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Biomedical subjects

W M Bennett

Publications and source records attributed to W M Bennett.

At least 199 records · Page 11Linked to original sources
PubMed1987

Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease.

A total of 11 patients with refractory pain secondary to autosomal dominant polycystic kidney disease underwent ultrasound guided percutaneous aspiration of cyst fluid on the affected side. Surgical reduction of cyst volume was performed if pain recurred. Dramatic relief of pain was observed after both procedures. The probability of a patient being free of renal pain at 18 months was 33 +/- 17 per cent for aspiration and 81 +/- 12 per cent for an operation. Individual patients had relief of pain for more than 4 years. There was no deleterious effect on renal function after either aspiration or an operation. Blood pressure improved in the 5 patients with hypertension. There were no complications of percutaneous cyst aspiration. One patient required neurolysis of the drain site after cyst reduction.

Adolescent↗
PubMed1987

Trimethoprim-sulfamethoxazole in cyst fluid from autosomal dominant polycystic kidneys.

Cyst infection in patients with autosomal-dominant polycystic kidney disease (ADPKD) is often refractory to therapy, in part because of the limited entry of commonly used antibiotics into cyst fluid. To study the efficacy of trimethoprim-sulfamethoxazole in cyst infection, cyst fluid was obtained by percutaneous aspiration or at surgery from eight patients with ADPKD receiving trimethoprim-sulfamethoxazole. Cysts were categorized as nongradient or gradient by cyst-fluid sodium concentration. Trimethoprim-sulfamethoxazole concentrations within cysts were determined and cyst fluid inhibitory and bactericidal titers were assessed in vitro against Escherichia coli, Proteus mirabilis and Streptococcus fecalis. The mean cyst fluid trimethoprim and sulfamethoxazole concentrations were 15.2 micrograms/ml and 42.5 micrograms/ml, respectively. Preferential accumulation of trimethoprim was observed in gradient cysts, exceeding serum levels more than eightfold. Sulfamethoxazole penetrated cysts to a lesser extent, with concentrations ranging from 10 to 70 percent of the serum level. Cyst fluid sampled prior to trimethoprim-sulfamethoxazole administration (control) demonstrated no antibacterial activity, while cyst fluid inhibitory and bactericidal titers following antibiotic administration were 1:32 or greater in most instances. These studies indicate that trimethoprim-sulfamethoxazole is likely to be efficacious in the treatment of cyst infection in polycystic kidneys.

Adult↗
PubMed1987

Modification of experimental nephrotoxicity with fish oil as the vehicle for cyclosporine.

Cyclosporine-associated renal dysfunction is well recognized. While renal vasoconstriction appears to be a major pathogenic factor, the precise mechanism responsible for the altered hemodynamics is unclear. To investigate whether alterations in renal eicosanoid metabolism could be involved, we substituted fish oil rich in eicosapentaenoic acid (EPA), an inhibitor of cyclooxygenase metabolites, for the conventional olive oil cyclosporine vehicle. Male rats were pretreated with 1.0 cc fish oil or olive oil by gavage. After 14 days, cyclosporine (12.5 mg/cc vehicle) was added to the oil and animals received cyclosporine 50 mg/kg for an additional 14 days. Pair-fed control animals received fish oil or olive oil alone. Glomerular filtration rate (GFR) was severely reduced in the cyclosporine-in-olive-oil (CSA + OO) group (0.28 +/- .05 ml/min/100 g) vs. olive oil (OO) controls (0.70 +/- .04) (P less than 0.001). While GFR was reduced in the cyclosporine-in-fish oil group (CSA + FO) vs. fish oil (FO) controls (0.47 +/- .07 vs. 0.74 +/- .04), it was significantly higher than in the CSA + OO group (P less than 0.05). Trough whole-blood cyclosporine levels were not significantly different in the two groups. While CSA + OO appeared to elevate renal cortical content of thromboxane B2 (65.7 +/- 7.3 pg/mg tissue vs. 46.9 +/- 5.3 for OO), both the CSA + FO and FO groups had reduced levels (31.1 +/- 2.7 and 29.5 +/- 2.3, respectively). In addition, there was a striking reduction in proximal tubular vacuolar changes in the CSA +/- FO vs. CSA + OO group. We conclude that the use of EPA-rich fish oil as the vehicle for cyclosporine results in improved renal function and morphology and is associated with depressed renal cortical levels of vasoconstrictor thromboxane B2.

Animals↗
PubMed1987

Induction of contraction in isolated rat aorta by cyclosporine.

Cyclosporine (CsA) is a new immunosuppressive agent that has adverse effects of nephrotoxicity and de novo appearance of hypertension. It has been hypothesized that the mechanism of the contrary effects is through an action of CsA on vascular smooth muscle. To test this hypothesis, thoracic aortas were isolated from Wistar Kyoto rats and ring segments prepared for measurement of tension. CsA (5 X 10(-6) M) induced a slow increase in tone of the isolated rings with a response at 3 hr of 0.70 +/- 0.17 N/m2 X 10(4). This contraction was significantly inhibited by the Ca2+ channel blocker verapamil (0.30 +/- 0.08 N/m2 X 10(4) after 3 hr, P less than 0.05) and by the noncompetitive alpha-antagonist phenoxybenzamine (0.06 +/- 0.07 N/m2 X 10(4) after 3 hr, P less than 0.05). The competitive alpha-antagonist phentolamine had mixed effects. CsA does not irreversibly alter vascular smooth muscle contractile ability since a 3 hr exposure to the agent had no effect on either the maximal contractile response or sensitivity to KCl. We conclude that CsA can directly induce contraction in vascular smooth muscle, perhaps by inducing a release of norepinephrine from adrenergic nerve terminals. The data are consistent with the hypothesis that CsA induces nephrotoxicity and de novo hypertension through a contractile effect on vascular smooth muscle.

Animals↗
PubMed1987

Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function.

Dose-related cyclosporine-induced renal dysfunction is the most frequent adverse effect noted with this exciting immunosuppressive drug. To investigate pathogenetic factors involved, we studied renal tubular function and afferent arteriolar morphology during severe experimental cyclosporine-induced reduction in glomerular filtration rate. Pair-fed male rats were given cyclosporine 50 mg/kg or olive oil vehicle alone by gavage for periods of 3-14 days. Glomerular filtration rate declined progressively, reaching a nadir of 0.18 +/- .05 ml/min/100 g vs. .86 +/- .03 ml/min/100 g in controls at 14 days (P less than 0.001). Despite the severe reduction in glomerular filtration rate there was no difference in fractional sodium excretion, fractional lithium excretion, enzymuria, or in vitro renal cortical slice uptake of tetraethylammonium in cyclosporine and vehicle-treated animals. Light microscopy showed vacuolar changes without evidence of tubular necrosis at 7 and 14 days in cyclosporine-treated rats. Progressive decline in the diameter of the afferent arteriole was noted by scanning electron microscopy. By day 14 the lumenal diameter of afferent arterioles from cyclosporine-treated animals was 8.9 +/- 0.4 micron vs. 13.5 +/- 0.4 micron in controls (P less than 0.05). We conclude that afferent arteriolar vasoconstriction rather than direct tubular injury is a major pathogenetic factor in experimental cyclosporine nephrotoxicity.

Acute Kidney Injury↗
PubMed1987

Responsibilities of primary physicians in organ donation.

As transplantation success rates have improved, the demand for donor organs has steadily increased. A shortage of donor organs has led to legislation requiring hospital personnel to provide families routinely with the opportunity to authorize organ donation. Primary physicians have an important role in identifying potential donors while continuing to assure that the survivors' needs are met. The major implications of organ donation for the primary physician are reviewed. Patients who die will more frequently be eligible as cornea, skin, or bone donors, but the criteria for both tissue and internal organ donation are reviewed. Ethical issues unique to organ donation and responses of survivors to donation requests are described. If appropriately offered, the opportunity to authorize an anatomic gift can be a source of comfort to survivors while the donation provides the benefits of transplantation to persons on organ waiting lists.

Ethics, Medical↗
PubMed1987

Nephrotoxicity of common drugs used in clinical practice.

Drug-induced nephrotoxicity is an increasingly recognized complication of a wide variety of therapeutic agents. The nephrotoxicity of three of the most commonly used drug groups are reviewed in this article. They include antibiotics, radiocontrast agents, and nonsteroidal anti-inflammatory drugs. Since the clinical spectrum of drug-induced nephrotoxicity is broad, it is imperative that the clinician recognize these nephrotoxic syndromes while they are reversible with discontinuation of the offending drug.

Anti-Bacterial Agents↗
PubMed1986

Renal mitochondrial integrity during continuous gentamicin treatment.

Rats were given gentamicin over a period of 21 days. At 5, 10, 14 and 21 days renal cortical mitochondria were isolated, and respiratory and Ca2+ transport functions and cytochrome concentrations were determined. The mitochondrial data were correlated with indicators of deteriorating renal function and tissue gentamicin accumulation. During the first 10 days of chronic gentamicin treatment, mitochondrial cytochrome oxidase and cytochrome c concentrations declined significantly. This decline was followed by a partial spontaneous recovery by days 14 and 21. Cytochrome b concentration was not significantly different from normal. Parallel with the cytochrome concentration changes, State 3 respiratory activities with all substrates studied and the rates of Ca2+ accumulation declined during the first 10 days and recovered spontaneously thereafter. It is concluded that chronic gentamicin treatment leading to renal failure inhibits mitochondrial energy-linked functions, which inhibition is induced by rate-limiting synthesis of those mitochondrial respiratory chain enzymes coded outside the mitochondrion.

Adenosine Triphosphate↗
PubMed1986

Modification of experimental aminoglycoside nephrotoxicity.

Some of the factors that modify experimental aminoglycoside nephrotoxicity are reviewed. Maneuvers ready to be tested for effectiveness in the clinical use of these drugs are highlighted. The use of concomitant penicillins and changes in dosing strategy seem to be particularly exciting new leads toward elimination of clinical aminoglycoside nephrotoxicity.

Aminoglycosides↗
PubMed1986

Clinical characteristics and diagnostic considerations in acquired renal cystic disease.

Acquired multiple bilateral cystic transformation of kidneys has been increasingly noted in patients with long-standing renal failure treated by chronic dialysis. To study the clinical characteristics of this newly described disease and assess the utility of available diagnostic methods, 130 patients with chronic renal failure (100 on dialysis, 30 nondialyzed) were studied with ultrasonography and/or computerized tomography (CT). Among patients on dialysis, 22% had acquired renal cystic disease (ARCD), an additional 30% had one to three solitary cysts, and 48% had no cysts. In nondialyzed patients, 7% had ARCD, 53% had one to three solitary cysts, and 40% had no cysts. Among these 130 chronic renal failure patients (nondialyzed and dialyzed), 21 of 86 males compared to 1 of 44 females had ARCD (P less than 0.001). Duration of dialysis therapy and age were greater in patients with ARCD (49.8 +/- 8 months, 55 +/- 4 years, respectively) compared to those with solitary cysts (28 +/- 6 months, 45 +/- 2 years) or no cysts (15 +/- 3 months, 42 +/- 2 years). The diagnostic accuracy of ultrasound (US) was compared to CT. CT is purportedly 100% accurate in the characterization of renal cysts. We are disappointed at the low level of diagnostic accuracy for both CT and US in the detection of renal cysts in chronic uremia. It appears both a negative CT and ultrasound are necessary to absolutely exclude either ARCD or solitary cyst.

Adult↗
PubMed1986

Action and toxicity of cyclosporine.

Cyclosporine is a potent new immunosuppressive agent that has proven particularly useful in organ transplantation. The unique action of the drug on T-cell immunity without myelosuppression is summarized. Cyclosporine pharmacology and adverse reactions, particularly nephrotoxicity, are reviewed in this paper.

Acute Kidney Injury↗
PubMed1986

Achieving oral health in patients with renal failure and renal transplants.

The protocols for oral evaluation and treatment of patients with renal failure and renal transplants are presented. Guidelines for dental treatment planning are outlined, and extraction versus conservation of teeth is discussed. Information on special considerations involving dialysis, antibiotic prophylaxis, drug therapy, and immunosuppression is provided. The goal of treatment is to restore maximum function while minimizing the risk of oral infection after transplantation.

Anti-Bacterial Agents↗
PubMed1986

Effect of calcium on in vitro para-aminohippurate accumulation by rat renal cortical slices.

In previous studies para-aminohippurate (PAH) accumulation by renal cortical slices was reduced in calcium-free medium when slices are pretreated with calcium (Ca) chelators. Addition of Ca to the incubation medium of these slices reversed the effects of Ca chelation. Based on these studies, it has been proposed that Ca is required for maximum PAH transport by renal cortical epithelium. However, in the studies presented here, we found that PAH accumulation by rat renal cortical slices not exposed to a chelator varied inversely with incubation medium Ca. Differences in accumulation of PAH was not demonstrable until 90 minutes incubation. Also unaffected was the apparent Vmax and Km of initial accumulation and efflux constant. Addition of EDTA to Ca++-free medium reduced PAH accumulation suggesting chelating agents act by a different mechanism than removal of extracellular calcium.

Aminohippuric Acids↗