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Biomedical subjects

Peter Husslein

Publications and source records attributed to Peter Husslein.

At least 19 recordsLinked to original sources

Universal antenatal screening for syphilis: is it still justified economically? A 10-year retrospective analysis.

OBJECTIVE: Because universal prenatal screening for syphilis has recently been called into question, we documented the development of syphilis in Austria and analysed the effectiveness of current antenatal syphilis screening practices. METHODS: The development of syphilis in Austria and Vienna was determined based on the data published by the Austrian Bureau of National Statistics (Statistik Austria) and the Vienna Health Authority (Gesundheitsamt Wien, MA15), respectively. The data obtained for Vienna were then compared with those for the remaining eight federal provinces. Also, we retrospectively analysed a total of 34,312 sera obtained between 1988 and 1999 from women screened for syphilis at delivery at the laboratory of the Department of Dermatology, University of Vienna. Serological screening was done with both the Venereal Disease Research Laboratory (VDRL) and the Treponema pallidum haemagglutination (TPHA) assays. Finally, we determined the number of cases of congenital syphilis diagnosed in Vienna between 1988 and 1999. RESULTS: In the past 10 years, the annual number of reported syphilis cases has remained fairly constant. In 1999 and 2000, there were 8.1 and 11.0 notifications of syphilis per 100,000 inhabitants in the capital Vienna, compared with 0.7 and 0.9 in the remaining provinces with a mainly rural character. At delivery, there were 96 cases of maternal syphilis that were both TPHA- and fluorescent treponemal absorption (FTA-ABS)-reactive, corresponding to a seroprevalence of 2.8 per 1000 births. Only 24 of the TPHA-reactive sera were VDRL-reactive. In Vienna, there were three stillbirth deliveries due to congenital syphilis and six cases of confirmed congenitally syphilis between 1988 and 1999. CONCLUSION: Universal syphilis screening may no longer be justified economically. The usefulness of VDRL-based syphilis screening should be reassessed. The screening focus should shift to regions with a high seroprevalence of syphilis. Universal syphilis screening does not appear warranted.

Adult↗

Transcriptional regulation of the human chorionic gonadotropin beta gene during villous trophoblast differentiation.

Expression of the trophoblast-specific subunit of human chorionic gonadotropin, CGbeta, is associated with fusion of cytotrophoblasts into a multinuclear syncytium. Here, we studied regulation of the CGbeta5 gene in trophoblasts undergoing in vitro syncytialization. Transfection of luciferase reporters harboring different lengths of the CGbeta5 upstream sequence revealed that the proximal promoter region (-345 to +114) is sufficient to govern differentiation-dependent induction. Mutational analyses suggested that two selective promoter factor (Sp) and three activating protein 2 (AP-2) recognition sequences are necessary for full activity of the promoter. During syncytialization these elements interacted with increasing amounts of the transcription factors Sp1, Sp3, and AP-2alpha in electrophoretic mobility shift assay, but only AP-2alpha binding rose upon elevation of cAMP levels with forskolin. Increasing expression of different isoforms of Sp1 and Sp3 could also be detected by Western blot analyses. Sp1/Sp3 localized to syncytial nuclei both in differentiated cultures and in term placental tissue, suggesting assembly of functional transcriptional complexes. Costaining of the transcription factors with E-cadherin on term placental sections revealed that 47 and 33% of cytotrophoblast nuclei were negative for Sp1 and Sp3, respectively. In contrast, immunohistochemistry of early tissue demonstrated expression of Sp1 in the majority of cyto- and syncytiotrophoblasts, whereas Sp3 was absent from the syncytium. Sp1 and Sp3 induced wild-type/mutant promoter constructs upon transfection in Sp-deficient SL-2 cells, indicating that the Sp elements function as activating sequences. The data suggest that increasing concentrations of Sp1, Sp3, and AP-2alpha enhance transcription of CGbeta in differentiating term trophoblasts, whereas a different combination of factors may control expression in early placentas.

Base Sequence↗

Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine fetal death: a multicenter study.

OBJECTIVE: We determined whether gene polymorphisms associated with thrombophilia and vascular disease as etiologic factors were involved in the pathogenesis of pregnancy-associated complications. METHODS: We conducted a multicenter case-control study in which we studied 94 women with late unexplained intrauterine fetal death (IUFD) and 94 healthy women with at least one uncomplicated full-term pregnancy and no history of IUFD. We obtained blood samples from all subjects and analyzed their DNA for 12 common polymorphisms of thrombophilic and vascular genes (factor V Leiden, factor V H1299R, prothrombin G20210A, factor XIII V34L, MTHFR C677T, MTHFR A1298C, beta-fibrinogen-455 G to A, PAI-1 4G/5G, GPIIIa L33P, HFE C282Y, apolipoprotein B R3500Q, and apolipoprotein E2/E3/E4). RESULTS: We found no significant association between any of the polymorphisms investigated and IUFD. Subgroup analyses involving various combinations of polymorphisms and in which gestational age and fetal weight were corrected for also showed no significant results. CONCLUSIONS: Our data represent the largest study to date with respect to thrombophilic and vascular gene polymorphisms in IUFD. In accordance with others, we challenge the importance of thrombophilic and vascular gene polymorphisms in the pathogenesis of this condition.

Adult↗

Tumor necrosis factor-alpha inhibits trophoblast migration through elevation of plasminogen activator inhibitor-1 in first-trimester villous explant cultures.

We have tested the hypothesis that elevated concentrations of TNF alpha could impair trophoblast invasion. Using first-trimester placental explant cultures, we have demonstrated that the cytokine inhibits in vitro migration of extravillous trophoblasts (EVT) on collagen I, and invasion through Matrigel. To elucidate the underlying mechanism, proliferation and differentiation of EVT in vitro were analyzed by immunohistochemistry of serial sections, Western blotting, zymography, ELISA, and RT-PCR from RNA pools of mechanically separated cell populations. At 24 h of cultivation in the presence or absence of TNF alpha, anchorage and proliferation of trophoblasts had occurred to generate cell columns containing viable, post-mitotic, differentiated EVT [positive for integrins alpha 1 and alpha 5, matrix metalloproteinase (MMP)-2, and human leukocyte antigen-G1; negative for proliferating cellular nuclear antigen, cytokeratin 18 neoepitope, and in 5-Bromo-2-deoxy-uridine labeling]. At 72 h, control cells had broken away from the column to migrate through the extracellular matrix; whereas, in contrast, TNF alpha-treated EVT remained as contiguous cell columns, despite increased MMP-9 expression. Thus, in vitro MMP9 activity appears not to be essential for trophoblast migration. Expression of plasminogen activator inhibitor (PAI)-1 was elevated in TNF alpha-treated EVT, and adding antibodies that inhibit PAI-1 activity restored migration, whereas tissue-inhibitor-of-metalloproteinases-1-blocking antibodies were ineffective. Induction of PAI-1 by TNF alpha could be related to restricted trophoblast invasion in preeclampsia.

Cell Cycle↗

Women's position during labour: influence on maternal and neonatal outcome.

AIM: To assess the maternal, perineal and neonatal outcomes of an upright position compared with a supine position during vaginal delivery, in terms of defined outcome variables. METHODS: This case-control study was carried out at the Department of Obstetrics and Gynaecology of the University Hospital Vienna between 1997 and 2002. A total of 307 women who delivered in an upright position were enrolled in the study. Upright position was defined as free squatting and was also described as an alternative birth position. 307 controls, delivering in a supine position, were selected from the delivery database as the next parity-matched normal spontaneous vaginal delivery. Our analysis was restricted to a sample of women with a gestational age > 37 weeks, a normal sized fetus and a pregnancy with cephalic presentation. Women with medical or obstetric risk factors were excluded. RESULTS: A statistically significant decrease for the use of medical analgesia (p = 0.0001) and oxytocin (p = 0.001) was observed in women using the upright birth position. The length of the first and second stages of labour did not significantly differ between the two groups (p > 0.05). A significantly lower rate of episiotomy was detected in women who delivered in an upright position compared with women delivering supine (p = 0.0001). The frequency of perineal tears, and vaginal and labial trauma did not differ between the two groups (p > 0.05). When analysing maternal blood loss, no significant differences between the two groups were found (p > 0.05). No differences in APGAR score < 7 at 1 and 5 minutes or cord pH < 7.1 were observed (p > 0.05). CONCLUSIONS: The data indicate that labouring and delivering in an upright position is associated with beneficial effects such as a lower rate of episiotomy, and a reduced use of medical analgesia and oxytocin. In our opinion, the best recommendation is to give low-risk maternity patients the option of bearing in the mode that is most comfortable for them.

Adult↗

Elevated serum concentrations of androgens in women with pregnancy-induced hypertension.

Alterations of steroid hormone profiles have been suggested to be involved in the pathophysiology of pregnancy-induced hypertension (PIH). The aim of our study was first to investigate serum concentrations of testosterone, dihydrotestosterone, androstenedione and dehydroepiandrostenedione sulfate in women with PIH and normotensive pregnant women and secondly to evaluate an association between elevated serum concentrations of androgens and the development of severe disease. Serum concentrations of androgens were measured in 40 patients with PIH and 40 normotensive pregnant women, matched for gestational age, determined by enzyme linked immunosorbent assay. Multivariate logistic regression models were used to analyze the influence of elevated serum concentrations of androgens on the occurrence of PIH and the development of severe disease. The median serum concentrations of androstenedione and testosterone were significantly elevated in women with PIH compared to controls (6.3 and 5.0 ng/ml, 1.8 and 1.1 ng/ml, p = 0.005 and p = 0.04, respectively). The difference between the median serum concentrations of dihydrotestosterone and dehydroepiandrostenedione sulfate in women with PIH and controls was not significant. Elevated serum concentrations of androstenedione revealed a significant influence on the odds of presenting with PIH (p = 0.043) and were significantly associated with the development of severe disease (p = 0.014). Women with PIH have elevated serum concentrations of androstenedione and testosterone. Moreover, elevated serum concentrations of androstenedione are associated with development of severe disease.

Adult↗

Expression of the human Hand1 gene in trophoblastic cells is transcriptionally regulated by activating and repressing specificity protein (Sp)-elements.

The tissue-specific basic helix-loop-helix protein Hand1 is essential for the formation of trophoblast giant cells of the murine placenta. In humans, Hand1 is detectable in trophoblastic tumour cells suggesting an equivalent role in trophoblast differentiation. To understand its mode of expression we have cloned and characterized the human Hand1 gene promoter. Primer extension analyses suggest that transcription initiates 19 nucleotides downstream of the TATA element of the proximal 5' flanking region. Expression of luciferase reporter constructs harboring deletions of the 9.5 kb Hand1 5' flanking sequence defines a promoter region within 274 bp upstream of the transcriptional start site. Compared to a reporter bearing only the TATA box, the proximal promoter activates transcription up to 30-fold. However, transcriptional activity of the region was observed in both Hand1-expressing and non-expressing cell lines. Sequencing, DNAseI footprint analyses and electrophoretic mobility shift assays reveal the presence of four GC-rich sequences, which show different affinities to the endogenous specificity proteins (Sp), and a CCAAT box. In vitro, the Sp-elements mainly interact with Sp1 and Sp3 while the CCAAT element is recognized by the alpha CAAT binding factor protein. Mutant luciferase reporters bearing single active or inactive recognition sites demonstrate that two of the four Sp-binding sites (I and IV) contribute little to the overall transcription rate. The two other Sp-cognate sequences, II and III, downregulate and activate reporter expression 2.3- and 2.6-fold, respectively. Co-transfections of Sp1/Sp3 expression vectors and mutated reporter constructs in Sp-deficient SL2 cells indicate that the Sp-binding site II and III indeed function as repressing and activating enhancer sequences. In summary, the data suggest that constitutive expression of the Hand1 gene in cultured cells is regulated by a complex interplay of Sp-proteins interacting with activator and repressor elements.

5' Flanking Region↗

The effect of epidural analgesia on obstetric lacerations and neonatal outcome during spontaneous vaginal delivery.

The aim of this study was to determine if epidural analgesia is associated with increased risk of obstetric lacerations during spontaneous vaginal delivery. We also assessed the effect of epidural analgesia on maternal and neonatal parameters. This multicenter study consisted of an analysis of data from the delivery databases of the University Hospital of Vienna and the Semmelweis Women's Hospital Vienna. This study was restricted to a sample that included all women with uncomplicated pregnancy, a gestational age >37 weeks and a pregnancy with cephalic presentation. Epidural analgesia was started during the first stage of labour. Techniques and management styles of epidural analgesia were the same in both hospitals. We found that women undergoing epidural analgesia had a prolonged second stage of labour, a higher rate of episiotomy and an increased use of oxytocin. Some of these adverse effects might be caused by the higher rate of primipara in the epidural group. However, epidural analgesia showed no evidence of a detrimental effect on the integrity of the birth-canal and on neonatal outcome during spontaneous vaginal delivery.

Analgesia, Epidural↗

Reduction of preeclampsia in multiple pregnancies by a dedicated monitoring protocol.

OBJECTIVE: To evaluate the effect of a dedicated monitoring protocol on the incidence of pregnancy-induced hypertension disorders (preeclampsia, HELLP [hemolysis, elevated liver enzymes, low platelets] syndrome, gestational hypertension) during a 5-year period in 417 women with multiple gestations. METHODS: At the Department of Obstetrics and Fetomaternal Medicine, Vienna University, an outpatient care protocol for women with multiple pregnancies was established. Between March 1997 and February 2002, 379 twins and 38 triplets were followed up. Mean visits of dichorial and monochorial twins were nine and 11, respectively. Triplets were asked to at least 12 follow-up visits. RESULTS: Any kind of pregnancy-associated hypertensive disorders necessitating cesarean delivery developed in eight women (seven with twins, one with triplets; 1.76%). Three cases of preeclampsia, three cases of HELLP syndrome, and two cases of pregnancy-induced hypertension were diagnosed. Perinatal outcome of all 17 newborns was excellent without any mortality and only minor morbidity. All mothers left the hospital in a fully recovered condition. CONCLUSION: Because of our results we hypothesize that our monitoring protocol with frequent visits, continuous personal obstetric care, and timed delivery is effective in reduction of pregnancy-induced hypertension in multiple pregnancies.

Adult↗

Elevated serum concentrations of the angiogenesis inhibitor endostatin in preeclamptic women.

OBJECTIVE: Changes in serum levels of angiogenic factors such as vascular endothelial growth factor or placental growth factor were associated with preeclampsia. The aim of our study was to investigate the concentrations of endostatin, a potent endogenous inhibitor of angiogenesis and endothelial or tumor cell growth, in preeclamptic patients. METHODS: Levels of soluble endostatin were determined by enzyme-linked immunosorbent assay and Western blot analysis in sera of nonpregnant women, healthy pregnant women, and patients with different forms of preeclampsia. RESULTS: Statistical analyses of age-matched study groups revealed elevated medians of endostatin concentration for severely (30.5 ng/mL) and mildly (26.05 ng/mL) preeclamptic patients compared with healthy pregnant (17.2 ng/mL) and nonpregnant women (17.2 ng/mL). Western blot analysis confirmed the up-regulation of soluble endostatin molecules (24 kD) in sera of severely preeclamptic patients. CONCLUSION: Elevated concentrations of endostatin could play a role in the pathophysiology of preeclampsia by counteracting the effects of vascular endothelial growth factor. The inhibitor could also be responsible for the observed growth-inhibitory effects of preeclamptic plasma on endothelial cells.

Adult↗

Elective cesarean section vs. spontaneous delivery: a comparative study of birth experience.

BACKGROUND: To investigate birth experience and medical outcome in women with elective cesarean section (CS) compared with women with intended vaginal delivery. METHODS: A total of 1050 pregnant women were included in this prospective trial. Psychological factors, pain levels and birth experience were investigated using a self-designed questionnaire and three established psychological tests in gestational week 38, and 3 days and 4 months postpartum. In addition, medical data were evaluated from the records. RESULTS: Out of 903 women with planned vaginal birth, in 484 women (53.6%) minimal perineal surgery had to be performed after birth, 41 women (4.5%) had vacuum deliveries, and in 93 cases (10.3%) emergency CS had to be performed. In the 147 elective CS (103 based on medical and 44 on psychological factors), a significantly lower rate of maternal and fetal complications was observed when compared with vaginal birth (5.4% vs. 19.3%; p < 0.0001). Birth experience (Salmon test) was significantly better in elective CS compared with vaginal delivery, but worse in women with emergency CS and worst in those with vacuum delivery. We found that 83.5% of women with vaginal delivery would choose the same mode of birth again, 74.3% of women with CS on demand, and 66% of women with medically necessary CS. Only 30.1% of women with emergency CS wanted to receive CS at the next birth. CONCLUSIONS: Elective CS is a safe and psychologically well tolerated procedure. The results are comparable with uncomplicated vaginal delivery and far superior to secondary intervention such as vacuum delivery or emergency CS.

Adolescent↗

Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of antibiotic treatment of bacterial vaginosis in pregnancy to reduce preterm delivery. STUDY DESIGN: We performed a meta-analysis of published, English-language, randomized, placebo-controlled clinical trials of antibiotic treatment of bacterial vaginosis in pregnant women with intact amniotic membranes at <37 weeks of gestation. Primary outcomes included preterm delivery, perinatal or neonatal death, and neonatal morbidity. RESULTS: Ten studies with results for 3969 patients were included. In patients without preterm labor, antibiotic treatment did not significantly decrease preterm delivery at <37 weeks of gestation, in all patients combined (odds ratio, 0.83; 95% CI, 0.57-1.21) nor in high-risk patients with a previous preterm delivery (odds ratio, 0.50; 95% CI, 0.22-1.12). In both groups, significant statistical heterogeneity was observed. A significant reduction in preterm delivery and no statistical heterogeneity were observed in 338 high-risk patients who received oral regimens with treatment durations of > or =7 days (odds ratio, 0.42; 95% CI, 0.27-0.67). Nonsignificant effects and no statistical heterogeneity were observed in low-risk patients (odds ratio, 0.94; 95% CI, 0.71-1.25) and with vaginal regimens (odds ratio, 1.25; 95% CI: 0.86-1.81). In one study antibiotic treatment in patients with preterm labor led to a nonsignificant decrease in the rate of preterm deliveries (odds ratio, 0.31; 95% CI, 0.03-3.24). CONCLUSION: The screening of pregnant women who have bacterial vaginosis and who have had a previous preterm delivery and treatment with an oral regimen of longer duration can be justified on the basis of current evidence. More studies are needed to confirm the effectiveness of this strategy, both in high-risk patients without preterm labor and in patients with preterm labor.

Anti-Bacterial Agents↗

Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis.

OBJECTIVE: We performed a meta-analysis to evaluate bacterial vaginosis as a risk factor for preterm delivery. STUDY DESIGN: Selection criteria were (1). the data appeared in original, published English-language reports of prospective studies or control groups of clinical trials that included women at <37 weeks of gestation with intact amniotic membranes, (2). all the women had to have been screened for bacterial vaginosis that was diagnosed by either clinical criteria or criteria that were based on Gram stain findings, and (3). the outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death. RESULTS: Eighteen studies with results for 20,232 patients were included. Bacterial vaginosis increased the risk of preterm delivery >2-fold (odds ratio, 2.19; 95% CI, 1.54-3.12). Higher risks were calculated for subgroups of studies that screened for bacterial vaginosis at <16 weeks of gestation (odds ratio, 7.55; 95% CI, 1.80-31.65) or at <20 weeks of gestation (odds ratio, 4.20; 95% CI, 2.11-8.39). Bacterial vaginosis also significantly increased the risk of spontaneous abortion (odds ratio, 9.91; 95% CI, 1.99-49.34) and maternal infection (odds ratio, 2.53; 95% CI, 1.26-5.08). No significant results were calculated for the outcome of neonatal infection or perinatal death. CONCLUSION: Bacterial vaginosis, early in pregnancy, is a strong risk factor for preterm delivery and spontaneous abortion.

Abortion, Spontaneous↗

Awareness of Austrian physicians of risk factors for the development of atherosclerosis.

OBJECTIVE: In industrialised countries, coronary heart- (CHD) and other atherosclerosis-associated diseases (AAD) are, with an increasing incidence, responsible for almost half of the deaths among their respective populations. There is unequivocal evidence that medicine should try to achieve a reduction in manifestations of atherosclerosis by efficient preventive strategies. A variety of guidelines have been published during the last decades; nevertheless there is a gap between established recommendations and its application in everyday practice by Austrian physicians. The aim of this survey was to investigate physicians' knowledge of and attitude towards risk factors, preventive strategies and therapy of CHD and other AAD. METHODS: The self-administered questionnaire was mailed to 1000 physicians. We obtained an answer from a total of 286 physicians (general practitioners, GP) and specialists in internal medicine, IMS), who were asked about selected items concerning CHD and other AAD and an eventual modification in attitude towards diagnosis and treatment according to their own, personal risk profile. RESULTS: Risk factors for developing AAD such as elevated CH was identified in 77% (74% GP vs. 84% IMS), hypertension in 77% (76% GP vs. 81% IMS), elevated TG in 37% (40% GP vs. 26% IMS), excess alcohol consumption in 14% of all interrogated physicians (16% GP vs. 9% IMS) respectively. 77% (75% GP vs. 81% IMS) of the physicians considered the CH/HDL-ratio to be important in primary prevention and 83% (81% GP vs. 87% IMS) in secondary prevention; Lipoprotein(a) was considered important in only 9% (8% GP vs. 14% IMS) and 24% (19% GP vs. 41% IMS), respectively. CONCLUSION: In summary, all mentioned risk factors were heavily underestimated by Austrian physicians, partly leading to insufficient evaluation and therapeutic interventions. Secondary prevention was managed quite satisfactorily by both GP and IMS according to the Austrian guidelines. The knowledge about primary prevention strategies was significantly worse in GP compared to IMS. There is still a great need for information and training-programs for Austrian physicians to make primary and secondary prevention strategies work more effectively.

Adult↗

Physical characteristics of newborn babies after vaginal delivery: a 25-year study from Vienna.

This retrospective analysis evaluated whether the gestational age, mean birth weight, length and shoulder width of vaginally delivered newborns have increased during the last 25 years in Vienna, Austria. Women who have given birth at the University of Vienna Medical School Hospital were divided into four age groups: under 20 years, 20-24 years, 25-29 years, and 30 years of age or over. Patient data collected between 1976 to 2000 were grouped into five periods: 1976-1979, 1980-1984, 1985-1989, 1990-1994, and 1995-2000. A highly significant increase of all four parameters was observed for all age groups between 1976 and 2000. The changes were most marked in the 25-29 year age group.

Adolescent↗