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Biomedical subjects

M Winkler

Publications and source records attributed to M Winkler.

At least 19 recordsLinked to original sources
PubMed1995

Feed contamination with Candida krusei as a probable source of mycotic mastitis in dairy cows.

Over 3 months, yeasts were isolated in pure culture from milk samples obtained from 8 lactating cows with acute mastitis and from 1 cow with subacute mastitis. Eight of the isolates were identified as Candida krusei; 1 isolate was not submitted for identification. The affected cows were assigned to separate milking groups and had not been treated by intramammary administration of antibiotic before the outbreak. Remission of disease without treatment was observed, followed by shedding of the yeast in milk for 2 to 5 weeks. Median somatic cell counts in the affected cows before, during, and 2 months after the onset of clinical signs were 93,000; 1,793,000; and 135,000 cells/ml, respectively. Wheat silage was found to be the probable source of the infecting microorganism, whereas inadequate milking hygiene resulted in its persistence in the herd. Following replacement of the silage and improvement of the milking hygiene, the outbreak ceased. Candida krusei thus may cause mastitis in cattle not only following intramammary antibiotic treatment, but also in conditions of heavy environmental contamination, in conjunction with inadequate milking hygiene.

Animal Feed↗
PubMed1995

Influence of bile on cyclosporin absorption from microemulsion formulation in primary liver transplant recipients.

We analysed the absorption, after oral application, of a new galenic form of cyclosporin A (CyA-NOF) in liver-grafted patients (n = 12) during the 1st week (days 2-4) after transplantation. Pharmacokinetic profiling was performed with an open or clamped T tube in situ or with the T tube absent. The pharmacokinetic parameters of CyA-NOF were influenced by T tube clamping and bile diversion. The highest AUC, Cmax and earliest Tmax values were found in patients without a T tube in situ, indicating that absorption of CyA-NOF in patients during the early course after liver transplantation is not bile-independent. CyA-NOF, at a dose of 7.5 mg/kg, was enterally absorbed with appropriate AUC and Cmax levels. Patients receiving a starting dose of 7.5 mg/kg were successfully maintained on CyA-NOF during the subsequent clinical course.

Absorption↗
PubMed1995

[Sterility as a sequela of tubal schistosomiasis].

A 21-year old african women presented with primary sterility in the outpatient department of our university hospital. Screening examinations, including ultrasound, demonstrated a tumour of 5.8 x 4.1 cm diameter on the left ovary. While performing laparotomy to extirpate this tumour, bilateral occlusion of the tubes was discovered by chromopertubation.This diagnosis led us to perform bilateral salpingostomy and reimplantation of the Fallopian tubes. In addition to the ovarian tumour (dermoid), fragments of the Fallopian tubes were sent for histological examination, which revealed eggs of schistosomes probably of the species Schistosoma haematobium. Since tourism to and immigration from endemic areas is increasing, schistosomiasis should be considered when it is not possible to elucidate the cause of sterility by classical means.

Adult↗
PubMed1995

Platelet factor 4 injection produces acute pulmonary hypertension in the awake lamb.

BACKGROUND: Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morphologic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs. METHODS: The authors evaluated the hemodynamic response and plasma release rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically monitored lambs. Each lamb underwent up to three random challenges with a 2-h recovery period between each challenge. RESULTS: In two lambs, systemic anticoagulation with heparin followed by reversal of anticoagulation with an intravenous bolus of rPF4 (4 mg/kg) led to acute pulmonary vasoconstriction and hypertension with the release of thromboxane (peak pulmonary artery pressure [Ppa] 40 and 33 mmHg and peak plasma thromboxane B2 50 and 30 ng/ml, respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B2 from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction lasted approximately 5 min and was completely prevented by pre-treatment with oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) followed by protamine (2 mg/kg) consistently produced acute pulmonary vasoconstriction and hypertension. CONCLUSIONS: Intravenous injection of human rPF4 into the awake lamb produces acute pulmonary vasoconstriction and hypertension associated with thromboxane release into circulating blood. The effects of rPF4 on the pulmonary vasculature should be evaluated in primates before rPF4 is substituted for protamine in reversing heparin anticoagulation in humans.

Animals↗
PubMed1995

Clinical pharmacology of cefixime in unweaned calves.

Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC90) of field isolates of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5-4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 micrograms/mL for the milk-fed calves and 1.76 micrograms/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.

Administration, Oral↗
PubMed1995

In vivo lipopolysaccharide pretreatment inhibits cGMP release from the isolated-perfused rat lung.

Administration of bacterial lipopolysaccharide (LPS) to rats stimulates synthesis of nitric oxide (NO), a free radical molecule that activates soluble guanylate cyclase, thereby increasing intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration and inducing systemic vasodilatation. To investigate the effect of endotoxemia on the pulmonary NO/cGMP signal transduction system, we measured the release of cGMP by isolated-perfused lungs of rats that received an intraperitoneal injection of LPS (1 mg/kg) or saline 2 days earlier. Over 90 min, 1.4 +/- 0.78 and 0.079 +/- 0.016 nmol cGMP accumulated in pulmonary perfusates of saline- and LPS-treated rats, respectively (P < 0.05). Despite addition to the perfusate of Zaprinast, superoxide dismutase, or A23187, markedly less cGMP was released from the lungs of rats exposed to LPS than from the lungs of control rats. In contrast, after ventilation with 100 parts per million NO gas, cGMP accumulating in the perfusate of the lungs of both groups of rats was markedly increased, and the quantity of cGMP released from the lungs of LPS-treated rats was similar to that released by control rat lungs (2.8 +/- 0.57 vs. 3.3 +/- 0.88 nmol, P = NS). With the use of immunoblot techniques, equal concentrations of constitutive endothelial NO synthase were detected in the lungs of rats treated with saline or LPS. These results demonstrate that the NO/cGMP signal transduction system is abnormal in the lungs of rats exposed to LPS, at least in part, at the level of endothelial NO synthase activation.

Animals↗
PubMed1995

Nutrition care given new importance in JCAHO standards.

The 1995 standards developed by the Joint Commission on Accreditation of Healthcare Organizations are now in effect. In an unprecedented shift, the manual focuses on performance rather than structure and process. It emphasizes the interdisciplinary delivery of care, including nutrition care. This article describes the new standards as they relate to nutrition support professionals.

Joint Commission on Accreditation of Healthcare Or↗
PubMed1995

A risk-benefit assessment of tacrolimus in transplantation.

Tacrolimus is a new macrolide immunosuppressant that was isolated from Streptomyces tsukubaensis in 1984. In vitro, on a molecular basis, tacrolimus is 50 to 100 times more potent that cyclosporin. Since 1989, numerous clinical trials have been completed comparing the usefulness of tacrolimus with that of cyclosporin for baseline immunosuppression in solid organ transplantation. Almost all of these studies demonstrated the superior immunosuppressive potency of tacrolimus. However, in most of these trials, tacrolimus-based immunosuppression was associated with a higher overall frequency of drug-related adverse effects compared with cyclosporin. Based on the efficacy and tolerability profile of tacrolimus that has been demonstrated in the various clinical trials so far, tacrolimus is a relevant alternative to cyclosporin for baseline immunosuppression in liver transplantation. In addition to primary immunosuppression, conversion from cyclosporin to tacrolimus should be performed during episodes of severe graft rejection (e.g. resistant to steroid bolus therapy). The future role of tacrolimus for baseline immunosuppression in kidney and thoracic organ transplantation has yet to be defined by ongoing studies.

Humans↗
PubMed1995

[Results of surgical therapy of early stomach cancer].

Between 1972 and 1993 232 patients with early gastric cancer have been resected at the Surgical University Hospital of Mannheim. At the time of surgery 9.9% of the patients had lymph node involvement, 2 of them had distant metastases. In 59.9% of the cases (n = 138) a subtotal distal gastric resection, in 34.1% (n = 79) a total gastrectomy and in 6.4% (n = 15) a proximal or an atypical resection were performed. Following distal resection and total gastrectomy a radical lymphadenectomy of the compartments I and II was performed. The hospital lethality was 5.2%, the morbidity 18.1%. There were no statistical significant differences between the different surgical methods. The cumulative-5-year-survival rate was 80% without any statistically significant differences between the surgical methods and the histological types according to the Japanese classification of early gastric cancer.

Female↗
PubMed1994

Site-specific mutagenesis of residues in the human C5a anaphylatoxin which are involved in possible interaction with the C5a receptor.

To check and clarify existing data on receptor-interacting residues in the human C5a anaphylatoxin, we tested mutant C5a proteins obtained by site-directed mutagenesis of a recombinant human C5a (rhC5a) cDNA clone for structural and functional integrity. Amino acid positions in three different regions of the molecule were investigated: Arg74 at the C-terminus, Arg40 and Pro45 located in the core region, and Lys14 and Lys19, Lys20 in the N-terminus. Des-Arg74-rhC5a displayed only a residual 3-4% functional activity in the myeloperoxidase-release assay from human granulocytes while retaining the three-dimensional solution structure of wild-type (wt)-rhC5a as shown by circular dichroism (CD) spectroscopy. Des-Arg74-rhC5a was able to activate the human C5a receptor transiently expressed in Xenopus oocytes, but was inactive in the heterologous guinea pig (gp) ileum-contraction assay. These results reveal profound differences between the guinea pig and human C5a-receptor ligand-binding characteristics. Exchange of the core residue Arg40 by a glycine did not significantly affect functional C5a activity, in contrast to a previous observation [Mollison, K. W., Mandecki, W., Zuiderweg, E. P., Fayer, L., Fey, T. A., Krause, R. A., Conway, R. G., Miller, L., Edalji, R. P., Shallcross, M. A., Lane, B., Fox, J. L., Greer, J. & Carter, G. W. (1989) Identification of receptor-interacting residues in the inflammatory complement protein C5a by site-directed mutagenesis, Proc. Natl Acad. Sci. USA 86, 292-296], nor did exchange of the conserved Pro45 residue by the C3a analogue glutamic acid, a mutation expected to alter the whole geometry of the loop connecting helix III-helix IV (including Arg40) of the C5a molecule. Thus, participation of this loop in receptor interaction appears unlikely. While exchange of the N-terminal Lys14 residue by alanine did not significantly affect functional activity, a double replacement of Lys19 and Lys20 by alanine residues reduced activity more than 30-fold. These results confirm Lys19 and/or Lys20 as a putative receptor-interacting site, although we could not obtain a CD spectrum of this important mutant due to poor expression.

Amino Acid Sequence↗
PubMed1994

A chaotic systems analysis of the nasal cycle.

The nasal cycle is a chaotic ultradian rhythm with a period ranging from about 75 to 200 minutes. It has been shown to correlate highly with EEG amplitude in the contralateral hemisphere at virtually all frequencies, suggesting a connection between this rhythm and laterality of brain function. During a three-week period, five participants estimated airflow from both nostrils every 30 minutes during waking hours. Estimates were recorded on Likert scales and analyzed in three distinct phases: (1) reconstructing two-dimensional attractors by lagging and embedding; (2) computing Fourier frequency analyses; and (3) estimating fractal dimensions. Attractor reconstructions demonstrate noticeable order when compared to Monte Carlo reconstructions of the same data sets, and dimension estimates are in the fractal range. The attractor reconstructions, in combination with the frequency analyses, show distinct individual differences in the structure of the nasal cycle. The advantages of chaotic systems analyses over traditional behavioral statistics are discussed.

Activity Cycles↗
PubMed1994

The use of plasma levels for FK 506 dosing in liver-grafted patients.

FK 506 plasma levels were analyzed in 89 liver-grafted patients under FK 506-based immunosuppression. Plasma levels were found to be influenced by the patients' liver function: compared to patients without major liver dysfunction, those with cholestasis had higher plasma levels and these plasma levels were able to differentiate between rejection and toxicity. In patients with stable liver function, no clear difference was observed with regard to the plasma levels detectable during toxicity or rejection. We conclude that plasma levels can be used to determine the FK 506 dose but only in patients with cholestasis (i.e., during the early post-transplant course, or in patients with cholestatic rejection). In patients with stable liver function, plasma levels are only of limited clinical relevance.

Cholestasis↗
PubMed1994

Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.

The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.

Animals↗
PubMed1994

Comparison of different assays for the quantitation of FK 506 levels in blood or plasma.

In a prospective study, we evaluated the analytical performance of different assays for the quantitation of FK 506 in blood and plasma. The new whole blood IMX assay was compared with four modifications (liquid/liquid or solid/liquid extraction of blood or plasma respectively) of the standard enzyme-linked immunosorbent assay (ELISA). Both assays utilize the same monoclonal antibody for detection of FK 506. Using isolated FK 506 metabolites generated in vitro, this antibody was shown to recognize not only the unmodified parent drug but also FK 506 metabolites. In stable liver-grafted patients, sensitivity of both modifications of the whole blood ELISA was adequate. In contrast, in some stable patients, plasma ELISA was not able to detect FK 506; this was observed mainly after liquid/liquid extraction of FK 506. Sensitivity of the IMX assay was also low; in six of 10 stable liver-grafted patients, IMX levels were below the limit of detection. In all assays, FK 506 levels were found to be elevated during episodes of liver dysfunction; a possible explanation for this effect would be that of accumulation of cross-reacting FK 506 metabolites. As FK 506 metabolites are known to be less immunosuppressive than the parent drug, liver function should always be taken into account if IMX or ELISA levels are used for drug monitoring.

Antibodies, Monoclonal↗