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Biomedical subjects

M Winkler

Publications and source records attributed to M Winkler.

At least 91 records · Page 5Linked to original sources
PubMed1999

Parturition at term: parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment.

A relationship was sought between the tissue concentrations of interleukin (IL)-8, matrix metalloproteinase (MMP)-8 and MMP-9, and the numbers of the various leukocytes infiltrating the lower uterine segment stroma during parturition. Biopsy specimens of the lower uterine segment were obtained from 63 women undergoing Caesarean section at various stages of cervical dilatation at term. The concentrations of IL-8, MMP-8 and MMP-9 were determined with enzyme-linked immunosorbent assays, and the leukocytes were quantified immunohistochemically. The median IL-8 concentration (pg/mg total protein) rose significantly from 17.2 at < 2 cm dilatation, to 26.5 at 2 to < 4 cm dilatation, and 1954.0 at 4-6 cm dilatation, and remained at approximately this concentration at > 6 cm dilatation. The median MMP-8 concentration (ng/mg total protein) increased significantly from 32.2 at < 2 cm dilatation to 114.2 at > 6 cm dilatation. The median MMP-9 concentration (ng/mg total protein) rose significantly from 15.4 at < 2 cm dilatation to 102.1 at > 6 cm dilatation. The number of neutrophils was significantly higher at 4-6 cm and > 6 cm dilatation than at > 2 cm, reaching maximum values at > 6 cm dilatation. The findings in this study support the hypothesis that IL-8-induced infiltration of the cervical stroma by neutrophils and subsequent release of proteinases may play a key role in parturition.

Adult↗
PubMed1999

LC/ESI-MS allows simultaneous and specific quantification of SDZ RAD and cyclosporine, including groups of their metabolites in human blood.

An analytic technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI-MS) has been developed for the simultaneous determination of the new immunosuppressant SDZ RAD (40-O-[2-hydroxy)ethylrapamycin) and cyclosporine (Cs), including their metabolites in blood. With the time-sparing, automated on-line extraction technique, the recovery of SDZ RAD averaged 95% and that of Cs, 94%. The calibration lines were linear from 0.5 to 100 microg/L (r2 = 0.99) for SDZ RAD and from 10 to 1,000 microg/L (r2 = 0.99) for Cs. The method has been tested on blood samples from renal transplant recipients taken between 1 and 5 hours after oral SDZ RAD and Cs administration. In blood, we found the following metabolites: Hydroxy-SDZ RAD, dihydroxy-SDZ RAD, demethyl-SDZ RAD, and the ring-opened form of SDZ RAD. The main metabolite of SDZ RAD in blood was hydroxy-SDZ RAD. This novel LC/ESI-MS technique provided an excellent method for simultaneous quantitative monitoring of SDZ RAD and Cs, including their relevant groups of metabolites in patients treated simultaneously with these immunosuppressants.

Chromatography, High Pressure Liquid↗
PubMed1999

Changes in the cervical extracellular matrix during pregnancy and parturition.

The key function of the uterine cervix to maintain pregnancy is biochemically characterized by an increased synthesis of proteins (e.g., collagen), proteoglycans, and glycoproteins (e.g., fibronectin) as well as by defined interactions between these components of the extracellular matrix. In contrast to the slow phase of the cervical ripening process in late pregnancy, cervical dilatation during parturition requires the rapid production and action of catabolic enzymes leading mainly to collagen degradation and changes in its architecture but also to degradation of other fundamental matrix proteins. Evidence suggests that an increased production of TNF-alpha and IL-1 beta, e.g., induces a rise in the expression of endothelial adhesion molecules with subsequent extravasation of neutrophils into the cervical stroma and that the chemotaxis and degranulation of these cells is triggered by an increased concentration of IL-8. Rising concentrations of hyaluronan at this time have been considered as potent inducers of IL-1 beta and TNF-alpha synthesis by various leukocyte populations. The increase in IL-6 synthesis stimulates prostaglandin and leukotriene production causing dilatation of cervical vessels and further promoting the extravasation of leukocytes. The proteases released after degranulation of neutrophils encounter an already destabilized collagenous fiber network. Since a sustained action of proteases may lead to severe tissue damage, this process is strictly limited in time and is controlled by increasing concentrations of tissue inhibitors of protease in the lower uterine segment immediately after delivery. The clinical consequences of this basic research is to develop new concepts in a more causal treatment of cervical pathology during pregnancy and parturition.

Cervix Uteri↗
PubMed1999

The role of houseflies (Musca domestica) in harbouring Corynebacterium pseudotuberculosis in dairy herds in Israel.

A study was conducted to assess the role of houseflies, Musca domestica L. in harbouring Corynebacterium pseudotuberculosis in dairy farms in Israel. The bacterium was isolated in June 1993 from 40 wild houseflies which had fed on a lesion on a cow, and from 28 laboratory flies fed on contaminated milk from a cow infected with mastitis. The bacterium was recovered from the body surface of 10 flies (of a total of 160) 10 min after being dipped entirely in a bacterial broth. The bacterium was recovered from the body surface of 10 flies (of a total of 40) 5 min after being fed on contaminated milk. When 110 flies were fed on contaminated sugar cubes, the bacterium was recovered externally from 70 flies 5 min later, and from an additional 20 flies 10 min after feeding. Of 110 flies, 80 excreted bacteria in saliva from 5 min to 3 h after feeding on contaminated milk. Bacteria were isolated from the intestine of 40 of 60 flies between 1 h and 4 h after feeding on contaminated milk. Bacteria were found in the faeces of 30 of 60 flies, between 1 h and 4 h after feeding on contaminated milk. In the light of these findings, and given the fact that this species of fly has a predilection to feed on milk residues of cow teats, the authors concluded that the housefly plays an important role in harbouring and disseminating C. pseudotuberculosis in dairy herds in Israel. In contrast, stable flies (Stomoxys calcitrans L.) are not important in the habouring and dissemination of the bacteria, since bacteria were not recovered 5, 10, 15, 30 min, 2 h or 24 h after membrane feeding on a mixture of bacterial broth and blood.

Animals↗
PubMed1999

A risk-benefit assessment of oxytocics in obstetric practice.

Substances that stimulate contractions of the myometrium have found wide applications in present day obstetrics. Above all, fully synthetic, uterus-selective prostaglandin analogues are used for preoperative priming of the cervix for termination of pregnancies in the first trimester as well as for the induction of abortions in the second trimester and have proved to have a much higher efficacy than oxytocin. Because of the pharmacological synergism of their cervix ripening and myometrium stimulating activities, the local use of natural prostaglandin E2 preparations (used intracervically as a gel or vaginally as a gel or as a tablet) is unequivocally superior to use of oxytocin with its almost exclusive contraction stimulating activity for induction of labour, especially for women with an unripe cervix. In women with a ripe cervix, oxytocin and prostaglandins are equally effective with oxytocin having the major advantage of its better controllability on continuous intravenous infusion (plasma elimination half-life of 10 minutes). Over the past 50 years, the use of oxytocin and ergot alkaloids preparations as prophylaxis against postpartum atonia has led to a marked reduction in maternal deaths. The same is true to a major extent for therapy for uterine atonia where the intravenous infusion of dinoprost is an indispensable and life-saving procedure after the failure of systemic administration of oxytocin or ergot alkaloid preparations. On the other hand, the administration of oxytocics can be accompanied by a wide range of adverse systemic and uterine effects and complications ranging from severe cardiovascular incidents with a fatal outcome through to the threat of uterine hyperstimulation with fetal asphyxia to uterine rupture. For these reasons, an adequate knowledge of the pharmacokinetics as well as the systemic and uterine activities and adverse effects of these substances is an essential prerequisite for every physician in evaluating differential indications for their use and adequate monitoring for mother and infant. Of particular importance is the use of prostaglandins for cervical priming prior to termination of pregnancies in the first and second trimesters and the use of native prostaglandin and oxytocin for inducing delivery in cases of fetal deaths as well as vital infants. Both substances play a decisive role at the beginning of delivery. Cervical priming and induction of contractions would not be conceivable without prostaglandin and oxytocin. The pharmacological properties of the 2 substances can be used in different ways for the induction of delivery. Oxytocin ergot alkaloids and prostaglandin are essential for the management of postpartum uterine atonia where their use often represents a decisive, life-saving intervention.

Abortion, Induced↗
PubMed1999

[Xenotransplantation of the liver].

The development of pigs transgenic for human regulators of complement activation resulted in the nearly total elimination of episodes of hyperacute rejection following discordant solid organ xenotransplantation. Following discordant heart or kidney transplantation, in subhuman primates, graft survival rates of up to several months can be observed. In contrast to these organs, the xenotransplantation of the liver is associated with the inherent problem of the immunological and metabolic compatibility of the large variety of xenoproteins generated. Based on a review of data mainly derived from experimental ex-vivo xenoliver perfusions in patients with hepatic coma, whole organ orthotopic or heterotopic liver xenotransplantation currently is not likely to become a relevant option for the treatment of patients with endstage liver failure. In contrast, clinical studies utilizing different forms of bioartificial liver assist devices are currently underway. Based on preliminary data published, this form of liver support therapy might enter the clinic in the near future.

Animals↗
PubMed1999

Ribonuclease-resistant RNA controls (Armored RNA) for reverse transcription-PCR, branched DNA, and genotyping assays for hepatitis C virus.

BACKGROUND: Comparison and evaluation of molecular diagnostic assays for the detection and quantification of hepatitis C virus (HCV) RNA have been limited by the lack of RNA controls and calibrators. Armored RNA technology is a means for producing RNA that is completely protected from plasma ribonucleases. This method produces recombinant pseudoviral particles that are noninfectious and contain predefined RNA sequences. METHODS: A consensus 412-base sequence from the 5'NCR/Core region of HCV subtype 2b was derived from 34 individually sequenced HCV genotype 2b variants. A DNA fragment encoding the consensus HCV-2b sequence was synthesized de novo, cloned, and expressed as an Armored RNA control. The resulting HCV-2b Armored RNA (AR-HCV-2b) contained the complete HCV-2b consensus RNA sequence encapsidated within a protective protein coat. RESULTS: AR-HCV-2b was fully recoverable from human plasma incubated at 4 degrees C for >300 days. The particles were tested in three clinical assay formats: Amplicor HCV Monitor 1.0, Quantiplex HCV RNA 2.0, and INNO-LiPA HCV II. When added into seronegative, nonviremic plasma, AR-HCV-2b showed reproducible signals and linear dilutions in both the Amplicor and Quantiplex assays. AR-HCV-2b was correctly identified as subtype 2b in the INNO-LiPA line probe assay. CONCLUSION: The HCV-2b Armored RNA control is a versatile, durable, ribonuclease-resistant viral RNA control that is compatible in three different clinical assay formats.

Base Sequence↗
PubMed1999

[Evidence-based medicine: labor induction with prostaglandins].

OBJECTIVE: Because 10-15% of all births in Germany are induced with prostaglandins (PG), a survey of the scientific evidence for the efficacy of PG in promoting cervical ripening was undertaken. PATIENTS AND METHODS: Randomized controlled trials and meta-analyses of the efficacy of the local (intravaginal and intracervical) administration of PGE2 and PGE1 compared to the effects of conservative management (no specific therapy), placebo, and intravenous oxytocin were evaluated. RESULTS: PGE2 was found to be more effective than conservative management and placebo, and to reduce significantly the incidences of cesarean section and instrumental vaginal delivery, without having any impact on measures of fetal outcome. PGE2 was also found to be more effective than oxytocin, especially when the cervix is unripe (Bishop score < or = 5): unsuccessful induction was less frequent and the induction-delivery intervals were shorter, although fetal outcome and the incidences of cesarean section and instrumental vaginal delivery were unaffected. Initial experience also indicates that PGE1 given at a dosage of 25 micrograms every three hours is more effective than intravenous oxytocin or local PGE2, but this advantage appears to be accompanied by an increase in the incidence of uterine hyperstimulation and associated fetal heart rate changes. CONCLUSIONS: It is surprising that, even today, there is little hard scientific data concerning the efficacy of PG in the induction of cervical ripening. This fact should be discussed with the parturient. Further randomized controlled trials using well-defined, standardized measures are needed to clarify the situation.

Administration, Intravaginal↗
PubMed1998

Clinical, bacteriological and epidemiological aspects of clinical mastitis in Israeli dairy herds.

A 4-year retrospective study was performed to determine the clinical, bacteriological and epidemiological aspects of acute clinical mastitis in seven Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by abnormal changes in the milk and udder with concurrent decrease of at least 25% in daily milk production. A total of 1190 quarters were affected with clinical mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7% of quarter cases) than the front quarters. The annual herd-year-incidence varied from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR) was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and then decreased. Most clinical mastitis cases were associated with coliform bacteria (60.2% of cases), environmental streptococci (18.6%), coagulase-negative staphylococci (8.7%) and samples from which no bacterial growth was detected (8.1%). Most cases of clinical mastitis occurred in the early stages of lactation, with 51.4% of all cases, 52.3% of coliform cases and 54.6% of environmental streptococci mastitis cases occurring during the first 4 months of lactation. The median days in milk at diagnosis was 118 days. The incidence was lower in the dry summer months. The ratio of peak to low incidence was 1.62 with a calculated peak incidence in January.

Animals↗
PubMed1998

Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis.

The relationship between in vitro sensitivity to antimicrobials and the outcome of treatment was studied in 228 cows with coliform mastitis. All the cows were treated with a preparation containing sulphonamide and trimethoprim, and 197 of them were also treated with a non-steroidal anti-inflammatory drug (NSAID). The relationship between in vitro sensitivity to sulphonamide/trimethoprim and recovery was analysed by multivariate logistic regression. The possible confounding effects of treatment with an NSAID, days in lactation, parity, herd, and type of infecting organism were tested. Only treatment with an NSAID had a significant confounding effect and was included in the final statistical model. The recovery rate of the 165 cows infected by coliforms that were sensitive to sulphonamide/trimethoprim (89.1 per cent) was higher than that of the 63 cows infected by coliforms that were resistant to sulphonamide/trimethoprim (74.6 per cent). The odds ratio of recovery for the cases associated with organisms that were sensitive to sulphonamide/trimethoprim relative to the cases associated with organisms that were resistant to sulphonamide/trimethoprim was 2.75, with a 95 per cent confidence from 1.25 to 5.85. The odds ratio of recovery for the cases treated with an NSAID relative to the cases treated with sulphonamide/trimethoprim only was 2.76 with a 95 per cent confidence interval from 1.12 to 6.79.

Animals↗
PubMed1998

Expression of cell adhesion molecules by endothelium in the human lower uterine segment during parturition at term.

OBJECTIVE: Our purpose was to determine whether the expression of certain adhesion molecules by endothelium in the human lower uterine segment at term varies with the degree of cervical dilatation. STUDY DESIGN: Biopsy specimens of the lower uterine segment of 34 women undergoing cesarean section at term at various stages of cervical dilatation were immunostained for endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-endothelial cell adhesion molecule. RESULTS: The expression of endothelial leukocyte adhesion molecule-1 was significantly greater at more than 6 cm dilatation than at less than 2 cm (p = 0.00031) as was that of vascular cell adhesion molecule-1 (p = 0.033). Expression of intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule did not vary with the degree of cervical dilatation. CONCLUSION: Cervical dilatation is associated with up-regulation of certain endothelial cell adhesion molecules. The findings support the hypothesis that certain processes associated with cervical dilatation at term resemble those involved in the acute inflammatory reaction.

Cervix Uteri↗
PubMed1998

Interleukin-1beta and interleukin-8 concentrations in the lower uterine segment during parturition at term.

OBJECTIVE: To assess the roles of interleukin-1beta, interleukin-8, and fibroblasts in the lower uterine segment during parturition. METHODS: Lower uterine segment biopsy specimens were obtained from 36 women undergoing cesarean delivery at various stages of cervical dilation (less than 2 cm, n = 8; 2 to less than 4 cm, n = 9; 4-6 cm, n = 10; more than 6 cm, n = 9). The concentrations of interleukin-1beta and interleukin-8 in protein extracts prepared from the tissue samples were measured by enzyme immunoassays. The effect of incubation with interleukin-1beta (30 U/mL) on interleukin-8 secretion by lower uterine segment fibroblasts in vitro also was determined. RESULTS: The median interleukin-1beta concentration in the specimens increased from 1.3 pg/mg of total protein at less than 2 cm of dilation to 22.2 pg/mg of total protein at 4-6 cm of dilation (P < .05). No further increase was detectable after 6 cm of dilation. The interleukin-8 concentration increased from 17.2 pg/mg of total protein at less than 2 cm of dilation to 2080.7 pg/mg of total protein at 4-6 cm of dilation (P < .05), thus paralleling the increase in interleukin-1beta concentration. Interleukin-1beta induced a significant increase in interleukin-8 secretion by fibroblasts in vitro, from 0.8 ng/10(6) cells to 35.6 ng/10(6) cells. CONCLUSION: The increase in interleukin-8 concentration in the lower uterine segment during parturition may be induced by interleukin-1beta and fibroblasts may be one of the sources of this interleukin-8.

Adult↗
PubMed1998

Study of fast switching processes due to electric and magnetic fields--an NMR approach.

Solid state NMR techniques have been developed to investigate dynamic molecular effects (e.g., molecular reorientations) due to simultaneously applied external electric fields on electrically sensitive materials such as liquid crystals (LC), liquid crystalline polymers (LCP) and polymeric electrets. Such effects can be observed only on relatively thin systems (10-200 microm). That means that many scans are necessary to achieve a sufficiently high signal-to-noise-ratio in the spectra (500-1000 scans). If the material is also magnetically sensitive, the electric field can be used to orient molecules in a starting orientational state and by switching-off the voltage to access fast reorientation processes in the magnetic field B0. Until now, the behaviour of orientable molecular systems under the influence of electric fields has been investigated by means of a more or less quasistatic approach (LCP: 100 V, electrets: 1 kV) in equilibrium states. The achievable time resolution depends on the desired signal-to-noise-ratio. For the case of proton NMR this means a time resolution of about 10 min. However, very often switching processes occur on a much shorter time scale. Using conventional techniques it is impossible to observe fast (ca. 100 micros) electrically or magnetically induced reorientation processes. In this work, we present a concept to overcome the problems outlined above and to extend the area of our current in situ NMR investigations on thin electrically-switched or poled polymeric layers. The basic idea is to include synchronized electric pulses during the NMR experiment using the preparation and/or mixing periods of a 1D or 2D pulse sequence for the application of an orienting field (electric or magnetic) and to use the reversibility of the molecular switching phenomenon to achieve a sufficient signal-to-noise-ratio. The techniques extend the range of possible investigations from about 100 micros to approximately T1 for correlated spectra (and to longer times of applied fields for uncorrelated spectra). Results are shown for a nematic LC and a nematic polymer having a similar side chain.

Electromagnetic Fields↗