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Biomedical subjects

F Brunner

Publications and source records attributed to F Brunner.

At least 73 records · Page 4Linked to original sources
PubMed1983

Intravenous cyclosporine kinetics in renal failure.

Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.

Chromatography, High Pressure Liquid↗
PubMed1983

The plasmid pattern as an epidemiologic tool for Salmonella typhimurium epidemics: comparison with the lysotype.

In the study of a limited epidemic of Salmonella typhimurium infections, the plasmid content (pattern) of bacteria was used as an epidemiologic tool outside the hospital environment. Comparisons were made with lysotyping, resistance pattern determination (14 antibiotics), and biotyping. Plasmid pattern determination was found to be as useful and accurate as lysotyping, whereas resistance pattern determination was of more limited interest. However, in this report biotyping was of no use.

Bacteriophage Typing↗
PubMed1983

The effects of chronic renal insufficiency on the pharmacokinetics of doxycycline in man.

The pharmacokinetics as well as erythrocyte and plasma protein binding of doxycycline were studied in fifteen patients with various renal function impairments after oral doxycycline polyphosphate single administration. Plasma half-life (t 1/2), area under the plasma concentration-time curve (AUC), urinary excretion, renal clearance, erythrocyte and plasma protein binding (%) were regressed vs creatinine clearance. No significant correlations were observed between t 1/2 or AUC and renal function nor plasma protein binding and plasma albumin concentrations. Significant correlations were obtained between urinary excretion, renal clearance, erythrocyte binding, plasma protein binding and creatinine clearance. Significant correlation was obtained between haematocrit and erythrocyte binding. Constancy of overall elimination parameters in renal failure is due to parallel increase in plasma free fraction of doxycycline.

Adult↗
PubMed1983

The role of tubuloglomerular feedback in acute impairment of renal function in obstructive jaundice.

Acute renal functional impairment not infrequently accompanies liver dysfunction and, particularly with bile duct obstruction, may be extremely severe. Recent studies suggest that tubuloglomerular feedback (TGF) activated by circulating non-electrolyte factors which occur during liver dysfunction may contribute to the intense renal vasoconstriction thought to be central to the functional renal impairment. In this study, serum from two patients with obstructive jaundice (OJ) and renal impairment, and from rats with OJ due to bile duct ligation were either dialysed or treated with furosemide, known to block electrolyte-mediated TGF. These sera, when perfused into loops of Henle in rat nephrons, induced a significant fall of 28% in stop-flow pressure, an indirect measure of glomerular capillary pressure thus implying arteriolar vasoconstriction. These findings are consistent with the hypothesis that circulating, non-electrolyte factors, which stimulate TGF, occur in cases of obstructive jaundice and that these may contribute to the renal impairment.

Acute Kidney Injury↗
PubMed1983

Disease-induced modifications of drug pharmacokinetics.

This article attempts to help in the understanding of the mechanisms responsible for a modified drug pharmacokinetic profile in disease states. The main factors influencing the fate of the drug as it moves from the site of administration to the sites of elimination are depicted. Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow. Pathological states may affect the binding of drugs to plasma proteins, mainly human serum albumin and alpha 1 acid glycoprotein. The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution. The distribution can also be influenced by circulatory disorders modifying local blood flows and thus impeding drug entry into the tissues. Many diseases can alter hepatic and/or renal clearance. This is not surprising since the elimination mechanisms are dependent upon many factors such the enzymatic status of the liver, plasma protein binding, and blood flow to both the liver and the kidney. Some examples such as the modification of furosemide pharmacokinetics in acute renal failure, the impaired metabolism of opiate analgesics in hepatic insufficiency, the alterations of the usual disposition process in salicylic acid intoxication, and the influence of cardiac failure upon some drugs pharmacokinetics, have been chosen to illustrate some of the aspects discussed. Some simple rules for making a rational selection of drugs in pathological states are also outlined.

Acute Kidney Injury↗
PubMed1982

[Clinical relevance of N-acetylglucosaminidase determination in urine of kidney transplant recipients with and without cyclosporin A].

From January to September 1981 urinary gamma-N-acetyl-glucosaminidase (NAG) excretion was measured in 23 cadaver kidney recipients up to 90 days posttransplant. Conventional immunosuppression with azathioprine and prednisone was used in 12 patients, and cyclosporin A (CyA) in 11 patients. The purpose of this study was to assess the clinical value of NAG determinations in the diagnosis of acute rejection episodes and CyA-induced nephrotoxicity. A total of 26 acute rejection episodes were observed. 14 (54%) of these were associated with a significant increase in NAG excretion. The other 46 episodes of increased NAG excretion (77% of a total of 60 episodes) were unrelated to acute rejection reactions. No obvious reason was apparent in 39 instances (63%). Nine out of 11 patients treated with CyA showed one or more increases in NAG excretion, but the number of such episodes did not differ between patients with CyA serum concentrations below 500 ng/ml and those with levels above 500 ng/ml. Histological signs of CyA toxicity in graft biopsies correlated well with increased NAG excretion. It is concluded that increases in NAG excretion are not sensitive and specific enough to be of definite help in the diagnosis of acute rejection and/or CyA-induced nephrotoxicity.

Acetylglucosaminidase↗
PubMed1982

Single dose pharmacokinetics of fendiline in humans.

Fendiline was administered intravenously (3 mg) and orally (50 mg and 75 mg) in a cross-over study to six healthy volunteers. The plasma levels of unchanged fendiline and of total radioactivity were measured. Fendiline was absorbed well and its concentration declined biexponentially with mean terminal half-lives of 20-35 h. Since the drug is extensively metabolized, only 12% of total radioactivity in plasma corresponded to fendiline in the case of intravenous administration as compared to less than 2% after oral administration. 56-65% of the administered dose are excreted via the urine and 18-25% with the feces within five days.

Adult↗
PubMed1981

[Endotoxin effect on intravascular volume and kidney function in an acute experiment in the rat].

The effect of intravenous endotoxin (Sal. abortus equi) in a semilethal dose in rats was very individual. Animals showing a drop in creatinine clearance were termed sensitive (E II), and animals without effect on the creatinine clearance non sensitive (E I). In the sensitive animals a reduction of intravascular space by albumin loss into the extravascular space, a decrease of renal blood flow and an average fall in creatinine clearance of 40% were found. The non sensitive animals (E I), on the other hand, showed no significant change in albumin space but, in contrast to E II, their hematocrit fell, a fact interpreted as vasodilatation and inflow of fluid. In these animals (E I) no change in creatinine clearance was measured. Orthograde tubular perfusion of endotoxin through the loop of Henle elicited no tubular glomerular feedback response. In these sensitive animals (E II), the absence of tubular glomerular feedback vasoconstriction, hypovolemia and a fall in blood pressure suggest a prerenal cause for this type of acute renal failure. Additional factors responsible for acute renal failure are discussed.

Animals↗
PubMed1981

[Pharmacokinetics and biotransformation of oxametacine in healthy volunteers (author's transl)].

The bisphasic time-concentration course of the total plasma activity can be ascribed to 2 metabolites--oxametacine-glucuronide and desmethylindometacinamid(DMA)-glucuronide. The rate of biotransformation for oxametacine (1-p-chlorbenzoyl-2-methyl-5-methoxy-3-indolylacethydroxamic acid) is high. In contrast to laboratory animals the metabolic degradation of the mother substance to indometacine is negligible. Oxametacine is therefore not a pro-drug for indometacine in man. The main routes of biotransformation in man are: demethylation, conjugation, with active glucuronic acid, reduction to the acid amide and debenzoylation. For the 75 mg single dose urinary recoveries of the main metabolites, DMA-glucuronide and desbenzoyldesmethylmetacinamide (DBDMA)-glucuronide are 22.9% and 9.2%, respectively. The total recovery was found to be 97.55% of the dose, this being made up of 48.49% renal and 49.06% fecal excretion.

Adult↗
PubMed1980

[Psychiatric aspects in the starting and ending of chronic dialysis].

Various symptoms are discussed which are of importance in patients undergoing maintenance dialysis for chronic renal failure, such as depression, organic brain syndrome, ambiguity regarding a chronic "incurable" disease, sexual dysfunction and suicidal behaviour. A number of criteria that should be considered at the beginning and termination of regular dialysis treatment are described. Six case reports of selected patients with chronic renal failure and psychiatric problems are discussed. For psychiatric reasons one female patient was not started on maintenance dialysis. One of the patients, a female, did well on maintenance dialysis. One patient died due to medical complications for which treatment was withheld. Two patients decided to quit maintenance dialysis with their doctor's approval. One patient committed suicide unexpectedly.

Depression↗
PubMed1980

[Blood transfusions and kidney transplantation: selection or conditioning of recipients?].

Pretransplant blood transfusions have been shown in retrospective studies to prolong the survival of kidney grafts. We have therefore introduced a new prospective transfusion policy. All patients waiting for a kidney transplant received if possible 5 transfusions at monthly intervals, then 1 every 6 months. From 1.1. 1977 to 31.12. 1978 we transplanted 51 transfused patients. In the present study we investigated: 1. the occurrence of lymphocytotoxic antibodies, 2. the time on dialysis until transplantation and 3. the kidney graft survival. 65% of all patients never had antibodies. Only 6 patients produced antibodies with broad spectrum activity. The occurrence of these antibodies did not significantly influence the graft survival. The majority of the patients without antibodies waited 5 months for transplantation. The few hyperimmunized waited far longer, but nevertheless all finally got a transplant. The actuarial graft survival rate at 1 year was 72%. The results of our program with systematic pretransplant transfusions indicate that the advantages of transfusions override the risk of hyperimmunisation.

Antibody Formation↗
PubMed1977

[Cranial mucormycosis in a patient with a transplanted kidney].

Mucormycosis is a very serious complication of debilitating diseases, and particularly of diabetes. Presently the treatment of choice is amphotericine B. A patient is described who, like most other renal transplant patients with mucormycosis, had cranial localization of this disease and diabetes. The clinical findings were classical and the diagnosis was confirmed histologically.

Adult↗