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Biomedical subjects

H M Sharma

Publications and source records attributed to H M Sharma.

At least 55 records · Page 3Linked to original sources

Central pontine myelinolysis following saline treatment of a diabetic rat for dehydration.

Central pontine myelinolysis (CPM) was observed at necropsy in an emaciated 333-day-old BB Wistar insulin-dependent diabetic rat that had been treated for dehydration by subcutaneous injection of normal saline. There was a large area of nearly complete demyelination involving most of the basal portion of the pons, part of the tegmentum, and the base of the middle cerebellar peduncles. There was a relative sparing of neurons and axons, but some unidentifiable large cells with degenerative changes in the cytoplasm were present. No oligodendrocytes or reactive astrocytes were seen and there was no evidence of inflammation or infarction. Although diffuse demyelination can be induced in rats by rapid fluctuation of serum electrolytes, no studies have experimentally induced central pontine myelinolysis nor has it been observed incidentally in animals previously.

Animals↗

Pathological lesions in the spontaneously diabetic BB Wistar rat: a comprehensive autopsy study.

A total of 145 BB Wistar diabetic rats, 46 of their nondiabetic siblings, and 43 outbred Wistar rats were autopsied and the frequency of lesions in all organ systems were determined. Common strain-related lesions included pulmonary infections, granulomas, lymphoid hyperplasia, lymphomas, lymphocytopenia, eosinophilia, supradiaphragmatic accessory lobes of the liver, and prostatic atrophy. These suggest some basic strain-related abnormalities of the immune system that were selected by the process of inbreeding. Diabetes-related lesions were insulitis, testicular atrophy, cataracts, hepatic fatty change, pancreatitis, lymphocytic thyroiditis, hypoglycemic brain damage, central pontine myelinolysis, stomach erosions, and idiopathic megacolon. Many of these are sequelae of human juvenile-onset diabetes and support the validity of the BB Wistar rat as an animal model for human diabetes mellitus. The absence of several important sequelae of the human disease (i.e., diabetic nephropathy, atherosclerosis, and severe microangiopathy) suggests a degree of infidelity as a model for human diabetes mellitus. Nonspecific lesions occurring in all three groups of rats included myocardial degeneration and fibrosis, splenic extramedullary hematopoiesis, and chronic progressive glomerulonephropathy.

Age Factors↗

Vesiculobullous systemic lupus erythematosus. Report of two cases and a review of the literature.

Vesicles and bullae complicating systemic lupus erythematosus (SLE) are relatively uncommon. Two young women with SLE presented with vesiculobullous eruptions on sun-exposed areas that resembled dermatitis herpetiformis (DH) histologically. There were active visceral manifestations of SLE in both patients, including mesangioproliferative glomerulonephritis. Granular deposits of IgG and/or IgM, along with IgA, were demonstrated along the basement membrane of skin by direct immunofluorescence microscopy. Review of fifteen additional cases of vesiculobullous SLE reported in the literature suggests that this cutaneous manifestation of SLE is associated with a high incidence of IgA deposits in skin and glomerulonephritis. The following criteria for the diagnosis of a distinct subset of vesiculobullous skin lesions occurring in patients with SLE are proposed: (1) a diagnosis of SLE based upon American Rheumatism Association (ARA) criteria; (2) vesicles and bullae arising upon but not limited to sun-exposed skin; (3) histopathology compatible with DH; (4) negative indirect immunofluorescence for circulating basement membrane zone (BMZ) antibodies; (5) direct immunofluorescence reveals IgG and/or IgM and often IgA at the BMZ.

Adult↗

Organic anion infusions exacerbate experimental acute renal failure.

UNLABELLED: This investigation proposed to determine whether high organic anion (OA) loads per nephron increase renal susceptibility to acute ischemic and nephrotoxic injury. Anesthetized Sprague-Dawley rats were infused with a control infusate, Na2SO4, or an OA (hippurate, p-aminohippurate, cephalothin; 0.125-1.0 mg/min). After a 40-min control period, acute renal injury was induced by either bilateral renal pedicle cross-clamping (X25 min) or by HgCl2 administration (12 mg/kg i.v.). Glomerular filtration rate (clearance of [125I]iothalamate) was determined every 20 min before and after renal injury. Non-OA-infused rats lost 51 +/- 4% (ischemia) and 40 +/- 4% (HgCl2) of control GFR. OA infusion exacerbated this loss of renal function (ischemia, 89 +/- 2%; HgCl2, 84 +/- 4%). Renal histology demonstrated that OA-treated acute renal failure (ARF) rats had more vacuolar degeneration of proximal tubular cells (HgCl2, ischemia) and greater tubular dilatation (ischemia) than did non-OA-treated ARF rats. These functional and histologic responses to OA infusion were not OA dose dependent. Discontinuation of OA infusion did not cause a subsequent rise in GFR. Na2SO4 infusion had no detrimental effects on ischemic ARF. Control rats subjected to prolonged OA infusion (1 mg/min X 5 h) maintained stable GFR and had normal renal histology. ARF rats infused with low-dose cephalothin had terminal serum cephalothin concentrations within a range commonly seen in humans. CONCLUSION: organic anion infusions can exacerbate early functional and histologic parameters of experimental ARF.

Acute Kidney Injury↗

Spontaneous thyroiditis in BB Wistar diabetic rats.

Spontaneous lymphocytic thyroiditis was observed at necropsy in 36 BB Wistar diabetic rats (63.2%) and in eight of their nondiabetic siblings (42.1%). The incidence of thyroiditis decreased both with age and with longer duration of diabetes. All rats with pancreatic insulitis (a manifestation of the onset of diabetes) also had thyroiditis. BB Wistar rats with insulitis had more severe lymphocytic thyroiditis, characterized by lymphocytic, plasmacytic, and macrophage infiltration of thyroid interstitium and follicles. A milder, mostly perivascular and interstitial lymphocytic thyroiditis was characteristic of lesions in rats which did not have insulitis. The histological appearance of the thyroiditis suggests that these rats may be subject to autoimmune disease at the onset of diabetes which involves sites other than just the pancreas.

Aging↗

Acute amino acid nephrotoxicity.

Previous clinical and experimental data suggest that a limited number of AAs with particular molecular characteristics can adversely affect renal function. The present investigation was conducted to better define the scope and the molecular basis of this nephrotoxicity. Sprague-Dawley rats (N = 31) undergoing a solute diuresis were subjected to 80 min infusions (125 mumol/kg/min) of cationic AAs (lysine, arginine), anionic AAs (glutamic acid, aspartic acid), or neutral AAs (alanine, glycine). Rats infused for 80 min with equimolar amounts of urea or dextrose served as controls (N = 8). GFR (Cioth) were measured 40 min before, during, and 140 min after these infusions. Albumin excretion rates were determined by radioimmunoassay. All AA infusates induced significant (p less than 0.001) reductions in GFR compared to the control infusates (cationic AAs: 62% +/- 4; anionic AAs: 57% +/- 5; neutral AAs: 33% +/- 1; controls: 8% +/- 4) (X +/- S.E.M.). However, only cationic AAs induced a significant increase in albumin excretion (360% +/- 72; p less than 0.001). AA-treated rats had histologic changes with mild tubular injury compared to control rats. These data indicate the following. (1) AAs have in common a nephrotoxic potential. (2) This nephrotoxicity arises, in part, from the nonvariable portion of AA molecules since glycine, which has no variable (R) group, induced a significant reduction in GFR (32% +/- 1). (3) The ability of AAs to decrease GFR is enhanced by certain R groups. However, R group charge is not a critical factor in producing this response. (4) AA-induced increments in albumin excretion and reductions in GFR must arise via independent mechanisms. Since AA infusions are commonly used in patients with ARF the possibility that such therapy might have a deleterious effect on renal function and on the subsequent recovery from ARF should be entertained.

Acute Kidney Injury↗

Leukemia and arthritis: including reports on light, immunofluorescent, and electron microscopy of the synovium.

Leukemia is a well described cause of arthritis. Articular manifestations may be present for months before the diagnosis of leukemia becomes evident. Leukemic arthritis may mimic other diseases. The etiology of leukemic arthritis can be diverse, but is often attributed to leukemic involvement of synovium. We describe a case where evaluation, including immunofluorescent and electron microscopy of open synovial biopsy specimens, revealed no obvious cause of the arthritis.

Adult↗

Quantitating the severity of proximal tubular brush border injury by a simple direct binding radioimmunoassay.

The purpose of this investigation was: (1) to establish a simplified radioimmunoassay (RIA) for quantitating renal tubular epithelial antigens (RTE) in urine; (2) to ascertain whether urine RTE concentrations as measured by this technique correlate with the severity of acute nephrotoxic and ischemic injury; and (3) to ascertain whether increased urinary RTE is a specific marker of renal tubular injury. A direct binding RTE RIA was established using 125I labelled anti-RTE antibody and 10% polyethylene glycol to separate bound from unbound anti-RTE 125I. This RIA is simpler than previously described RTE assay methods since: (1) double antibody separation techniques are eliminated; (2) RTE antigen purification from crude proximal tubular fragments is no longer necessary; and (3) immunoglobulin G(IgG) rather than more radiosensitive RTE is used as the radioligand. To test the utility of this assay as a marker of acute tubular injury anesthetized rats were subjected to graded nephrotoxic (HgCl2: 0--20 mg/kg) or bilateral renal ischemic (0--32 min) insults. Glomerular filtration rates (GFR) (clearance iothalamate 125I) and RTE concentrations were measured sequentially. Post-renal injury, RTE concentrations rose above control values and the degree of elevation strongly correlated with the severity of GFR depression (r = 0.72--0.81; p less than 0.02--0.05). The source of this increased urinary RTE was the proximal tubule since brush border loss was demonstrated histologically and because no RTE could be detected in serum. Rats whose GFRs were acutely depressed by inducing either volume depletion or acute experimental glomerulonephritis (nephrotoxic serum nephritis) all had normal urine RTE concentrations. These results suggest that RTE quantitation by this technique may provide a specific and early quantitative index of the severity of acute nephrotoxic and ischemic renal injury.

Animals↗

Testicular atrophy in the spontaneously diabetic BB Wistar rat.

Complete gross and microscopic postmortem examinations were performed on 100 BB Wistar diabetic rats, 27 BB Wistar nondiabetic siblings, and 41 Wistar rats, and the incidence of testicular lesions was tabulated. Testicular atrophy was the predominant finding in all three groups of rats, but atrophy occurred at a much younger age in the diabetic rats. There was a strong relationship between the duration of diabetes and the presence of atrophy, which was stronger than the relationship between age and atrophy. The testicular atrophy observed in the diabetic rats was morphologically similar to the senile testicular atrophy in the nondiabetic rats. Histologic findings that were associated with increasing severity of atrophy were multinucleated giant cells in the lumens of seminiferous tubules, increased interstitial connective tissue, Leydig cell hyperplasia, and thickening of the tunica albuginea. Testicular atrophy has also been reported in human diabetics. Therefore, the BB Wistar rat may be a useful model for investigating this aspect of diabetes mellitus.

Age Factors↗

Papillary carcinoma of rete testis.

A case of a rare papillary adenocarcinoma of the rete testis (epididymis) with a solitary metastasis to a periaortic lymph node is reported. The favorable outcome over a three and one-third-year period after radical orchiectomy and retroperitoneal lymphadenectomy has been observed. We believe this is the first report of such a tumor being treated with lymphadenectomy.

Adenocarcinoma, Papillary↗

Unusual giant cell tumor arising in a male breast.

An unusual giant cell tumor of the breast of a 72 year old man is reported. The microscopic and ultrastructural features of the tumor are presented in detail. Unusual and previously unreported myofibroblastic an myoepithelial differentiation of the spindle cell component is described. The possible histogenesis of the tumor is discussed.

Aged↗

Spontaneous gastric erosions and ulcerations in BB Wistar rats.

One hundred thirty-four BB Wistar diabetic rats, 31 nondiabetic siblings, and 30 Wistar rats were necropsied. Gastric erosions and ulcers were observed in 43 (32.1%) of the diabetic rats and three (9.7%) of their nondiabetic siblings. None of the Wistar rats showed evidence of gastric mucosal injury. Lesions were most frequently found in the thick-walled, glandular portion of the stomach and were morphologically consistent with stress ulcers. BB Wistar rats may be valuable for studies on gastric stress ulcers.

Animals↗