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Biomedical subjects

F P Brunner

Publications and source records attributed to F P Brunner.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effects of intravenous aspirin on prostaglandin synthesis and kidney function in intensive care patients.

The effects of intravenous acetylsalicylic acid (1.0 g bolus) on renal function and prostaglandin synthesis were evaluated in a prospective, controlled study in eight patients in an intensive care unit. Four of these patients had congestive heart failure. Administration of acetylsalicylic acid caused significant antidiuresis (-56%), antinatriuresis (-82%), renin suppression (-26%) and decreased GFR (-41%). All of these changes were completely reversible within 1-2 hours and tended to be more pronounced in the patients with congestive heart failure. Urinary excretion of prostaglandin E2 was depressed profoundly (-93%) and did not return to more than 45% of control 6 h after the administration of acetylsalicylic acid. We conclude that intravenous acetylsalicylic acid affects kidney function in a manner similar to other prostaglandin synthesis inhibitors. Its effects are, however, short-lived. The inhibition of urinary PGE2 excretion outlasts GFR depression, antidiuresis, antinatriuresis and renin suppression by several hours.

Aged↗
PubMed1986

Cyclosporine A nephrotoxicity in Goldblatt renovascular hypertension in rats.

Experiments were conducted on a renovascular model of hypertension to investigate the effect of high blood pressure and CyA nephrotoxicity combined on arteriolar and tubular morphology and renal function. A two kidney, one clip model of Goldblatt hypertension was selected in which were given 20 or 40 mg/kg/d CyA by gastric gavage for 3-4 weeks while receiving isotonic saline as drinking fluid. CyA was found to suppress feeding and drinking and, as a result, lead to volume depletion and weight loss, with a corresponding lowering of blood pressure and renal function and an increase in plasma renin. When CyA and control animals were pair-fed these effects disappeared, except for a modest depression of renal function, unaccompanied by a reduction in urinary concentrating power. Histological damage to the tubules was equally prevalent in both kidneys despite different levels of renal perfusion, suggesting that plasma concentration, rather than toxin delivery, determines tubular damage. The occurrence of arteriolopathy and glomerulosclerosis was infrequent, and if present, it was only found in the unclipped kidney and was not potentiated by CyA. Glomerular prostaglandin synthesis after substrate incubation was suppressed by CyA to an equal extent in both kidneys, clipped and unclipped.

Animals↗
PubMed1986

Effect of cyclosporine in rats with reduced renal mass.

The longterm effect of cyclosporine (CyA) on chronic renal failure was studied in female Wistar rats subjected to 4/5 to 5/6 nephrectomy by partial infarction of the left kidney followed by contralateral nephrectomy. CyA was added to a standard rat diet containing 25% protein. Each rat received 14 g of food daily containing 0 (control), 1.2 (group A), 2.4 (group B), or 4.8 (group C) mg CyA. The number of rats that did not survive the whole experimental period of 20 weeks on the CyA containing diets was similar to the control. In the surviving rats no difference between groups could be detected regarding body weight, serum creatinine and creatinine clearance. Proteinuria rose progressively up to 15 weeks in the control group and similarly in groups A and B. Mean proteinuria in group C was about half the control mean at 5-20 weeks. Systolic blood pressure differed little between groups A, B and control, but was significantly lower than control in group C at 10-20 weeks. Histologically groups B and C showed significantly less glomeruli with segmental sclerosis and less hypertensive vasculopathy than groups A and control. Histological signs of tubular CyA toxicity correlated with the doses applied: inclusion bodies were more frequent in all groups while the score of vacuolisation was increased significantly in group C only. In conclusion, CyA appears not to adversely affect or - at moderately toxic dosage - even to slow down progressive glomerular sclerosis in rats with reduced renal mass.

Animals↗
PubMed1986

Effect of cyclosporine A on ischemic renal failure in the rat.

The influence of cyclosporine A on renal function was investigated in unilaterally nephrectomized rats subjected to 30 or 45 min of ischemia. Acute i.v. administration of high dose CyA equivalent to 1000 mg/kg/d, did not produce a decrease in glomerular filtration or renal blood flow within 2 hours and its influence on proximal tubular pressure could be attributed to the cremophor vehicle. Chronic oral administration of 20 mg/kg/d CyA after ischemia produced no alteration in renal function after 2 or 9 days, but 40 mg/kg/d CyA lowered renal function demonstrably by 9 days. When pair-fed to eliminate CyA-induced weight loss as a cause of depressed renal function, the loss of renal function after 9 days was smaller but still evident. At this time renal cortical prostaglandin E2 and thromboxane B2 production were also reduced, but plasma renin remained unaltered because of the exclusion of volume depletion through weight loss. These kidneys showed no signs of delayed regeneration from ischemic renal injury but did show signs of tubulotoxicity, which seemed to be more apparent after longer periods of ischemia.

Acute Kidney Injury↗
PubMed1986

Morphology of cyclosporine nephrotoxicity in the rat.

Cyclosporine (CSA) nephrotoxicity was investigated in the rat. Morphologically, CSA nephrotoxicity is characterized by the following features: (a) Tubular inclusion bodies (TIB) corresponding to autolysosomes and giant mitochondria; (b) tubular vacuolization (TV) due to dilatation of the endoplasmatic reticulum; (c) tubular microcalcification (TM); and (d) tubular regeneration (TR). The morphologic features are limited to (a and b) or predominate (c and d) in the proximal tubule. CSA tubulopathy as defined above is dose dependent, independent of the route of a drug administration, develops quickly (within a week), is reversible after CSA withdrawal, is more pronounced in male than in female rats and shows no clear cut differences in various rat strains. Body weight shows a dose dependent reduction. The functional changes are usually slight. No significant correlation exists between functional changes and morphologic lesions. The type of CSA nephrotoxicity in the rat is very similar to CSA-tubulopathy in man but associated with less severe functional changes.

Animals↗
PubMed1986

Acutely impaired renal function during intravenous administration of cyclosporine A: a cremophore side-effect.

The parenteral application of a cyclosporine A (CyA)-containing solution in high doses, 0.7 mg/kg/min, was associated with an acute reduction in renal blood-flow and a depression in creatinine clearance to approximately one half of control values. Exactly the same effect can be produced by the intravenous administration of the vehicle, cremophore, a polyoxyethylated castor-oil derivative. Although these observations are not of great clinical importance, since the doses of CyA used in man are much lower and the drug is generally taken orally, they are of considerable importance when studying the effects of CyA under experimental conditions. For the purpose of examining the influence of CyA on renal function, cremophore-containing solutions should be avoided.

Animals↗
PubMed1986

The potassium content of heart muscle following cyclosporine.

The potassium content of cardiac muscle was examined after 9 or 22 days of cyclosporine A administration in normal rats and rats exposed to either renovascular, Goldblatt hypertension or renal ischemia. Cyclosporine A did not result in any alteration in cardiac muscle potassium compared to untreated rats in either group, even though the animals which had been subjected to renal ischemia and cyclosporine A plasma potassium was raised compared to animals subjected just to renal ischemia. The potassium content of cardiac muscle, however, was found to be raised in the hypertrophic hearts of the Goldblatt, renovascular hypertensive animals, both with and without cyclosporine.

Animals↗
PubMed1985

Renal mercury content in HgCl2-induced acute renal failure in furosemide/saline-protected and nonprotected rats.

Renal mercury content, urinary mercury excretion and renal function were studied in rats with acute renal failure (ARF) induced by subcutaneous injection of 2, 3, 6, or 10 mg/kg HgCl2. Similarly poisoned rats were protected against ARF by continuous intravenous infusion of furosemide and saline. Excellent protection was obtained in rats receiving 2,3, and 6 mg/kg HgCl2, whilst some animals developed moderate azotemia after 10 mg/kg HgCl2. Renal mercury content 48 h after HgCl2 injection did not differ appreciably between protected and nonprotected groups of rats and showed no relation to the dose of HgCl2 injected or to the degree of renal failure. Urinary Hg excretion was variable during the first 24 h after HgCl2 injection and tended to be higher with higher dosage unless the animals became anuric early on. Hg excretion during the second 24 h was independent of dosage, but was comparatively high in functionally well protected rats and low in oliguric animals with severe renal failure. Attempts at detoxication with the potent chelating agent complexon I after 6 mg/kg HgCl2 failed completely: Renal mercury content was similar to that in the other groups of rats and every single rat so treated developed severe anuric renal failure. Although dose-dependent functional injury after HgCl2 may be related to the amount of Hg reaching the kidney during the initial phase, we have to conclude that HgCl2 toxicity is unrelated to the amount of Hg found in renal tissue at 48 h. Furthermore, furosemide/saline protection does not act through increasing urinary Hg excretion or decreasing the amount of toxin accumulating in renal tissue.

Acute Kidney Injury↗
PubMed1984

[Tumors and kidney transplantation].

Incidence and type of de novo tumours were studied retrospectively in 187 consecutive patients who had received kidney transplants between 1967 and 1981 and undergone immunosuppressive therapy for 2 months or longer. Up to the end of June 1983, 18 patients (9.6%) had developed 22 malignancies and 7 of them had died from the tumour. The risk of developing a malignancy appeared to increase with prolonged immunosuppression. No significant difference was noted between patients with and without tumours regarding primary renal disease, duration of pretransplant dialysis, and type or total dose of immunosuppressive drugs. The risk of developing any malignancy appeared to be some 20 times that in the general population. The practical management of patients with de novo tumours is described in the light of our own patient material and the recent literature. Finally, two further oncological problems are discussed: first, the incidental grafting of malignant cells with the transplant, and second, how to proceed in a transplant candidate with a previous malignancy.

Adult↗
PubMed1983

Withdrawal of azathioprine in renal transplant patients with chronic active hepatitis: is it wise or not?

Withdrawal of azathioprine in renal transplant recipients with chronic active hepatitis and persisting HBs antigenemia was recommended for its beneficial effect on the course of liver disease. We report here three cases in which azathioprine treatment was stopped for this reason. One of these patients lost his graft due to irreversible vascular rejection 6 years after successful transplantation. Decrease of graft function paralleled azathioprine withdrawal in a second patient. Data from other reports indicate that cessation of azathioprine treatment may be followed by decreased graft function or even graft loss. We conclude that the risk of altered graft function is substantial and this is too high a price to pay for a procedure that may not prevent chronic active hepatitis from progressing cirrhosis.

Azathioprine↗