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Biomedical subjects

M Winkler

Publications and source records attributed to M Winkler.

At least 145 records · Page 8Linked to original sources
PubMed1996

[The role of cytokines in the induction of labor, cervical ripening and rupture of the fetal membranes].

Even today prematurity is the major cause of perinatal mortality. Prematurity has multiple causes. There is a growing body of evidence supporting the association between silent intrauterine infection and preterm birth. Bacterial products may activate macrophages ubiquitous present in the decidua, placenta and fetal membranes. These cells after activation secrete a large variety of mediators including tumour necrosis factor alpha (TNFalpha) and interleukin (IL)-1. Besides these cytokines IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, epidermal growth factor, granulocyte-colony stimulating factor and transforming growth factor beta have been identified in intrauterine tissues and in the amniotic fluid. The majority of these substances (TNFalpha, IL-1, IL-2, IL-3, IL-6) can stimulate the prostaglandin-biosynthesis by intrauterine tissues (amnion, chorion, decidua), some of them have antiinflammatory effects (IL-10, transforming growth factor alpha). These effects are mediated by receptors on the target cells; specific receptor antagonists (for example for IL-1) were found in high concentrations in amniotic fluid during normal pregnancy. This cytokine network is in a sensitive balance and probably associated with an uncomplicated course of pregnancy. Systemic or localized infections as well as tissue injury initiate the induction of the prostaglandin synthesis cascade thus leading to pregnancy loss via augmented cytokine secretion. Furthermore, cytokines may be involved in the regulation of preterm and term cervical ripening. The changes in mechanical properties of the cervix are associated with a reduction of collagen content and alterations in the glycosaminoglycan pattern within the cervical extracellular matrix. IL-1 can stimulate the synthesis of collagenases, and IL-8 may play an important role in the regulation of the invasion of neutrophilic granulocytes into the cervical stroma with subsequent degranulation and release of proteases. The cytokine-stimulated collagenase production in the fetal membranes is responsible for the reduction of their tensile strength and may be associated with rupture of the membranes. The cytokine network seems to be a sensitive regulation system. Disturbances of its balance by environmental (e.g. infection) or intrauterine influences (e. g. extension by the fetus) may lead to termination of pregnancy.

Amniotic Fluid↗
PubMed1996

[Serum concentrations of the MCA tumor marker during pregnancy].

MCA (Mucin like carcinoma associated antigen) is used as a marker for the follow-up control of breast cancer patients, and high levels of MCA have been observed during the course of pregnancy. The aim of our study was to determine the value of MCA as a tumor marker in the follow-up of young breast cancer patients with subsequent pregnancy. We determined the MCA concentration in the sera of 201 pregnant women in the course of gravidity in order to find the degree and time of increase MCA shows during normal pregnancy. 121 serum samples of healthy, non-pregnant women were analysed for MCA in comparison. Up to the 19th week of gestation, the concentration of MCA did not show any differences in comparison to non-pregnant healthy women (n = 121, median: 7 U/ml: 25% percentile: 7 U/ml: 75% percentile: 10 U/ml (control collective). Median: 6 U/ml: 25% percentile: 5 U/ml: 75% percentile: 10 U/ml (gestational week 5-19)). After the 23rd week of gestation, the MCA concentration was elevated. After the 35th week of gestation, all women had MCA levels which were significantly higher than in healthy, non-pregnant women. Median: 100 U/ml: 25% percentile: 71 U/ml: 75% percentile: 147 U/ml (gestational week 36-42). Therefore the tumor marker MCA can be used in the followup of breast cancer only until the 19th week of gestation. After the 23rd gestational week very high MCA concentrations are observed in some cases and can not be distinguished from MCA augmentation due to advanced breast cancer.

Antigens, Neoplasm↗
PubMed1996

Tacrolimus (FK506) metabolite patterns in blood from liver and kidney transplant patients.

The metabolite patterns of tacrolimus in blood were evaluated in 41 kidney and liver graft recipients. Trough concentrations of tacrolimus and its metabolites were measured by HPLC-mass spectrometry and microparticle enzyme immunoassay in parallel. A statistically significant correlation between results of both assays was observed for kidney and liver transplant patients (r = 0.77, P <0.001 and r = 0.71, P <0.001, respectively). The main metabolites in blood were demethyl, demethylhydroxy, didemethyl, didemethylhydroxy, and hydroxy tacrolimus. These metabolites added up to 42% (range 0-145%) of the tacrolimus concentration in liver transplant patients and to 44.8% (range 16-152%) in kidney transplant patients. During episodes of impaired liver function, concentrations of tacrolimus and its metabolites were increased compared with normal liver function, indicating accumulation of metabolites, in particular second-generation metabolites such as didemethyl and didemethylhydroxy tacrolimus. Stepwise regression analysis including tacrolimus, its metabolites, and liver function parameters suggested a model including serum activities of gamma-glutamyltransferase, alkaline phosphatase, and alanine aminotransferase as predictors for increased concentrations of demethyl tacrolimus, didemethyl tacrolimus, and the parent drug.

Adolescent↗
PubMed1996

[Comparative study of the quality of life after stomach resection].

In the present study, 195 patients, following total gastrectomy (n = 105) or subtotal gastric resection (n = 90) for carcinoma without evidence of recurrence, were examined with regard to their quality of life using the Gastrointestinal Quality-of-Life Index (GLQI). After subtotal gastric resection patients achieved statistically significant better scores concerning disease-therapy-related symptoms and physical functions, resulting in a better overall score (p < 0.02). However, it seems to be questionable whether these statistically significant differences are of clinical relevance in the patient's daily life. Preservation of the gastric stump with the aim of improving postoperative quality of life should never be allowed to compromise oncological radicality.

Disease-Free Survival↗
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

[Reliability of the detection of fetal fibronectin using monoclonal antibody FDC-6].

Detection of amniotic fluid in the vagina is commonly used to diagnosed rupture of amniotic membranes. In 1991 an immunoassay was introduced which is based on the detection of a fetal fibronectin isoform using the monoclonal antibody FDC-6. Fetal fibronectin is said to be absent from normal adult tissues and plasma, but present in fetal tissues. The low concentration of fetal fibronectin in maternal plasma is said not to interfere with the test results. Theoretically, demonstration of significant amounts of fetal fibronectin in vaginal secretions may be considered an unequivocal sign of leakage of amniotic fluid or, at least, of pre-rupture stretching of the membranes. We evaluated results of the membrane immunoassay and enzyme immunoassay, which are both based on the monoclonal antibody FDC-6. Fetal fibronectin has been determined in a clinically unambiguous context in amniotic fluid as well as in vaginal swabs and blood samples. In amniotic fluid, all membrane immunoassays performed were positive. The concentration of fetal fibronectin during the third trimester of pregnancy was lower than in the second trimester. Only 9/15 cases were positive for fetal fibronectin if vaginal swabs were taken 12 hours after unequivocal rupture of membranes and no amniotic fluid was visible in the vagina. Vaginal swabs of women with regular contractions showing cervical dilation of > 2 cm were positive for fetal fibronectin in all cases (20/20) whereas no fetal fibronectin could be determined in vaginal swabs obtained from clinically inapparent pregnant women. In all blood samples of pregnant women fetal fibronectin was detected and, surprisingly, also in blood samples of non-pregnant women, as well as in vaginal swabs of non-pregnant women with vaginal bleeding. In cases of unequivocal rupture or intactness of membranes, the results of both assays correspond well with the clinical findings. 12 hours after rupture of membranes the test may become negative if no amniotic fluid is visible in the vagina. As all blood samples had been positive for fetal fibronectin we conclude that vaginal bleeding will probably interfere with the test. The most surprising result is the apparent presence of fetal fibronectin in the blood samples of non-pregnant women. This observation can only be explained by a cross-reaction of the FDC-6 antibody with hepatic fibronectin.

Adult↗
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

[Subpartal diagnosis of umbilical cord encirclement using color-coded Doppler ultrasonography and correlation with cardiotocographic changes during labor].

Umbilical cord complications are the most common cause of pathologic fetal heart tones during delivery. The inauguration of colour-coded Doppler ultrasound in obstetrics has made the definite diagnosis of umbilical cord encirclement during delivery possible. The prospective study introduced here examines the question of how exactly an encirclement can be seen by Doppler during delivery, its influence on cardiotocographic results, delivery mode, and fetal outcome. 107 patients in labour with cervical dilatation were examined in a prospective study using colour-coded Doppler ultrasound to determine cases of umbilical cord encirclement. In 50 cases, encirclement could be visualised, 48 of which were confirmed post partum. Encirclement could be ruled out in 57 other cases. A sensitivity of 96% and specificity of 100% resulted. No significant differences could be found with regard to mode of delivery and fetal outcome. However, the umbilical cord in cases of encirclement was significantly longer than when no encirclement occurred. Assessment of fetal heart tones demonstrated a significantly higher rate of variable decelerations in the patient group with umbilical cord encirclement compared to that without. In conclusion, our results show that the early diagnosis of umbilical cord encirclement during delivery allows appropriate assessment of fetal heart tone changes,justifying temporising management under continuous monitoring with possible micro-blood analysis.

Asphyxia Neonatorum↗
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

Simplified high-performance liquid chromatography-mass spectrometry assay for measurement of tacrolimus and its metabolites and cross-validation with microparticle enzyme immunoassay.

In this study, a modified, specific assay for measurement of tacrolimus and its metabolites in blood and urine from transplant patients using high-performance liquid chromatography (HPLC) linked to mass spectrometry (MS) is described. Samples were prepared for HPLC-MS by modified solid-liquid extraction. The original two-step washing procedure was replaced by a single washing step, and samples were eluted with acetonitrile/water instead of dichloromethane, thus avoiding an evaporation step. Samples were injected automatically every 3 min into the HPLC-MS system. Time-consuming gradient elution was replaced by isocratic elution. This procedure resulted in a lower limit of quantitation of 0.2 microgram/L. The interassay variability was 14.5% for 5 micrograms/L and 15.8% for 25 micrograms/L. The intrassay variability was 11.2% for 5 micrograms/L and 4% for 25 micrograms/L. The recovery for tacrolimus in blood was 90.4% for 1 microgram/L, 78.9% for 10 micrograms/L, and 81.3% for 25 micrograms/L. Measurement of tacrolimus and its metabolites in samples from various transplant patients showed that the main metabolites found in blood and urine are demethyl-tacrolimus, di-demethyl-tacrolimus and demethyl-hydroxy-tacrolimus. Cross validation of the modified HPLC-MS assay with a microparticle enzyme immunoassay showed a significant correlation between the two assays, with r = 0.915.

Acetonitriles↗
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↗