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A K Shetty

Publications and source records attributed to A K Shetty.

96 records · Page 6Linked to original sources

Fetal brain transplantation in kainic acid lesioned caudate nucleus of adult rats.

This study confirmed that bilateral kainic acid (KA) injection at the caudate produces aphagia and adipsia in rats. The reduction in food and water intake was fatal after a higher dosage of the drug. To test the effect of transplantation on the mortality rate, KA was first injected in the left caudate, in one set of rats. After a gap of three days, fetal striatal tissue was unilaterally transplanted at this lesioned site, along with a second injection of KA in the right caudate. Successful transplantation, as ascertained morphologically, did not significantly alter the mortality rate. The morphometric study revealed that the neurons of the transplant were larger in size, and their numerical density lower than those of the caudate of normal rats. Only very few neurons of the transplant developed functional connectivity with the host, as demonstrated by electrophysiological studies.

Animals↗

Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis.

OBJECTIVE: To assess the efficacy of low-dose oral methotrexate (MTX) therapy for children with severe iritis. METHODS: MTX in a weekly dose of 7.25 to 12.5 mg/m2 was administered orally to four patients (two with juvenile rheumatoid arthritis [JRA] and two with sarcoidosis) with severe iritis not adequately controlled by topical and systemic corticosteroid therapy. The treatment was initiated with half of the total dose and increased every 2 weeks until the final dose was reached. Iritis was graded from 0 to +4 according to the density of cells in the anterior chamber of the eye. RESULTS: There were three girls and one boy with a mean age of 10.5 years. Two patients were African American and two were Caucasian. The mean age at onset of iritis was 6 years. The mean duration of MTX therapy was 28.8 months. Significant improvement was noted in two of the four patients in ocular inflammation, demonstrated by reduction of cell density from +4 to +1. Two patients had a mild improvement of the iritis. However, corticosteroids were significantly reduced in all patients. One patient was completely off steroids within 30 months of MTX therapy. In the remaining three cases, the steroid dose was successfully tapered from 0.82 mg/kg/d to 0.15 mg/kg/d (mean doses) within a mean duration of 20 months. No side effects were observed with MTX therapy. CONCLUSION: Low-dose MTX therapy was effective and safe, and displayed steroid-sparing properties in four children with severe iritis.

Administration, Oral↗

Prolonged postlesion transplantation delay adversely influences survival of both homotopic and heterotopic fetal hippocampal cell grafts in Kainate-lesioned CA3 region of adult hippocampus.

Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival when transplanted at an early postlesion delay of 4 days into the lesioned CA3 region of adult hippocampus. However, survival of these homotopic grafts following placement at late postlesion time points when the host milieu is considerably less receptive to grafts is unknown. We hypothesize that an extended postlesion delay at the time of grafting will lead to significant diminution in cell survival of both homotopic and heterotopic fetal transplants grafted to lesioned adult CNS. We quantitatively investigated absolute cell survival of 5'-bromodeoxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following transplantation into the lesioned CA3 region of adult rat hippocampus, at a delay of 45 days after a unilateral intracerebroventricular administration of kainic acid (KA). Survival of these grafts was also analyzed in intact CA3 of the hippocampus contralateral to KA administration for comparison. In lesioned CA3 region, CA3 (homotopic) and CA1 (heterotopic) grafts exhibited comparable but only moderate survival, with a recovery of only 21-31% of injected cells. Cell survival in these grafts into lesioned hippocampus was similar to survival of grafts placed into the contralateral intact CA3 region. These results are in sharp contrast to increased graft survival measured following transplants performed at 4 days postlesion. In such grafts placed early, there was both a significantly higher cell survival than grafts placed into the intact CA3 region and also a characteristic differential survival based on graft cell specificity to the lesioned CA3 region (Zaman et al., Exp. Neurol., 161:535-561, 2000). Thus, the enhanced conduciveness of lesioned CA3 region for survival of homotopic CA3 cell grafts observed at 4 days postlesion wanes by 45 days postlesion to that of intact CA3 region, in spite of residual loss of CA3 neurons with the lesion. Strategies that considerably augment graft cell survival may therefore be critical for optimal integration of fetal grafts into the adult CNS at late postlesion time points.

Animals↗

Role of MRI in diagnosis of childhood sarcoidosis with fever of unknown origin.

Childhood sarcoidosis is a disease with multisystem organ involvement, and initial presentation as fever of unknown origin (FUO) is relatively common. We describe herein three children (aged 9, 7, and 11 years) with sarcoidosis who were seen initially with FUO. Common clinical and laboratory features include fever of > 2 weeks' duration, weight loss, fatigue, leg pain, anemia, increased erythrocyte sedimentation rate, elevated immunoglobulin G level, negative antinuclear antibodies and rheumatoid factor, and negative purified protein derivative and Candida skin tests. Two patients had iridocyclitis, one had hilar adenopathy, and two had angiotensin-converting enzyme serum levels. All three had no evidence of pulmonary infiltrates on chest radiographs. Bone marrow biopsies for all three were normal, and with no evidence of malignancy. Plain radiographs of the lower extremities and bone scan were normal. Magnetic resonance imaging (MRI) of the lower extremities revealed intact bone architecture and multifocal nodular lesions within the marrow. Bone biopsy from the tibia performed on two patients showed normal bone trabeculae and a solitary noncaseating epithelioid cell granuloma. Noncaseating granuloma was found on reevaluation of the bone marrow biopsy in the third patient. All three patients had negative marrow stains and cultures for fungi and mycobacteria. We conclude that MRI was very useful in the diagnosis of sarcoidosis in children with FUO.

Child↗

Low-dose methotrexate as a steroid-sparing agent in a child with Takayasu's arteritis.

Takayasu's arteritis (TA) is a chronic inflammatory arteriopathy affecting the large vessels and has been described predominantly in young adult women. In children it presents as an aggressive disease usually requiring chronic corticosteroid therapy. At present, low dose oral methotrexate (MTX) appears to be an effective steroid-sparing agent in adult patients with active TA. We report a 4-year-old child with Takayasu's arteritis who was initially placed on oral prednisone (2 mg/kg/day) therapy. Three months later, low-dose oral MTX (10 mg/m2/week) was added. Prednisone was successfully tapered over the following year to 0.2 mg/kg every other day. A repeat angiography following 12 months of therapy revealed a dramatic improvement of the vascular lesions. No toxicity was observed with MTX therapy. In conclusion, low-dose oral MTX appeared to be an efficient, safe and steroid-sparing agent in the treatment of a young child with TA.

Adrenal Cortex Hormones↗