Non-random, individual-specific methylation profiles are present at the sixth CTCF binding site in the human H19/IGF2 imprinting control region.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Bruno Carbonne.
Explore the source record for details and available documents.
We report a case of isolated voluminous fetal ascites discovered during a routine fetal ultrasound at 22 weeks' gestation. Analysis of the fluid showed it to be chyliform and ruled out other causes of fetal ascites. Regular bimonthly ultrasound scans monitored its progressive diminution and then its disappearance. Examination showed the child to be normal at birth. Though the literature indicates that prognosis is usually favorable for infants with isolated fetal chylous ascites, spontaneous regression during pregnancy is an uncommon finding.
Preeclampsia is the major pregnancy-induced hypertensive disorder. It modifies the expression profile of placental genes, including several serine protease inhibitors (SERPINs). The objective of this study was to perform a systematic expression analysis of these genes in normal and pathological placentas and to pinpoint epigenetic alterations inside their promoter regions. Expression of 18 placental SERPINs was analyzed by quantitative RT-PCR on placentas from pregnancies complicated by preeclampsia, intrauterine growth restriction, or both and was compared with normal controls. SERPINA3, A5, A8, B2, B5, and B7 presented significant differences in expression in >or=1 pathological situation. In parallel, the methylation status of the CpG islands located in their promoter regions was studied on a sample of control and preeclamptic placentas. Ten SERPIN promoters were either totally methylated or totally unmethylated, whereas SERPINA3, A5, and A8 presented complex methylation profiles. For SERPINA3, the analysis was extended to 81 samples and performed by pyrosequencing. For the SERPINA3 CpG island, the average methylation level was significantly diminished in preeclampsia and growth restriction. The hypomethylated CpGs were situated at putative binding sites for developmental and stress response (hypoxia and inflammation) factors. Our results provide one of the first observations of a specific epigenetic alteration in human placental diseases and provide new potential markers for an early diagnosis.
Expression of imprinted genes is classically associated with differential methylation of specific CpG-rich DNA regions (DMRs). The H19/IGF2 locus is considered a paradigm for epigenetic regulation. In mice, as in humans, the essential H19 DMR--target of the CTCF insulator--is located between the two genes. Here, we performed a pyrosequencing-based quantitative analysis of its CpG methylation in normal human tissues. The quantitative analysis of the methylation level in the H19 DMR revealed three unexpected discrete, individual-specific methylation states. This epigenetic polymorphism was confined to the sixth CTCF binding site while a unique median-methylated profile was found at the third CTCF binding site as well as in the H19 promoter. Monoallelic expression of H19 and IGF2 was maintained independently of the methylation status at the sixth CTCF binding site and the IGF2 DMR2 displayed a median-methylated profile in all individuals and tissues analyzed. Interestingly, the methylation profile was genetically transmitted. Transgenerational inheritance of the H19 methylation profile was compatible with a simple model involving one gene with three alleles. The existence of three individual-specific epigenotypes in the H19 DMR in a non-pathological situation means it is important to reconsider the diagnostic value and functional importance of the sixth CTCF binding site.
Explore the source record for details and available documents.
BACKGROUND: Various surgical procedures are currently performed for the treatment of posthysterectomy vesicovaginal fistula. Most of them are carried out via an abdominal incision. OBJECTIVE: Report of our experience with Latzko's operation, a simple purely transvaginal procedure. METHODS: Retrospective study of vesicovaginal fistulas treated by a Latzko procedure between June 1991 and June 2005. RESULTS: Eleven patients were operated on. Two (18%) had a prior failed attempt of vesicovaginal fistula repair. Mean size of the fistulas was 12+/-11 mm (range: 2-40 mm). Mean operative duration was 62+/-33 min (range: 20-110 min). All fistulas healed. No intraoperative complications were observed. There was only one postoperative complication, a lower urinary tract infection in one patient. Mean hospital stay was 6+/-4 days (range: 2-12 days). CONCLUSIONS: The Latzko procedure is an efficient, safe, and simple technique for the management of vault vesicovaginal fistulas, and can therefore be proposed as the first-line surgical treatment.
BACKGROUND: As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes. RESULTS: Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of Intra-Uterine Growth Retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. CONCLUSION: We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5 x 10(-5)), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals.
In this paper, we applied a new theoretical model of uterine contraction to a large panel of human pregnant and nonpregnant myometrial strips, treated or not by corticotrophin-releasing hormone (CRH). This model is based on a fine analysis of the contraction curves. This analysis yielded four mathematical parameters (beta, theta, tau 1, and tau 2) related to excitability, duration of plateau phase, and time constants for relaxation describing, respectively, the different portions of the contraction cycle. This leads to specific differences in spontaneous contractile activity between pregnant and nonpregnant states. The relaxing effect of CRH in the pregnant state is presumably correlated with the origin of the strips (the lower uterine segment). Besides our observation of a specific receptor-dependent relaxing effect of CRH in both pregnant and nonpregnant myometrium, we could identify highly significant effects at given CRH concentration for beta in nonpregnant myometrium and for theta, tau 1, and tau 2 in pregnant myometrium. In addition, highly significant differences were found between pregnant and nonpregnant myometrium. Also, we discovered a strong correlation between theta and tau 1, specifically in the pregnant state. Although the biochemical signification of these results remains to be elucidated, they contribute to emphasize the complex network of CRH action at the myometrial level. Furthermore, our approach could pave the way toward a better analysis of the efficacy of the uterine contractile behavior.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Preterm labour is a frequent cause of admission to hospital during pregnancy. However, in most cases, preterm labour is diagnosed with reference to clinical criteria only. Since the clinical assessment of uterine contractions and of cervical changes is highly subjective, few of the patients admitted to the hospital with suspected preterm labour will ultimately deliver preterm. There is a need for sensitive methods of detecting patients who are genuinely at high risk of preterm birth, but on the other hand, specific methods of reducing unnecessary treatments or hospital admissions are also required. Recently, a few techniques such as ultrasonographic measurement of cervical length and fetal fibronectin have been introduced into clinical practice with the aim of improving prediction of the risk of actual preterm delivery. In the future, the assessment of cervical status may be based not only on anatomical changes, but also on functional criteria. New techniques are being developed for evaluation of the mechanical properties of the cervix (cervical distensibility), noninvasive measurement of its collagen content (light-induced fluorescence of cervical collagen), or even direct assessment of the changes in cervical water content (magnetic resonance imaging). Correlations have been found between these measurements and the risk of preterm birth, but clinical studies are still needed to allow better assessment of the predictive value of these new methods in clinical practice.
Explore the source record for details and available documents.
Tocolytic agents are drugs designed to inhibit contractions of myometrial smooth muscle cells. Such an effect has been demonstrated in vitro or in vivo for several pharmacological agents, including beta-adrenergic agonists, calcium channel antagonists, oxytocin antagonists, NSAIDs and magnesium sulfate. However, the aim of tocolysis is not only to stop uterine contractions or to prevent preterm delivery, but to prevent perinatal morbidity and mortality associated with preterm birth. The achievement of this goal has not yet been clearly demonstrated for any of the drugs available, and the use of tocolytic agents may appear controversial. Therefore, it is important to avoid maternal and fetal toxicity when tocolytic agents are used. During pregnancy, all steps of drug pharmacokinetics are altered. Absorption of drugs administered orally is limited because of delayed stomach emptying and reduced intestinal motility. The volume of distribution of drugs is increased. The metabolic activity of the liver is increased, accelerating the metabolism of lipophilic drugs. Renal filtration is increased, leading to enhanced renal elimination of water-soluble drugs. These modifications are generally responsible for reduced plasma concentration and reduced half-life of most drugs. These specific modifications have to be taken into account when using a drug in pregnant women. The aim of this review is to provide the reader with pharmacological data about drugs currently used to treat preterm labour. Such data in pregnant women may affect the choice of optimal drug dosage and route of administration.
Oxytocin antagonists are synthetic analogues that have the nonapeptide structure of oxytocin. They act by competing with oxytocin for receptors in the myometrium. Animal experiments and pilot clinical studies have examined several agents and, of these, atosiban has been the object of extensive clinical trials. In a large placebo-controlled trial with >500 patients, atosiban reduced the number of premature deliveries over 7 days compared with placebo with no more adverse effects than placebo. In large multicentre studies comparing atosiban with beta-adrenoceptor agonists, the efficacy of the two medications was similar for pregnancy prolongation for 48 hours and for 7 days. The adverse effects, particularly cardiovascular, were considerably more frequent in the patients receiving beta-adrenoceptor agonists, who had to stop treatment significantly more often than the atosiban recipients. No fetal adverse effects were seen with atosiban and, in particular, no effect on baseline fetal heart rate, unlike with the beta-adrenoceptor agonists. Neonatal outcome did not differ significantly according to the treatment. The usefulness of maintenance treatment after the initial 48 hours has not been confirmed. Thus, the effectiveness of oxytocin antagonists appears to be similar to beta-adrenoceptor agonists and the former are not accompanied by measurable adverse effects. Oxytocin antagonists were designed specifically as tocolytics and have been validated by the European Drug Agency. They may be the treatment of choice for preterm labour, particularly in patients at risk of cardiovascular complications (e.g. multiple pregnancy, heart disease, etc.).
OBJECTIVE: To compare the predictive value of intrapartum fetal pulse oximetry to that of fetal scalp blood pH for an abnormal neonatal outcome in the case of thick meconium. STUDY DESIGN: A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was monitored using a Nellcor N-400 fetal pulse oximeter in case of abnormal FHR. The last readings of fetal oxygen saturation and fetal scalp blood pH before birth were used to assess the ability of both techniques to predict an abnormal neonatal status. RESULTS: At a 30% cutoff, the negative predictive value of fetal oxygen saturation was not altered in case of meconium when compared to clear amniotic fluid (79 and 83%, respectively). Fetal scalp blood pH at a 7.20 threshold had a poor negative predictive value in case of meconium when compared to clear amniotic fluid (56% versus 88%, respectively). The receiver operator characteristic curve showed similar performance of fetal scalp blood pH and pulse oximetry in cases with clear amniotic fluid. In cases with meconium, the performance of fetal scalp blood pH was poor, whereas that of pulse oximetry remained unchanged. In three cases with meconium below the vocal cords, a drop in fetal oxygen saturation was observed during labor whereas fetal scalp blood pH remained within normal values. CONCLUSION: The predictive value of fetal scalp blood pH is poor in case of meconium, whereas the predictive value of pulse oximetry seems to be unchanged in this situation.
OBJECTIVE: To assess the effects on maternal, fetal and neonatal outcomes of nifedipine (and other calcium channel blockers) administered as a tocolytic agent to women in preterm labour. METHODS: Standard methods of the Cochrane Collaboration and its Pregnancy and Childbirth Review Group were used. All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in preterm labour between 20 and 36 weeks' gestation, were considered. MAIN RESULTS: The systematic review includes 12 randomised controlled trials with a total of 1029 participating women. No trials were identified in which calcium channel blockers were compared with a placebo or no alternative tocolytic treatment. Calcium channel blockers appear to be more effective than betamimetic agents in prolonging pregnancy for 7 days or longer, are much less likely to cause maternal side-effects and are associated with reduced neonatal morbidity. CONCLUSION: Calcium channel blockers (especially nifedipine) can be considered safer and more effective tocolytic agents than betamimetics.