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Biomedical subjects

M S Kumar

Publications and source records attributed to M S Kumar.

At least 19 recordsLinked to original sources
PubMed1998

Effects of halothane and methoxyflurane on regional brain and spinal cord substance P-like and beta-endorphin-like immunoreactivities in the rat.

Effects of acute exposure (2 hr) to either 1.5% halothane or 0.5% methoxyflurane were investigated in the Sprague Dawley rat. Pituitary (PIT) and central nervous system (CNS) substance P (SP)-like and beta-endorphin (beta-end)-like immunoreactivities were evaluated immediately after anesthetic exposure (2 h), after righting reflex (4 h) or 24 hr postexposure (24 h). Only halothane significantly reduced SP-like immunoreactivity in olfactory bulbs in both the 2-h and 4-h groups. Halothane elevated SP-like immunoreactivity of hippocampus at all three time periods, and in the hypothalamus at 2 h. Both anesthetics significantly depleted thalamic concentrations of SP-like immunoreactivity. Methoxyflurane anesthesia resulted in a drastic decrease in SP-like immunoreactivity in PIT at all three time periods periods, while halothane elevated PIT concentrations of this peptide at 4 h. Both anesthetics significantly decreased beta-end-like immunoreactivity in the olfactory bulbs and thalami at 2, 4, and 24 h. However, halothane alone significantly elevated beta-end-like immunoreactivity in the spinal cord at 24 h. Halothane significantly elevated PIT beta-end-like immunoreactivity at 2 and 24 h, while methoxyflurane significantly lowered it in the 4-h group, but elevated the levels of the same in the 24-h group. Brain stem beta-end immunoreactivity were significantly reduced at 2 h by both anesthetics, and at 4 h by methoxyflurane. Results indicate that halothane and methoxyflurane may differ significantly in their actions on SP and beta-end secreting neurons in the CNS.

Analysis of Variance↗
PubMed1998

Novel quinolone derivatives as potent antibacterials.

Several 7-(3R,4R-N,N'-dialkyl diaminopyrrolidinyl)-substituted quinolones were synthesized and evaluated for antibacterial activities. 5-Amino-7-(3R,4R-N,N'-dimethyldiamino-6,8-difluoro-1,4-dihydro-1-c yclopropyl -4-oxoquinoline-3-carboxylic acid was found to have potent antibacterial activity against gram +ve organisms.

Anti-Bacterial Agents↗
PubMed1998

Long-term function and survival of elderly donor kidneys transplanted into young adults.

BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.

Adult↗
PubMed1998

Alterations in catecholamine turnover in specific regions of the rat brain following acute exposure to nitrous oxide.

The effects of nitrous oxide (N2O) on steady-state concentrations and turnover rates of catecholamines in the olfactory bulb, hypothalamus, brain stem, hippocampus, striatum, thalamus, cerebral cortex, and spinal cord were determined in rats. Animals were exposed for 2 h to either 60% N2O or air. Immediately following exposure, all animals were injected intraperitoneally with alpha-methylparatyrosine (alphaMPT), a competitive inhibitor of tyrosine hydroxylase, and sacrificed at 0, 30, or 90 min postinjection. Brain catecholamine concentrations were determined using high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC). Results indicate that N2O exposure significantly elevates steady-state concentrations of norepinephrine (NE) in the hypothalamus and striatum yet decreases amine levels in the brain stem region. Steady-state levels of dopamine (DA) were not significantly altered in any region of the CNS by N2O exposure. Acute exposure to N2O also resulted in significant decreases in the turnover rate of NE in the brain stem, yet it increased turnover of this amine in the olfactory bulb, hypothalamus, and striatum. Acute exposure to N2O resulted in a decreased turnover rate of DA in the hippocampus and striatum. In contrast, N2O appears to increase DA turnover in the olfactory bulb. These results indicate that acute exposure to N2O in rats causes region-specific alterations in steady-state levels and turnover rates of DA and NE within the central nervous system.

Analysis of Variance↗
PubMed1998

Effects of halothane and methoxyflurane on the hypothalamic-pituitary-adrenal axis in rat.

Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague-Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated. Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment's time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic. Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.

Adrenocorticotropic Hormone↗
PubMed1998

Community-based outreach HIV intervention for street-recruited drug users in Madras, India.

OBJECTIVE: Community-based outreach to drug injectors is an important component of human immunodeficiency virus (HIV) prevention strategy. The purpose of this chapter is to evaluate the effectiveness of community-based outreach HIV intervention that has been implemented in two locations in the city of Madras, India, to reduce risk behaviors for HIV transmission. METHODS: Baseline data were collected for street-recruited injecting drug users (IDUs) at two outreach locations in Madras, India (n = 250), and follow-up data are available at 18 months (n = 61). Baseline (n = 150) and follow-up data (n = 87) were obtained from control group of IDUs recruited from locations at which outreach services were not utilized. RESULTS: Significant decline in injecting risk behavior was noted at 18-month follow-up from baseline for the IDUs recruited from outreach locations. CONCLUSION: Results indicate that outreach service for drug users produce significant changes in injecting risk behavior but that sexual risk behavior is difficult to change. There are problems in implementing and evaluating the interventions, and the research findings are limited because HIV serodata were not studied for all participants.

Adolescent↗
PubMed1997

Surgical wound infection in renal transplantation: outcome data in 102 consecutive patients without perioperative systemic antibiotic coverage.

BACKGROUND: The incidence of surgical wound infection in the presence of immunosuppression has been reported in the literature to approach 7%. Perioperative systemic antibiotic therapy is routinely used to reduce the occurrence of wound infections. This therapy is not without complications, including adverse effects and development of resistant strains. DESIGN: Surgical wound infection rates during the first 100 days after renal transplantation were studied in 102 consecutive patients. Eighty-one patients underwent cadaveric transplantation and 21 patients underwent living-related donor transplantation from February 1, 1991, to January 1, 1992. No systemic perioperative antibiotic coverage was used, but local antibiotic irrigation was part of the perioperative protocol. SETTING: Hahnemann University Hospital, Philadelphia, Pa, is a large, tertiary care center. Patients were initially hospitalized and were discharged during the 100-day follow-up period based on clinical status and improvement in renal function. PATIENTS: Twenty-seven (25%) of 102 patients had diabetes mellitus. INTERVENTIONS: Induction immunosuppression consisted of azathioprine, prednisone, and anitlymphocyte globulin, while maintenance immunosuppression consisted of azathioprine, prednisone, and cyclosporine. Acute allograft rejection episodes were treated with steroids and/or OKT3 (Ortho Pharmaceutical Group, Raritan, NJ). RESULTS: Two surgical wound infections (2%) occurred. In both, infection was superficial, resolving with wound drainage and intravenous antibiotics. The surgical wound infection rate was not significantly affected by age, sex, allograft source, or presence of diabetes mellitus. CONCLUSIONS: Despite immunosuppression, the incidence of surgical wound infection was minimal, comparing favorably to rates reported for renal transplantation with the use of systemic antibiotics. Possible explanations for the low incidence of surgical wound infections include local wound irrigation, meticulous hemostasis, improved organ procurement techniques, and continuity in perioperative care.

Adult↗
PubMed1996

In vivo depletion of pancreatic acinar tissue simplifies islet preparation for transplantation.

A copper deficient diet is reported to reduce acinar tissue in vivo. We investigated the suitability of this method to reduce in vivo acinar tissue mass of a rat pancreas prior to transplantation of dispersed pancreatic tissue. We also studied islet function in the acinar depleted pancreas and the outcome of transplantation of islets from such pancreata. Eighty-two Wistar Furth rats were divided into two groups with 42 animals in the control group receiving regular diet, and 40 receiving copper deficient diets (Cudt) plus tetraethylene- pentamine penta-hydrochloride (TEPA) as a chelating agent. All animals in the control group and 34 (85%) in the Cudt group tolerated this diet and survived for 60 days or longer. At the end of 60 days, all experimental animals were converted to a regular diet until the pancreata were harvested for islet transplantation. Eight rats in the Cudt group, which were converted to a regular diet for 2 weeks, and 2 in the control group were randomly selected and sacrificed to study the pancreas for acinar depletion and islet morphology. An intravenous glucose tolerance test (IVGTT) in the control group (n=24) and the Cudt group (n=25) showed K-values of 1.891+/-0.7 and 1.107+/-0.47, respectively (P-ns). Histology of pancreata showed normal acinar tissue in the control group and reduction of acinar tissue mass in the Cudt group. Furthermore, immunohistochemistry for insulin, glucagon, and somatostatin showed positively staining, while amylase was negative in the Cudt group, compared with the positive stain for cells in the control group. Standard collagenase digestion of the pancreas showed islets were surrounded by scant amounts of acinar tissue in the Cudt group compared with the control group. The islet count in the control group was 523+/-126 and 611+/-52 in the Cudt group. The mean volumes of dispersed pancreatic tissue were 0.3875+/-0.14 and 0.0668+/-0.029 ml per rat in the control and Cudt groups, respectively (P<0.05). Transplantation of dispersed pancreatic tissue from the control group into the spleen of two diabetic Wistar Furth rats resulted in the death of the recipients within 24 hr. To avoid this complication, purified islets from the control group were used for transplantation. Purified islets from 5 donor pancreata from the control group and dispersed pancreatic tissue from 3 pancreata in the Cudt group were transplanted into each recipient. Islet function was seen in 75% of the rats transplanted with purified islets from the control group, and in 67% receiving dispersed pancreatic tissue from the Cudt group. Rats with sustained islet function for 30 days following islet transplantation developed diabetes following splenectomy. The islet cells were positively stained for insulin these splenectomy specimens. This study demonstrates that rats maintained on a copper deficient diet for 60 days show depletion of collagenase digested volume of whole pancreatic tissue occurred in the Cudt as compared with the control group. Transplantation of dispersed pancreatic tissue from the acinar depleted pancreas was successful in reversing diabetes. We conclude that Cudt containing TEPA depletes exocrine tissue and facilitates pancreas digestion for successful transplantation of islets into the portal system.

Animals↗
PubMed1996

Effect of low and high doses of nitrous oxide on preproenkephalin mRNA and its peptide methionine enkephalin levels in the hypothalamus.

The effect of exposure to nitrous oxide (N2O) on the levels of preproenkephalin mRNA in the hypothalamus of rats was examined. In the first experiment, rats were exposed to 1000 ppm N2O for 8 h a day over 4 days. Compared with controls (which were exposed to air over the same duration), the N2O exposed animals exhibited significant elevations in preproenkephalin mRNA levels in the hypothalamus. In a second experiment, rats were exposed to 60% N2O or air for 12, 24 and 48 h duration, and hypothalamic levels of preproenkephalin mRNA as well as methionine enkephalin were analyzed. Compared with controls, N2O exposed rats exhibited significant elevations in preproenkephalin mRNA levels. The levels on preproenkephalin mRNA were significantly higher after 48 h of N2O exposure than after 12 h of N2O exposure. Similarly, the concentration of methionine enkephalin was significantly higher after 24 and 48 h of exposure of N2O than after exposure to 12 h of N2O or air. These results indicate that (a) exposure to N2O results in significant elevations in preproenkephalin mRNA levels, (b) the increased preproenkephalin mRNA levels appear to be proportional to the concentration of N2O exposure as well as the duration of N2O exposure, and (c) N2O-induced elevation in preproenkephalin mRNA levels is associated with corresponding increase in tissue concentrations of methionine enkephalin. In total, these results suggest that N2O selectively stimulates synthesis of methionine enkephalin in the diencephalic region of the brain.

Animals↗
PubMed1995

Randomized clinical trial of antithymocyte globulin induction in renal transplantation comparing a fixed daily dose with dose adjustment according to T cell monitoring.

Antithymocyte globulin (ATG) has been used successfully for induction therapy as well as for treatment of established allograft rejection. However, this therapy has often been associated with problems of overimmunosuppression and increased costs. In a randomized clinical trial, we compared the immunosuppressive benefits, complication rates, and treatment costs when ATG is given as a fixed daily dose or when the dose is adjusted daily according to its biologic effects on T cells. Forty-five recipients of cadaver renal allografts were randomized into two groups. In group 1 (n = 23), ATG (ATGAM) was administered in variable doses to maintain the absolute number of peripheral CD3 T cells at 50-100/microliters. In group 2 (n = 22), ATG was given at a fixed dose of 15 mg/kg/day. All patients received azathioprine and prednisone. ATG was discontinued at 7-14 days when cyclosporine was introduced. In both groups, CD2, CD3, CD4, CD8, and CD19 cells were measured by flow cytometry and the levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, Il-7, and IL-10 were measured by ELISA. In group 2, the levels of all T cell subsets were profoundly suppressed. In group 1, the number of CD3 and other T cells was maintained at about 100 cells/microliters, while the CD19 T cells remained unsuppressed. Cytokine levels were greatly suppressed in group 2 compared with group 1, except for IL-10 levels, which remained elevated in the latter group. Patient survival, graft function, and the incidence of acute and recurrent rejections were similar in the two groups. Bone marrow suppression and infective complications were greater in group 2 than in group 1. The mean daily dose and the total quantity of ATG used in group 1 were significantly smaller than in group 2, resulting in a savings of $2,398.00 per patient per treatment. It is concluded that monitoring of ATG by its biologic effects on T cells is a rational and safe method of regulating the dose of this important agent; in this way, it is possible to reduce the total amount of the drug given to patients with consequent reduction in undesirable complications as well as in the cost of treatment without loss of immunosuppressive benefits.

Adult↗