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Biomedical subjects

M Winkler

Publications and source records attributed to M Winkler.

At least 289 records · Page 16Linked to original sources

Internal magnetic gradient fields in glass bead packs from numerical simulations and constant time diffusion spin echo measurements.

Internal magnetic field gradients in water saturated glass bead packs were studied by numerical simulations and a constant time spin echo (CTSE) experiment. The CTSE is comprised of two spin echo refocusing periods where each of the two evolution periods, tau1 and tau2, is varied so that the total evolution, 2(tau1 + tau2), is held constant. The experiment is similar to that introduced by Norwood and Quilter and allows the effects of dephasing due to diffusion in a magnetic field gradient to be separated from other relaxation mechanisms. In our experiments, the magnetic susceptibility difference between the pore fluid and glass beads creates the internal field gradient. CTSE measurements were performed at 7 T (300 MHz 1H) for water saturated in 50 microm diameter glass bead pack. We find that the internal gradients in the center of the pore bodies, where free diffusion applies, is in the range of 10 to 100 G/cm. This fluid volume accounts for < or =10% of the total pore volume. From direct numerical simulations of the internal magnetic field based on a first principles calculation, we find that the major fraction, >90%, of the pore volume has internal gradients of order 500 to 5,000 G/cm. Signals from water in these large gradients is not observed in our CTSE measurements.

Glass↗

A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term.

OBJECTIVE: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions. METHODS: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot. RESULTS: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously. CONCLUSION: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Adult↗

[Concentration of estrogen and progesterone receptors in the lower uterine segment at term labor].

BACKGROUND: To determine cytosol estrogen and progesterone receptor concentrations in the human lower uterine segment in different stages of cervical dilatation during parturition at term. PATIENTS AND METHODS: Biopsy specimens of the lower uterine segment were obtained from 51 women undergoing non-elective cesarean section at term. The stage of cervical dilatation at the time of cesarean section was < 2 cm (N = 14), 2 to < 4 cm (N = 13), 4 to 6 cm (N = 11) or > 6 cm (N = 13). The cytosolic estrogen and progesterone receptor concentrations were determined by enzyme immunoassays. RESULTS: Median estrogen receptor concentrations at < 2 cm and at 2-< 4 cm cervical dilatation were 2.12 fmol/mg protein and 2.03 fmol/mg protein, respectively. After a significant drop at 4-6 cm cervical dilatation (median: 1.08 fmol/mg protein), estrogen receptor concentrations raised again at > 6 cm cervical dilatation (median: 2.00 fmol/mg protein). Median progesterone receptor concentration was 84.7 fmol/mg protein at < 2 cm cervical dilatation, diminished significantly at 2-< 4 cm cervical dilatation (36.6 fmol/mg protein) and increased at further cervical dilatation (4-6 cm: 75.7 fmol/mg protein; > 6 cm: 83.7 fmol/mg protein). CONCLUSIONS: These data suggest that predominantly a decrease in cytosolic concentration of the progesterone receptor at the beginning of the active phase of first stage labor may play a crucial role in the hormonal control of cervical dilatation during parturition at term.

Adult↗

A primate model for discordant pig to primate kidney xenotransplantation without hyperacute graft rejection.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to intragraft deposition of preformed recipient immunoglobulin M (IgM) antibodies with subsequent complement activation finally leading to complete and rapid destruction of the xenograft (hyperacute graft rejection, HAR). Current therapeutic strategies for abrogation of HAR include pretransplant antibody absorption by specific or nonspecific extracorporeal column perfusion, ex vivo donor organ perfusion, the administration of substances interfering with complement activation, or even the genetic alteration of the donor. Here, in the pig to cynomolgus monkey species combination, we are describing an experimental model for abrogation of HAR by using large, relative to the recipient weight, oversized donor kidneys as xenotransplants. Porcine kidney xenotransplantation (n = 15) was performed using large white pigs of different weights and ages as organ donors and cynomolgus monkeys as recipients. In grafts with an organ weight below 50 g (20 to 48 g, median 25 g), primary nonfunction (PNF) of the porcine kidney was observed in 11 out of 12 cases and complete HAR in 5 out of 12 experiments. In contrast, none of three grafts with a donor organ weight >70 g showed signs of HAR or PNF. In one animal, a second porcine kidney from the same donor (23 g) was successfully transplanted immediately after HAR and subsequent removal of a first porcine kidney (20 g). By using appropriate immunohistochemistry stainings of reperfusion biopsies, profound deposition of recipient natural antibodies in both small and large xenografts was shown, with only scarce deposition of C3 and C5b-9 in the latter, indicating only incomplete intragraft activation of the complement cascade in these organs. Intraoperative cardiac output (CO) measurements performed in 7 experiments demonstrated a 20 to 50% decrease in CO following reperfusion in 6 out of 7 grafts irrespective of the donor organ weight. The intraoperative decrease in CO was not associated with perioperative morbidity or mortality. The use of oversized doner kidneys can enable the study of a variety of immunologic and physiologic sequela beyond HAR associated with life-supporting discordant primate kidney transplantation.

Acute Disease↗

Effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on metabolism and regional function in the underperfused canine myocardium.

We investigated the effects of sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on regional myocardial function and metabolism in anesthetized, thoracotomized dogs subjected to a 53.5% reduction in flow through the circumflex branch of the left coronary artery (LCX). Regional function in the area supplied by the LCX and the left anterior descending coronary artery (LAD) was assessed by means of two pairs of subendocardially inserted ultrasonic transducers. Hemoglobin content, oxygen saturation, pH, PCO2, PO2, lactate, glucose, and free fatty acids were determined in arterial and local venous blood obtained from the area supplied by the LCX. POCA (20 mg/kg/20 min i.v.) induced a transient decrease in left ventricular power and cardiac output. Arterial free fatty acid (FFA) levels increased continuously throughout the experiment, whilst arterial glucose levels showed a continuous decrease. FFA uptake, lactate release, and oxygen uptake were reduced in the underperfused area by POCA. At the same time, POCA induced a transient increase in end-diastolic segment length and a sustained decrease in systolic shortening during the ejection phase in the underperfused area. No changes in regional function were observed in the area perfused by the nonconstricted LAD.

Acyltransferases↗

Transient drug-induced myocardial dysfunction is not ameliorated by PGI2 in dogs.

Prostacyclin (PGI2), a potent vasodilatory substance that effectively inhibits platelet aggregation is under clinical investigation for the treatment of angina pectoris. We studied the effects of PGI2 on transient drug-induced myocardial dysfunction in anesthetized, thoracotomized dogs. Regional myocardial function was assessed using two pairs of piezoelectric transducers and a multidimensional measuring gauge; one pair was implanted in the distribution area of the left circumflex branch (LCX) and the other in the distribution area of the descending branch (LAD) of the left coronary artery. After intravenous injection of isoproterenol (ISO), which led to an increase in systolic shortening in the LCX and LAD areas, a critical stenosis was performed on the LCX and maintained at this level. Intravenous ISO injection now induced regional dysfunction in the LCX-dependent segment with the occurrence of systolic bulging. Infusion of PGI2 at a dosage of 100 ng/kg/min caused a decrease in arterial blood pressure and an increase in heart rate, but had no effect on regional myocardial function. ISO-induced myocardial dysfunction in the critically stenosed LCX segment, which was observed before PGI2 administration, was not ameliorated, but rather aggravated, by PGI2. It may be concluded that PGI2 does not improve normal or ISO-stimulated myocardial function in pressure-dependent perfused areas of the heart.

Animals↗

[The value of adjuvant ampicillin therapy in idiopathic premature labor].

Evidence suggests that subclinical intrauterine infection may play an etiologic role in preterm labour. To test the hypothesis, that treatment with antibiotics might delay delivery, we retrospectively have investigated 104 women in idiopathic preterm labour who were given ampicillin additional to tocolysis and 90 comparable women without antibiotic treatment. There were no significant differences between the two groups in regard to prolongation of gestation, gestational age at delivery, fetal weight, fetal well-being or connatal infections. Adjuvant ampicillin treatment of women in idiopathic premature labour without other signs or indicators of subclinical intrauterine infection seems not beneficial.

Ampicillin↗

[Parametrial hematoma after forceps delivery].

We report on a large intraligamentous haematoma developed after low forceps delivery. The diagnosis was made from symptoms and signs, rectal examination, and sonographic findings. The haematoma was incised and clots were evacuated by laparotomy. The bleeding vessel could be ligated. The 31-year-old woman left our hospital on the 12th postoperative day.

Adult↗

Differentiation between postoperative scar and recurrent disk herniation: prospective comparison of MR, CT, and contrast-enhanced CT.

Twenty-five symptomatic postlumbar surgery patients had findings on lumbar spinal noncontrast CT that were equivocal for distinguishing recurrent disk herniation from postoperative epidural fibrosis (scar). Contrast-enhanced CT and lumbar MR imaging were performed to differentiate these two conditions. Of the 14 levels, surgically explored, the diagnosis of scar or recurrent disk herniation was correct with contrast-enhanced CT at 10 levels and with MR imaging at 11 levels. At the levels operated on less than 2 years prior to MR imaging, scar more frequently demonstrated intermediate than low signal intensity. Scar older than 2 years most often showed low signal intensity. These preliminary findings suggest that MR may be useful in differentiating postoperative fibrosis from recurrent disk herniation in a significant proportion of patients whose unenhanced CT scans are equivocal.

Cicatrix↗

[Sampling of the chorionic villi: transcervical fine-needle and endoscopic aspiration].

In 63 cases chorionic villi sampling has been performed under complete anesthesia just before legal abortion; nine of them were endoscopic transcervical and 54 transcervical by means of a catheter under direct ultrasonic control. 81% offered useful chorionic villi, 17.4% only decidual material. The last 21 aspirations by means of a catheter between the 8th and the 12th week of gestation (p.m.) caused no problem at all. From the first punction on useful chorionic material has been obtained.

Abortion, Legal↗

[Infection and uterine contraction].

A great number of studies on women as well as experiments on animals support the association of silent intrauterine infection with the initiation of preterm labour. However, the success of antibiotic therapy in reducing bacteria-induced labour in animals could only be confirmed in few reports concerning women in preterm labour. Disregarding direct effects of bacterial products such as Phospholipase-A2 and endotoxins evidence suggests that immunological effects (release of Cytokines) may enhance the synthesis of prostaglandins in the uterus, placenta and fetal membranes. New therapeutical approaches are in discussion, but only time will tell whether a reduced rate of women with failed tocolysis will be the result.

Chorioamnionitis↗

[Puerperium after threatened premature labor--effects of infection screening in pregnancy].

Subclinical intrauterine infection is one of the causes of preterm birth. Adjuvant antibiotic treatment can improve the prolongative effects of tocolysis in patients with preterm labour. This study was conducted to evaluate the effectiveness of screening for infection and of antibiotic treatment in reducing postpartal infectious complications in patients with so called idiopathic preterm labour being treated with tocolysis intravenously. At the time of admission, we obtained cervical swabs of 138 patients for bacteriological investigation. 23 of the 37 patients with pathologic cervical colonisation were treated with antibiotics in addition to tocolysis. In women in preterm labour with pathologic cervical microbial colonisation, the frequencies of infectious complications in the puerperium were markedly increased compared to women without cervical colonisation. Adjuvant antibiotic therapy during pregnancy significantly reduced such complications. Additional antibiotic treatment of patients in idiopathic preterm labour with indicators of silent intrauterine infection seems beneficial not only for prolongation of gestation, but also for the reduction of postpartal infectious morbidity.

Adult↗

[Microbiologic cervix and amniotic fluid studies in early 2nd trimester: prognostic value for subsequent course of pregnancy?].

Our purpose was to determine the impact of cervical and amniotic fluid colonization in the early second trimester on the course of pregnancy. Cervical canal and amniotic fluid specimens were obtained from 167 patients without increased risk for prematurity. The specimens were examined for facultative-pathogenic bacteria (including mycoplasmas), fungi and Chlamydia trachomatis. The outcome of pregnancies was assessed in correlation with the microbiological findings. Of the patients studied 37% were cervically and 9% were intraamniotically colonized. Mycoplasmas dominated (cervix: 70%, amniotic fluid: 33%). In only two cases the same species was demonstrated at both sites. Women intra-amniotically colonized with microorganisms did not demonstrate a higher frequency of premature labor and premature rupture of membranes. Women with cervical detection of microorganisms demonstrate a tendency to higher frequencies of prematurity.

Amniocentesis↗