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Biomedical subjects

W Rath

Publications and source records attributed to W Rath.

At least 73 records · Page 4Linked to original sources
PubMed1999

Detection of prostate-specific antigen immunoreactivity in amniotic fluid.

OBJECTIVE: To examine whether prostate-specific antigen (PSA) is present in amniotic fluid, whether the amniotic fluid PSA concentration changes with gestational age, and whether there is an association between amniotic fluid PSA and fetal sex. METHODS: The PSA concentration was measured in the amniotic fluid of 48 pregnant women. Thirty-four samples were obtained during routine amniotic fluid analyses performed during gestational weeks 16-18, whereas 14 samples were obtained during cesarean section performed after gestational week 36. RESULTS: PSA was detected in all amniotic fluid samples. The median amniotic fluid PSA was 0.193 ng/ml during gestational weeks 16-18 and 0.39 ng/ml after gestational week 36 (p = 0.1). Furthermore, no significant association was seen between amniotic fluid PSA and fetal sex. The median amniotic fluid PSA level was 0.233 ng/ml for the 21 boys and 0.222 ng/ml for the 27 girls investigated (p = 0.72). CONCLUSIONS: These results confirm recent literature reports that PSA may serve as a growth regulator during normal fetal development. However, further studies are necessary to elucidate the exact role of PSA during fetal development.

Amniotic Fluid↗
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

Doppler sonographic findings for hypertension in pregnancy and HELLP syndrome.

Doppler examinations of the umbilical artery, both uterine arteries, and the fetal middle cerebral artery were performed in the third trimester in 18 patients with pregnancy induced hypertension, 52 patients with preeclampsia, and 32 patients with HELLP syndrome and the results were correlated with the parameters fetal outcome. For 74% of the patients this was the first pregnancy, in 93% of the cases a cesarean section was necessary; 66% of the newborn babies were dystrophic and 90% of them were born prematurely. The blood flow in one uterine artery was restricted in 95% of all 102 pregnant women, only 5% did not show any pathological findings. A pathological blood flow was observed on Doppler sonography in the umbilical artery in 70% of the group and 39% showed a pathologically increased perfusion of the fetal middle cerebral artery. The average birth weights and gestational ages in the study group were markedly reduced in comparison with healthy pregnant women (pregnancy induced hypertension: 1620 g/35 weeks; preeclampsia: 1660 g/34 weeks; HELLP syndrome: 1160 g/31 weeks, respectively). The lowest values for average birth weight and gestational age occurred when all four investigated blood vessels showed pathological Doppler findings: 1180 g/31 weeks (0 to 1 pathological vascular findings: 2780 g/38 weeks; 2 pathological vascular findings: 1845 g/34.5 weeks; 3 pathological vascular findings: 1330 g/31 weeks). This Doppler study underlines the importance of examining four blood vessels: the uterine, the umbilical, and the fetal middle cerebral arteries for a complete analysis of the fetoplacental hemodynamics. On account of the severely impaired hemodynamics observed in the placentas of our patients with hypertensive diseases in pregnancy or HELLP syndrome, we believe the early diagnosis of these disorders by Doppler sonography and an early start of therapy to be essential.

Adolescent↗
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

Dialysis and pregnancy--a case report and review of the literature.

We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week. During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable. Fetal development was appropriate for gestational age. However, pregnancy was complicated by polyhydramnios, which necessitated i.v. tocolysis. In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery. Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued. We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions. In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth. The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia. In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach. Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications.

Adult↗
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↗
PubMed1999

[Pre-eclampsia--endothelial damage of endothelial activation?].

There is considerable evidence that endothelial damage, followed by the release of vasoactive substances contributes to the pathophysiology of preeclampsia. Because of controversial experiences in literature we wanted to evaluate the potential cytotoxic effect of preeclamptic sera on cultured endothelial cells. Therefore cultured human umbilical vein endothelial cells (HUVEC) were stimulated with sera obtained from preeclamptic patients, while sera from normotensive pregnant and nonpregnant women served as controls. To prove the viability of these cells we performed ethidiumbromide/acridinorange immunostaining and determined t-PA/PAI-1 release into the supernatant. These experiments could not show any cytotoxic effect on endothelial cells. In ongoing studies we measured the concentrations of adhesion molecules, markers of endothelial activation, in maternal sera, in the supernatant of cultured endothelial cells, and on cell surface after stimulation with the above mentioned sera. In the supernatant we couldn't determine any different concentrations of adhesion molecules after stimulation with the different sera, but using immunofluorescence-microscopy an increased concentration of those molecules could be detected on the endothelial surface after stimulation with preeclamptic sera than compared to sera from normotensive controls. In conclusion, our experiments support the hypothesis that sera from preeclamptic women may cause endothelial activation.

Cell Adhesion Molecules↗
PubMed1999

[Trophoblast invasion in pre-eclampsia].

It is generally accepted that insufficient invasion of trophoblast cells into the myometrial portions of the spiral arteries is thought to play a crucial role in the development of preeclampsia. As a consequence, uteroplacental vessels fail to undergo adaptive changes which are imperative to provide a sufficient blood supply to the placenta. Consecutive placental hypoxia is supposed to cause secretion/shedding of still unidentified placental metabolites resulting in different forms of pregnancy-induced hypertension. This review presents published data concerning the causes of insufficient trophoblast invasion in preeclampsia. Expression of HLA-G by extravillous trophoblast cells seems to be altered, resulting in activation of the maternal immune system. The pattern of integrin expression as well as the secretion of proteases is reported to be disturbed, which could lead to a reduced invasive potential of the trophoblast cells. Recent data indicate a pathophysiological role of NK-cells and macrophages in the altered trophoblast invasion. Also angiotensinogen Thr235 polymorphism seems to alter early physiologic changes in spiral arteries. In summary, preeclampsia seems to be induced by a multifactorial disturbance of trophoblast invasiveness which is characterized by reduced invasiveness of the trophoblast cells themselves and by an activated maternal immune response blocking the invasion by the semiallogenic trophoblast.

Female↗
PubMed1999

[Hypertensive illnesses in pregnancy: when is ambulatory management possible, when is hospitalization indicated?].

Hypertensive disorders complicating pregnancy are the most common medical complications of pregnancy and are a major cause of maternal and perinatal morbidity and mortality. Thorough ambulatory obstetric care is likely to achieve a risk reduction. The main topics of ambulatory obstetric care are early identification of typical signs of preeclampsia, detection of uteroplacental insufficiency, and their consequences, detailed information of the patient, and early admission to a specialised obstetric care unit or perinatal center. Early diagnosis, close medical supervision, and timely delivery are the keys of the treatment of preeclampsia.

Ambulatory Care↗
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

Cervical dilatation: induction by antigestagens via adhesion molecules. An in vitro examination in endothelial cell cultures.

Cervical ripening at term resembles an inflammatory reaction with invasion of activated granulocytes into the cervical stroma. Our objective was to investigate the influence of the antigestagen onapristone alone and in combination with other substances associated with cervical ripening on the expression of the inflammation-associated adhesion molecules ELAM-1, ICAM-1 and VCAM-1. Human endothelial cell cultures were stimulated with onapristone (200 ng/ml), TNF-alpha (100 U/ml), IL-8 (20 ng/ml) and PGE2 (3 ng/ml) separately and in combination (n = 6). The expression of adhesion molecules was determined qualitatively and quantitatively by immunofluorescence staining and flow cytometry with statistical evaluation by Kolmogorov-Smirnov analysis. Onapristone upregulated slightly the expression of ELAM-1 (19%). The costimulation of onapristone and TNF-alpha provoked an additive expression of VCAM-1 (64%) beyond the effect of TNF-alpha alone, while the costimulation of onapristone and PGE2 as well as the combination with IL-8 did not result in an additional stimulatory effect. All results were statistically significant (p < 0.001). This result supports our hypothesis that onapristone may lead to an increased adhesion of granulocytes to the capillary endothelium thereby initiating cervical ripening.

Cell Adhesion Molecules↗
PubMed1998

The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth.

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator of the acute phase response IL6 was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n = 10), adult volunteers serving as control (n = 17). Additionally, circulating cytokines were determined in cord and in maternal blood immediately after delivery (n = 27, respectively). Significant production of TNF alpha, IL8, IL10 and IL6 was observed in cord blood after lipopolysaccharide stimulation and was similar to cytokine production in adult blood. The plasma concentrations of TNF alpha were significantly higher in cord than in maternal blood, while plasma concentrations of IL10 and IL6 were significantly lower. Our results demonstrate fully developed capability of whole cord blood to synthesize pro- and anti-inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In vivo, however, higher circulating TNF alpha and lower IL10 and IL6 levels in cord blood suggest that the inflammatory stress associated with normal delivery does not induce detectable anti-inflammatory response in neonates at birth.

Adult↗
PubMed1998

Pulsation of blood flow in the umbilical vein during the second trimester of pregnancy correlated to fetal malformation and chromosomal abberation.

In the present study the flow profile of the umbilical vein between the 14th and 24th weeks of pregnancy was examined for the first time in connection with pathological pregnancies and chromosomal/fetal anomalies, and compared with the flow pattern of normal pregnancies. The aim of our study was to clarify whether at this early stage in gestation the diagnosis of the fetal condition should be extended to include the monitoring of the umbilical vein and to assess the possibility of making predictions about the further course of pregnancy. 50 pregnant patients without complications, 21 patients later developing pregnancy-induced hypertension/intrauterine growth retardation, 16 pregnancies with fetal anomalies, and 4 pregnancies with chromosomal aberrations were scanned with color Doppler sonography to determine the flow spectra of the umbilical vein in a free loop. Admission criteria were single-child pregnancies and precise knowledge of the duration of gestation. Pulsations of the venous blood flow, which are physiological during the first three months of pregnancy, cease in normal pregnancies from the beginning of the second trimester. In cases where pregnancy-induced hypertension/intrauterine growth retardation developed, 2 out of 21 patients showed pulsations. In the pregnancies in which fetal and/or chromosomal anomalies occurred, pulsations in the flow pattern of the umbilical vein were detected in 14 out of 20 cases. The pulsations of the venous blood flow, which are attributable to a late diastolic reflux component in the venous circulation, are common finding in fetal/chromosomal anomalies. In our opinion, the flow spectrum of the umbilical vein should therefore be incorporated in sonographic screenings, and if pulsations are detected, we advise careful sonographic abnormality diagnostics and an investigation of the karyotype.

Adolescent↗
PubMed1998

The importance of extracellular matrix in the induction of preterm delivery.

Evidence suggests that in the lower uterine segment at term an increased production of tumor necrosis factor (TNF) alpha and interleukin (IL)-1 beta induces an increase in the expression of adhesion molecules by the endothelium. The expression of endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 were found to increase from a cervical dilatation of 2-3 cm and reaches a maximum at cervical dilatation of more than 6 cm. Increased adhesiveness of the endothelium leads to extravasation of neutrophils into the cervical stroma. The chemotaxis and degranulation of these cells is triggered by a rise in the concentration of IL-8 found in the lower uterine segment when cervical dilatation progresses. A significant increase in stroma invasion by neutrophils with progressive cervical dilatation was observed. This finding coincides with a rise in the granulocytic matrix metalloproteinases (MMP)-8 and MMP-9 concentrations up to complete cervical dilatation. We found similar patterns of cytokine concentrations in the lower uterine segment of patients with preterm delivery: at 2-3 cm dilatation the concentrations of IL-1 beta, IL-6- und IL-8 were significantly higher than at less than 2 cm. Concomitantly, we also found an increase in MMP-8, MMP-9 and tissue inhibitor of metalloproteinases-1 concentrations from less than 2 cm to 2-3 cm cervical dilatation. These findings suggest that the changes in the lower uterine segment during preterm parturition seem to be similar to those at term and both resemble an inflammatory process.

Cervix Uteri↗
PubMed1998

[Current trends in the surgical management of ovarian cancer].

Ovarian cancer is the leading cause of death from gynaecological malignancies in western countries, it is diagnosed at an advanced stage in approximately 75% of patients. The current standard treatment for ovarian cancer consists of maximum cytoreductive surgery to reduce tumor residuum to a minimum, followed by platin-based chemotherapy. If an unsuspected ovarian cancer is detected at diagnostic laparoscopy, staging and debulking by laparotomy should be undertaken without delay. For apparently early stages (I or II), appropriate surgical staging is extremely important and will result in the upstaging of about one-third of patients (usually to Stage III). Several retrospective clinical trials show that successful cytoreduction and systemic lymphonodectomy result in an improved survival, but prospective randomized studies have not been performed to evaluate this benefit. Patients who cannot initially be cytoreduced to an optimal stage should be considered candidates for interval cytoreduction after chemotherapy. Repeated surgical debulking in relapsed patients will probably only benefit a small subset of selected patients (e.g. disease-free interval > 2 years). Surgery may also be important for palliation, such as for the treatment of bowel obstruction to improve the patients quality of life. The question still remains whether the observed improved survival rates for patients with ovarian cancer are an effect of primary cytoreductive surgery or tumor biology.

Antineoplastic Combined Chemotherapy Protocols↗