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Biomedical subjects

A K Shetty

Publications and source records attributed to A K Shetty.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pattern of long-distance projections from fetal hippocampal field CA3 and CA1 cell grafts in lesioned CA3 of adult hippocampus follows intrinsic character of respective donor cells.

Fetal hippocampal grafts transplanted to the lesioned CA3 of adult hippocampus can extend axonal projections to many regions of the host brain. However, the identity of grafted cells that project to specific host regions is unknown. We hypothesize that the pattern of long-distance axonal projections from distinct fetal hippocampal cells grafted to lesioned CA3 is specified by the intrinsic nature of respective donor cells rather than characteristics of the host graft region. We grafted fetal hippocampal CA3 or CA1 cells into kainic acid lesioned CA3 of adult hippocampus at four days post-lesion. Neurons projecting to either the contralateral hippocampus or the ipsilateral septum were then measured in these grafts at four months post-grafting using Fluoro-Gold and DiI tract tracing. CA3 grafts located close to the degenerated CA3 cell layer showed a high propensity for establishing projections into the contralateral hippocampus (commissural projections) compared to similarly located CA1 grafts, which exhibited negligible commissural projections. Similar distinction was observed between the two graft types even when they were located only partially in the lesioned CA3. Among CA3 grafts, those placed near the degenerated CA3 cell layer established significantly greater commissural projections than those placed only partially in the CA3 region. Septal projections, in contrast, were robust from both CA3 and CA1 grafts. This differential projection pattern between CA3 and CA1 grafts resembles projections of CA3 and CA1 cells in intact hippocampus.These results demonstrate that the intrinsic character of grafted fetal cells determines the type of efferent projections from fetal grafts into different targets in the lesioned adult host brain. However, the extent of efferent projections from specific grafts is also influenced by the location of grafted cells within the host region. Thus, graft-mediated appropriate reconstruction of damaged circuitry in the lesioned brain may require grafting of homotopic donor cells. Further, the robust and specific projections observed from CA3 grafts is likely beneficial for functional recovery of hippocampus following CA3 injury and hence of significance towards developing a graft-mediated therapy for human temporal lobe epilepsy.

Animals↗
PubMed2000

Syndrome of hypokalemic metabolic alkalosis and hypomagnesemia associated with gentamicin therapy: case reports.

Nephrotoxicity, as evidenced by renal insufficiency is a well-known consequence of gentamicin therapy. We report two patients with gentamicin-induced syndrome of hypokalemic metabolic alkalosis and hypomagnesemia. Both had complete recovery of renal tubular function after cessation of antibiotic therapy. These cases emphasize the need to routinely monitor patients receiving gentamicin therapy for electrolyte abnormalities to avoid potential morbidity.

Acute Kidney Injury↗
PubMed2000

Syndrome of microcephaly, mental retardation, and tracheoesophageal fistula associated with features of Rett syndrome.

We report a 12-year-old girl with features of the syndrome of microcephaly, mesobrachydactyly, and tracheoesophageal fistula, who also developed distinctive features of Rett syndrome including regression of milestones with repetitive actions, autistic-like behavior, stereotypic hand movements, and seizures. This unique combination of clinical manifestations appears to constitute a "new syndrome." We speculate that this association may represent a contiguous gene syndrome.

Adolescent↗
PubMed2000

Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome.

OBJECTIVE: To review the experience with intravenous immunoglobulin (IVIG) therapy in patients with Stevens-Johnson syndrome (SJS) in our institution. METHODS: All charts of patients with SJS admitted to Children's Hospital between November 1988 and June 1998 were reviewed. RESULTS: Twelve patients with SJS were detected. There were 8 males and 4 females, with a mean age 6 years (range 10 mo to 17 yrs). All patients presented with high fever and cutaneous and mucous membrane changes, and the diagnosis SJS was confirmed by a dermatologist. Of the 12 patients with SJS, 7 were treated with IVIG, 2 with corticosteroids, and 3 with supportive care. IVIG was administered in a single infusion at 1.5-2 g/kg, and was given on an average of hospital day 3 (range 1-8 days). The average duration of fever was 8 days (range 3-14) in the IVIG treated patients compared to 14 days (range 6-20) in the non-IVIG treated group (p = 0.06). The mean hospital stay was 12 days (range 4-22) for the patients treated with IVIG and 15 days (range 6-25) for the non-IVIG treated group (p = 0.5). No toxicity was observed with IVIG therapy. CONCLUSION: Duration of fever was shortened in patients treated with IVIG, although statistical significance was marginal. The hospital stay was slightly shortened in patients treated with IVIG; however, statistical significance was not reached. Prospective and controlled, multicenter studies are needed to further investigate these preliminary findings.

Adolescent↗
PubMed1999

Aging impairs axonal sprouting response of dentate granule cells following target loss and partial deafferentation.

Compared to other brain regions, the hippocampus shows considerable susceptibility to the aging process. Aging may impair the compensatory plastic response of hippocampal neurons following lesions, target loss, and/or deafferentation. We hypothesize that sprouting of dentate granule cell axons (mossy fibers) in response to target loss and partial deafferentation diminishes with age. We quantified mossy fiber sprouting into the dentate supragranular layer (DSGL) following intracerebroventricular kainic acid administration in young adult, middle-aged, and aged rats, using Timm's histochemical method. Mossy fiber ingrowth into the DSGL was assessed in the septal hippocampus at 2- and 4 months postlesion by measuring both the average width and the relative density of sprouted terminals. Kainic acid lesions produced degeneration of CA3 pyramids with sparing of CA1 and dentate granule cells in all age groups. Although young adults demonstrated robust DSGL mossy fiber sprouting, sprouting was significantly reduced in both middle-aged and aged rats. Compared to the case in young adults, the overall sprouting in middle-aged animals was reduced by 52% at 2 months and 50% at 4 months postlesion, whereas in aged rats the sprouting was reduced by 53% at 2 months and 64% at 4 months postlesion. Aged animals also showed an overall reduction of 28% compared to middle-aged animals at 4 months postlesion. Dramatically reduced sprouting in aged animals may represent a deficit in recognition of target loss and partial deafferentation by aged granule cells and/or an impaired up-regulation of factors that stimulate neurite outgrowth in the aged brain.

Aging↗
PubMed1999

Neurite outgrowth from progeny of epidermal growth factor-responsive hippocampal stem cells is significantly less robust than from fetal hippocampal cells following grafting onto organotypic hippocampal slice cultures: effect of brain-derived neurotrophic factor.

Epidermal growth factor (EGF)-responsive stem cells from both developing and adult central nervous system (CNS) can be expanded and induced to differentiate into neurons and glia in vitro. Because of their self-renewal and multipotent properties, these cells can potentially provide an unlimited tissue source for neural grafting in neurodegenerative disorders. However, the capability of neurons derived from these stem cells to project axons to distant targets following grafting, thereby enabling the restoration of damaged CNS circuitry, remains unknown. We hypothesize that grafted EGF-responsive stem cells and their progeny are not competent to project axons into distant target sites unless exposed to specific neurotrophic factors. We compared neurite outgrowth between gestation day 14 primary mouse hippocampal cells and EGF-generated secondary neurospheres of postnatal mouse hippocampal stem cells, following grafting onto the CA3 region of organotypic hippocampal slice cultures prepared from postnatal rats. Neurite outgrowth from grafted cells was visualized using immunohistochemical staining for the mouse specific antigen M6. Fetal hippocampal cells showed extensive and specific neurite outgrowth into many regions of the slice, including the CA1 region and distant subiculum, by 7 days after grafting. In contrast, neurite outgrowth from neurosphere cells was nonspecific and restricted to the immediate surrounding region after either 7 or even 15 days following grafting. Application of brain-derived neurotrophic factor (BDNF) (5 ng in 0.5 microL) to slices on day 1 after grafting significantly enhanced neurite outgrowth from neurosphere cells, but overall neurite outgrowth from neurosphere cells remained decreased compared to that from fetal hippocampal cells. These results underscore that EGF-responsive stem cell-derived neurons possess limited intrinsic capability for long-distance neurite outgrowth compared to fetal neurons. However, neurite outgrowth from EGF-responsive stem cell-derived neurons can be enhanced by treating with specific neurotrophic factors such as BDNF.

Animals↗
PubMed1999

Vulnerability of the dentate gyrus to aging and intracerebroventricular administration of kainic acid.

The hippocampal formation is highly vulnerable to the aging process, demonstrating functional alterations in circuitry with aging. Aging may also change the sensitivity of the hippocampal formation to excitotoxic lesions. In this study, using young adult, middle aged, and aged Fischer 344 rats, we evaluated morphometric changes in the dentate gyrus as a function of age and also in response to an administration of an excitotoxin (kainic acid) into the right lateral ventricle. The dentate gyrus was measured for changes in the area of dentate hilus and the dentate granule cell layer, alterations in the width of the dentate granule cell layer, and degree of dentate hilar cell loss. With aging, the hilar area increased in size while the area and width of the dentate granule cell layer remained constant. However, the most striking change with aging was a significant reduction in the number of dentate hilar neurons. Intracerebroventricular kainic acid produced consistent lesions in the entire ipsilateral CA3 region, and the size of CA3 lesion was identical in all three ages of animals. Following the lesion, areas of both the dentate hilus and the granule cell layer were significantly decreased in only young adult and middle aged animals whereas the width of the dentate granule cell layer was significantly increased only in the middle aged group. In contrast, dentate hilar neurons were significantly reduced in all ages of animals with the maximum reductions in neuron number observed in the aged group. Thus, aging in the dentate gyrus is characterized by a significantly decreased number of dentate hilar neurons and also a significantly increased susceptibility of dentate hilar neurons to excitotoxic damage.

Aging↗
PubMed1999

Membranous nephropathy associated with childhood sarcoidosis.

Sarcoidosis is a chronic multisystemic granulomatous disease of unknown etiology. It is relatively rare in children. Renal involvement in sarcoidosis is described less commonly than other organ involvement such as pulmonary, eye, musculoskeletal, and skin. We report a 13-year-old girl with sarcoidosis and nephrotic syndrome. Renal biopsy showed findings of membranous nephropathy. She received intravenous pulse methylprednisolone and oral cyclophosphamide with resolution of the symptoms of fever and edema, and improvement of the proteinuria. Her condition is stable with no progression of her renal disease. To the best of our knowledge, this is the first report of membranous nephropathy associated with childhood sarcoidosis.

Adolescent↗
PubMed1999

Nephrotic syndrome associated with Toxocara canis infection.

This case report describes nephrotic syndrome in a 7-year-old boy coincident with Toxocara canis infection. This rare association was confirmed by elevated Toxocara-specific IgM titres. Treatment with corticosteroids resulted in remission of renal symptoms as well as abatement of the T. canis infection. The relationship between T. canis infection and glomerular disease is still unclear; nephrotic syndrome may be another manifestation of T. canis infection.

Animals↗
PubMed1999

Typhoid hepatitis in children.

Liver involvement is commonly observed in patients with typhoid fever. However, a hepatitis-like picture with fever and jaundice is unusual and infrequently reported in the paediatric literature. Our aim was to characterize the clinical picture, biochemical features, and prognosis of typhoid hepatitis. One hundred cases of typhoid fever (age 0 to 12 years), proven by positive blood cultures to Salmonella typhi, were studied with special reference to hepatic dysfunction. Of these, eight patients were found to have hepatitis during the course of their illness. All had high fever, tender hepatomegaly, elevated serum bilirubin (in the range of 2.5-5.8 mg/dl), and elevated serum alanine transaminase levels (in the range 100-620 IU/l). All the eight patients showed complete clinical and biochemical recovery in response to appropriate antibiotics. The clinical picture of typhoid hepatitis frequently mimics acute viral hepatitis. In tropical areas, the differential diagnosis of a child presenting with fever and jaundice should include typhoid hepatitis.

Child↗