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K Vetter

Publications and source records attributed to K Vetter.

At least 37 records · Page 2Linked to original sources
PubMed1998

Endothelial-cell permeability and protein kinase C in pre-eclampsia.

BACKGROUND: Oedema and vascular leakage play a part in the pathogenesis of pre-eclampsia. We tested the hypothesis that serum from pre-eclamptic patients increases endothelial-cell permeability and examined possible signal-transduction pathways. METHODS: We studied eight patients with pre-eclampsia, eight normotensive pregnant women, eight non-pregnant women, five pregnant patients with pre-existing hypertension, and four hypertensive non-pregnant women. Cultured human umbilical-vein endothelial-cell monolayers were used and permeability was measured by albumin flux. The part played by protein kinase C (PKC) signalling was examined by down-regulation with phorbol ester and with the inhibitors Goe 6976 and staurosporine. PKC isoforms were assessed by western blot and confocal microscopy. Antisense oligodesoxynucleotides (ODN) were used to test for specific PKC isoforms. FINDINGS: Serum from pre-eclamptic women increased endothelial permeability significantly (by 100%, p<0.01). The change in permeability decreased rapidly after delivery. Serum from normotensive pregnant women and non-pregnant women had no effect. Permeability was not influenced by serum from patients with essential hypertension or pregnant patients with pre-existing hypertension. Serum from pre-eclamptic patients induced a translocation of PKC isoforms alpha and epsilon within the cells. Goe 6976 and staurosporine (10(-8) mol/L) inhibited the increase in permeability induced by serum from pre-eclamptic patients. Down-regulation of PKC alpha and, to a lesser extent, PKC epsilon by antisense ODN also inhibited the pre-eclampsia-induced permeability increase. INTERPRETATION: Serum from pre-eclamptic patients contains a factor or factors that increase endothelial-cell permeability. The effect of pre-eclamptic serum may be mediated by PKC alpha and epsilon.

Adult↗
PubMed1998

Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value.

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.

Adult↗
PubMed1998

The umbilical ring--the first rapid in the fetoplacental venous system.

In this study, the effect of the umbilical ring on blood flow velocities in the umbilical vein was examined using Doppler sonography. The maximum blood flow velocity in the umbilical vein was measured just before and behind the umbilical ring in eleven normal singleton pregnancies at 24-34 gestational weeks. The maximum velocity increased in each single case (p < 0.0001), the mean increase was from 16 cm/sec to 31 cm/sec. Thus, the narrowing of the umbilical ring serves as the first rapid in venous fetoplacental circulation. The physiological role of the acceleration of venous blood flow remains to be elucidated. Possible functions include stabilizing venous blood flow or preferential streaming.

Blood Flow Velocity↗
PubMed1997

Molecular anatomy of the perivascular sheath in human placental stem villi: the contractile apparatus and its association to the extracellular matrix.

In previous studies, we have shown that smooth muscle cells and myofibroblast subpopulations of the perivascular stem villous sheath of the human placenta contain focal adhesion plaques and talin immunoreactivity. The close association of these cells to elastic and collagen fibres have led to the assumption of a functional myofibroelastic unit within the perivascular stem villous sheath. Interactions between the extracellular matrix and smooth muscle cells depend on a variety of structural protein assemblies. In the present study, we examined, by immunocytochemistry, whether the molecular assembly of extracellular matrix proteins and molecules of focal adhesions, known to be essential for signal transduction in smooth muscle cells, are also found in smooth muscle cells of the perivascular stem villous sheath of the human placenta. Vascular and extravascular smooth muscle cells were immunoreactive for alpha-actinin, vinculin, paxillin and tensin, the integrin chains alpha1 and beta1, and the basement membrane components laminin and heparan/-chondroitin sulfate proteoglycan perlecan. pp125(FAK) did not react. In the extracellular matrix of blood vessel walls and the perivascular stem villous sheath, we found immunoreactivity of fibronectin and collagen types I, VI and undulin (collagen type XIV). From our data we conclude that within the perivascular stem villous sheath, there exists a system of signal transduction molecules, indicating a cross talk between the smooth muscle cells of this sheath and their surrounding extracellular matrix.

Actins↗
PubMed1997

Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.

Endothelial cell activation is important in the pathogenesis of preeclampsia; however, the nature of the activation is unknown. We investigated 22 patients with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptic patients induces expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured endothelial cells. We then asked whether the corresponding integrin adhesive counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18), macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the pregnant women, the measurements were conducted both before and after delivery. Integrin expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum from preeclamptic patients increased endothelial cell ICAM-1 expression but not VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in endothelial cells compared with serum from normal nonpregnant or normal pregnant women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1 expression in preeclamptic patients (r = .80, P < .001) before but not after delivery. Expression of the integrin counter receptors on leukocytes was similarly increased in preclampsia and normal pregnancy compared with the nonpregnant state. The expression decreased significantly after delivery in both groups. Our results demonstrate that serum from preeclamptic women induces increased ICAM-1 surface expression on endothelial cells, while the expression of the integrin counterreceptors was not different. The effect on endothelial cells may be related to an increase in [Ca2+]i. The effect on cultured endothelial cells and the rapid decrease after delivery suggests the presence of a circulating serum factor which increases endothelial cell [Ca2+]i and enhances adhesion molecule expression.

Adult↗
PubMed1996

Elastic fibres are an essential component of human placental stem villous stroma and an integrated part of the perivascular contractile sheath.

The stroma of human placental stem villi is believed to consist only of reticular and collagen fibres. In the present study we were able to show for the first time by light (orcein staining) and electron microscopy large amounts of elastic fibres in the stem villous stroma. Electron microscopically, homogeneous elastin was found alone or in association with microfibrils. In addition, microfibrils were observed forming long bands. These three structures, generally known to form elastic connective tissue, were seen in close connection with placental extravascular smooth muscle cells, which belong to the perivascular contractile sheath (PVCS) of stem villi. Elastin was associated with these smooth muscle cells and connected to collagen fibres via microfibrils. Collagen fibres were additionally interconnected by spike-like structures. Extravascular smooth muscle cells revealed numerous adhesion plaques which occupied conspicuously long cytoplasmic faces of the plasma membrane. In cryostat sections, immunoreactivity of talin, an attachment protein of adhesion plaques linking intracellular alpha-actin filaments with extracellular fibronectin, was detected in extravascular and vascular (media) smooth muscle cells. The arrangement of placental extravascular smooth muscle cells, elastic and collagen fibres suggests a functional myofibroelastic unit within the PVCS, which surrounds the large foetal blood vessels possibly contributing to elasticity and supporting tensile and/or contracting forces within the stem villi.

Actins↗
PubMed1996

Fetal fibronectin in vaginal specimens predicts preterm delivery and very-low-birth-weight infants.

OBJECTIVE: The purpose of this study was to evaluate the association of vaginal fetal fibronectin expression to risk of preterm delivery and delivery of very-low-birth-weight infants. STUDY DESIGN: Vaginal secretions were obtained from women between 22 and 35 weeks' pregnant with minimal cervical dilation (< or = 2 cm) and threatened preterm delivery. The secretions were analyzed for the presence of fetal fibronectin. Other clinical information including cervical dimensions, uterine activity, serum C-reactive protein concentration, vaginal pH, evidence of vaginal or systemic infection, and vaginal bleeding were also obtained. RESULTS: Of the 112 patients recruited, 40 (35.7%) were delivered prematurely (<37 weeks). For prediction of preterm delivery, the fetal fibronectin test result had a sensitivity, specificity, and positive and negative predictive values of 67.5, 90.3, 79.4, and 83.3%, respectively (odds ratio 19.3, p < 0.0001). Women with a positive fetal fibronectin test had a nearly 13-fold increased probability of being delivered of an infant weighing <1500 gm than did women with a negative fetal fibronectin test (32.4% vs 2.5%, p<0.0001). Categoric analysis and multiple logistic regression demonstrated that fetal fibronectin was an independent risk factor for prediction of preterm delivery and birth weight <1500 gm. CONCLUSION: Vaginal fetal fibronectin expression is an independent risk factor for preterm delivery and birth of very-low-birth-weight infants in symptomatic women with intact amniotic membranes and minimal cervical dilatation.

Chi-Square Distribution↗
PubMed1996

[Glucose tolerance in pregnancy and amniotic fluid insulin in labor].

Maternal glucose tolerance in pregnancy is determined by an oral glucose tolerance test (oGTT). The presented study deals with the question whether the risk of the fetus developing hyperinsulinism can be correctly estimated by the result of the oGTT. Investigations were made if there is a correlation between the oGTT and the mean blood glucose levels (MBG) and the fetal glucose metabolism measured by amniotic fluid insulin (AFI) at birth. 158 amniotic fluid samples were collected during labour. In 136 samples insulin levels below the threshold of 7 microU/ml were found, in 22 samples above 7 microU/ml. An oGTT was performed in all pregnancies (threshold: 95/165/145/125 mg%). 52 women showed normal oGTT, 28 had impaired glucose tolerance (IGT) with one pathologic value and 78 women had gestational diabetes (GDM) with two elevated values. Elevated insulin levels > 7 microU/ml were found in 6% of the cases with normal oGTT, in 29% of the cases with IGT and in 14% when GDM was diagnosed (p = 0.02). The MBG was significantly higher in cases with elevated AFI than with normal AFI, 92 mg% versus 83 mg% (p = 0.02). Therefore hyperinsulinism of the fetus was found twice as often in cases with IGT than in GDM diagnosed by oGTT. Borderline glucose tolerance with only one pathologic value in the oGTT has more affect on the fetal glucose metabolism than has been assumed up to now. This may be caused by insufficient therapeutic intervention and deterioration of glucose tolerance during pregnancy. The diagnosis of IGT should be followed by therapeutic efforts and intensive care of the fetus as in cases of GDM.

Adult↗
PubMed1995

[Immune status of pregnant patients especially in possible premature labor].

In this study it could be shown that pregnant women having a normal course of pregnancy had significantly higher levels of T-lymphocytes and T-helper cells compared with non-pregnant women. Also other parameters belonging to cellular immune defence showed a similar--in the sense of an improved immune function--trend (even though this was not statistically significant). In pregnant women with symptoms of threatened prematurity significantly lower levels for lymphocytes. T-lymphocytes and T-helper cells were measured than in women who had a normal course of pregnancy. The ratio was also clearly reduced--in those cases where later preterm labour did actually occur it was particularly low at 1.1. In the group of pregnant women with premature labor the number of those who found the situation "very stressful" amounted to 65% and in the group whose course of pregnancy was normal, the percentage was 26%. The results of this study point to the fact that in pregnant women with premature labor the immune function is often impaired and it can be assumed that this provides favourable conditions for ascending infections which then cause a higher risk of prematurity. Further studies should be made concerning the causal connections which we have postulated between physical and psychological overstrains and impairment of the immune function.

Arousal↗
PubMed1995

[Diagnostic and clinical value of Doppler ultrasound in obstetrics].

The diagnostic value (efficiency) of Doppler ultrasound in obstetrics is assessed by studying the association or correlation between Doppler measurement parameters and pregnancy outcome parameters, without influencing the clinical management. The clinical value (efficacy) is however assessed by studying the ability to improve the outcome of pregnancy if Doppler ultrasound is used in obstetrical management for the purpose of possible intervention. The accepted method for assessment of the diagnostic value is the observational study, and the best method for the assessment of the clinical value is the randomised controlled management study (clinical trial). Observational studies concerning the diagnostic value have been widely reported in the literature. According to these studies significant relationships between abnormal Doppler findings and the following obstetrical problems were found: intrauterine growth retardation, preterm delivery, acidosis determined by fetal blood sampling, abnormal intrapartum fetal heart rate, neonatal depression and acidosis, and admission to neonatal intensive care unit. However from these studies it cannot be concluded that pregnancy outcome will be improved by using this information clinically. This problem can only be properly addressed by appropriate clinical management studies. The majority of the published randomised controlled trials showed beneficial effect from Doppler ultrasound application in high-risk pregnancy management. These effects included a significant decrease in the duration of antenatal and neonatal hospital stay, the rate of labour induction, and the rate of emergency Caesarean section. At the same time there was no difference in the gestational age at delivery or in the total Caesarean section rate. None of these trials alone was large enough to demonstrate a statistically significant reduction in perinatal mortality. However cumulative meta-analysis allows pooling to evaluate the results from separate but similar studies. The results from such an analysis showed that in high-risk pregnancies managed with Doppler there is a significant decrease of 50 per cent in perinatal mortality and in stillbirths of anatomically normal fetuses. It is important to note that there was no increase in neonatal or maternal morbidity associated with the use of Doppler ultrasound, and that the reduction in perinatal mortality was not the result of a delay in timing fetal death.

Blood Flow Velocity↗
PubMed1995

Does recombinant human erythropoietin not only treat anemia but reduce postpartum (emotional) distress as well?

Based on the established rhEPO treatment of anemia in endstage renal failure, which results in improved quality of life, and on the clinical observation that patients with postpartum anemia treated with rhEPO seemed to gain a more stable mood, we inferred that there is a beneficial side-effect of rhEPO on postpartum blues. The aim of this study was to test the hypotheses 1) that postpartum anemia aggravates, and 2) that treatment of postpartum anemia with rhEPO reduces maternity blues. The results show that on the fifth day postpartum anemic patients score consistently worse than nonanemic women on the Symptom Checklist SCL-90-R, indicating more symptoms and distress in general, and also more symptoms characteristic of maternity blues (p < 0.05). On a "Blues Questionnaire," postpartum anemia expresses itself with a reduced "well-being" (p < 0.001). Thus, our first hypothesis was verified. There were no differences by the fifth day postpartum between anemic patients receiving either rhEPO or placebo. Our second hypothesis was thus not confirmed within this limited time. We conclude as clinicians that postpartum anemia should be treated effectively to reduce distress and hence the risk for postpartum affective disorders. Follow-up studies after rhEPO treatment beyond the first week post partum are needed. In addition, in investigations on postpartum affective disorders, the hemoglobin concentration should be considered.

Anemia↗
PubMed1993

Considerations on growth discordant twins.

Some considerations as to the pathophysiology of growth discordancy in twins are presented. Based on findings of Doppler flow measurements in growth discordant twins an alternative mechanism to that of twin-twin transfusion is presented which leads to a small stuck twin with an oligohydramnios and an oversized twin surrounded by a polyhydramnios. Based on feto-fetal interrelations the smaller fetus with an insufficient placental supply sends out growth-stimuli that finally result in increased growth of the other fetus with a normal placental function. Only in multiple pregnancies can such a signal have the effect of growth promotion on the fetus with normal supply. The result is being called Growth Factor Sequence, and in contrast to feto-fetal transfusion there is no difficulty to understand why the smaller fetus may have an enddiastolic block in the fetoplacental circulation. Thus, as long as feto-fetal transfusion is not proven, different pathomechanisms--like that of the Growth Factor Sequence--have to be taken into account in cases of discordant twins.

Amniotic Fluid↗