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Biomedical subjects

M Fortier

Publications and source records attributed to M Fortier.

At least 19 recordsLinked to original sources

Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

AIMS/HYPOTHESIS: The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. MATERIALS AND METHODS: NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. RESULTS: Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. CONCLUSIONS/INTERPRETATION: The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

Animals↗

Modulation of juvenile brook trout (Salvelinus fontinalis) cellular immune system after Aeromonas salmonicida challenge.

In fish, the first line of defence against infectious microorganisms is based on non-specific cellular immune mechanisms (innate immunity). In this study, we measured the non-specific immune parameters (natural cytotoxic cells (NCC) activity, lymphoproliferation, percentage of phagocytosis and phagocytic activity) in brook trout (Salvelinus fontinalis) infected by a virulent strain of Aeromonas salmonicida. Eight days post-infection, the mortality of infected fish reached 70%. A transient immunostimulation of the NCC activity was noticed 24h post-infection, but there was no significant difference at 48 h. Then, infection of brook trout with A. salmonicida induced a biphasic immune response. At 24h post-infection, lymphoproliferation was drastically depressed but returned to control level at 96 h. A slight increase in the percentage of phagocytosis and the phagocytic activity was noticed throughout the experiment. Conversely the cell mortality was significantly higher in infected fish compared to control. The modulation of immunological parameters might reveal important clues on how innate immunity might protect fish from bacterial infections.

Aeromonas salmonicida↗

Differential effects of ionic strength, divalent cations and pH on the pore-forming activity of Bacillus thuringiensis insecticidal toxins.

The combined effects of ionic strength, divalent cations, pH and toxin concentration on the pore-forming activity of Cry1Ac and Cry1Ca were studied using membrane potential measurements in isolated midguts of Manduca sexta and a brush border membrane vesicle osmotic swelling assay. The effects of ionic strength and divalent cations were more pronounced at pH 10.5 than at pH 7.5. At the higher pH, lowering ionic strength in isolated midguts enhanced Cry1Ac activity but decreased considerably that of Cry1Ca. In vesicles, Cry1Ac had a stronger pore-forming ability than Cry1Ca at a relatively low ionic strength. Increasing ionic strength, however, decreased the rate of pore formation of Cry1Ac relative to that of Cry1Ca. The activity of Cry1Ca, which was small at the higher pH, was greatly increased by adding calcium or by increasing ionic strength. EDTA inhibited Cry1Ac activity at pH 10.5, but not at pH 7.5, indicating that trace amounts of divalent cations are necessary for Cry1Ac activity at the higher pH. These results, which clearly demonstrate a strong effect of ionic strength, divalent cations and pH on the pore-forming activity of Cry1Ac and Cry1Ca, stress the importance of electrostatic interactions in the mechanism of pore formation by B. thuringiensis toxins.

Animals↗

Imiquimod 5% cream in the treatment of anogenital warts in female patients.

OBJECTIVE: To investigate the efficacy and safety of imiquimod 5% cream in the treatment of anogenital warts in a female population. METHODS: In two open-label studies, female patients with anogenital warts applied imiquimod 5% cream three times a week for up to 16 weeks. Patients who cleared their warts were monitored for a 6-month follow-up period. Patients could be re-treated with imiquimod 5% cream for up to an additional 16 weeks if their warts recurred or new warts developed during the follow-up period. The treatment period could also be extended for up to an additional 16 weeks if patients only experienced partial clearance during the initial 16-week treatment period. RESULTS: Of the female patients who applied imiquimod 5% cream, 75% (449/600) experienced complete clearance of their warts (treatment failure analysis). This includes 46 patients who experienced total clearance when they applied imiquimod for longer than 16 weeks as their warts had only partially cleared in the initial 16 weeks of therapy. During the 6 months of follow-up after the initial treatment period, 15% of patients had recurrent warts. Thirty-nine (75%) of those patients experienced total clearance again after they re-applied imiquimod for up to an additional 16 weeks. The most frequently observed local skin reaction was erythema. CONCLUSION: In these studies, imiquimod 5% cream was an effective and well-tolerated treatment for anogenital warts in females and continued to be safe and effective in the small proportion of patients who needed to re-apply imiquimod after wart recurrence.

Adult↗

Risks of induction of labour in uncomplicated term pregnancies.

Our objective was to evaluate the risks of maternal and perinatal morbidity associated with induction of labour in uncomplicated term pregnancies. We conducted a retrospective cohort study including 7,430 women, not referred from another institution, with a single baby in vertex presentation, and delivering between 38 and 40 weeks of pregnancy. Among these women, 3,546 were excluded for prelabour pregnancy complications. Relative risks (RR), adjusted for parity, were computed to compare 3,353 women who went into labour spontaneously with 531 women whose labour was induced. Induction of labour was found to be associated with a higher risk of caesarean section [RR = 2.4, 95% CI 1.8, 3.4]. Use of non-epidural [RR = 1.5, 95% CI 1.2, 1.8] and of epidural analgesia [RR = 1.4, 95% CI 1.1, 1.7] was more frequent after labour induction. Resuscitation [RR = 1.2, 95% CI 1.0, 1.5], admission to the intensive care unit [RR = 1.6, 95% CI 1.0, 2.4] and phototherapy [RR = 1.3, 95% CI 1.0, 1.6] were more frequent after induction of labour. Results were similar when controlling simultaneously for parity, maternal age, gestational age, year of delivery, birthweight and the physician in charge of delivery in a logistic regression analysis. The results of this study suggests that induction of labour is associated with a higher risk of caesarean section and of some perinatal adverse outcomes. Induction of labour should be reserved for cases where maternal and perinatal benefits outweigh the risk of these complications.

Adult↗

Evaluation of a modified sanitary napkin as a sample self-collection device for the detection of genital chlamydial infection in women.

A modified sanitary napkin was compared with endocervical swab and urine specimens for the detection of urogenital Chlamydia trachomatis infection. Endocervical swabs and/or first-catch urine were collected from 510 women at medical or community settings in Quebec City. Participants were also asked to wear a modified sanitary napkin (Ezy-Detek) during 4 consecutive hours and to bring it back to the clinic or mail it to the laboratory. Endocervical and urine specimens were tested using the Cobas Amplicor CT/NG assay (Roche Diagnostic Systems) according to the manufacturer's instructions, as were specimens collected with the napkin after adequate preparation. If the PCR test result was positive on the endocervical sample or on any two samples, a woman was considered to be infected. PCR testing results on paired samples were identical for 493 (96.6%) of 510 women. According to the definition given above, 58 (11.3%; 95% confidence interval [CI], 8.7 to 14.5%) women were infected with C. trachomatis. The sensitivity and specificity of PCR testing on modified sanitary napkin specimens were, respectively, 93.1% (54 of 58; 95% CI, 83.3 to 98.1%) and 98.9% (447 of 452; 95% CI, 97.4 to 99.6%) compared to 81.0% (47 of 58; 95% CI, 68.6 to 90.1%) and 100% (451 of 451; 95% CI, 99.2 to 100%) for urine specimens. The positive and negative predictive values were, respectively, 91.5% (54 of 59) and 99.1% (447 of 451) for the sanitary napkin specimens compared to 100% (47 of 47) and 97.6% (451 of 462) for urine samples. These results suggest that a modified sanitary napkin represents an effective noninvasive device for self-collection of specimens to detect urogenital C. trachomatis infection.

Adolescent↗

Managing atypical squamous cells of undetermined significance in Papanicolaou smears.

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.

Adolescent↗

Human papillomaviruses and vulvar vestibulitis.

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.

Adult↗

The surgical treatment of vulvar vestibulitis syndrome: a follow-up study.

This study evaluated the effectiveness of vestibulectomy in relieving coital pain and improving sexual function in women diagnosed with vulvar vestibulitis. Vulvar vestibulitis syndrome, a chronic, nonspecific inflammation of the vulvar vestibule, probably represents the most frequent subtype of premenopausal dyspareunia. Participants were 38 women who underwent vestibulectomy at a university hospital between 1986 and 1994. Telephone interviews were conducted to assess whether vestibulectomy or other subsequent treatments affected coital pain and sexual functioning. Length of postoperative follow-up ranged from 1.1 to 10 years, with a mean of 3.3 years. Vestibulectomy yielded a positive outcome for 63.2% of the participants and moderate to no improvement for the other 36.8%. The surgery was linked to a significant increase in intercourse frequency for the entire sample and to an increase in oral and manual stimulation for the women with successful surgical outcomes. No other factors were significantly associated with treatment outcome.

Adult↗

Determinants of persistent detection of human papillomavirus DNA in the uterine cervix.

To identify factors associated with persistence of human papillomavirus (HPV) DNA in the uterine cervix, 179 women who were 18-49 years old and who had normal cytologies and positive cervical HPV DNA test at a routine periodic examination were analyzed. Among them, 91 (50.8%) remained HPV-positive a few months (mean, 11 weeks) later. Persistence was higher in women who had used oral contraceptives for > or = 2 years (odds ratio, 3.9; 95% confidence interval, 1.5-10.3) compared with those who never used oral contraceptives or used them for <2 years. HPV types 16, 18, and 31/33/35 appeared more persistent (odds ratio, 2.5; 95% confidence interval, 1.0-6.2) than other types. Persistence seemed to increase with virus load and decrease with increasing interval between examinations.

Chronic Disease↗

Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts.

OBJECTIVE: To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and/or perianal warts produces a 30% or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy. DESIGN: Randomised, triple-blind, placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery. SETTING: International, multicentre study in 10 genitourinary medicine clinics. PATIENTS: Two hundred and fifty patients with anogenital warts. MAIN OUTCOME MEASURES: Lasting response at week 38. RESULTS: Standard efficacy analysis at week 38 showed a lasting response in 51% (35/68) of 3 MIU interferon-treated patients, 48% (30/63) of 1 MIU interferon-treated patients and 43% (29/67) of placebo-treated patients. CONCLUSIONS: With the doses and regime described, treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy.

Adult↗

Interleukin-4, transforming growth factor beta 1, and dexamethasone inhibit superantigen-induced prostaglandin E2-dependent collagenase gene expression through their action on cyclooxygenase-2 and cytosolic phospholipase A2.

Signalling via MHC class II in human fibroblast-like synoviocytes selectively induces interstitial collagenase gene expression over its natural inhibitor, the tissue inhibitor of metalloproteinase (TIMP), through a prostaglandin E2 (PGE2)-dependent pathway involving cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2). In the present study, we investigated the effect of three different agents the T-cell-derived cytokine IL-4, transforming growth factor beta 1 (TGF-beta 1), and dexamethasone (DXS) on this response. Our results indicate that treatment of superantigen-stimulated synoviocytes with DXS or IL-4 inhibited collagenase gene expression without affecting TIMP gene expression. In contrast, treatment of superantigen-stimulated synoviocytes with TGF-beta 1 resulted in an inhibition of collagenase induction and an increase in TIMP gene expression. IL-4, TGF-beta 1, and DXS abolished PGE2 production and the expression of COX-2 and cPLA2 but failed to affect the constitutive expression of COX-1 and secreted PLA2. Moreover, all agents abolished protein production and phosphorylation of COX-2 and cPLA2, respectively. The inhibitory effect of the three agents on collagenase gene expression was partially reversed by exogenous PGE2, which confirms that major histocompatibility complex class II-induced collagenase gene expression is regulated through a PGE2-mediated pathway. These data highlight a mode of action of a classical anti-inflammatory agent (DXS) and of two cytokines with recognized anti-inflammatory characters (IL-4 and TGF-beta 1) on a major histocompatibility complex class II-induced response and support the involvement of COX-2 and cPLA2 in major histocompatibility complex class II-induced interstitial collagenase production in human fibroblast-like synoviocytes.

Arthritis, Rheumatoid↗

Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions.

This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.

Adult↗

MR imaging of chest wall lesions.

To assess the magnetic resonance (MR) imaging findings of chest wall lesions, images from 45 patients were reviewed by two experienced chest radiologists. The study included 14 benign and 31 malignant lesions. Images were obtained on 1.5-T imagers with use of conventional T1-, proton-density, and T2-weighted sequences in transverse, coronal, and sagittal imaging planes. Where appropriate, motion artifact was minimized with respiratory compensation, spatial presaturation, flow compensation, and cardiac gating. Twelve of 14 benign lesions showed well-defined, smooth margins compared with 10 of 31 malignant lesions (P < .05). The remaining 21 malignant lesions had irregular or ill-defined margins and evidence of muscle, bone, or vascular invasion. A capsule or pedicle was seen only in benign lesions. Characteristic MR signal intensity was seen in all four lipomas and in the only arteriovenous malformation. The remaining benign and malignant lesions showed nonspecific signal intensity characteristics. MR imaging allows the detection of muscle, bone, or vascular invasion by chest wall tumors. However, as in other musculoskeletal regions, MR imaging does not allow confident distinction of benign from malignant chest wall lesions.

Adolescent↗

Performance and metabolic effects of benzodiazepine during submaximal exercise.

The present study examined whether benzodiazepine (BZ) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. Seven triathletes completed two cycling trials at 85% maximum O2 uptake starting 3 h after an ingestion of either a placebo (PLA) of gelatin or BZ (1.5 mg lorazepam) and continuing until exhaustion, according to a double-blind randomized protocol. Blood samples were collected at rest; 5, 10, and 15 min; and exhaustion for dopamine (DA), norepinephrine (NE), epinephrine (Epi), adrenocorticotropic hormone (ACTH), cortisol (CORT), insulin (INS), free fatty acid, blood glucose, and lactate (La) determinations. Time of cycling was not significantly changed after BZ or PLA administration (22.9 +/- 2.5 vs. 23.5 +/- 3.8 min, respectively). A decrease in CORT and an increase in INS (P < 0.05) were observed with BZ before cycling. In comparison with rest, exercise resulted in a decrease in INS and an increase in all the other variables investigated (P < 0.001), but DA, NE, Epi, ACTH, CORT, La, and free fatty acid were significantly less elevated under BZ (P < 0.05). No change was found in glucose and INS levels between the two treatments at the end of the test. There was a strong correlation under both PLA and BZ conditions between DA, NE, Epi, and ACTH and also between Epi and La levels. From these data, BZ intake did appear to alter metabolism but did not influence performance during intense submaximal exercise.

Adrenocorticotropic Hormone↗

Vulvar vestibulitis syndrome: an exploratory case-control study.

OBJECTIVE: To assess the prevalence of genital bacterial infection among women with vulvar vestibulitis syndrome and to evaluate the association of several potential risk factors with the occurrence of the syndrome. METHODS: Fifty-seven women referred for dyspareunia who satisfied Friedrich's criteria and had symptoms for at least 6 months were recruited as cases. Controls included 173 patients without dyspareunia seen at a private clinic. Cases and controls were aged 18-35 years and were not pregnant. RESULTS: Among cases, the prevalences were low for genital infection with gonorrhea (0%), Chlamydia (0%), Trichomonas (0%), Mycoplasma (0%), Gardnerella (14%), and Candida (8.8%). Ureaplasma was detected in the Bartholin glands of ten affected women (17.5%). Human papillomavirus DNA was detected in only three cases (5.3%) based on polymerase chain reaction assays on vestibular biopsies. The relative risk (RR) of the syndrome was related to some aspects of sexual and reproductive history. In particular, the RR in women who had used oral contraceptives (OCs) early (before age 17) reached 11.0 (95% confidence interval [CI] 1.3-97.1) relative to those who had never used OCs. Women who had first intercourse at age 15 or earlier had a 3.3-fold increase in RR (95% CI 1.4-8.0) compared to those who had first intercourse at age 16 or later. CONCLUSION: Our data provide little support for the idea that infection causes the vulvar vestibulitis syndrome. Hormonal factors such as early OC use may be involved in the etiology of this condition.

Adolescent↗

Mitogen(s) for endometrial-like cells can be detected in human peritoneal fluid.

OBJECTIVE: To characterize the presence of mitogen(s) in the peritoneal fluid (PF). DESIGN: Aliquots of PF aspirated at laparoscopy were assessed for mitogenic activity by the rate of [3H]-thymidine incorporation into the deoxyribonucleic acid of various cell lines. SETTING: Peritoneal fluids were obtained from patients having a laparoscopy for the investigation of infertility or pelvic pain or for tubal ligation. PATIENTS: Seven women with laparoscopic evidence of endometriosis (stage I and II) and six without evidence of endometriosis. INTERVENTION: None. MAIN OUTCOME MEASURE: After 24 hours of culture in absence of serum, NIH/3T3 mouse embryo fibroblasts, (KLE) human endometrial adenocarcinoma cells, and primary cultures of rabbit endometrial cells were incubated in the presence of appropriate amounts of PF or bovine serum albumin (control) for 22 hours before adding the [3H]-thymidine for 2 hours. RESULTS: Aliquots of PF containing greater than 100 micrograms/mL total protein concentration stimulated the proliferation of all cell types. This mitogenic effect was dose-dependent and was greatest on endometrial-like cells. The mitogenic activity was fully recovered after adsorption on dextran-coated charcoal and was sensitive to tryptic digestion and to heat. It could not be retained on cartridge of C18 silica and was calculated to have a molecular weight greater than 30,000 by gel permeation chromatography. CONCLUSIONS: Peritoneal fluid from women with or without endometriosis contain growth factor(s) that are proteinaceous in nature and capable of stimulating the proliferation of endometrial-like cells and fibroblasts. These mitogens could play a role in the pathogenesis of endometriosis.

Animals↗