Maryse Berthiaume

Rapid evaluation of the absence of inflammation after rupture of membranes

Abstract Objectives: The aim of this study was to validate the results of an immunochromatographic bedside test to detect IL6 and IL8 in vaginal secretions after rupture of membranes (ROM) with results obtained by ELISA tests. Methods: A prospective cohort of 60 women with ROM or preterm ROM (PROM) was recruited. An immunochromatographic bedside test was performed with vaginal secretions samplings at admission, every 48 hrs until labor and during labor. Remaining samples were frozen for ELISA analysis. The results of bedside tests were compared to those from ELISA analysis for 114 samples. Results: With all samples combined, the positive predictive values were 50% for IL6 and 86.8% for IL8 and the negative predictive values were 97.4% for IL6 and 53.3% for IL8. Kappa coefficients were 0.54 for IL6 and 0.41 for IL8. Conclusion: Our findings show that a bedside test can detect the absence of IL6 in vaginal secretions. This result suggests that bedside test could be used for expectant management after premature PROM to inform the attending physician of the absence of inflammation in vaginal secretions.

Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium

OBJECTIVE The aim of this study was to assess the involvement of lipoxygenase (LOX) metabolic pathways in uterine tissues from pregnant women as well as the combined inhibition of LOX and cyclooxygenase (COX) on contractile activity. STUDY DESIGN Uterine biopsies were performed from consenting women undergoing elective caesarean sections at term (n = 24). Western blot analysis and isometric tension measurements were performed in vitro on fresh human myometrial strips. Concentration-response curves to arachidonic acid (AA) 861 and baicalein (5- and 12-LOX inhibitors, respectively) were performed. The combined effects of baicalein and indomethacin were also assessed. Contractile activities were quantified by calculating both amplitude and the area under the curve over 20 minute periods. RESULTS 5- and 12-LOX were present in all tested tissues. Addition of AA861 or baicalein resulted in tocolytic effects (P < .05). Finally, the combined inhibition of both COX and 12-LOX pathways resulted in additive tocolytic effects. CONCLUSION 5- and 12-LOX pathways modulate human myometrium contractility.

Short and inflamed cervix predicts spontaneous preterm birth (COLIBRI study).

Abstract Objective: To develop a new strategy of predicting spontaneous preterm birth (sPTB) by combination of transvaginal ultrasound (TVUS) assessment and inflammatory proteins detection in vaginal secretions. Methods: Prospective study of 87 women referred for cervical length assessment with a standardized TVUS combined to vaginal secretions sampling. Samples were analyzed for presence of 10 cytokines. Main outcome was sPTB (<37 weeks of gestation). Associations were assessed with the chi-square, Fisher’s exact test (p < 0.05) and Wald’s logistic regression. Results: sPTB occurred in 25.3% of women at a median gestational age of 35.6 weeks of gestation. Short cervix (<25 mm) (n = 24) was associated with sPTB (p < 0.01) as interleukine (IL)-1β, IL-8 and IL-10 in vaginal secretions (p < 0.05). In multivariate analysis, short cervix and IL-8 in vaginal secretions were independently associated with sPTB (OR 3.58 (95%CI 1.02; 12.61) and 14.55 (95%CI 1.64; 128.83), respectively) as their combination (OR 4.33 (95%CI 1.25; 14.95)). By categorizing cervical length by presence of IL-8, sPTB occurred in 55.6% of women with a short inflamed cervix. Conclusion: COLIBRI study used a novel, single-step method of vaginal secretions sampling during TVUS and demonstrated that combination of short cervix and IL-8 in vaginal secretions is a promising sPTB predictive test.

Why eicosanoids could represent a new class of tocolytics on uterine activity in pregnant women

OBJECTIVE The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity. STUDY DESIGN Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation of the area under the curve. The effects of eicosanoids and specific enzyme inhibitors were assessed. Fractions from various uterine tissues were analyzed by Western blot. RESULTS Data demonstrate the presence, in some tested tissues, of cytochrome P-450 epoxygenase and soluble epoxide hydrolase, which respectively produce and degrade epoxyeicosatrienoic acid regioisomers. Inhibition of soluble epoxide hydrolase with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid or omega-hydroxylase with N-methylsulfonyl-12,12-dibromododec-11-enamide resulted in a tocolytic effect; N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide, which is an epoxygenase inhibitor, had no effect. Exogenous epoxyeicosatrienoic acids displayed significant tocolytic effects on spontaneous contractile activities. CONCLUSION Epoxy- and hydroxyeicosanoids represent new bioactive, arachidonic acid by-products with in vitro tocolytic activities. These findings suggest that cytochrome P-450 isozymes may represent relevant pharmacologic targets under physiopathologic conditions.

Time-dependent effect of in utero inflammation: a longitudinal study in rats.

Abstract Objective: To determine the impact of the duration of fetal exposure to inflammation on the neurological outcome of pups. Method: Time-pregnant Sprague–Dawley rats (n = 32) received intraperitoneal injection of lipopolysaccharides (LPS; 500 µg/kg), or an equivalent volume of vehicle 3, 6, 12 and 24 h before C-section. Maternal serum and amniotic fluid were tested for cytokines. Motor activity of resuscitated pups (n = 58) was analyzed using the open-field test (20 d). Brains were collected for histopathological examination. Results: Perinatal mortality increased with the duration of fetal exposure to LPS. All parameters tested with the open-field test were lower in the LPS 12 h exposure group compared to the control group (p < 0.05). Tissue inhibitor of metalloproteinase 1 (TIMP-1) was statistically increased in maternal blood after 3, 6 and 12 h of LPS injection (p < 0.05 versus control). Conclusion: A threshold of duration of exposure to inflammation is demonstrated, before which delivery should be performed in order to prevent brain damage.

Effect of cytochrome P-450 epoxygenase and hydroxylase metabolites on rat myometrium contractility in non-pregnancy, late pregnancy and late pregnancy under inflammatory conditions

The aim of the present experimental study was to assess the tocolytic effect of eicosanoids on myometrium from non‐pregnant and pregnant rats with or without an induced inflammatory condition.

Effect of interleukin‐6 receptor blockade on feto‐maternal outcomes in a rat model of intrauterine inflammation

To study the effect of blocking the inflammatory cascade with interleukin‐6 receptor antibody (anti‐IL‐6R) on feto‐maternal outcomes in a rat model.

Le « vide spirituel paradoxal » en salle de naissance hypothèse de travail et enjeux méthodologiques

Cet article explore ce que nous entendons par « vide spirituel paradoxal » en salle de naissance québécoise : s’il semble évident que la naissance est une expérience humaine intense qui a été longtemps entourée par une dimension spirituelle, cette dernière demeure largement inexplorée en contexte contemporain. Nous préciserons d’abord notre hypothèse de travail : 1) en définissant son aspect paradoxal émergeant du contexte médical actuel ; 2) en cherchant à mieux saisir le terme spirituel pour qu’il reflète la présente originalité du contexte religieux et spirituel ; et 3) en illustrant le vide par le silence de la littérature à ce propos. Nous toucherons ensuite à l’aspect terrain des recherches entreprises par le groupe interdisciplinaire SPIritualité et Naissance (groupe SPIN) sur la spiritualité des parents lors de la naissance de leur enfant, ayant mené à ce jour à : 1) une rencontre multidisciplinaire d’experts (médecine, théologie, parents) analysée avec deux grilles (Galek et al., 2005 ; Hall, 2001) ; et 2) une première catégorisation des types d’expériences spirituelles pouvant être vécues par les parents lors de la naissance. Nous conclurons par un cahier de charges qui devraient réduire les résistances rencontrées par le milieu médical au sujet du projet SPIN et sur les suites du projet. This article explores what we have called the “paradoxical spiritual void” in the delivery rooms of Quebec. If it seems evident that birth is an intense human experience that has had a spiritual dimension for a very long time, this dimension remains largely unexplored in the contemporary context. First, we set out our working hypothesis: 1) by defining its paradoxical aspect emerging from the actual medical context; 2) by trying to get a better grasp of the term spiritual so as to make it reflect the originality of the actual religious and spiritual context; and 3) by illustrating the void by way of the silence of literature on the topic. Then, we enlarge on the practical aspects of the research conducted by the multidisciplinary group SPIrituality and Birth (in French: SPIN) on the spirituality of parents during the birth of their child, which has so far led to: 1) a multidisciplinary meeting of experts (medical, theological, parental) using two analytical frameworks (Galek et al., 2005; Hall, 2001); and 2) a first categorization of types of spiritual experience that can be lived by parents during birth. We conclude by specifying measures that should reduce the resistance met by the medical world concerning the SPIN project and its future developments.

Inhibition of epoxy-eicosanoid degradation improves the tocolytic effects of indomethacin in the uterus from pregnant women

The incidence of preterm birth is an increasing problem. Indomethacin, a non-specific cyclooxygenase inhibitor, has been largely used as tocolytic in the treatment of preterm labor. The aim of the present study was to assess a putative synergistic tocolytic effect between the inhibition of the production of prostanoids and stabilization of epoxides fatty acids, particularly arachidonate on spontaneous uterine contractile activity. The experimental work was performed on uterine biopsies from consenting women undergoing elective cesarean delivery at term. Isometric tension measurements were performed on fresh human myometrial strips. Contractile activities have been monitored upon individual and combined treatments of indomethacin, DDMS, an inhibitor of hydroxy-eicosanoids production and AUDA, an inhibitor of epoxy-eicosanoids degradation. Interestingly, a significant and consistent synergic effect was observed when indomethacin and AUDA were simultaneously added, raising the possibility of a combined clinical use of cyclooxygenase and sEH inhibitors in attempt to treat preterm labor.