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Biomedical subjects

B H Brouhard

Publications and source records attributed to B H Brouhard.

At least 37 records · Page 2Linked to original sources

The combination of lovastatin and enalapril in a model of progressive renal disease.

Puromycin-induced nephrotic syndrome is an animal model of progressive renal disease. Both angiotensin converting enzyme inhibitors and lipid-lowering agents have been used to preserve renal structure and function in this model, although neither completely prevents progression. We tested the hypothesis that the combination of the two agents would be more protective than either alone. Rats were divided into five groups; all were uninephrectomized. Four groups were given puromycin at a dose of 10 mg/100 g body weight (BW) with additional doses of 4 mg/100 g BW given intraperitoneally at 4, 5, and 6 weeks thereafter. One group was given enalapril (EN) 50 mg/l dissolved in the drinking water; the second received lovastatin (L) 15 mg/kg given daily by gavage; the third received both agents; the fourth was left untreated, and the final group received no puromycin and served as the control group. Eight weeks after the initial dose of puromycin, glomerular filtration rate (GFR), as inulin clearance, and protein excretion were determined and blood was collected for cholesterol and triglycerides. Blood pressure was not different between any of the groups. At the end of the study period, serum cholesterol [mean +/- SD, 252 +/- 185 mg/dl (L), 135 +/- 101 mg/dl (L + EN)] and triglycerides (239 +/- 200, 148 +/- 158 mg/dl) were significantly lower (P < 0.001) in the lovastatin-treated groups than in the untreated puromycin group (535 +/- 255 mg/dl and 579 +/- 561 mg/dl, cholesterol and triglyceride, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cognitive functioning and school performance in children with renal failure.

Although previous studies have documented neuropsychological deficits in children with end-stage renal disease, few have evaluated and compared the cognitive functioning and the school performance of children with renal failure. The current study evaluated the influence of chronic renal failure on cognitive functioning and school performance in children and adolescents with end-stage renal disease undergoing dialysis and after renal transplantation. Participants were given standardized IQ and achievement tests to assess cognitive functioning and ability. Academic performance was determined by evaluating grades for the semester in which the testing was performed; a grade point average (GPA) was calculated based on a 4.0-point scale. The 11 dialysis patients and 13 transplant patients were comparable in age, race, sex, and socioeconomic status. Overall IQ and subtest scores demonstrated no differences between the two groups. Performance on the Woodcock-Johnson achievement tests showed that the transplant patients did better on achievement tests of written language (P = 0.04) and in school performance in English compared with dialysis patients (P < 0.05). Furthermore the dialysis patients tended to be below age and grade level in all areas, whereas the transplant patients were achieving at or above these levels. There were significant differences in the age equivalent scores between the dialysis and transplant patients in the areas of mathematics and written language (P < 0.05). However, when grades were evaluated there were no differences in overall GPA or in the mathematics GPA. Days absent were not different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pancreatic and islet replacement therapy for insulin-dependent diabetes mellitus.

The only known cure for insulin-dependent diabetes mellitus is transplantation of functioning islet cells, either alone or via transplantation of the entire pancreas in sufficient mass to restore normal carbohydrate metabolism. Such therapy may also ameliorate or eliminate certain long-term consequences of diabetes. More than 3,000 patients have received pancreas transplants at 150 centers worldwide since 1966. Urinary drainage of pancreatic exocrine secretions has dramatically improved long-term survival, especially when a kidney was transplanted at the same time. Metabolic control then resumes normal function for up to six years, in some cases preventing or reversing long-term complications of diabetes. While nephropathy and neuropathy can be prevented and even somewhat reversed, retinopathy and neuropathy resist improvement. The large number of islets that must be harvested makes islet cell transplantation difficult to achieve, although the process has been accomplished in humans with limited success.

Child↗

Effects of enalapril on adriamycin-induced nephrosis.

Adriamycin induces proteinuria and glomerular changes in rats similar to those found in human focal segmental glomerulosclerosis (FSGS). Progression of this lesion may be slowed by use of angiotensin converting enzyme inhibition. To evaluate this we injected two groups of Sprague-Dawley rats with Adriamycin (2 intravenous doses of 2 mg/kg given at an interval of 3 weeks). One group of rats received enalapril (50 mg/l) in their drinking water. Control rats were injected with saline. After 28 weeks, the mean whole kidney glomerular filtration rate was significantly less and proteinuria and sclerotic index were significantly greater in rats receiving adriamycin compared with controls (P < 0.05). Administration of enalapril did not decrease proteinuria (545 +/- 398 mg/day vs 494 +/- 325 mg/day, P >0.05) or improve the glomerular filtration rate (0.31 +/- 0.18 ml/min per g kidney weight vs 0.41 +/- 0.21 ml/min per g, P = 0.27). However, treatment with enalapril significantly reduced the mean glomerular sclerotic index compared with untreated rats (1.62 +/- 0.88 vs 0.82 +/- 0.49, P = 0.05). Enalapril may be beneficial in preserving glomerular structure in this experimental model of FSGS.

Administration, Oral↗

Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus.

To test the hypothesis that bone mineral density (BMD) is lower in children with insulin-dependent diabetes mellitus (IDDM), we measured BMD of the lumbar vertebrae (L-2 to L-4) by dual-photon absorptiometry in 31 boys and 25 girls, mean age 12.3 years, with IDDM of varying clinical duration (range 0.1 to 14.8 years). Mean standard deviation scores (z scores) were determined for L-2-L-4 BMD, weight, height, weight percentile, and weight-adjusted L-2-L-4 BMD index (L-2-L-4 BMD/weight), with reference data from a previously described white, nondiabetic, age-matched control group (n = 221). Compared with nondiabetic control subjects, male patients with short-term IDDM and all female patients with IDDM did not have significantly different L-2-L-4 BMD, weight, weight percentile, height, or BMD index. Boys with IDDM longer than 1 year had significantly lower weight, weight percentile, and height than did age-matched control subjects. When L-2-L-4 BMD of boys with long-term diabetes was corrected for weight, the L-2-L-4 BMD index was significantly greater than that of control subjects, indicating that weight was disproportionately lower than BMD. There were no significant linear correlations between metabolic control and L-2-L-4 BMD. When L-2-L-4 BMD was adjusted for differences in body weight, spinal BMD values in children with IDDM were not lower than in control subjects. These findings indicate that in children with IDDM, as in previously studied nondiabetic youths, body weight and spinal BMD are highly correlated; although BMD is reduced in some children with diabetes, the reduction parallels reductions in growth, and may simply reflect a normal response of the skeleton to a lower weight-bearing load.

Absorptiometry, Photon↗

The outcome of renal transplantation in children without prolonged pre-transplant dialysis.

Controversy in the literature exists over whether or not it is beneficial to maintain a patient on dialysis for a prolonged time before transplantation. Because no data exist comparing children who have had prolonged dialysis before transplantation to those who have none, we reviewed the charts of all children transplanted at the Children's Hospital of the Cleveland Clinic Foundation. Of those, we selected three groups for analysis: group one (n = 12) consisted of patients who had had less than or equal to 10 weeks of dialysis before transplantation (6.8 +/- -2.2 weeks, +/- = SD); group two (n = 21) were patients who had had more than 10 weeks of dialysis (142 + +/- -148 weeks). Both groups had two years of follow-up data. Group three (n = 13) consisted of patients who had had less than two years of follow-up (18.7 +/-/-7 months) but no dialysis before transplantation. There were no differences in mode of dialysis between groups one and two nor in the type of transplant (living-related donor vs. cadaveric). Significantly, the patients in group three received more cyclosporine A and less anti-lymphocyte globulin than the other two groups (p less than 0.05). Patients in group two received more transfusions (11.9 +/- 14.3) than patients in group one (4.0 +/- 2.7) and group three (3.5 +/- 7.3). There were no differences in number of patients who experienced at least one rejection episode among the three groups. Although the mean serum creatinine concentration at two years of follow-up was higher in group two (3.6 +/- -3.9 mg/dl), this was not significantly different from group one (1.7 +/- -0.7 mg/dl) or group three (1.9 +/- -0.5, n = 7). Sixty-three percent of patients in group one, 60% of patients in group two and 91% in group three had functioning allografts at two years follow-up. Although there may be other considerations, our data do not indicate any increase in rejection or decrease in graft survival in children who do not receive prolonged dialysis.

Adolescent↗

Enhanced GFR response to oral versus intravenous arginine administration in normal adults.

Both oral protein ingestion and intravenous amino acid infusions have been shown to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normal subjects. Although the mechanism of this effect is not known, the renal responses to these loads have been associated with increases in peripheral glucagon concentrations. Conflicting data exist concerning the role of glucagon in the hyperfiltration response after an oral protein meal or administration of an intravenous amino acid mixture. Using a single amino acid as the stimulus for hyperfiltration, we compared the renal responses in six normal subjects to 30 gm oral arginine-HCl, intravenous arginine-HCl, and intravenous glucagon infused at the rate of 10 ng/kg/min. GFR, RPF, and glucagon concentration, as well as levels of plasma amino acids and selected gastrointestinal hormones, were measured for six 30-minute clearance periods after each load. Significant rises in mean peak GFR were noted after both oral arginine (104 +/- 5 ml/min x 1.73 m2 to 145 +/- 9 ml/min x 1.73 m2, p less than 0.02) and intravenous arginine (118 +/- 10 ml/min x 1.73 m2 to 134 +/- 11 ml/min x 1.73 m2, p = 0.02) administration. Mean peak RPF rose significantly after oral arginine (510 +/- 26 ml/min x 1.73 m2 to 710 +/- 32 ml/min x 1.73 m2, p less than 0.01) but not after intravenous arginine (616 +/- 60 ml/min x 1.73 m2 to 687 +/- 64 ml/min x 1.73 m2, p = 0.18). Intravenous glucagon infusion also increased both mean peak GFR (99 +/- 9 ml/min x 1.73 m2 to 149 +/- 10 ml/min x 1.73 m2, p less than 0.01) and RPF (514 +/- 48 ml/min x 1.73 m2 to 771 +/- 38 ml/min x 1.73 m2, p less than 0.01) significantly. We found the mean peak percent rise in GFR (43% +/- 13%) and RPF (42% +/- 12%) after oral arginine to be notably greater than that after intravenous arginine (14% +/- 5% and 13% +/- 9%, respectively). However, the mean peak percent rise in glucagon concentration after oral arginine was significantly lower than that after intravenous arginine (62% +/- 25% versus 479% +/- 176%, respectively, p = 0.04). Infusion of glucagon increased GFR (54% +/- 13%) and RPF (55% +/- 12%) to a degree similar to that seen after oral arginine, but again with a significantly higher mean peak percent rise in peripheral glucagon concentrations when compared with the rise after oral arginine (798% +/- 348% vs 62% +/- 25%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗