Biomedical subjects
Publications and source records attributed to B K Girdhar.
A patient of lepromatous leprosy, who received a high dose of clofazimine as part of multidrug therapy, for chronic erythema nodosum leprosum (ENL) had frequent 'haemoptysis'. The haemoptysis was later found to be due to expectoration of clofazimine. This interesting, and perhaps first case of such an occurrence, is reported.
The effect of circulating immune complexes, isolated in the form of polyethylene glycol (PEG) precipitates from leprosy patients, on lymphocyte proliferation was studied. The results obtained showed that PEG precipitates obtained from the borderline lepromatous/lepromatous (BL/LL) types of leprosy patients and those undergoing erythema nodosum leprosum (ENL) had significant suppressive effects on the lymphocyte proliferation induced by Mycobacterium leprae antigens in healthy responders. The percent decreases in the mean values of delta cpm in the presence of PEG precipitates from the BL/LL and ENL groups were found to be 46.8 +/- 22.4 and 65.0 +/- 24.3, respectively. However, no significant suppressive effects (except for ENL PEG precipitates) of these PEG precipitates were observed on the lymphocyte proliferation induced by tuberculin (PPD). Further, PEG precipitates alone (in the absence of M. leprae antigen) from the BL/LL and ENL groups were found to have no effect on the lymphocyte proliferation.
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The ELISAs for polyclonal antibodies against Mycobacterium leprae (ML-ELISA) and specific antibodies against epitopes on 35 kDa protein (SACT-ELISA) and phenolic glycolipid I (PG-ELISA) of M. leprae were evaluated comparatively in a group of 88 tuberculoid leprosy patients. The overall seropositivity rate with a battery of 3 tests (68%) was not significantly higher than that obtained with ML-ELISA alone (55%) for IgG class of antibodies. Seropositivities for SACT-ELISA and PG-ELISA were, respectively, 38% and 26%. ML-ELISA for IgM class of antibodies was least sensitive, showing only 8% positivity. A significant correlation was noted between individual values of the three assays, but the positive proportions overlapped maximally in the case of ML-ELISA (IgG) and SACT-ELISA. Further, positivity for the latter two assays, particularly SACT-ELISA, showed significant associations with the extent of 'active' (largely untreated) infection. Immunoblotting revealed that the main antibody response was directed towards M. leprae antigens in the molecular weight range of 20-40 kDa and the densitometry results of this zone correlated significantly with corresponding SACT-ELISA and ML-ELISA (IgG) values.
Infestation of the nose with larvae of certain files can occur in leprosy patients. This results in severe distress and agony and can cause extensive tissue damage. The predisposing factors, clinical presentation and treatment is described.
An assessment has been made of 108 neuritic leprosy patients to find out if the number of affected nerves and the clinical presentations of these patients give any indication of the underlying severity (classification) of the disease. Detailed clinical recordings, skin smears, lepromin testing with Dharmendra antigen, and a leukocyte migration inhibition test (LMIT) using sonicated Mycobacterium leprae antigens were done in these patients. Nerve biopsies of available affected nerves were taken in 39 patients. The results show that neuritic leprosy patients also have a spectrum. However, none of the clinical parameters, including the number and distribution of affected nerves, the immune response and the nerve histology, were found to be inter-related. Further, even though all of the patients were skin-smear negative, a significant proportion showed lepromatous histology and nearly two thirds had a moderate-to-heavy bacterial load within the nerves.
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The Mycobacterium leprae-specific antibody assays--a serum antibody competition test (SACT-ELISA) for the epitope on the 35-kDa protein, and an enzyme immunoassay for the disaccharide epitope of phenolic glycolipid-I (PGDS-ELISA)--were evaluated as tools for the serological monitoring of chemotherapy in 20 lepromatous and 6 tuberculoid leprosy patients. In addition to estimates for M. leprae-specific antibodies, assessments of the bacterial index (BI) and clinical activity of the disease were also carried out prospectively in these patients on two to four occasions over a period of 19 months. In most cases, a decline in the BI, clinical scores, and antibody levels was observed during the course of treatment. The relative rate of decline was steepest and least variable with the SACT-ELISA, followed by the PGDS-ELISA and the BI. In some patients who showed a static or even an increased BI, despite marked clinical improvement, the antibody levels decreased. These data indicate that, unlike the BI, there is a greater dependence of specific antibody levels on the viability of M. leprae. This, combined with the fact that antibody titers would reflect the antigen load in the whole body, makes M. leprae-specific serology a promising tool for monitoring chemotherapy in leprosy patients.
Cryostat sections of skin and nerve lesions of leprosy were stained with monoclonal antibodies recognising Mycobacterium leprae antigens and indirect immunofluorescence. In both the tuberculoid and lepromatous lesions, PGL1, 55-65-kDa, 17-kDa protein antigens and cross-reactive non-protein antigens were present. 65-kDa antigens were seen mainly in the skin lesions of lepromatous leprosy. The infiltrates in both the skin and nerve granulomas of tuberculoid and lepromatous leprosy showed membranous staining with monoclonal antibodies recognising PGL1 and 55-65-kDa antigens. Bacilli in the lesions and the cells in the lymph node granulomas of patients with tuberculosis or the infiltrates in the lesions of tinea corporis or sections of normal skin did not show any staining with these monoclonal antibodies. These results confirm that M. leprae antigens are present and are expressed on the infiltrating cells of leprosy lesions.
An immunological technique for demonstration of Mycobacterium leprae antigen in sera was developed by using specific as well as cross-reactive monoclonal antibodies. The sandwich immunoradiometric assay which we developed is a simple, robust assay that is sensitive to the nanogram level. Sera from 72 leprosy patients were screened for the presence of antigen by this assay. A total of 69% of untreated tuberculoid leprosy patients showed 35-kDa antigen positivity, and 45% of these patients showed anti-35-kDa antibody positivity. Consistently higher antigen positivity rates for the 35-, 12-, and 30- to 40-kDa components of M. leprae were observed in lepromatous leprosy patients than in tuberculoid leprosy patients. During the course of therapy the antigen positivity rate gradually declined, and the antigen could not be detected in any of the 15 patients with subsided cases of leprosy. As antigen is presumably in excess before the antibody response is evoked, our experimental approach for antigen detection is likely to be useful by itself or along with antibody detection for diagnosis of early leprosy.
Immunohistological analysis of infiltrates of nerves in patients with neuritic leprosy was carried out using monoclonal antibodies defining T cell subsets, Langerhans cells, HLA DR antigens, and indirect immunofluorescence. In all, eight nerves were analyzed. 2 of the 8 nerves showed epithelioid cell granulomas surrounded by large numbers of lymphocytes. The predominant lymphocytes in these granulomas were activated T cells expressing CD3 and HLA DR antigens. The proportion of CD3+ and CD4+ cells was higher than that of CD8+ cells. The ratio of CD4+/CD8+ cells in these two biopsy specimens was 5.6 and 1.5, respectively. In these nerves CD4+ cells were diffusely scattered into epithelioid cell granulomas, while CD8+ cells were localized at the periphery of the granuloma. The remaining six nerves showed macrophages containing numerous bacilli, and a few lymphocytes and plasma cells diffusely distributed into the granuloma. In these nerves, only occasional lymphocytes expressing CD3 or CD4 or CD8 and HLA DR antigens were noticed. In two fo the biopsy specimens, a small proportion of CD8+ cells were visualized. Macrophages and Schwann cells were HLA DR+ in all nerves. CD1+ cells were not seen in the infiltrates of any of these nerves. A similar pattern and distribution of cells was noticed in the nerve granulomas of tuberculoid and lepromatous leprosy. These findings suggest that the mechanisms of nerve damage in the patients with neuritic leprosy could be either immunological or non-immunological, depending on the nature and characteristics of the infiltrates.
A comparison was made of the numbers of epidermal Langerhans cells in active and regressed lesions of tuberculoid and lepromatous leprosy using the OKT6 and OKIa monoclonal antibodies. A reduction in the numbers of CD1+ epidermal Langerhans cells was noticed in the regressed lesions of both the tuberculoid and lepromatous leprosy lesions unlike the active lesions. The majority of infiltrates in both types of regressed lesions were HLA-DR+ and CD1-.
This report pertains to a patient who had untreated diffuse lepromatous disease of 8- to 10-years' duration. Two peripheral nerves were beaded, which on biopsy showed histoid features. Because of its rarity, the case is reported.
Out of 3350 leprosy patients attending the surgical outpatient department for various ulcerative lesions, 18 patients had typical symptoms of myiasis. Maggots were collected in 5 cases from the nose, in 3 cases from ulcers of the hand and in 10 cases from ulcers of the foot. It was possible to rear the maggots into flies in 8 out of 18 cases. The flies were identified as Sarcophaga ruficornis and Chrysomyia bezziana.
A study was done on the characteristics of infiltrating cells in the nerves of 9 patients with pure neuritic leprosy, by preparing a single cell suspension. The patients had no skin lesion. Histopathological examination revealed that 2 of the 9 nerves showed granulomas characteristics of tuberculoid leprosy, while the remaining 7 had features of lepromatous granulomas. In the nerves showing tuberculoid granulomas, a high proportion of lymphocytes were T cells as they formed rosettes with sheep erythrocytes and only a few percent were EAC rosette forming cells. On the other hand, the nerves showing lepromatous granulomas contained only occasional lymphocytes which formed E and EAC rosettes. Macrophages from the granulomas of all the nerves were esterase positive, peroxidase negative, contained M. leprae and did not exhibit C3 surface receptors.
The length of treatment advocated for leprosy has been very long and arbitrary. During the past few years, attempts have been made to reduce the length of treatment required. World Health Organization (WHO) has recommended six months therapy for paucibacillary leprosy. The present study was undertaken to see the extent of histological changes that occur with this therapy. Thirty four untreated tuberculoid (TT/BT) leprosy patients were biopsied initially and after completion of fixed course of this treatment. Clinically, 50 percent of the patients showed regression of disease activity at the end of six months. Morphology of the lesions was studied, in clinically active and inactive cases on completion of therapy. It was found that after six month's therapy, histology of the lesions was similar, whether the case was active or not. After the prescribed treatment, biopsy showed marked reduction in the extent of granuloma, along with significant increase in lymphocytes and a increase in epithelioid cells in these granulomas.
Circulating immune complexes isolated from different types of leprosy sera as polyethylene glycol (PEG) precipitates were found to be efficient activators of the alternative pathway of complement. PEG precipitates from BL/LL leprosy patients and those with erythema nodosum leprosum were found to activate both the classical pathway and the alternative pathway of complement efficiently, while PEG precipitates from TT/BT leprosy patients and borderline tuberculoid patients in reaction were found to active the alternative pathway of complement but not the classical pathway. No significant differences were observed between the PEG precipitates from reactional and nonreactional TT/BT and BL/LL patients in their complement activating ability.