PubMed Health⌕ Search

Biomedical subjects

F Brunner

Publications and source records attributed to F Brunner.

At least 73 records · Page 4Linked to original sources
PubMed1984

The underlying bases of pharmacological results in agreement or disagreement with the law of initial value.

Dose-response studies in vitro and in vivo revealed four types of alterations of dose-response curves along with changes in the baseline, two of them in accordance and two in disagreement with Wilder's law of initial value (LIV). The following conclusions have been drawn: The magnitude of drug-induced changes is in agreement with the LIV under conditions where the ED50 of a compound studied is not affected by changes in the baseline. Disagreement with the LIV is due to factors which potentiate the action of a compound at higher initial values. Not the initial value or activity by itself determines the response to drugs or stimuli; the response is dependent on the factor(s) changing the initial value.

Animals↗
PubMed1984

Assessment of adrenergic beta-blockade in the anesthetized rat at different baseline values.

The influence of different baseline values (blood pressure, heart rate) on ED50- and Emax-values of isoprenaline dose-response curves (DRC) in the presence and absence of beta-blocking drugs was assessed in urethane-anesthetized rats. The results show that Urethane is a suitable anesthetic in this animal model. Different baselines have no influence in ED50-values. Assessment of potency of competitive antagonists (pA2) from complete DRC appears unaffected by differences in baseline or in Emax. Pharmacologic effects (heart rate, blood pressure) are better depicted as absolute effect values than delta-values.

Adrenergic beta-Antagonists↗
PubMed1984

Plasma protein binding of metbufen, a new non-steroid anti-inflammatory drug, in humans.

The binding of 14C-metbufen to human serum albumin and to plasma of cirrhotic patients was measured by equilibrium dialysis at 37 degrees C, pH = 7.4. Between 0.37-373 microM, binding of metbufen to human serum is linear and 99% complete. HSA is the only binding protein with two classes of saturable binding sites. The binding parameters are n1 = 3-5; K1 = 40000 M-1; n2 = 5-8; K2 = 2000 M-1 and n1 = 2; K1 = 148000 M-1, n2 = 7.5; K2 = 2800 M-1 to serum (600 microM HSA) and HSA (600 microM), respectively. The higher affinity constants of pure commercial HSA than found in serum and the lower number of binding sites are thought to be due to albumin polymerization in commercial HSA. In plasma from cirrhotic patients (total bilirubin: 232 microM; HSA = 450 microM), at 7.5 and 30 microM, metbufen-free fractions increased from 1.4 to 2.4% and 1.3 to 3.6%, respectively. At 2 or 8 micrograms/ml, metbufen is not displaced by salicylic acid (300 micrograms/ml), CPIB (200 micrograms/ml), furosemide (2 micrograms/ml), itanoxone (20 micrograms/ml), tolbutamide (100 micrograms/ml), warfarin (3 micrograms/ml), or diazepam (0.75 micrograms/ml). Finally, metbufen interacts with both the diazepam and warfarin binding sites of HSA to some degree.

Anti-Inflammatory Agents↗
PubMed1984

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.

Adult↗
PubMed1983

Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.

Azathioprine↗
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↗