeks. Histopathology of the biopsies of 6 of 10 subjects between 9 and 10 months showed a further BI decrease attributable to rIFN-gamma and not to the subsequently instituted chemotherapy.

Adolescent↗
PubMed1993

Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions.

Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary (MB) leprosy; 41 similarly classified patients served as controls. All patients received standard multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional incidence of neuritis were seen among vaccinated individuals during reactional episodes.

Bacterial Vaccines↗