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Biomedical subjects

W Heyl

Publications and source records attributed to W Heyl.

At least 19 recordsLinked to original sources
PubMed2006

Caesarean section on request: a comparison of obstetricians' attitudes in eight European countries.

OBJECTIVE: To explore the attitudes of obstetricians to perform a caesarean section on maternal request in the absence of medical indication. DESIGN: Cluster sampling cross-sectional survey. SETTING: Neonatal Intensive Care Unit (NICU) associated maternity units in eight European countries. POPULATION: Obstetricians with at least 6 months clinical experience. METHODS: NICU-associated maternity units were chosen by census in Luxembourg, Netherlands and Sweden and by geographically stratified random sampling in France, Germany, Italy, Spain and UK. An anonymous, self-administered questionnaire was used for data collection. MAIN OUTCOME MEASURES: Obstetricians' willingness to perform a caesarean section on maternal request. RESULTS: One hundred and five units and 1,530 obstetricians participated in the study (response rates of 70 and 77%, respectively). Compliance with a hypothetical woman's request for elective caesarean section simply because it was 'her choice' was lowest in Spain (15%), France (19%) and Netherlands (22%); highest in Germany (75%) and UK (79%) and intermediate in the remaining countries. Using weighted multivariate logistic regression, country of practice (P<0.001), fear of litigation (P= 0.004) and working in a university-affiliated hospital (P= 0.001) were associated with physicians' likelihood to agree to patient's request. The subset of female doctors with children was less likely to agree (OR 0.29, 95% CI 0.20-0.42). CONCLUSIONS: The differences in obstetricians' attitudes are not founded on concrete medical evidence. Cultural factors, legal liability and variables linked to the specific perinatal care organisation of the various countries play a role. Greater emphasis should be placed on understanding the motivation, values and fears underlying a woman's request for elective caesarean delivery.

Adult↗
PubMed2005

Increased soluble VCAM-1 serum levels in preeclampsia are not correlated to urinary excretion or circadian blood pressure rhythm.

OBJECTIVE: Soluble vascular cell adhesion molecule-1 (VCAM-1) is known to be elevated in serum of patients with preeclampsia, but there are no data available on the significance of urinary VCAM-1 excretion in preeclampsia. The aim of our study was to uncover possible circadian rhythms of VCAM-1 plasma levels and urinary VCAM-1 excretion in uncomplicated and hypertensive pregnancies and to ascertain their relation to blood pressure. STUDY DESIGN: A total of 10 normotensive and 10 preeclamptic pregnant women were included in this study. Venous blood was collected hourly, and urine samples were taken every 2 h over a period of 24 h. VCAM-1 levels were determined by ELISA. We compared these results with the circadian blood pressure rhythm. RESULTS: The median VCAM-1 plasma levels were significantly (P < 0.01) increased in preeclamptic patients (851.5 ng/mL) in comparison to normotensive pregnant women (659.3 ng/mL) without any circadian rhythm being apparent; however, the urinary excretion of VCAM-1 showed a typical circadian rhythm, with a higher excretion rate during daytime. CONCLUSION: For the first time we have demonstrated that urinary VCAM-1 excretion in pregnancy shows a circadian rhythm without correlation to plasma levels or the circadian blood pressure rhythm. In contrast, VCAM-1 serum levels did not show a diurnal rhythm. We assume that VCAM-1 serum levels do not correlate with systemic blood pressure or urinary excretion.

Adult↗
PubMed2001

Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women.

Impaired invasion of uteroplacental arteries by extravillous trophoblast cells is a key pathogenic mechanism of preeclampsia. We previously demonstrated that reduced trophoblast invasion into uteroplacental spiral arteries was associated with an excess of macrophages in and around these arteries. To explore the significance of these observations, we correlated the extent of extravillous trophoblast apoptosis in placental bed biopsy specimens with macrophage distribution and studied the effect of macrophages upon trophoblast apoptosis in vitro. Extravillous trophoblast hybrid cells were cocultured with activated macrophages exposed to exogenous tumor necrosis factor alpha (TNFalpha), anti-tumor necrosis factor receptor I (TNF-RI), and tryptophan depletion, and the rates of trophoblast apoptosis were measured. Extravillous trophoblast hybrid cells showed increased rates of apoptosis following exposure to exogenous TNFalpha, with tryptophan depletion, and when cocultured with activated macrophages. The proapoptotic effects of macrophages in vitro were completely inhibited only by simultaneous addition of tryptophan and anti-TNF-RI. Our data indicate that macrophages, residing in excess in the placental bed of preeclamptic women, are able to limit extravillous trophoblast invasion of spiral arterial segments through apoptosis mediated by the combination of TNFalpha secretion and tryptophan depletion. The mechanisms by which macrophages are activated and recruited to the placental bed are presently unknown but are likely central to the pathogenesis of preeclampsia.

Adult↗
PubMed2000

Hormonal treatment of endometrial cancer.

In developed western countries endometrial cancer is the most common malignant tumor of the female genital tract. 75% of cases are diagnosed in stage I where cure rates of 75-90% are achieved. In stage II, 5-year survival rates amount only to 50%, in stage III up to 30%, and in stage IV to less than 10%. Despite the preponderance of early stage endometrial cancer, about 20-30% of affected patients will die from this disease. As surgical treatment and/or irradiation are not able to control advanced disease, many investigators have been searching for systemic treatment modalities. Cytotoxic chemotherapy achieves high initial response rates of about 40-60%. Recurrence, however, occurs after a median duration of only a few months. As endometrial cancer develops from hormone dependent cells, endocrine treatment has been the traditional palliative therapy of advanced tumor stages. Several studies to date have failed to demonstrate an efficacy of adjuvant hormonal therapy in cases of high-risk endometrial cancer. For the conservative treatment of precancerous, non-invasive hyperplastic lesions of the endometrium, endocrine therapies have been shown to be efficacious.

Antineoplastic Agents, Hormonal↗
PubMed2000

Clinical value of detecting microalbuminuria as a risk factor for pregnancy-induced hypertension in insulin-treated diabetic pregnancies.

OBJECTIVE: We evaluated the role of clinical non-overt stage III diabetic nephropathy concerning the development of more frequent hypertensive complications during pregnancies of women requiring insulin. METHODS: 122 unselected pregnant women treated with insulin were enrolled in the study, of whom 56 were type-1 diabetic patients and 66 patients had gestational diabetes. In 24-h urine samples, excretion rates of albumin (UAE) and beta(2)-microglobulin were determined by nephelometric analysis and a radioimmunoassay, respectively. These parameters were also measured in the serum as well as HbA(1c), fructosamine and daily blood glucose profiles. RESULTS: Sixteen (15.7%) women had an elevated UAE (>30 mg/24 h), of whom three had macroalbuminuria (UAE>300 mg/24 h). Thirteen (12.7%) insulin-treated women showed microalbuminuria during pregnancy, eight with type-1 diabetes and five with gestational diabetes requiring insulin. In the entire group hypertension was observed in seven (6.9%) women of whom six had microalbuminuria. The sensitivity and specificity were 85.7% and 92.6%, respectively. The positive predictive value reached 46.2%, whereas the negative predictive value was 98.9%. CONCLUSION: Measurement of UAE in diabetic pregnancies seems to be an useful additional parameter for risk evaluation of hypertensive disorders.

Adolescent↗
PubMed2000

[Lethal osteochondrodysplasias: prenatal and postnatal differential diagnosis].

PURPOSE: Lethal osteochondrodysplasias show an abnormal maturation and a disturbed growth of cartilage and bones. They represent a heterogeneous group of rare genetic diseases. Their incidence is 1 to 3 in 10,000 births. MATERIAL AND METHODS: We report altogether 5 cases: two of thanatophoric dysplasia, one of achondrogenesis type II and two cases of the rare fibrochondrogenesis. The differential diagnosis in respect to ultrasonographic, morphologic, radiographic and histopathologic criteria of the most common of these diseases are discussed together with a review of the literature. RESULTS: On the basis of the ultrasound finding of the short-rib-syndrome, it is possible to differentiate between viable and lethal osteochondrodysplasias at 19 to 22 weeks of gestation. The short-rin-syndrome leads to pulmonary hypoplasia. CONCLUSIONS: It is essential to obtain an exact diagnosis postnatally by radiographic and histopathological examinations to counsel the parents concerning the risk of recurrency. The risk in this heterogeneous group of genetic diseases ranges between less than 1% up to 50% depending on the final diagnosis. Our two cases of fibrochondrogenesis in a consanguineous couple strongly suggest an autosomal recessive inheritance in this disease.

Adult↗
PubMed2000

Hormonal interactions in endometrial cancer.

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.

Contraceptives, Oral, Hormonal↗
PubMed1999

The role of soluble adhesion molecules in evaluating endothelial cell activation in preeclampsia.

OBJECTIVE: Adhesion molecules, such as vascular cell adhesion molecule 1, are known to be increased in the serum of patients with preeclampsia, indicating that these molecules are possible markers of endothelial cell activation. We investigated the influence of serum from women with preeclampsia on the expression of adhesion molecules by cultured endothelial cells. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in Ham/Iscove modified Dulbecco's medium containing 20% pooled human serum, l -glutamine (200 mmol/L), penicillin, and streptomycin. We stimulated these cells for 24 hours with sera from patients with preeclampsia and then determined the levels of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, E-selectin, and P-selectin in the supernatant and in the maternal serum by means of enzyme-linked immunosorbent assay. These results were compared with those of sera obtained from normotensive pregnant and nonpregnant women. In addition, the expressions of these adhesion molecules on the endothelial surface were determined by immunofluo-rescence microscopy. RESULTS: Only for vascular cell adhesion molecule 1 and E-selectin were elevated plasma levels found in hypertensive patients, whereas intercellular cell adhesion molecule 1 and P-selectin showed similar plasma levels in all the patients. No differences in the levels of the adhesion molecules were found between the supernatants of endothelial cell cultures after stimulation with sera from patients with preeclampsia and those after stimulation with normotensive control sera. In contrast, with immunofluorescence microscopy we could detect higher amounts of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, and E-selectin on the endothelial surface after stimulation with sera from women with preeclampsia. CONCLUSION: Although vascular cell adhesion molecule 1 and E-selectin were elevated in maternal serum samples from women with preeclampsia and on the endothelial surface after stimulation with such sera, there were no detectable increases in the levels of both of these adhesion molecules in the supernatant of cultured endothelial cells. We therefore assume that sera from women with preeclampsia may cause endothelial cell activation. Because we could not detect elevated concentrations of any of the investigated adhesion molecules in the supernatant of endothelial cells, we believe that factors other than sera from women with preeclampsia seem to play a major role in the release of soluble forms of adhesion molecules from the endothelial membrane.

Adult↗
PubMed1999

Elevated soluble adhesion molecules in women with pre-eclampsia. Do cytokines like tumour necrosis factor-alpha and interleukin-1beta cause endothelial activation.

OBJECTIVE: The purpose of the present study was to evaluate the clinical significance of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) for endothelial cell activation in pre-eclampsia. Therefore, we determined and compared the correlations between these cytokines and circulating adhesion molecules in the sera of pre-eclamptic pregnant women, normotensive pregnant women and nonpregnant women. METHODS: The soluble adhesion molecules VCAM-1, ICAM-1, E-selectin, and P-selectin were determined in the serum of 38 pre-eclamptic pregnant women and 40 normotensive pregnant and nonpregnant controls using ELISA-techniques. We correlated these serum concentrations with the serum levels of TNF-alpha and IL-1beta, respectively, also determined by ELISA. RESULTS: Elevated serum levels of VCAM-1 and E-selectin could be detected in pre-eclamptic patients, with and without HELLP-syndrome. In contrast, no increased serum concentration of ICAM-1, P-selectin, TNF-alpha and IL-1beta were found in these patients. While significant correlation between VCAM-1 and E-selectin could be determined (r=0.604; p<0.001) no unambiguous correlations, however, were found between TNF-alpha or between IL-1beta and the examined adhesion molecules or the selectins. CONCLUSIONS: In contrast to in vitro investigations on cultured umbilical vein endothelium, our experimental results indicate that the cytokines TNF-alpha and IL-1beta can not explain endothelial cell activation, and that their measurement in serum is not useful for the detection of pre-eclampsia.

Adult↗
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

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

[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↗
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

Uteroplacental and fetoplacental blood flow in a patient with renal anemia.

We report on Doppler sonographic findings of a dialysis patient with renal anemia during otherwise uncomplicated pregnancy. Uteroplacental and fetoplacental flow relationships before, as well as after the dialysis treatments during the course of the pregnancy were in the normal range. The favorable flow condition in the utero- and fetoplacental circulation was associated with a low hematocrit. This in accordance with previous reports indicates a more favorable maternal and fetal outcome in association with a low hematocrit/hemoglobin concentration.

Adult↗
PubMed1997

Prophylaxis and treatment of bladder dysfunction after Wertheim-Meigs operation: the positive effect of early postoperative detrusor stimulation using the cholinergic drug betanecholchloride.

The efficacy of betanecholchloride in the postoperative treatment of bladder dysfunction is controversial. We therefore performed a comparative study on the effect of this therapy for the prophylaxis of detrusor hypotonia after Wertheim-Meigs operation. Forty patients with cervical cancer FIGO stage Ib/IIa were divided into two study groups. The control group (24 patients) only received betanecholchloride if the residual urine persisted above 50 ml after the 10th postoperative day. The study group (16 patients) received 50 mg betanecholchloride three times a day from the 3rd postoperative day onward. In this group postoperative catheter treatment, and consequently hospital stay, were significantly shorter (9.6 versus 13.3 days and 15.5 versus 18.6 days). The residual urinary volume normalized faster (8.0 versus 13.0 days) and the rate of cystitis was lower (18.8 versus 25%). According to our study, a prophylactic application of the parasympathomimetic drug betanecholchloride diminishes postoperative complications associated with bladder dysfunction after Wertheim-Meigs operation.

Adult↗