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Biomedical subjects

V P Shetty

Publications and source records attributed to V P Shetty.

At least 19 recordsLinked to original sources
PubMed2005

Clinical, histopathological and bacteriological study of 52 referral MB cases relapsing after MDT.

Fifty-two BB-LL relapse cases referred to our centre during 1997-2003 were investigated in detail. Twenty-four cases had been treated with extended MB-MDT [until smear negativity (NON-FDT)]. The remaining 28 cases (54%) had received one of the fixed duration regimens (FDT), of whom 11 had 24 months and 6 had 12 months of WHO MB-MDT. Eleven cases had received rifampicin/ofloxacin (RO) treatment. Follow-up slit skin smear reports were available for 41 cases, all but three cases had been smear negative at some point after release from treatment. None of the cases showed any clinical or bacteriological evidence of upgrading, i.e. LL to BT where as downgrading BB to BL occurred in five cases. The duration between cessation of treatment and reappearance of lesions (DCTR) varied from 2 to 15 years. The mean DCTR was longest (9.4 years) for the NON-FDT and 24 months MB-MDT cases. The mean DCTR was significantly lower in the 12 months MB-MDT and RO treated cases (6.8 and 6.2 years, respectively). Four of RO treated cases and four cases with multiple episodes of reaction had DCTR less than 5 years. Inadequate treatment/poor killing of Mycobacterium leprae results in early onset relapse, whereas 'persisting' or 'drug resistant mutants' contribute to late onset relapse.

Drug Therapy, Combination↗
PubMed2004

Alterations in neurofilament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study.

Using a specific antibody (SMI 31), the state of phosphorylation of high and medium molecular weight neurofilaments (NF-H and NF-M) was studied in 22 leprous and four nonleprous human peripheral nerves by means of immunohistochemistry, sodium dodecyl sulfate-poly acrylamide gel electrophoresis (SDS-PAGE) and Western immunoblot (WB). The results thus obtained were compared with morphological changes in the respective nerves studied through light and electron microscopy. Many of the leprous nerves showing minimal pathology revealed lack of or weak staining with SMI 31, denoting dephosphorylation. Remyelinated fibres stained intensely with SMI 31 antibody. The WB analysis of Triton X-100 insoluble cytoskeletal preparation showed absence of regular SMI 31 reactive bands corresponding to 200 and 150 kDa molecular weight (NF-H and NF-M, respectively) in 10 nerves. Three of the 10 nerves revealed presence of NF protein bands in SDS-PAGE but not in WB. Presence of additional protein band (following NF-M) was seen in four nerves. Two nerves revealed NF-H band but not NF-M band and one nerve showed trace positivity. In the remaining five nerves presence of all the three NF bands was seen. Thus, 77.3% (17/22) of human leprous nerves studied showed abnormal phosphorylation of NF protein(s). The ultrastructural study showed abnormal compaction and arraying of NF at the periphery of the axons in the fibres with altered axon to myelin thickness ratio (atrophied fibres) as well as at the Schmidt-Lantermann (S-L) cleft region. Such NF changes were more pronounced in the severely atrophied axons suggesting a direct correlation. The observed well-spaced NF in the remyelinated fibres under ultrastructural study was in keeping with both intense SMI 31 staining and presence of NF triplet bands seen in WBs in four of leprous nerves that showed a large number of regenerating fibres suggesting reversal of changes with regeneration. Findings in the present study suggest that atrophy, that is, the reduction in axonal calibre and paranodal demyelination, seen in leprous nerves may result from dephosphorylation of NF-H and NF-M proteins.

Alzheimer Disease↗
PubMed2003

Viability and drug susceptibility testing of M. leprae using mouse footpad in 37 relapse cases of leprosy.

Mycobacteria leprae isolates obtained from 37 referral relapse cases of leprosy (37 skin and 10 nerve biopsy samples) received during the years 1994-2001, were tested for viability and drug sensitivity in the mouse footpad. A significant M. leprae yield in the footpads of control mice was obtained, with 32/47 (68%) isolates (from 26 cases) thus confirming viability. Of the 28 isolates successfully drug tested, 6 (21%) were resistant to one or more drugs. All except one, were multidrug treated cases (5/24 = 21%). One of the isolates was resistant to all three drugs, i.e., dapsone (di-aminodiphenyl sulphone, DDS), rifampin (RFP), and clofazimine (CLF). Two were resistant to two drugs, i.e., DDS and RFP, and each of the others were mono resistant to DDS, RFP, or CLF. Notably, one of the isolates that showed combined resistance to DDS and RFP was derived from a borderline tuberculoid case. Also, in one case skin and nerve showed that discordance viz: M. leprae derived from skin were resistant to RFP, while those derived from nerve tested sensitive to all three drugs, indicating tissue related difference.

Animals↗
PubMed1999

Clinical and electrophysiological evaluation of nerve function impairment following cessation of multidrug therapy in leprosy.

Seventeen multibacillary (MB) and 15 paucibacillary (PB) cases of leprosy who had had regular and adequate multidrug therapy (MDT) were examined clinically and electrophysiologically at periodic intervals for 1 year following cessation of MDT. All the major nerves were assessed for nerve function impairment (NFI). Overall, two MB (13.3%) and three PB (20%) cases showed signs of deterioration clinically and/or electrophysiologically. The nerve conduction (NC) follow-up studies revealed no significant improvement in the sensory conduction in both the MB and PB groups of nerves, whilst motor conduction showed a significant improvement at the first 6-monthly follow-up among the MB group of nerves. At the study onset, sensory impairment (MB = 62%, PB = 25%) predominated over motor in terms of both severity and frequency. The lower extremity was more frequently and severely affected than the upper in both groups of patients. As an individual test, NC measurement proved to be more sensitive in detecting NFI, but the combination of physical palpatation for nerve thickening and graded nylon test (GNT) was closely comparable to measurement of nerve conduction.

Biopsy, Needle↗
PubMed1999

Sciatic nerve of normal and T200x5R Swiss white mice fails to support multiplication of intraneurally injected M. leprae.

In a preliminary study we have shown that freshly harvested Mycobacterium leprae, when injected into the sciatic nerve in normal and immunosuppressed (TR) mice, induce massive but localized epithelioid and macrophage granuloma, respectively, in 3-4 weeks. In order to determine the fate of M. leprae injected intraneurally into normal and TR mice, in the present study we measured sequentially the viability, fold increase and clearance, if any, using semi-quantitative methods. The average M. leprae yield per nerve assessed at regular intervals, beginning at 24 hr and including 72 hr, 1 week, 2, 3, 4, 12, 24 and 48 weeks, showed neither a significant increase nor a decrease in either the normal or the TR mice. The viability of M. leprae, assessed using the standard mouse foot pad method, showed a significant decrease as compared to baseline growth effective at 24 hr and remained static until approximately 4 weeks. A further decline and total loss of viability was noted by 12 months. The results show that injection of M. leprae via the intraneural route in both normal and TR mice failed to sustain the viability and failed to support the multiplication of the organisms.

Animals↗
PubMed1997

Higher incidence of viable Mycobacterium leprae within the nerve as compared to skin among multibacillary leprosy patients released from multidrug therapy.

As identified by a significant growth in the footpads of immunosuppressed mice, the incidence of viable bacteria in a group of 26 multibacillary (BL-LL) patients released from multidrug (MDT) treatment was found to be two times more in the nerves (46%) as compared to skin (23%). Evidently there was a positive correlation between the overall bacterial load and the incidence of viable organisms. Bacterial growth was also observed in two out of five cases where neither the skin nor the nerve homogenate had shown any presence of acid-fast bacilli. Histopathology of biopsies, skin as well as nerve, including those having viable bacteria did not show any features of active disease.

Adolescent↗
PubMed1996

Primary resistance to single and multiple drugs in leprosy--a mouse footpad study.

Skin biopsy homogenates obtained from three cases of lepromatous leprosy with no prior history of antileprosy treatment were tested in the mouse footpad for the sensitivity of Mycobacterium leprae to multiple drugs. One of the inocula was sensitive to all the three drugs tested using the highest concentration each of DDS 0.01 g%, RFP 0.03 g% and CLF 0.01 g%. The 2nd inocula showed growth in the presence of 0.01 g% DDS only. While the 3rd inocula (Pt. KU) tested resistant to all the three drugs in the first, i.e. man to mouse, as well as in the second passage, i.e. mouse to mouse.

Adult↗
PubMed1994

Immunohistological localization of mycobacterial antigens within the peripheral nerves of treated leprosy patients and their significance to nerve damage in leprosy.

The presence and distribution of Mycobacterium leprae-specific and cross-reacting antigens within the peripheral nerves of multidrug-treated patients with leprosy was investigated to gain a better understanding of the mechanism of nerve damage and the effect of multidrug therapy (MDT) on it. There was no specific qualitative difference in the type of antigens in the leprosy spectrum. However, our results indicate that there may be differential handling of antigens by the macrophages as compared to Schwann cells. This could play a key role in the pathogenesis of the disease. Multidrug treatment is effective in arresting the progression of the disease process as well as in reducing the viable bacterial load, both in borderline lepromatous and lepromatous (MB) and borderline tuberculoid and tuberculoid (PB) cases. However, the presence of M. leprae antigens in all the multidrug-treated MB nerve lesions and 87% of PB nerve lesions suggest that the antigens persist for a prolonged period. Hence, the risk of immunological reaction and antigen-associated silent nerve damage may continue even after majority of M. leprae were killed. The findings give further support to the view that most of the nerve damage is due to bacterial antigens.

Adolescent↗
PubMed1993

A morphological study of nerve biopsies from cases of multibacillary leprosy given multidrug therapy.

Nerve biopsies were examined from 17 cases of lepromatous leprosy given WHO-recommended multidrug therapy (MDT) for 2 years. The pathological changes were assessed qualitatively and quantitatively to judge the effectiveness of MTD. The nerves varied very considerably in the severity of their lesions. Some regenerating fibres were seen in most of the nerves. In a few cases, the nerves were almost entirely populated by regenerated fibres, confirming that MTD was effective in halting the disease process within the nerve. Mycobacterium leprae showed morphological features of degenerate bacilli. Some pathological features of the lepromatous lesion are described.

Adult↗
PubMed1993

Animal model to study the mechanism of nerve damage in leprosy--a preliminary report.

Intraneural injection of 10-20 x 10(6) viable Mycobacterium leprae into the sciatic nerve of normal, unsensitized, Swiss white mice gives rise to a tuberculoid type of granulomatous response in 2 weeks. The same dose of viable M. leprae when injected into the sciatic nerves of unsensitized immunosuppressed mice (T200 x 5R) elicited a macrophage response. When macrophages were systemically immobilized using an intraperitoneal injection of silica quartz dust in normal mice, the lesion produced was of the lepromatous type, suggesting a role for the macrophage in the induction of the tuberculoid type of granulomatous response. In all of these in situ experiments, M. leprae failed to enter the Schwann cells.

Animals↗
PubMed1992

Persistence of Mycobacterium leprae in the peripheral nerve as compared to the skin of multidrug-treated leprosy patients.

Skin and nerve biopsies obtained from 18 multibacillary (MB) and 16 paucibacillary (PB) cases of leprosy who had been fully treated by the WHO regimen were assessed for bacterial load using different staining techniques. In addition skin and nerve homogenates of 10 MB cases were tested for 'persistor' Mycobacterium leprae using immunosuppressed mice. While significant amounts of integral bacilli and BCG cross-reactive antigen of M. leprae were detected both in skin and nerve tissues of all the MB cases (100%), 56% of skin and 62% of nerve biopsies of PB cases also showed the presence of BCG cross-reactive antigen. Detection of 'persistor' M. leprae in 2/10 skin biopsies (20%) and 3/10 nerve biopsies (30%) of MB cases was thought to be unexpectedly high after 2 years of MDT.

Drug Therapy, Combination↗