Search PubMed⌕ Search

Biomedical subjects

W M Bennett

Publications and source records attributed to W M Bennett.

At least 19 recordsLinked to original sources
PubMed1992

Polycystic kidney disease: II. Diagnosis and management.

Ongoing research will no doubt change the way we diagnose and manage cystic kidney diseases in the not-too-distant future (probably before the turn of the century). The immediate clinical benefits are the more modest: Genetic tests have not replaced imaging techniques for the diagnosis of ADPKD, and clinical management of all cystic kidney diseases is still largely empiric.

Chromosome Aberrations↗
PubMed1992

On the probability that kidneys are different in autosomal dominant polycystic disease.

We hypothesized that highly variable cyst fluid sodium concentrations are a characteristic of every kidney in autosomal dominant polycystic kidney disease (ADPKD). We added our data on sodium concentrations in 124 fluids from ten ADPKD kidneys to data published by others of concentrations in 32 fluids from five kidneys. The values ranged from 3 to 207 mEq/liter; none fell between 59 and 74 mEq/liter. Fluids were designated as low (< 60 mEq/liter; 50 fluids) or high (> 60 mEq/liter; 106 fluids) sodium fluids. Transmission electron microscopy identified differences in the depths of apical tight junctions between cells from cyst walls of 12 of the low and 10 of the high sodium fluids from two kidneys (mean +/- SE depths of 2039 +/- 74 A vs. 386 +/- 18 A respectively; P < 0.0001). When fluids were grouped by kidney of origin, six of the 15 kidneys had only high sodium fluids. The probability that chance had led to the sampling of only high sodium fluids in these organs, given that 32% of all fluids were low sodium fluids, was calculated at < 0.00015. The possibility must be considered that all kidneys are not alike in ADPKD.

Adult↗
PubMed1992

Duration of the protective effect of polyaspartic acid on experimental gentamicin nephrotoxicity.

It is known that daily polyaspartic acid (PAA) protects the kidney from gentamicin nephrotoxicity in a standardized rat model despite marked cortical accumulation of the aminoglycoside. The present experiments address the duration of PAA protection. When administered every other day, PAA provided functional and histologic protection against gentamicin-induced toxicity. A stepwise reduction in nephroprotection occurred as the dosage interval was prolonged.

Animals↗
PubMed1992

Cyst decompression surgery for autosomal dominant polycystic kidney disease.

A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.

Adult↗
PubMed1992

Therapeutic implications of arachidonic acid metabolism in transplant-associated acute renal failure.

Acute renal failure is common in kidney transplantation due to immunologic, nephrotoxic, and ischemic events. In this paper the subject of posttransplant acute renal failure is reviewed in relation to arachidonic acid metabolism. Although experimental abnormalities noted in ischemia, rejection, and cyclosporin nephrotoxicity are discussed separately, it is obvious that in the clinical situation there is great overlap. The effects of altering the substrate arachidonic acid by feeding of dietary omega-3 fatty acids, both experimentally and clinically, are discussed. Finally, the limited clinical trials of prostaglandin analogues in renal transplant patients show conflicting conclusions as regards beneficial effects on rejection and renal function. Careful clinical studies of compounds with proven efficacy in animals are needed if acute renal failure posttransplant is to be modified or prevented.

Acute Kidney Injury↗
PubMed1992

Zidovudine pharmacokinetics in five HIV seronegative patients undergoing continuous ambulatory peritoneal dialysis.

A few reports in the literature describe zidovudine (AZT) pharmacokinetics in patients undergoing hemodialysis; however, the effect of continuous ambulatory peritoneal dialysis (CAPD) on the drug's disposition has not been studied. The pharmacokinetics of AZT were evaluated in five patients, age 37-62 years, who were seronegative for the human immunodeficiency virus and were undergoing CAPD. Serial plasma, urine, and dialysate samples were collected after oral administration of AZT 200 mg. Samples were assayed using radioimmunoassay (RIA). Model-independent analysis was used to determine total plasma clearance, apparent volume of distribution, mean residence time, and half-life. Net peritoneal dialysis clearance was calculated to measure the effect of CAPD on AZT disposition. We found wide interpatient variability in AZT pharmacokinetics. Peak serum concentrations ranged from 0.3-47.8 microns and area under the curve from 0.5-26.1 mg x hour/L. These differences resulted in corresponding differences in clearance (range 66-3176 ml/min/1.73 m2) and volume of distribution (range 16-825 L). Interpatient variability in glucuronidation may partially account for this variability. Net peritoneal dialysis clearance of AZT was 5 ml/minute. Although the effect of peritoneal dialysis on AZT disposition was negligible, clinicians should be aware of the large differences in the way in which individual patients with renal dysfunction handle this drug.

Administration, Oral↗
PubMed1992

Drug dosing guidelines in patients with renal failure.

The metabolism and excretion of many drugs and their pharmacologically active metabolites depend on normal renal function. Accumulation and toxicity can develop rapidly if dosages are not adjusted in patients with impaired renal function. In addition, many drugs that are not dependent on the kidneys for elimination may exert untoward effects in the uremic milieu of advanced renal disease. A familiarity with basic pharmacologic principles and a systematic approach are necessary when adjusting drug dosages in patients with abnormal kidney function. The distinct steps involve calculating the patient's glomerular filtration rate, choosing and administering a loading dose, determining a maintenance dose, and a decision regarding monitoring of drug concentrations. If done properly, therapy in renal patients should achieve the desired pharmacologic effects while avoiding drug toxicity. Physicians must not oversimplify the pharmacologic complexities presented by patients with renal failure by relying excessively on nomograms and "cookbook" equations. In addition to a reduced glomerular filtration rate, patients with renal disease often have alterations in pharmacokinetics such as bioavailability, protein binding, hepatic biotransformation, and volume of distribution. An awareness of biologically active or toxic metabolites of parent compounds that accumulate when the glomerular filtration rate is reduced is also necessary to avoid toxicity. The effects of dialysis on drug elimination and the need for supplemental dosing are additional considerations in patients undergoing renal replacement therapy.

Drug Monitoring↗
PubMed1991

The effect of tobramycin on the renal handling of vancomycin.

Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin. For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.

Adult↗
PubMed1991

Pharmacokinetics of ganciclovir in a patient undergoing hemodialysis.

The pharmacokinetics and effect of hemodialysis on the clearance of ganciclovir were evaluated in a patient with cytomegalovirus (CMV) retinitis and pneumonitis requiring dialytic support. A dose of 300 mg ganciclovir (5 mg/kg) was administered by intravenous infusion over a 60-minute period. Blood samples were obtained over the next 10 hours and used to assess plasma ganciclovir concentrations. The patient underwent hemodialysis the following day during which paired arterial and venous blood samples were obtained to determine dialyzer clearance of this antiviral agent. High-performance liquid chromatography was used to quantify ganciclovir plasma concentrations. Ganciclovir levels declined in a monoexponential manner following infusion and prior to dialysis. The patient's peak ganciclovir concentration was markedly elevated (20 micrograms/mL) compared with previously reported peak concentrations in patients with normal renal function. Similarly, the elimination half-life (t1/2) was increased (6.3 hours) in this patient compared with values reported in patients with normal renal function. The volume of distribution (0.21 L/kg) and total body clearance prior to hemodialysis (35.5 mL/min) were diminished in this patient. Hemodialysis reduced ganciclovir levels by approximately 62% with an extraction coefficient of 0.29 resulting in a dialyzer clearance of 48.3 mL/min. This supports supplementation of ganciclovir in patients receiving this antiviral agent when they are undergoing hemodialysis. Additionally, close monitoring of ganciclovir concentrations in patients with abnormal renal function is necessary in order to make appropriate dosage adjustments.

Adult↗
PubMed1991

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study.

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.

Adult↗
PubMed1991

Long-term protection of polyaspartic acid in experimental gentamicin nephrotoxicity.

Polyaspartic Acid (PAA) protects the kidney from experimental gentamicin nephrotoxicity despite large increases in renal cortical gentamicin content. In these experiments, prominent cytoplasmic vacuoles were noted in all animals that received PAA with or without gentamicin. The present study showed that there were no renal structural or functional consequences of PAA given alone or with gentamicin for up to 14 days, followed by a 16-week washout period. Creatinine clearance was similar to that of controls in animals that received gentamicin and in those that received PAA alone. Thus, complete functional protection was conferred by PAA and gentamicin, confirming previous reports from our laboratory. There was no protection by PAA from the nephrotoxic effects of mercuric chloride and cis-platinum.

Animals↗
PubMed1991

Cyclosporine-induced renal dysfunction: correlations between cellular events and whole kidney function.

The main adverse reaction to the immunosuppressive drug cyclosporine is dose-dependent renal dysfunction. Although renal vasoconstriction without major tubular dysfunction is usually noted, recent studies have demonstrated an inhibition of renal cortical microsomal protein synthesis. Sprague-Dawley rats and appropriate pair-fed controls were given cyclosporine orally in doses of 5, 10, 25, and 50 mg/kg/day for periods up to 10 days. A dose-dependent decline in glomerular filtration rate and effective renal plasma flow was maximal by day 3 and did not worsen despite continued dosing. Microsomal protein synthesis as measured by [3H]leucine incorporation was also depressed in a dose-dependent fashion; however, inhibition did not reach the nadir until day 4, 1 day after renal dysfunction was established. When cyclosporine was discontinued, microsomal protein synthesis was normalized by 4 days after drug withdrawal; in contrast, the return of glomerular filtration rate and effective renal plasma flow to normal required 8 days after drug discontinuation. Tubular function as measured by fractional excretion of lithium, enzymuria, and urinary osmolality was well maintained despite the depression of renal hemodynamics. There was no evidence of tubular necrosis by light or electron microscopy. Although cyclosporine produces reductions in renal microsomal protein synthesis, measured by "run-off" translation assays, these effects appear unlikely to be the direct cause of acute renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A multicenter clinical trial of epoetin beta for anemia of end-stage renal disease.

Patients with anemia of end-stage renal disease were studied for 36 weeks to determine efficacy, safety, and long-term benefits of epoetin beta administration. A total of 131 patients participated in the 12-week, double-blind, placebo-controlled portion of the multicenter study. For the first 6 weeks (fixed-dose period), patients were randomized to receive 100 U/kg of epoetin beta or placebo thrice weekly; in the second 6 weeks (dose-adjustment period), the dose of epoetin beta ranged from 50 to 150 U/kg thrice weekly. Of the 131 patients who entered the placebo-controlled period, 122 crossed over to a 24-week open-label period, where all patients received active drug and doses of epoetin beta could be individually titrated after the first 6 weeks. One hundred patients completed the 36-week study. In all phases of the study, epoetin beta was shown to produce a consistent, sustained increase in hemoglobin (baseline, 7.1 +/- 0.1 to 10.5 +/- 0.2 g/dL) and hematocrit (baseline, 21.5 to 32.7%), which virtually eliminated the need for packed red blood cell transfusions. Reticulocyte counts rose initially in response to epoetin beta and stabilized at levels higher than baseline throughout the remainder of the study period (baseline, 1.7 to 2.5%). The placebo group showed no change in these parameters during the double-blind period. Similar patterns of response were seen in the original placebo group after crossover to active drug (mean hemoglobin increase, 2.6 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗