Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation-a randomized trial.

BACKGROUND: Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. OBJECTIVE: This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. RESULTS: Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. CONCLUSION: Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Pelvic inlet area is associated with birth mode.

INTRODUCTION: To determine whether a pelvis is wide enough for spontaneous delivery has long been the subject of obstetric research. A number of variables have been proposed as predictors, all with limited accuracy. In this study, we use a novel three-dimensional (3D) method to measure the female pelvis and assess which pelvic features influence birth mode. We compare the 3D pelvic morphology of women who delivered vaginally, women who had cesarean sections, and nulliparous women. The aim of this study is to identify differences in pelvic morphology between these groups. MATERIAL AND METHODS: This observational study included women aged 50 years and older who underwent a CT scan of the pelvis for any medical indication. We recorded biometric data including height, weight, and age, and obtained the obstetric history. The bony pelvis was extracted from the CT scans and reconstructed in three dimensions. By placing 274 landmarks on each surface model, the pelvises were measured in detail. The pelvic inlet was measured using 32 landmarks. The trial was registered at the German Clinical Trials Register DRKS (DRKS00017690). RESULTS: For this study, 206 women were screened. Exclusion criteria were foreign material in the bony pelvis, unknown birth mode, and exclusively preterm births. Women who had both a vaginal birth and a cesarean section were excluded from the group comparison. We compared the pelvises of 177 women between three groups divided by obstetric history: vaginal births only (n = 118), cesarean sections only (n = 21), and nulliparous women (n = 38). The inlet area was significantly smaller in the cesarean section group (mean = 126.3 cm2 ) compared with the vaginal birth group (mean = 134.9 cm2 , p = 0.002). The nulliparous women were used as a control group: there was no statistically significant difference in pelvic inlet area between the nulliparous and vaginal birth groups. CONCLUSIONS: By placing 274 landmarks on a pelvis reconstructed in 3D, a very precise measurement of the morphology of the pelvis is possible. We identified a significant difference in pelvic inlet area between women with vaginal delivery and those with cesarean section. A unique feature of this study is the method of measurement of the bony pelvis that goes beyond linear distance measurements as used in previous pelvimetric studies.

Relationship between impaired BMP signalling and clinical risk factors at early-stage vascular injury in the preterm infant.

INTRODUCTION: Chronic lung disease, that is, bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and develops as a consequence of the misguided formation of the gas-exchange area undergoing prenatal and postnatal injury. Subsequent vascular disease and its progression into pulmonary arterial hypertension critically determines long-term outcome in the BPD infant but lacks identification of early, disease-defining changes. METHODS: We link impaired bone morphogenetic protein (BMP) signalling to the earliest onset of vascular pathology in the human preterm lung and delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors for lung injury mimicking clinically relevant conditions in a multilayered animal model using wild-type and transgenic neonatal mice. RESULTS: We demonstrate (1) the significant reduction in BMP receptor 2 (BMPR2) expression at the onset of vascular pathology in the lung of preterm infants, later mirrored by reduced plasma BMP protein levels in infants with developing BPD, (2) the rapid impairment (and persistent change) of BMPR2 signalling on postnatal exposure to hyperoxia and mechanical ventilation, aggravated by prenatal cigarette smoke in a preclinical mouse model and (3) a link to defective alveolar septation and matrix remodelling through platelet derived growth factor-receptor alpha deficiency. In a treatment approach, we partially reversed vascular pathology by BMPR2-targeted treatment with FK506 in vitro and in vivo. CONCLUSION: We identified impaired BMP signalling as a hallmark of early vascular disease in the injured neonatal lung while outlining its promising potential as a future biomarker or therapeutic target in this growing, high-risk patient population.

Altered relaxation times in MRI indicate bronchopulmonary dysplasia.

We developed a MRI protocol using transverse (T2) and longitudinal (T1) mapping sequences to characterise lung structural changes in preterm infants with bronchopulmonary dysplasia (BPD). We prospectively enrolled 61 infants to perform 3-Tesla MRI of the lung in quiet sleep. Statistical analysis was performed using logistic Group Lasso regression and logistic regression. Increased lung T2 relaxation time and decreased lung T1 relaxation time indicated BPD yielding an area under the curve (AUC) of 0.80. Results were confirmed in an independent study cohort (AUC 0.75) and mirrored by lung function testing, indicating the high potential for MRI in future BPD diagnostics. TRIAL REGISTRATION: DRKS00004600.

Cross-sectional analysis of CD8 T cell immunity to human herpesvirus 6B.

Human herpesvirus 6 (HHV-6) is prevalent in healthy persons, causes disease in immunosuppressed carriers, and may be involved in autoimmune disease. Cytotoxic CD8 T cells are probably important for effective control of infection. However, the HHV-6-specific CD8 T cell repertoire is largely uncharacterized. Therefore, we undertook a virus-wide analysis of CD8 T cell responses to HHV-6. We used a simple anchor motif-based algorithm (SAMBA) to identify 299 epitope candidates potentially presented by the HLA class I molecule B*08:01. Candidates were found in 77 of 98 unique HHV-6B proteins. From peptide-expanded T cell lines, we obtained CD8 T cell clones against 20 candidates. We tested whether T cell clones recognized HHV-6-infected cells. This was the case for 16 epitopes derived from 12 proteins from all phases of the viral replication cycle. Epitopes were enriched in certain amino acids flanking the peptide. Ex vivo analysis of eight healthy donors with HLA-peptide multimers showed that the strongest responses were directed against an epitope from IE-2, with a median frequency of 0.09% of CD8 T cells. Reconstitution of T cells specific for this and other HHV-6 epitopes was also observed after allogeneic hematopoietic stem cell transplantation. We conclude that HHV-6 induces CD8 T cell responses against multiple antigens of diverse functional classes. Most antigens against which CD8 T cells can be raised are presented by infected cells. Ex vivo multimer staining can directly identify HHV-6-specific T cells. These results will advance development of immune monitoring, adoptive T cell therapy, and vaccines.

Delayed interval delivery in multiple gestations: the Munich experience.

OBJECTIVE: To evaluate delayed interval deliveries in multiple gestations in regard of delayed interval and neonatal survival and to provide a protocol. METHODS: Data of multiple pregnancies with delayed interval delivery at a tertiary maternity unit between 2002 and 2017 were collected. Contraindications for evaluation of a delay of the delivery of the remaining child were: severe maternal blood loss, poor maternal general condition, preeclampsia, placental abruption, fetal distress, serious congenital malformations of the remaining child, chorioamnionitis, and premature rupture of membranes of the second fetus. A total of 14 cases was included in this retrospective monocentric analysis. RESULTS: The cohort comprised nine twin and five triplet pregnancies. Mean gestational age at delivery of the first fetus was 21 + 6 and 26 + 0 of the retained fetus, respectively. The earliest delivery of the first fetus was at 15 + 2 weeks. The mean interval of the delay was 29.3 days (2-82 days). Mortality of the first fetuses was 53.3%, while it was 17.6% for the retained fetuses. Maternal outcome was good in general: two cases of major blood loss occurred with the necessity of a blood transfusion. CONCLUSION: Delayed interval delivery is a reasonable approach in cases of an imminent preterm birth in multiple gestations which can be performed with a good fetal outcome and limited maternal risks. The situation when this procedure may be an option always comes unexpected. Therefore, the team of perinatologists should keep it in mind as one potential therapeutic approach. In addition, a standard protocol for the procedure should be established in the perinatal center.

Activation of the NF-κB pathway alters the phenotype of MSCs in the tracheal aspirates of preterm infants with severe BPD.

Mesenchymal stromal cells (MSCs) are released into the airways of preterm infants following lung injury. These cells display a proinflammatory phenotype and are associated with development of severe bronchopulmonary dysplasia (BPD). We aimed to characterize the functional properties of MSCs obtained from tracheal aspirates of 50 preterm infants who required invasive ventilation. Samples were separated by disease severity. The increased proliferative capacity of MSCs was associated with longer duration of mechanical ventilation and higher severity of BPD. Augmented growth depended on nuclear accumulation of NFκBp65 and was accompanied by reduced expression of cytosolic α-smooth muscle actin (α-SMA). The central role of NF-κB signaling was confirmed by inhibition of IκBα phosphorylation. The combined score of proliferative capacity, accumulation of NFκBp65, and expression of α-SMA was used to predict the development of severe BPD with an area under the curve (AUC) of 0.847. We mimicked the clinical situation in vitro, and stimulated MSCs with IL-1ß and TNF-α. Both cytokines induced similar and persistent changes as was observed in MSCs obtained from preterm infants with severe BPD. RNA interference was employed to investigate the mechanistic link between NFκBp65 accumulation and alterations in phenotype. Our data indicate that determining the phenotype of resident pulmonary MSCs represents a promising biomarker-based approach. The persistent alterations in phenotype, observed in MSCs from preterm infants with severe BPD, were induced by the pulmonary inflammatory response. NFκBp65 accumulation was identified as a central regulatory mechanism. Future preclinical and clinical studies, aimed to prevent BPD, should focus on phenotype changes in pulmonary MSCs.

MR pelvimetry: prognosis for successful vaginal delivery in patients with suspected fetopelvic disproportion or breech presentation at term.

PURPOSE: The purpose of this study was to correlate MR pelvimetric pelvic inlet measurements with mode of delivery and neonatal outcome in patients with suspected fetopelvic disproportion or breech presentation. METHODS: For this retrospective monocentric study, 237 consecutive MR pelvimetry reports (1999-2016) of pregnant women due to either suspected fetopelvic disproportion, pelvic deformation after trauma, or persistent breech presentation were retrieved from the radiologic database and matched with corresponding information from the obstetric database. RESULTS: Of 223 included women, 95 (42.6%) underwent planned cesarean section (pCS) and 128 (57.4%) underwent a trial of vaginal labour (TOL), of whom 93 (72.7%) delivered vaginally. Vaginal delivery was successful in 45 out of 64 (70.3%) cephalic cases and in 48 out of 64 (75.0%) breech cases. We found statistically significant differences in conjugata vera obstetrica (CV) and diameter transversalis (DT) between the groups TOL and pCS (CV: 12.5 ± 1.0 vs 12.1 ± 1.2 cm, p value 0.001; DT: 13.3 ± 0.9 vs 12.7 ± 0.9 cm, p value <0.001, respectively). However, there was no significant difference between successful VD and cesarean section after TOL (CV: 12.5 ± 0.9 vs 12.3 ± 1.1 cm, p value 0.194; DT: 13.4 ± 0.9 vs 13.2 ± 0.9 cm, p value 0.358, respectively). CONCLUSIONS: In our cohort, MR pelvimetry was a useful tool for prepartal assessment of the female pelvis in the selection of TOL candidates. Yet, it does not seem to yield additional predictive value for women with a previous vaginal delivery.

Human placental growth hormone: a potential new biomarker in gestational trophoblastic disease.

OBJECTIVES: Gestational trophoblastic disease (GTD) involves a spectrum of abnormal proliferations arising from the placental villous trophoblast. Although the incidence is low, a biomarker with short serum half-life would be a major clinical advance to monitor surgical and medical treatment reducing the socioeconomic burden of multiple control visits as well as patient's anxiety. Placental growth hormone (hGH-V) plays an important role in the regulation of normal placental growth and has shown angiogenic effects. We aimed to determine by immunohistochemistry (IHC) whether hGH-V is expressed in GTD and whether it can be detected in the patient's blood for potential monitoring of surgical or medical treatment procedures. METHODS: Tissue and sera were collected from women undergoing treatment for GTD in a tertiary care university hospital. We evaluated partial and complete hydatidiform moles, invasive moles and choriocarcinoma, n=16. Trophoblast specimens were examined by a newly developed IHC set-up for hGH-V in addition to gross morphologic and histopathological examination. Serum samples were analyzed by a highly sensitive hGH-V specific immunoassay. RESULTS: hGH-V was localized in all entities of GTD to the syncytiotrophoblast by immunohistochemistry. Serum hGH-V was detected for the first time in GTD and was present in a high percentage of all analyzed entities. CONCLUSIONS: hGH-V can be detected in all entities of GTD by IHC as well as by serum analysis and may therefore serve as a novel biomarker for the disease. Its clinical utility in diagnosis of GTD and monitoring surgical or medical treatment needs to be determined in further studies.

Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial.

BACKGROUND: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. OBJECTIVE: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. STUDY DESIGN: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. RESULTS: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. CONCLUSION: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

Monocyte signature as a predictor of chronic lung disease in the preterm infant.

Introduction: Inflammation is a key driver of morbidity in the vulnerable preterm infant exposed to pre- and postnatal hazards and significantly contributes to chronic lung disease, i.e. bronchopulmonary dysplasia (BPD). However, the early changes in innate immunity associated with BPD development are incompletely understood. Methods: In very immature preterm infants below 32 weeks gestational age (GA; n=30 infants), monocyte subtypes were identified by Flow Cytometry at birth and throughout the postnatal course including intracellular TNF expression upon LPS stimulation. Complementing these measurements, cytokine end growth factor expression profiles (Luminex® xMAP®; n=110 infants) as well as gene expression profiles (CodeLinkTM Human I Bioarray; n=22) were characterized at birth. Results: The abundance of monocyte subtypes differed between preterm and term neonates at birth. Specifically, CD14++CD16+ (intermediate) monocytes demonstrated a dependency on PMA and elevated levels of nonclassical (CD14+CD16++) monocytes characterized preterm infants with developing BPD. Postnatally, lung injury was associated with an increase in intermediate monocytes, while high levels of nonclassical monocytes persisted. Both subtypes were revealed as the main source of intracellular TNF-α expression in the preterm infant. We identified a cytokine and growth factor expression profile in cord blood specimen of preterm infants with developing BPD that corresponded to the disease-dependent regulation of monocyte abundances. Multivariate modeling of protein profiles revealed FGF2, sIL-2 Rα, MCP-1, MIP1a, and TNF-α as predictors of BPD when considering GA. Transcriptome analysis demonstrated genes predicting BPD to be overrepresented in inflammatory pathways with increased disease severity characterized by the regulation of immune and defense response pathways and upstream regulator analysis confirmed TNF-α, interleukin (IL) -6, and interferon α as the highest activated cytokines in more severe disease. Whereas all BPD cases showed downstream activation of chemotaxis and activation of inflammatory response pathways, more severe cases were characterized by an additional activation of reactive oxygen species (ROS) synthesis. Discussion: In the present study, we identified the early postnatal presence of nonclassical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes as a critical characteristic of BPD development including a specific response pattern of monocyte subtypes to lung injury. Pathophysiological insight was provided by the protein and transcriptome signature identified at birth, centered around monocyte and corresponding granulocyte activation and highlighting TNFα as a critical regulator in infants with developing BPD. The disease severity-dependent expression patterns could inform future diagnostic and treatment strategies targeting the monocytic cell and its progeny.

Corrigendum: Monocyte signature as a predictor of chronic lung disease in the preterm infant.

[This corrects the article DOI: 10.3389/fimmu.2023.1112608.].

Diverse Responses of Autoantibodies to the Angiotensin II Type 1 Receptor in Primary Aldosteronism.

Primary aldosteronism is a common form of endocrine hypertension mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). AT1R-Abs (autoantibodies to the angiotensin II type 1 receptor) have been reported in patients with disorders associated with hypertension. Our objective was to assess AT1R-Ab levels in patients with primary aldosteronism (APA, n=40 and BAH, n=40) relative to patients with primary hypertension (n=40), preeclampsia (n=23), and normotensive individuals (n=25). AT1R-Abs in whole sera were measured using 2 different ELISAs which gave contrasting results. A functional cell-based assay was used to quantify activation of the AT1R (angiotensin II type 1 receptor) using whole sera or affinity-purified antibodies in the absence or presence of losartan (a specific AT1R antagonist). Serum samples from all groups displayed different levels of AT1R activation with different responses to losartan. Patients with BAH displayed higher losartan-independent affinity-isolated agonistic AT1R-Ab levels compared with patients with APA (P<0.01) and with normotensive individuals (P<0.0001). In patients with APA, BAH, and primary hypertension combined, higher aldosterone-to-renin ratios and lower plasma renin concentrations were associated with higher compared with lower agonistic AT1R-Ab levels. In patients with primary aldosteronism, higher AT1R-Ab activity was associated with an increased likelihood of a diagnosis of BAH compared with APA and with the presence of adrenal hyperplasia detected by computed tomography. Taken together, these data suggest that agonistic AT1R-Abs may have a functional role in a subgroup of patients with primary aldosteronism.

MR Pelvimetry for Breech Presentation at Term- Interobserver Reliability, Incidental Findings and Reference Values.

PURPOSE: Antepartal MR pelvimetry is used to assess the viability of vaginal breech delivery. We evaluated the reliability of MR pelvimetric measurements as well as incidental findings noted by different clinicians and assessed potential reference values. METHODS: In this monocentric study, the radiologic database was searched for obstetric MR pelvimetries with singleton breech pregnancies between 1999 and 2016. 99 consecutive MR pelvimetries were included. A structured, independent review was performed by six observers with three clinical experience levels (attending, fellow, junior resident from the departments of radiology and obstetrics). Image analysis entailed the quantitative assessment of conjugata vera (CV) and diameter transversalis (DT), image quality and incidental findings. Obstetric data was retrieved from the obstetric database for reference value assessment. RESULTS: Interobserver agreement was strong throughout (mean intraclass correlation coefficient range: 0.889 - 0.968). The individual measuring biases ranged between 0 - 2 mm, and the average limits of agreement were ±â€Š3 mm. Regarding the mode of delivery, the recommended cesarean section (rCS) group showed significantly smaller CV measurements (CV: 11.37 ±â€Š0.73, p-value < 0.0001) than any other delivery group. No statistical difference in CV between the vaginal delivery and unplanned cesarean section groups was found (p-value 0.902). DT measurements only showed a significant difference between rCS and elective cesarean section (p-value 0.039). 134 incidental findings were noted. CONCLUSION: Strong interobserver agreement irrespective of the reader's experience level supports MR pelvimetry as a reliable method for identifying women with fetopelvic disproportion in breech presentation. For a comprehensive appraisal of incidental findings, radiologic expertise is vital. KEY POINTS: · MR pelvimetry is a reliable method irrespective of the reader's experience level.. · Conjugata vera measurements aid in the prepartal viability assessment of vaginal breech delivery.. · Incidental findings are relatively common.. CITATION FORMAT: · von Bismarck A, Ertl-Wagner B, Stöcklein S et al. MR Pelvimetry for Breech Presentation at Term- Interobserver Reliability, Incidental Findings and Reference Values. Fortschr Röntgenstr 2019; 191: 424 - 432.

Patterns of Plasma Glucagon Dynamics Do Not Match Metabolic Phenotypes in Young Women.

Context: The role of hyperglucagonemia in type 2 diabetes is still debated. Objective: We analyzed glucagon dynamics during oral glucose tolerance tests (oGTTs) in young women with one out of three metabolic phenotypes: healthy control (normoglycemic after a normoglycemic pregnancy), normoglycemic high-risk (normoglycemic after a pregnancy complicated by gestational diabetes), and prediabetes/screening-diagnosed type 2 diabetes. We asked if glucagon patterns were homogeneous within the metabolic phenotypes. Design and Setting: Five-point oGTT, sandwich enzyme-linked immunosorbent assay for glucagon, and functional data analysis with unsupervised clustering. Participants: Cross-sectional analysis of 285 women from the monocenter observational study Prediction, Prevention, and Subclassification of gestational and type 2 Diabetes, recruited between November 2011 and May 2016. Results: We found four patterns of glucagon dynamics that did not match the metabolic phenotypes. Elevated fasting glucagon and delayed glucagon suppression was overrepresented with prediabetes/diabetes, but this was only detected in 21% of this group. It also occurred in 8% of the control group. Conclusions: We conclude that hyperglucagonemia may contribute to type 2 diabetes in a subgroup of affected individuals but that it is not a sine qua non for the disease. This should be considered in future pathophysiological studies and when testing pharmacotherapies addressing glucagon signaling.

Age-dependent differences in DNA damage after in vitro CT exposure.

PURPOSE: Age dependent radiation sensitivity for DNA damage after in vitro blood exposure by computer tomography (CT) was investigated. MATERIALS AND METHODS: Radiation biomarkers (dicentrics and gammaH2AX) in blood samples of newborns, children under five years and adults after sham exposure (0 mGy), low-dose (41 mGy) and high-dose (978 mGy) in vitro CT exposure were analyzed. RESULTS: Significantly higher levels of dicentric induction were found for the single and combined newborns/children group compared to adults, by a factor of 1.48 (95% CI 1.30-1.68), after exposure to 978 mGy. Although a significant dose response for damage induction and dose-dependent repair was found, the gammaH2AX assay did not show an age-dependent increase in DNA damage in newborns/children compared to adults. This was the case for the gammaH2AX levels after repair time intervals of 30 minutes and 24 hours, after correcting for the underlying background damage. For the low dose of 41 mGy, the power of the dicentric assay was also not sufficient to detect an age-dependent effect in the sample size investigated. CONCLUSION: A 1.5-fold increased level of dicentric aberrations is detected in newborns and children under five years after 1 Gy radiation exposure.

Human placental growth hormone in ectopic pregnancy: Detection in maternal blood, immunohistochemistry and potential clinical implication.

OBJECTIVE: To investigate human placental growth hormone (hGH-V) in ectopic pregnancy (EP): detection in maternal blood, correlation with immunohistochemistry and possible role as a marker for the course of EP. DESIGN: Women presenting in the outpatient or emergency department of a tertiary care university hospital with a positive pregnancy test and strong suspicion of EP by ultrasound and/or symptoms were eligible for the study (n=70). Tissue specimens from the surgically treated patients (n=50) were examined by histopathology as well as by a hGH-V specific immohistochemistry set-up. A highly sensitive hGH-V specific immunoassay was used to analyse serum samples collected before treatment, day 1 post surgery samples and serial samples for medical treatment. RESULT(S): In EP patients' sera hGH-V was shown to be measurable for the first time (n=18). HGH-V however could not be detected in all patients' sera. HCG levels were significantly higher in the hGH-V serum positive group (p 0.001). HGH-V was localized to the syncytiotrophoblast in all specimens of EP examined by immunohistochemistry (n=10) regardless of the detection in the patient's blood. CONCLUSION(S): Placental growth hormone (hGH-V) was shown to be present both in ectopic pregnancy patients' sera and tissue. It may serve as a biomarker for monitoring the course and treatment of EP.

[Asymptomatic uterine rupture after two spontaneous vaginal deliveries following prior cesarean section]. / Gedeckte Uterusruptur nach zweimaligem Spontanpartus im Status nach Sectio caesarea bei der ersten Entbindung.

We present the case of an almost asymptomatic uterine rupture after two consecutive vaginal deliveries after a prior cesarean delivery (first child). Uterine rupture is rare even after a prior cesarean delivery, permitting a trial of labor after a cesarean delivery in spite of the increased risk of uterine rupture. Vaginal birth after previous cesarean delivery, however, demands a cautious approach. Appropriate recommendations have been published by the ACOG and the 'AG fOr fetomaternale Medizin' (a branch of the German Society of Obstetrics and Gynaecology). In our case diagnosis was made by an vaginal ultrasound examination 7.5 weeks after an uncomplicated vaginal delivery. An additional MRI examination did not result in substantial extra information. For that reason it will be indicated only in exceptional cases. To answer the question whether a vaginal ultrasound examination should routinely be offered after an uncomplicated vaginal delivery with a prior cesarean delivery in the history to preclude uterine rupture further studies are necessary.