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Dominique Cabrol

Publications and source records attributed to Dominique Cabrol.

At least 19 recordsLinked to original sources

PDE4 inhibition prevents preterm delivery induced by an intrauterine inflammation.

The aim of this study was to explore the anti-inflammatory properties of phosphodiesterase-4 (PDE4) inhibitors in vivo and their potential ability to prevent inflammation-induced preterm delivery. Indeed, intrauterine inflammation is the major etiology of very preterm delivery, the leading cause of neonatal mortality and morbidity. Intrauterine injection of Escherichia coli LPS in 15-day-pregnant mice induced an increase of PDE4 activity and PDE4B expression at the maternofetal interface, a rise of amniotic fluid levels of TNF-alpha, IL-1beta, IL-6, and IL-10 and provoked massive preterm delivery and fetal demise. Selective PDE4 inhibition by rolipram prevented the rise in the proinflammatory cytokines. Following the nuclear translocation of the transcription factor NFkappaB, as a marker of cellular activation after the inflammatory challenge, showed a time-dependent sequential activation of the gestational tissues, from the uterine mesometrial to the fetal compartment, particularly in the glycogen-trophoblastic cells of the placenta. This activation was disrupted by PDE4 inhibition, and inflammation-induced preterm delivery and fetal demise were prevented. PDE4 selective inhibitors may thus represent a novel effective treatment to delay inflammation-induced preterm delivery and to prevent adverse outcomes in infants.

3',5'-Cyclic-AMP Phosphodiesterases↗

Attempted vaginal versus planned cesarean delivery in 195 breech first twin pregnancies.

BACKGROUND: To compare neonatal and maternal outcomes for breech first twins according to whether vaginal or cesarean delivery was planned and to verify that in appropriate selected cases, attempted vaginal delivery is a reasonable choice. METHODS: A retrospective study of all twin pregnancies with the first twin in breech position and gestational age at least 35 weeks at birth at two French university hospital centers from January 1994 through December 2000. The primary outcome was a combined indicator of neonatal mortality and severe morbidity, as defined by one or more of the following: death before discharge, admission to neonatal intensive care unit, 5-minute Apgar score <7, cord blood pH <7.10, or birth trauma. RESULTS: Cesarean delivery was planned for 71 (36.4%) patients, and attempted vaginal delivery for 124 (63.6%), 59 (47.6%) of whom were delivered vaginally and 65 (52.4%) by cesarean during labor. Neither the combined negative outcome indicator nor neonatal mortality differed significantly for either twin or either group. There were no significant differences in maternal mortality or morbidity between the two groups. The frequency of deep vein thrombophlebitis or pulmonary embolism requiring anticoagulant therapy was significantly higher in the planned cesarean group [3/71 (4.2%) versus 0/124; p=0.047]. CONCLUSION: When appropriate criteria are used to decide mode of delivery, a careful intrapartum protocol is followed, and an experienced obstetrician, midwife, and anesthesiologist are in attendance, attempted vaginal delivery is a reasonable option for first twins in breech position.

Adult↗

Should phosphodiesterase 5 selective inhibitors be used for uterine relaxation?

Sildenafil citrate is a phosphodiesterase 5-selective inhibitor used successfully in treating erectile dysfunction. High doses of sildenafil can inhibit myometrial contractions. However, no study has demonstrated a role for phosphodiesterase 5 in myometrial contractility. No clinical trial using sildenafil to promote uterine relaxation should be initiated based on the currently available data.

3',5'-Cyclic-GMP Phosphodiesterases↗

Pragmatic comparison of beta2-agonist side effects within the Worldwide Atosiban versus Beta Agonists study.

OBJECTIVE: While beta2-agonists for the acute treatment of preterm labour unequivocally reduce the odds of delivery within 48 h and 7 days, they have been associated with substantial maternal and fetal side effects. We aimed to compare side effect profiles of beta2-agonist tocolytics. STUDY DESIGN: Pragmatic comparison of ritodrine, salbutamol and terbutaline from re-analysis of data obtained within three comparator arms of three simultaneous comparable randomised controlled trials of beta2-agonists against atosiban in 742 women in preterm labour. The prevalence of categoric side effects between treatment groups was analysed using a chi2 test. The differences in continuous variables between treatment groups were analysed in analyses of covariance. RESULTS: The prevalence of categoric side effects was similar with the three drugs, with the exception of the subjective symptom of palpitations (ritodrine 24.0%, terbutaline 9.3% and salbutamol 12.3%, P=0.003). There were also some differences in maternal diastolic blood pressure (P<0.001) and serum glucose levels (P<0.001), although these were small (<3 mmHg and < or =2.8 mmol/L, respectively) and clinically unimportant. CONCLUSION: Side effects were common with all three drugs. Thus, choosing one beta2-agonist over the other to minimise side effects has little rationale, especially now that safer tocolytics are available.

Adrenergic beta-Agonists↗

Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone. STUDY DESIGN: This prospective blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks' gestation. The primary outcome was preterm delivery before 35 weeks'gestation. RESULTS: Among the 359 women included, 48 (13.4%) delivered before 35 weeks' gestation. The sensitivity, specificity, and positive and negative predictive values of cervical length < or = 25 mm were 75%, 63%, 24%, and 94%, respectively, and of fetal fibronectin > or = 50 ng/mL, 63%, 81%, 33%, and 93%. Fetal fibronectin detection was significantly (P < .001) more specific than cervical length measurement. For selective use of fetal fibronectin detection after cervical length measurement, the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection (67%, 81%, 36%, and 94%). This strategy could have avoided 200 fibronectin tests. CONCLUSION: Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth.

Adult↗

Detection of interleukin 6 mRNA by RT-PCR in vaginal secretions: association with preterm delivery and neonatal infection in women with preterm labour and intact membranes.

OBJECTIVE: To find a biological marker associated with preterm delivery or neonatal infection in pregnant women with preterm labour and intact membranes. STUDY DESIGN: Cervical secretions were collected from 286 women hospitalized for preterm labour with intact membranes at 24-34 weeks' gestation. The outcomes studied were delivery before 33 and 35 weeks' gestation, chorioamnionitis, and neonatal infection, and their association with the presence of IL-6 mRNA in cervical secretions as detected by RT-PCR. The other infectious markers tested were: bacterial vaginosis and fetal fibronectin in cervical secretions; serum CRP and white blood cell count. RESULTS: The vaginal secretions of 13 of 286 women (4.7%) contained IL-6 mRNA. The only other marker tested significantly associated with IL-6 mRNA+ was the presence of streptococcus in vaginal secretions (30.8% versus 9.4% in the IL-6+ and-groups, p = 0.03). Although the difference did not reach statistical significance (p<0.06 and 0.08, respectively), in women with IL-6 mRNA in cervical secretions we observed a tendency to give birth before 33 and 35 weeks more often than the population as a whole. This group was at higher risk of neonatal infection (38.5% versus 15.1%; p = 0.04). After adjustment for infectious risk factors, IL-6 remained significantly associated with neonatal infection (OR = 4.6, 95% CI [1.1-18.9]). The sensitivity of IL-6 mRNA for neonatal infection was 11.1%. The specificity was 96.7%. CONCLUSION: The detection of IL-6 mRNA by RT-PCR in vaginal secretions allows identification of a small group of women at high risk of neonatal infection, independently of other markers of infection.

Adult↗

Is epidural analgesia a risk factor for occiput posterior or transverse positions during labour?

OBJECTIVE: The aim of this study was to assess whether the station of the fetal head at epidural placement is associated with the risk of malposition during labour. STUDY DESIGN: Retrospective study (covering a 3-month period) of patients in labour with singleton cephalic term fetuses and epidural placement before 5 cm of dilatation. We studied the following risk factors for malposition: station and cervical dilatation at epidural placement, induction of labour, parity and macrosomia. Malposition, defined as all occiput posterior and occiput transverse positions, was assessed at 5 cm of dilatation because of our policy of systematic manual rotation for malpositions. RESULTS: The study included 398 patients, 200 of whom had malpositions diagnosed at 5 cm of dilatation. In both the univariate and multivariate analyses, station at epidural placement was the only risk factor significantly associated with this malposition (adjusted OR: 2.49, 95% CI 1.47-4.24). None of the other factors studied was significantly associated with malposition: nulliparity (OR 1.45, 95% CI 0.96-2.20), macrosomia (OR 0.75, 95% CI 0.37-1.50), induction of labour (OR 0.84, 95% CI 0.49-1.45), or dilatation less than 3 cm at epidural administration (OR 1.16, 95% CI 0.59-2.30). Only three infants of the 365 delivered vaginally (0.8%) were born in occiput posterior positions. CONCLUSION: Epidural placement when the fetal head is still "high" is associated with an increased rate of occiput posterior and transverse malpositions during labour.

Adult↗

Regulation of the endothelin/endothelin receptor system by interleukin-1{beta} in human myometrial cells.

Proinflammatory cytokines produced at the fetomaternal interface, such as IL-1beta, have been implicated in preterm and term labor. The present study was performed to evaluate the influence of IL-1beta on the endothelin (ET)/ET receptor system in human myometrial cells. We report that myometrial cells under basal conditions not only respond to but also secrete ET-1, one of the main regulators of uterine contractions. Prolonged exposure of the cells to IL-1beta led to a decrease in prepro-ET-1 and ET-3 mRNA correlated with a decrease in immunoreactive ET-1 and ET-3 levels in the culture medium. Whereas ETA receptor expression at both protein and mRNA levels was not affected by IL-1beta treatment, we demonstrated an unexpected predominance of the ETB receptor subtype under this inflammatory condition. Whereas the physiological function of ETB remains unclear, we confirmed that only ETA receptors mediate ET-1-induced myometrial cell contractions under basal conditions. By contrast, prolonged exposure of the cells to IL-1beta abolished the contractile effect induced by ET-1. Such a regulation of IL-1beta on the ET release and the balance of ETA to ETB receptors leading to a loss of ET-1-induced myometrial cell contractions suggest that complex regulatory mechanisms take place to constraint the onset of infection-induced premature contractions.

Binding Sites↗

Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated prostaglandin E2 production and matrix metalloproteinase-9 activity in human amniochorionic membranes.

Chorioamniotic infection is a leading cause of preterm premature rupture of fetal membranes (amnion and chorion). Bacterial infection induces an inflammatory response characterized by elevated production of proinflammatory cytokines; the latter activate the production of both PGs that stimulate uterine contractions, and matrix metalloproteinases (MMPs) that degrade the extracellular matrix of the chorioamniotic membranes. The inflammatory response is under the control of cAMP content, which is partly regulated by phosphodiesterases (PDE). In this study, we investigated the role of the PDE4 family in the inflammatory process triggered by LPS in a model of amniochorionic explants. We found that PDE4 family is the major cAMP-PDE expressed in human fetal membranes and that PDE4 activity is increased by LPS treatment. Selective inhibition of PDE4 activity affected LPS signaling, because PDE4 inhibitors (rolipram and/or cilomilast) reduced the release of the proinflammatory cytokine TNF-alpha and increased the release of the anti-inflammatory cytokine IL-10. PDE4 inhibition reduced cyclooxygenase-2 protein expression and PGE(2) production and also modulated MMP-9, a key mediator of the membrane rupture process, by inhibiting pro-MMP-9 mRNA expression and pro-MMP-9 activity. These results demonstrate that the PDE4 family participates in the regulation of the inflammatory response associated with fetal membrane rupture during infection. The PDE4 family may be an appropriate pharmacological target for the management of infection-induced preterm delivery.

3',5'-Cyclic-AMP Phosphodiesterases↗

Detection of interleukin-6 in vaginal secretions of women with preterm premature rupture of membranes and its association with neonatal infection: a rapid immunochromatographic test.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of an interleukin-6 (IL-6) bedside test of vaginal secretions for neonatal infection in cases of preterm premature rupture of membranes. STUDY DESIGN: This prospective clinical study included 73 patients. Interleukin-6 protein in vaginal secretions was determined with an immunochromatographic bedside test in <20 minutes. RESULTS: Elevated C-reactive protein level (>20 mg/dL; odds ratio, 5.1; 95% CI, 0.9-28.6) and positive interleukin-6 level (odds ratio, 4.6; 95% CI, 1.2-18.4) were both associated with neonatal infection. After adjustment, only interleukin-6 remained associated with neonatal infection (odds ratio, 4.5; 95% CI, 1.1-18.5). The sensitivity of interleukin-6 for the prediction of neonatal infection was 79% (95% CI, 65-92); its specificity was 56% (95% CI, 42-70); its positive predictive value was 30% (95% CI, 12-47), and its negative predictive value was 92% (95% CI, 84-99). CONCLUSION: Interleukin-6 protein determination by this new immunochromatographic test is a noninvasive prenatal vaginal marker of neonatal infection.

Adult↗

Preterm torsion of a gravid uterus didelphys horn of a twin pregnancy.

BACKGROUND: Simultaneous pregnancy in each horn of a uterus didelphys is a rare and complex clinical situation. CASE: Torsion of one horn of a gravid didelphic uterus during a twin pregnancy was diagnosed during cesarean delivery after erroneous diagnosis of abruptio placentae. CONCLUSION: Localization of the placenta in a pregnancy complicated by uterine didelphys may improve the ability to diagnose hemiuterus torsion.

Abdominal Pain↗

Conservative treatment of placenta percreta: a safe alternative.

Placenta percreta was diagnosed antenatally in two patients in the same university medical school and conservative treatment was planned. Both uterine arteries were embolized. In one patient, embolization preceded cesarean section and in the other, embolization was done immediately after operation. In each case, the placenta was left in situ and disappeared 5-6 months after delivery.

Adult↗

Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.

OBJECTIVE: This study was undertaken to determine maternal and perinatal outcomes after expectant management of severe preeclampsia between 24 and 33 weeks' gestation. STUDY DESIGN: A prospective observational study of 239 women with severe preeclamptic and undelivered after antenatal steroid prophylaxis was performed. Pregnancy prolongation and maternal and perinatal morbidities were analyzed according to the gestational age at time of expectant management: 24 to 28, 29 to 31, and 32 to 33 weeks. Statistical analysis was performed by Student t test and chi(2) test. RESULTS: The days of pregnancy prolongation were significantly higher among those managed at less than 29 weeks (6) compared with the other groups (4). There were 13 perinatal deaths: 12 in those managed at less than 29 weeks and 1 in those managed at 29 to 31 weeks. Neonatal morbidities were significantly higher among those managed at less than 29 weeks compared with the other groups. There were no instances of maternal death or eclampsia. Maternal morbidities were similar among the groups. CONCLUSION: Expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center is associated with good perinatal outcome with a minimal risk for the mother.

Adult↗

Fetal adaptation to stress. Part I: acceleration of fetal maturation and earlier birth triggered by placental insufficiency in humans.

This review is an attempt to provide an integrative view for the biological changes triggered by fetal stress through a multidisciplinary approach. Acceleration of brain and lung maturation in certain risk pregnancies was first described clinically and confirmed by biochemical, electrophysiological and experimental data. Moreover, new experimental findings suggest that a fetal clock centrally mediated by fetal nutritional status could determine timing of parturition. However, some skepticism persisted about the usefulness of this body of knowledge for obstetrical management in developed countries. The interest concerning this adaptation to intrauterine stress was later renewed from various sources, as developed in Part II.

Adaptation, Physiological↗

Fetal adaptation to stress: Part II. Evolutionary aspects; stress-induced hippocampal damage; long-term effects on behavior; consequences on adult health.

Humans share adaptative capacities to stress with other species, as demonstrated on amphibians: the physiological response to experimental water volume and food deprivation results in the activation of the endocrine axes that drive metamorphosis, in particular the neuroendocrine stress system. Unfavorable effects may, however, occur, probably due to inappropriate timing and/or duration of stress: recent experiments are converging to show a profound impairment of hippocampal functioning in the offspring of mothers exposed to prenatal stress. Moreover, fetal changes are likely one of the risk factors for a number of diseases in adulthood.

Adaptation, Physiological↗

Monoamniotic twin pregnancies: antenatal management and perinatal results of 19 consecutive cases.

OBJECTIVE: To describe the obstetric management and perinatal outcome of antenatally diagnosed monoamniotic twin pregnancies (MATP) in a tertiary level maternity unit. SETTING: Port-Royal Maternity Hospital, Paris, France. POPULATION: MATP that progressed beyond 22 weeks seen from 1993 to 2001. METHODS: A retrospective chart review of all twin pregnancies. Diagnosis of MATP was made by ultrasonography and confirmed by placental pathology. MAIN OUTCOME MEASURE: Perinatal mortality. RESULTS: Among the 1242 twins pregnancies delivered during the study period, 19 were monoamniotic. Four fetuses (10% of all births) had malformations. Perinatal mortality was high (n= 12, 32%) because of fetal deaths (nine cases) and very preterm births (three neonatal deaths). No fetal deaths occurred after 29 weeks. Of the 15 women with at least one live fetus before labour, 6 gave birth by vaginal delivery (40%). No obstetric accidents occurred during vaginal deliveries. CONCLUSION: Perinatal mortality of MATP is still very high, even with accurate, early antenatal diagnosis, intensified surveillance and delivery provided in a tertiary level hospital. The main causes of perinatal deaths are cord accidents in utero, congenital anomalies and very preterm births.

Adult↗

Conservative versus extirpative management in cases of placenta accreta.

OBJECTIVE: To compare the impact of conservative and extirpative strategies for placenta accreta on maternal morbidity and mortality. METHODS: We retrospectively reviewed the medical records of all patients diagnosed with placenta accreta admitted to our tertiary center from January 1993 through December 2002. Two consecutive periods, A and B, were compared. During period A (January 1993 to June 1997), our written protocol called for the systematic manual removal of the placenta, to leave the uterine cavity empty. In period B (July 1997 to December 2002), we changed our policy by leaving the placenta in situ. The following outcomes over the 2 periods were compared: need for blood transfusion, hysterectomy, intensive care admission, duration of stay in intensive care, and postpartum endometritis. RESULTS: Thirty-three cases of placenta accreta were observed among 31,921 deliveries (1.03/1,000). During period B, there was a reduction in the hysterectomy rate (from 11 [84.6%] to 3 [15%]; P <.001), the mean number of red blood cells transfused (3,230 +/- 2,170 mL versus 1,560 +/- 1,646 mL; P <.01), and disseminated intravascular coagulation (5 [38.5%] versus 1 [5.0%]; P =.02), compared with period A. There were 3 cases of sepsis in period B and none in period A (P =.26). At least 2 women with conservative management subsequently had successful pregnancies. CONCLUSION: Leaving the placenta accreta in situ appears to be a safe alternative to removing the placenta.

Adult↗