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Biomedical subjects

Marc Boucher

Publications and source records attributed to Marc Boucher.

11 recordsLinked to original sources

Study of a novel hypervariable region in hepatitis C virus (HCV) E2 envelope glycoprotein.

A large share of hepatitis C virus amino acid sequence variation is concentrated within two hypervariable regions located at the N-terminus of the E2 envelope glycoprotein (HVR1 and HVR2). Interhost and intrahost comparison of 391 E2 sequences derived from 17 subjects infected with HCV using amino acid entropy revealed clustering of amino acid variability at a third site (residues 431-466), which was termed HVR3. Genetic distance analysis supported the division of HVR3 into three subdomains (HVR3a, HVR3b, and HVR3c). Study of synonymous and nonsynonymous nucleic acid substitutions confirmed that HVR3a was subjected to strong intrahost-selective pressure. Physicochemical and antigenicity predictions, conservation of key residues, and molecular modeling were concordant with one another and further validated the proposed organization of HVR3. Taken together, these results are suggestive of a role for HVR3 in cell surface receptor binding and viral entry akin to that proposed for HVR1 and HVR2.

Base Sequence↗

Characterization of humoral and cell-mediated immune responses directed against hepatitis C virus F protein in subjects co-infected with hepatitis C virus and HIV-1.

BACKGROUND: Hepatitis C virus (HCV) F protein is encoded in an alternate reading frame overlapping the core protein region. Its precise sequence, biological function and mode of expression are currently unclear. This study was conducted to examine the prevalence and characteristics of host humoral and cell-mediated immune responses directed against F protein in patients co-infected with HCV and HIV-1. METHODS: Mutations were introduced to allow the expression of HCV-1a F protein in the absence of core. This recombinant and a truncated form lacking the first 11 amino acid residues shared with core were expressed in Escherichia coli, and their amino acid sequences were verified by mass spectrometry. Vaccinia-F protein recombinants were used to test F protein-specific cytotoxic T lymphocyte (CTL) activity. The binding of F protein-derived peptides to HLA-A*0201 was studied to identify putative CTL epitopes. RESULTS: Sera from 23 of 39 patients infected with various HCV genotypes recognized the truncated form, including 13 of 25 subjects co-infected with HIV-1, indicative of antigenic crossreactivity and consistent with the conservation of F protein coding sequences between HCV genotypes. Crossreactive F protein-specific CTL precursors were detected in nine of 11 HCV-infected subjects, including seven of nine patients co-infected with HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes were identified. CONCLUSION: These results indicate that patients co-infected with HCV and HIV-1 can mount immunoglobulin and CTL responses directed against HCV F protein that are fully comparable in scope and magnitude with those observed in individuals infected with HCV alone.

Adult↗

HIV-1 genetic diversity in antenatal cohort, Canada.

We studied HIV genetic diversity in a cohort of 127 pregnant, HIV-infected women who received prenatal care at Sainte-Justine Hospital in Montreal, Canada, between 1999 and 2003. Clade assignments were derived by phylogenetic analysis of amplified pol sequences. Genotyping was successful in 103 of 127 women, 59 (57.3%) of whom were infected with clade B HIV-1, and 44 (42.7%) with nonclade B viruses, including subtypes A, C, D, F, G, and H. Four sequences remained unassigned. Forty-three of 44 women infected with non-clade B viruses were newcomers from sub-Saharan Africa, and subtype identity was consistent with those circulating in their countries of origin. These results highlight the epidemiologic importance of non-B HIV-1 in antenatal populations in a large North American urban center, underscore the influence of population movements on clade intermixing, and identify a group of patients who could be targeted for surveillance and drug therapy followup.

Adult↗

Cesarean delivery after successful external cephalic version of breech presentation at term: a comparative study.

OBJECTIVE: The purpose of this study was to evaluate the rate and indications of cesarean delivery after a successful external cephalic version. STUDY DESIGN: A case-control study was performed from patients who were delivered in a tertiary care center between 1987 and 2000. Each patient who underwent a successful external cephalic version (study group) was compared with the next woman with the same parity, who was delivered at term (control group). Nulliparous and multiparous women were analyzed separately. Chi-squared, Mann-Whitney, and Student t tests were used for statistical analysis. Multivariate logistic regression analysis was performed where appropriate. RESULTS: A total of 602 patients were included in this study. The rates of cesarean delivery in nulliparous women (29.8% vs 15.9%; P<.001) and in multiparous women (15.9% vs 4.7%; P<.001) were significantly higher when compared with the control group. Patients with successful external cephalic version were more likely to have a cesarean delivery for dystocia (nulliparous, 22.5% vs 11.9%; P=.01; multiparous, 10.9% vs 1.3%; P<.01). After an adjustment for confounding variables, a successful external cephalic version was associated with an increased rate of cesarean delivery at term (nulliparous: odds ratio, 2.04; 95% CI, 1.13-3.68; multiparous: odds ratio, 4.30; 95% CI, 1.76-10.54). CONCLUSION: The rate of cesarean delivery for dystocia is increased after a successful trial of external cephalic version in both nulliparous and multiparous women.

Adult↗

Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double-blind randomized trial.

OBJECTIVES: To compare the efficacy of a single 100 micro g intramuscular (IM) carbetocin injection, a long-acting oxytocin agonist, to a 2-hour 10 IU oxytocin intravenous (IV) infusion, in reducing the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition. METHODS: A randomized, double-blind, placebo-controlled study was conducted at 2 hospital centres, including 160 women with at least 1 risk factor for PPH. Eighty-three women received 100 microg carbetocin IM and an IV placebo immediately after placental delivery, while 77 women received placebo IM and oxytocin IV infusion. Complete blood count was collected at entry and 24 hours postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, blood loss, and drop in hemoglobin and hematocrit, were analyzed using chi-square, Fisher exact, and Student t tests. RESULTS: Population profile and risk factors for PPH were similar for each group. No significant difference was observed in the number of women requiring additional uterotonic medication (12 in each group). However, in the carbetocin group, 36 of the 83 women (43.4%) required at least 1 uterine massage compared to 48 of the 77 women (62.3%) in the oxytocin group (P <.02). Overall, uterotonic intervention was clinically indicated in 37 of the women (44.6%) receiving carbetocin compared to 49 of the women (63.6%) given an IV oxytocin infusion (P <.02). There were no differences in laboratory PPH indicators between the 2 groups.

Delivery, Obstetric↗

Sublingual nitroglycerin versus intravenous ritodrine as tocolytic for external cephalic version: a double-blinded randomized trial.

OBJECTIVE: The purpose of this study was to compare the efficacy of sublingual nitroglycerin with that of intravenous ritodrine as a tocolytic agent for external cephalic version in nulliparous women. STUDY DESIGN: We performed a double-blinded, randomized trial. Nulliparous patients, between 36 and 40 weeks of gestation, were assigned randomly to receive either (1) an intravenous infusion of ritodrine (111 microg/min) for 20 minutes, followed by two puffs of sublingual placebo or (2) an intravenous infusion of sodium chloride 0.9% (placebo) for 20 minutes, followed by two puffs of sublingual 0.4 mg of nitroglycerin. Three minutes after the administration of the sublingual spray, an external cephalic version was attempted. The rate of successful external cephalic version and side effects was compared between groups. RESULTS: Of 74 randomly assigned patients, 38 patients received intravenous ritodrine, and 36 patients received sublingual nitroglycerin. Although not statistically significant, the rate of the successful external cephalic version was higher in the ritodrine group compared with the nitroglycerin group (45% vs 25%, P =.075). The rate of headaches was higher in patients who received nitroglycerin (28% vs 8%, P =.02). Mean blood pressure and maternal heart rate were lower in the nitroglycerin group 10 minutes after the administration of the medication. However, there was no significant difference in the rate of palpitations, hypotension, or fetal bradycardia between the two groups. CONCLUSION: When compared with intravenous ritodrine, sublingual nitroglycerin was associated with a higher rate of headache, lower blood pressure, and a trend toward a lower rate of successful external cephalic version.

Administration, Sublingual↗

The relationship between amniotic fluid index and successful external cephalic version: a 14-year experience.

OBJECTIVE: This study was undertaken to assess the association between amniotic fluid index (AFI), success of external cephalic version (ECV), and obstetric outcome in patients undergoing ECV. STUDY DESIGN: A prospective observational study was performed that included all patients who had a trial of ECV from 1987 to 2000 in our center. Rates of success, fetal heart decelerations during trial at ECV, and cesarean deliveries were calculated. Groups were divided by an AFI performed immediately before ECV: AFI less than 10 cm, 10 to 15 cm, and more than 15 cm. RESULTS: In our group of 1361 patients undergoing ECV, the rate of success was related to the AFI in both parous women (49.1%, 63.5% and 72.1% [P<.001] for each AFI group, respectively) and nulliparous women (36.5%, 43.6%, and 57.3% [P<.001]). The rate of cesarean section delivery was related to AFI in nulliparous but not multiparous patients (P<.001). The rate of prolonged fetal heart rate decelerations was not significantly related to the AFI. CONCLUSION: The rate of successful ECV and cesarean section deliveries is related to the amniotic fluid volume. This information may be used to consent patient before a trial of ECV.

Amniotic Fluid↗

Sublingual nitroglycerin versus placebo as a tocolytic for external cephalic version: a randomized controlled trial in parous women.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual nitroglycerin as a tocolytic agent for external cephalic version in parous women. STUDY DESIGN: A double-blinded randomized controlled trial was performed. Patients with parity of >or=1 at 36 to 40 weeks of gestation who were eligible for external cephalic version were included. Patients were randomized to receive either two sublingual sprays of 400 mug of nitroglycerin or two sprays of placebo 3 minutes before the trial of external cephalic version. Rates of successful external cephalic version and side effects were compared between groups. RESULTS: Of 99 patients in the study, 50 patients received sublingual nitroglycerin, and 49 patients received placebo. There were no differences in maternal age, gestational age, estimated fetal weight, amniotic fluid index, and placental location between the two groups. The success rate of external cephalic version was 48% in the nitroglycerin group compared with 63% in the placebo group (P=.13). There was a higher incidence of headaches in the nitroglycerin group (42% vs 4%, P<.001). CONCLUSION: Sublingual nitroglycerin was associated with a higher rate of headache and did not improve the rate of successful external cephalic version.

Administration, Sublingual↗

Serum concentrations, efficacy, and safety of a new, intravenously administered varicella zoster immune globulin in pregnant women.

Chickenpox is teratogenic in humans, and varicella zoster immune globulin (VZIG) is given to pregnant women believed to be susceptible to the virus after contact with chickenpox. Available VZIG is given as intramuscular injections. The objective of this study was to evaluate the efficacy, safety, and serum concentrations of a new VZIG that can be given intravenously. The new VZIG (Cangene Pharm., Inc.) was compared to the standard VZIG (Massachusetts Public Health Biologic Laboratories) in a randomized protocol in 57 pregnant women seronegative to varicella zoster virus (VZV). Pregnant women received 125 units per 10 kg body weight to a maximal dose of 625 units. Women were evaluated on days 2, 7, 14, and 28 and at other times if symptoms developed into clinical varicella, which was scored by the Constitutional Illness Score. The new VZIG was comparable to the standard VZIG on all parameters of efficacy and safety. Levels of VZV antibodies at day 2 postinjection were significantly higher among those receiving the new preparation intravenously. The authors concluded that the new intravenous form of VZIG confers higher initial levels of VZV antibodies and is comparable in terms of its maternal efficacy and safety to the standard form of VZIG.

Adult↗