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Biomedical subjects

L A Hebert

Publications and source records attributed to L A Hebert.

At least 91 records · Page 5Linked to original sources

Effect of moderate daily exercise on acute glomerulonephritis.

Exercise can induce proteinuria, hematuria and cylindruria in normal individuals. This suggests that exercise adversely affects glomerular function. In this study we examined the impact of moderate daily treadmill exercise on the glomerulonephritis (GN) of 'one-shot' bovine serum albumin (250 mg/kg i.v.) serum sickness in rabbits. We found that exercise alone increased serum creatinine concentration (Scr) but exercise plus GN did not increase Scr further. Blood urea nitrogen values were unchanged. Albuminuria and the renal histopathology findings were not different between the exercised and non-exercised groups of rabbits. Muscle cytochrome oxidase and mitochondrial protein concentrations were not increased in the exercised animals. We conclude that exercise, below the level that causes exercise adaptation in muscle enzymes, does not adversely affect this form of acute GN.

Acute Disease↗

Stability of renal transplant function with alternate-day corticosteroid therapy.

Fifty-three renal transplant recipients with good to excellent renal function, while receiving daily maintenance or near-maintenance doses of azathioprine and methylprednisolone, were gradually converted to alternate-day corticosteroid therapy. Stability of allograft glomerular filtration rate (GFR) in each patient was assessed by calculating the slope of a plot of the reciprocal of the serum creatinine concentration vs time. After conversion to alternate-day therapy, GFR was stable in 80% but deteriorated in 20% of patients. However, most of the patients who experienced deteriorating GFR during alternate-day therapy regained stable renal function when given the same total corticosteroid dose but on a daily basis. This suggests but does not prove that maintenance-level daily corticosteroid therapy is better than maintenance-level alternate-day therapy in stabilizing allograft function. We conclude that maintenance-level alternate-day corticosteroid therapy should be used cautiously until a long-term prospective study determines whether there is an increased risk of losing renal function with this schedule and whether this potential risk is offset by reduced corticosteroid toxicity.

Adrenal Cortex Hormones↗

Plasmapheresis in the treatment of renal allograft rejection.

Thirty-four patients with renal allograft rejection unresponsive to conventional therapy underwent plasmapheresis. Twenty-four patients evidenced prompt and marked improvement and were discharged. Seventeen of these are presently stable off dialysis. Ten patients were not improved and required return to dialysis and/or transplant nephrectomy. Four hour warm, complement-dependent crossmatches which had become positive following transplant became negative following plasmapheresis in 3 patients who now have stable long-term function. Plasmapheresis appears promising in the treatment of refractory acute renal allograft rejection.

Cadaver↗

Some hemodynamic determinants of immune complex trapping by the kidney.

This study was undertaken to help clarify the relationship between capillary hemodynamic events and the tissue uptake of circulating immune complexes (IC). In each of 23 dogs, bovine serum albumin (BSA) and rabbit antiBSA soluble IC labeled with 125I were given by constant i.v. infusion, and IC uptake by a normally perfused kidney was compared to that of the contralateral kidney in which renal blood flow (RBF) was changed by renal artery constriction or raised ureteral pressure. In these same animals, IC uptake in 15 other major organ systems was also measured simultaneously. During IC infusion microspheres of 85Sr were injected to measure cardiac output and tissue blood flow, and red cells labeled with 51Cr were infused to mark tissue vascular volume. At completion of the IC infusion, tissue samples were taken from the kidneys and the 15 other major organs systems. From the isotope content of each tissue, we determined IC content, blood flow rate, vascular transit time, and fractional uptake of IC (FIC). In addition, glomeruli were isolated from renal cortex to assess IC uptake in glomerular versus renal nonglomerular tissue. We found that 1) for kidney, IC delivery rate, capillary hydrostatic pressure, and capillary ultrafiltration rate are less important than the plasma IC concentration in determining IC uptake; 2) for each organ studied, the principal determinant of IC uptake per gram of tissue, at any given PIC, is vascular volume per gram of tissue; 3) tissue vascular volume per gram of tissue may determine IC uptake per gram of tissue because tissue vascular volume determines the capillary surface area in contact with circulating IC or because tissue vascular volume determines tissue vascular transit time, at any given tissue blood flow rate.

Animals↗

Effect of glucocorticoids on WBC counts in splenectomized renal transplant recipients.

Change in peripheral blood WBC and differential cell count in response to oral glucocorticoids (steroids) was examined in 36 stable renal transplant patients receiving their usual steroid dose on a daily or alternate-day steroid schedule. Three hours following steroid therapy mean WBC count had increased significantly. Mean change in WBC count was +2,400 cells/cu mm with individual values ranging from -600 to +8,000/cu mm. No differences were observed between patients receiving daily or alternate-day regimens. Changes in WBC count were due almost entirely to an increase in segmented granulocytes and a decrease in lymphocytes. there was no correlation between dose of steroid and WBC responses. However, when retested, a given patient's WBC response to a given dose of steroid was reproducible. Differences between patients, with respect to WBC response to steroids, could not be explained by differences in azathioprine dose and was not related to initial WBC count hematocrit value, age, duration of transplant, or levels of serum creatinine, BUM, or serum phosphorus. Because of the clinical importance of the WBC count in the renal transplant recipient and the potential for large and unpredictable changes in WBC count in response to steroids, WBC and differential cell count should be obtained before the morning steroid dose.

Azathioprine↗

Infantile polycystic kidney disease in the adult.

We evaluated an adult with polycystic kidney disease that had been present since birth. Our evidence indicates that this patient is a unique example of survival into adult life of the recessively inherited, infantile form of polycystic kidney disease.

Adult↗

Interaction of rifampin and glucocorticoids. Adverse effect on renal allograft function.

Three renal transplant patients experienced progressive loss of renal allograft function during rifampin treatment for Mycobacterium tuberculosis. Previous studies have shown that rifampin causes induction of enzymes in hepatic microsomes that increase the catabolism of glucocorticoids. Evidence is presented that in our patients, the loss of renal allograft function during rifampin therapy was the result of decreased glucocorticoid effect presumably related to increased catabolism of the glucocorticoid drug they received. Thus, the adverse effects of rifampin on renal transplant function might be overcome by increasing the dose of glucocorticoid drug.

Adult↗

Measurement of the fractional uptake of macromolecules by the renal vascular bed compared to other vascular beds.

Macromolecules resembling soluble immune complexes can be made from heat-aggregated human gamma globulin (AHGG). In 15 rats, we studied vascular trapping of 125I-labeled AHGG (AHGG)-125I) given by constant I.V. infusion over 1 hour while tissue blood flow was marked by intermittant aortic arch injections of 85Sr-labeled microspheres. Red cells labeled with 51Cr (RBC-51Cr) were also infused so that when the tissues were removed at the end of the experiment, the vascular volume of each tissue specimen could be balculated to correct issue 125I for AHGG-125I which was not trapped but simply in transit in the bascular space at the time the tissue was removed. These data permitted us to calculate the fractional uptake of AHGG-125I (FM) for a given tissue in comparison to any other tissue. We chose to compared the FM of each tissue to the FM of renal cortex. This comparison was expressed as a ratio termed the FM ratio for the given tissue. The following tissues had FM ratios significantly greater than 1.00 (i.e., per unit blood flow, these tissues trapped AHGG-125I more avidly than renal cortex): liver, spleen, skin, stomach, fat, testes, and large bowel. The respective ratios were 381 +/- 74, 15.7 +/- 4.0, 11.8 +/- 4.0, 7.47 +/- 1.95, 6.24 +/- 1.0 +/-, 3.03 +/- 0.67, 2.86 +/- 0.72 (all p less than 0.025). The FM ratio for adrenal, heart, thymus, and diaphragm were not significantly different from 1.00. The FM ratio of lung and brain were significantly less than 1.00: 0.014 +/- 0.008 and 0.14 +/- 0.065, respectively (p less than 0.001 for both). In 13 experiments, glomeruli was 23.8 +/- 3.5 per cent as assessed by recovery of the microspheres contained in renal cortex. Compared to whole renal cortex, the isolated glomeruli contained only minor amounts of AHGG-125I. We conclude that tissues vary widely with respect to their ability to trap macromolecules. When uptake is viewed in terms of the amount of complex trapped per unit delivery rate, many organs trap AHGG-125I for more avidly than renal cortex. Furthermore, under the present experimental conditions, glomeruli are not the major intrarenal site of macromolecule uptake.

Animals↗

Whole kidney volume/pressure relationships.

We measured changes in kidney volume and intrarenal pressure produced by step-wise, steady state increases and decreases in ureteral pressure (UP). The purpose of such maneuvers, termed exercises, was to examine the relationship between changes in kidney volume and the changes in intrarenal pressure responsible for those in kidney volume. Changes in kidney volume were assessed from directly measured changes in kidney weight. Changes in the intrarenal pressure distending the renal capsule (renal subcapsular pressure [RSCP]) were measured by a strain guage diaphragm-type microtransducer placed between cortex and capsule. We measured these whole kidney volume/pressure events before and after saline loading and examined their relationship to changes in renal function following saline loading. We found that after four "exercises", the kidney became more complaint, i.e., occupied a larger volume at any given UP or RSCP, and that the compliance of the kidney was further increased following saline loading. However, about one hour after saline loading, RSCP returned to or below pre-saline loading levels and renal volume returned to pre-saline loading levels; nevertheless, the natriuresis persisted. Thus, an increase in renal volume is not necessary to sustain increased sodium and water excretion in post-saline loading. Finally, we found evidence that the renal capsule provides the major force opposing expansion of outer cortex when intrarenal pressure is increased.

Animals↗

Effect of renal decapsulation on renal function.

Marked increases in renal volume commonly occur in acute tubular necrosis and acute transplant rejection. Based on studies in the dog, we have previously suggested that the renal swelling observed in states of acute renal injury may be due principally to an increase in compliance of the kidney. The present study was undertaken in an effort to assess whether compliance-mediated increases in renal volume might affect renal function. In 15 dogs we compared the function of a decapsulated kidney (DK) to that of the contralateral intact kidney (IK); in 12 dogs we compared the function of a partially decapsulated kidney (PDK) to that of the contralateral IK. We compared the function of DK or PDK to IK, first under control conditions (ureteral pressure (UP) equals 0 mmHg), then at increased intrarenal pressure (UP equals 30 mmHg for both kidneys plus iv saline loading), and then during a recovery period (UP of both kidneys restored to 0 mmHg). The rationale is that probably DK is more compliant than IK; thus at increased intrarenal pressure DK volume should increase more than IK volume. Under control conditions DK and IK function were normal and equal; however, during increased intrarenal pressure, glomerular filtration rate (GFR) was about 20% less and Na and H20 excretion were about 30% less in DK than in IK. When intrarenal pressure was restored toward control by lowering UP to 0 mmHg, DK and IK function were once again equal. Similar but less marked changes occurred in the experiments comparing PDK and IK function. The impairment of renal function in DK vs. IK at increased intrarenal pressure was not explained by renal blood flow distribution, backdiffusion of glomerular filtrate, or by surface losses of fluid from DK. We suggest that impairment of renal function in DK vs. IK during increased intrarenal pressure is in some way related to the greater expansion of DK (21.0 +/- 0.02%) vs. IK (9.7 +/- 0.03%) at increased intrarenal pressure.

Aminohippuric Acids↗