Does the use of STAN combined with fetal heart rate monitoring improve labor room management in patients with abnormalities ?

Le RCF est utilisé en routine dans la surveillance du travail depuis plus de 30 ans sans avoir été évalué au préalable. Une augmentation du taux de césarienne a été constatée alors que son utilité sur l'amélioration du bien-être fœtal est contestée. L'imprécision de la signification des anomalies du RCF et la grande variabilité de leur interprétation pourraient en partie expliquer ces mauvaises performances. Dans un large essai suédois l'association du STAN au RCF a permis de diminuer les taux d'extraction pour anomalie du RCF et d'encéphalopathie néonatale modérée ou sévère. Constatant une divergence des pratiques obstétricales nordiques et françaises, nous avons évalué le STAN entre 2002 et 2006. L'objectif de cette thèse était de déterminer si l'association du STAN permet d'améliorer la prise en charge en salle de travail des patientes avec anomalie du RCF. Une étude d'observation sur 433 cas a permis de montrer que le STAN avait une sensibilité de 63% pour le diagnostic de l'acidose sévère et de 38% pour celui de l'acidose modérée. Dans un essai randomisé sur 799 patientes, l'utilisation du STAN n a pas entraîné une diminution du taux d'extraction pour anomalie du RCF, mais à permis une diminution de 56% du recours au pH au scalp. Nous avons montré, à partir de 30 tracés analysés par 7 obstétriciens, que le STAN permettait d'accroître l'homogénéité dans les décisions d'extraction grâce à la réduction des extractions non justifiées. Le STAN permet d'augmenter l'homogénéité des décisions d'extraction en salle de travail. L'incrémentation de la variabilité dans l'algorithme décisionnel du STAN est une piste pour augmenter la fiabilité du diagnostic de l'acidose.Fetal heart rate (FHR) has been routinely measured by cardiotocography (CTG) to monitor labor for more than 30 years, despite the absence of any formal evaluation. The rate of cesarean delivery has increased over this time, while the usefulness of FHR in improving fetal well-being has been contested. The imprecision in the significance of FHR abnormalities and the great variability in their interpretation may explain this poor performance in part. A large Swedish trial showed that the combination of the STAN (ST segment analysis) with CTG diminished the rate of operative intervention for fetal distress, as well as the rate of moderate or severe neonatal encephalopathy. In view of the divergences between the Nordic countries and France in obstetrical practices, we assessed the STAN in France between 2002 and 2006. The objective of this dissertation was to determine whether combining STAN with CTG improves in labor room management of patients with fetal distress. An observational study of 433 cases showed that STAN had a sensitivity of 63% for a diagnosis of severe acidosis and of 38% for moderate acidosis. In a randomized trial of 799 patients, the use of STAN did not reduce the rate of operative intervention for fetal distress but did lead to a 56% reduction in use of scalp pH tests. In an analysis of 30 tracings by 7 obstetricians, we showed that STAN increased the consistency of decisions for operative intervention by reducing the number of unjustified interventions. STAN increases the consistency of decisions for operative intervention in the labour room. Breaking down the degree of FHR variability into increments in the STAN decision algorithm is one pathway for increasing the reliability of its diagnosis of acidosis

Does the use of STAN combined with fetal heart rate monitoring improve labor room management in patients with abnormalities ?

Le RCF est utilisé en routine dans la surveillance du travail depuis plus de 30 ans sans avoir été évalué au préalable. Une augmentation du taux de césarienne a été constatée alors que son utilité sur l'amélioration du bien-être fœtal est contestée. L'impFetal heart rate (FHR) has been routinely measured by cardiotocography (CTG) to monitor labor for more than 30 years, despite the absence of any formal evaluation. The rate of cesarean delivery has increased over this time, while the usefulness of FHR i

Mitochondrial reactive oxygen species and apoptosis

International audienceProgrammed cell death (PCD) serves as a major mechanism for the precise regulation of cellnumbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despitethe striking heterogeneity of cell death induction pathways, the execution of the death program isoften associated with characteristic morphological and biochemical changes termed apoptosis.The central components of the intrinsic apoptotic pathway involve specific proteases (i.e.caspases) and mitochondria (Nunez et al., 1998; Raff, 1998). Although for a long time the absenceof mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today asthe central executioner of programmed cell death. This crucial position of mitochondria inprogrammed cell death control is not due to a simple loss of function (deficit in energy supplying),but rather to an active process in the regulation of effector mechanisms. This role is reinforced bythe observation that mitochondria contribute to PCD signaling via the production of reactive oxygenspecies, as shown in TNF-α or ceramide-induced cell death during which increased mitochondrialROS production appears as an early event of the induction phase. Recent other reviews cover theabundant literature dealing with the role of mitochondrion in cell death (Bernardi et al., 1998;Bernardi et al., 1999; Mignotte and Kroemer, 1999; Mignotte and Vayssière, 1998; Mignotte andVayssière, 1999; Reed et al., 1998; Susin et al., 1998). In this chapter, we examine on the one handthe data concerning the mitochondrial proteins involved in PCD, and on the other hand the role ofreactive oxygen species (ROS) in mitochondrial features of apoptosis

Mitochondrial reactive oxygen species in cell death signaling

International audienceDuring apoptosis, mitochondrial membrane permeability (MMP) increases and the release into the cytosol of pro-apoptotic factors (procaspases, caspase activators and caspase-independent factors such as apoptosis-inducing factor (AIF)) leads to the apoptotic phenotype. Apart from this pivotal role of mitochondria during the execution phase of apoptosis (documented in other reviews of this issue), it appears that reactive oxygen species (ROS) produced by the mitochondria can be involved in cell death. These toxic compounds are normally detoxified by the cells, failing which oxidative stress occurs. However, ROS are not only dangerous molecules for the cell, but they also display a physiological role, as mediators in signal transduction pathways. ROS participate in early and late steps of the regulation of apoptosis, according to different possible molecular mechanisms. In agreement with this role of ROS in apoptosis signaling, inhibition of apoptosis by anti-apoptotic Bcl-2 and Bcl-x L is associated with a protection against ROS and/or a shift of the cellular redox potential to a more reduced state. Furthermore, the fact that active forms of cell death in yeast and plants also involve ROS suggests the existence of an ancestral redox-sensitive death signaling pathway that has been independent of caspases and Bcl-2

Cost-Effectiveness Analysis of Vaginal Misoprostol versus Dinoprostone Pessary: a large noninferiority RCT in France

International audienceObjective: To assess the cost-effectiveness of vaginal misoprostol (PGE1) (25μg) compared to a slow-release dinoprostone (PGE2) pessary (10μg) for labor induction due to an unfavorable cervix at term. Methods: We used data from an open-label multicenter, randomized noninferiority trial which recruited women for whom labor was induced for medical reasons, a Bishop score ≤ 5 at ≥ 36 weeks, and a cephalic-presenting singleton pregnancy with no prior cesarean delivery. The Incremental Cost Effectiveness Ratio (ICER) was assessed from the payer’s perspective, with the focus on inpatient care costs and using the Caesarean Deliveries Avoided (CDA) rate as primary analysis and the rate of Vaginal Delivery within 24h (VD24) as secondary analysis. Results: Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4,410 and €4,399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol respectively. Dinoprostone is not cost-effective according to the CDA and misoprostol was either a cost-effective or a dominant strategy according to the VD24. Conclusion: Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals since the price is lower and it is easier to use

How important is consent in maternal serum screening for Down syndrome in France? Information and consent evaluation in maternal serum screening for Down syndrome: a French study.

OBJECTIVES: To evaluate the level of information and informed consent for maternal serum screening (MSS) for Down syndrome (DS) in the second trimester of pregnancy and analyse the exercise of autonomy towards the test by the women concerned. METHODS: We studied the population of pregnant women attending obstetric consultations in two French hospitals over a 3-month period. The women were assigned to three groups according to MSS results for DS: women at high risk of having a child with DS (group 1), women at low risk (group 2) and women who did not undergo the test (group 3). A questionnaire was completed before the medical consultation, to assess the quality of consent before amniocentesis for the group at high risk and before the second-trimester ultrasound scan for the other two groups. RESULTS: We analysed 305 questionnaires for 89, 137 and 79 women belonging to groups 1, 2 and 3 respectively. In total, 123 women (40.3% [IC 95%, 35-46%]) were considered to be well informed; 33 (10%, [IC 95%, 8-12%]) had a high level of knowledge, but made choices not consistent with their stated attitude, and 149 (49.7% [IC 95%, 45-56%]) were considered uninformed. Logistic regression analysis showed that maternal consent depended on three independent components: The score attributed to the doctor for information about MSS (t = 4.216, p < 0.001).Whether the patient belonged to group 1 (t = -2.631, p < 0.009).Educational level (< high-school diploma, high-school diploma or at least two years of higher education after high school) (t = 2.324, p < 0.02). The rate of consent increased with educational level and was highest for the women in group 1 and for those whose doctor had a high information score. CONCLUSIONS: Our findings clearly show that women are provided with insufficient information concerning MSS screening for DS in the second trimester of pregnancy for real and valid consent to be obtained. Copyright (c) 2007 John Wiley & Sons, Ltd

High glutathionylation of placental endothelial nitric oxide synthase in preeclampsia

Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•–). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction.The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1–20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis.In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease. Keywords: NO, ENOS, S-glutathionylation, Glutathione, Oxidative stress, O2, Pregnancy, Trophoblast, Migration, Preeclampsi

Bcl-2 can promote p53-dependent senescence versus apoptosis without affecting the G1/S transition

International audienceWith the aim to identify events involved in the determination of p53-dependent apoptosis versus growth arrest, we used rat embryo fibroblasts expressing a temperature-sensitive mutant (tsA58) of the SV40 large tumour antigen (LT). Heat-inactivation of LT leads to p53 activation and commitment to a senescent-like state (REtsA15 cell line) or apoptosis (REtsAF cell line). We report that senescence is associated with high levels of the anti-apoptotic Bcl-2 protein and a cell cycle arrest in G1 phase, whereas ap-optosis is associated with low levels of Bcl-2 and a cell cycle arrest in G2 phase. Here we show that Bcl-2, which can inhibit apoptosis and proliferation, turns the apoptotic phenotype into a senescent-like phenotype in G2 phase. This result suggests that Bcl-2-dependent inhibition of apoptosis could be crucial for the commitment to replicative senescence, whereas its ability to inhibit G1 progression would not be required

Association between gestational age and severe maternal morbidity and mortality of preterm cesarean delivery: a population-based cohort study

International audienc