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Biomedical subjects

J Moisan

Publications and source records attributed to J Moisan.

At least 19 recordsLinked to original sources

Toll-like receptors, cytokines and the immunotherapeutics of asthma.

Asthma is a complex disease caused by a poorly characterized set of genetic and environmental factors whose pathology is a result of immune dysregulation. Toll-like receptors are pathogen associated molecular pattern receptors expressed by many airway and pulmonary tissues as well as cells of the innate and adaptive immune system. Ligation of toll-like receptors can lead to a change in the expression levels of multiple inflammatory and anti-inflammatory mediators which are involved in the pathogenesis of asthma. These ligands and their receptors are therefore prime candidates in the search for immunotherapeutic treatments of asthma. The use of murine models of allergic asthma as tools for the genetic dissection of this disease should allow the molecular mechanisms underlying asthma to be identified and possibly used as further immunotherapeutic targets.

Animals↗

TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway.

Asthma is one of the leading causes of childhood hospitalization, and its incidence is on the rise throughout the world. Currently, the standard treatment for asthma is the use of corticosteroids to try to suppress the inflammatory reaction taking place in the bronchial tree. Using a murine model of atopic allergic asthma employing a methacholine-hyperresponsive (A/J) as well as a hyporesponsive (C57BL/6) strain of mice sensitized and challenged with ovalbumin, we show that treatment with a synthetic Toll-like receptor 7 (TLR7) ligand (S-28463, a member of the imidazoquinoline family) prevents development of the asthmatic phenotype. Treatment with S-28463 resulted in a reduction of airway resistance and elastance following ovalbumin sensitization and challenge. This was accompanied by a dramatic reduction in infiltration of leukocytes, especially eosinophils, into the lungs of both C57BL/6 and A/J mice following OVA challenge. Treatment with S-28463 also abolished both the elevation in serum IgE level as well as the induction of IL-4, IL-5, and IL-13 by OVA challenge. The protective effects of S-28463 were also observed in MK2 knockout, but not MYD88 knockout, mice. We did not observe a switch in cytokine profile from T(H)2 to T(H)1, as both IL-12p70 and IFN-gamma levels were reduced following S-28463 treatment. These results clearly demonstrate the anti-inflammatory effect of imidazoquinolines in an allergic asthma model as well as the clinical potential of TLR7 ligands in the treatment of allergic diseases.

Adaptor Proteins, Signal Transducing↗

Health-related quality of life in hypertension: impact of a pharmacy intervention programme.

BACKGROUND AND OBJECTIVE: In a previous study, we observed that a pharmacy-based intervention programme decreased the blood pressure of hypertensive patients. The objective of the present study was to assess the effect of this pharmacy programme on the health-related quality of life (HRQOL) of individuals treated for hypertension. METHODS: In a quasi-experimental cohort pilot study, we recruited 91 participants from nine pharmacies in the Quebec City area. We offered the intervention programme over a 9-month period to participants enrolled at four of the pharmacies. The other participants were not exposed to pharmaceutical services other than those usually given by their pharmacists. We used the SF-36 to evaluate HRQOL. Covariance analysis was used to test for significant differences of HRQOL scores between participants exposed and not exposed to the programme. RESULTS AND DISCUSSION: When compared with the non-exposed participants, those receiving the intervention and with high income had an improvement in vitality score (P=0.05). On the contrary, low-income exposed participants did not show this benefit and had a decline in mental health score (P=0.01). Improvement in vitality is likely due to increased physical activity and to a reduction in systolic blood pressure in the high-income exposed group. The negative effect of the programme on the mental health of those exposed in the low-income group might be due to the fact that the programme was not effective in reducing blood pressure and may therefore have caused anxiety. CONCLUSION: Pharmacists' interventions can have both a positive and negative impact on the HRQOL of individuals, treated with antihypertensive agents, depending on income level.

Aged↗

Tolerability of antihypertensive drugs in a community-based setting.

BACKGROUND: Outside the experimental environment of clinical trials, the tolerability of angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and the angiotensin II antagonist losartan has not been compared. OBJECTIVES: The purpose of this study was to estimate, in current clinical practice, the 3-month cumulative incidence of side effects among first-time users of losartan, ACEIs, and CCBs for hypertension. METHODS: We conducted a prospective cohort study through a network of 173 pharmacies across Canada to identify patients with hypertension who were newly prescribed monotherapy with losartan, an ACEI, or a CCB. Individuals were interviewed by telephone 3 times over a 3-month period to determine perceived side effects of the antihypertensive medication prescribed. Data were analyzed using a multivariate logistic regression model. RESULTS: Among the 663 eligible individuals, the 3-month cumulative incidence of perceived side effects was 52.5% (42/80), 60.2% (222/369), and 69.6% (149/214) for those treated with losartan, an ACEI, and a CCB, respectively. After adjustment for sex, age, level of education, number of symptoms perceived the week before entering the study, prior use of antihypertensive drugs, current use of any other drug, drug insurance coverage, and duration of hypertension, the odds of reporting a side effect were significantly higher among patients treated with an ACEI (odds ratio [OR] = 1.78: 95% CI, 1.02-3.12) or a CCB (OR = 2.65; 95% CI, 1.47-4.78) compared with patients treated with losartan. CONCLUSIONS: In a community-based setting, we observed that losartan is better tolerated than ACEIs and CCBs. Given that the occurrence of side effects may contribute to lower adherence to drug treatment, the low incidence of side effects associated with losartan makes it an attractive antihypertensive drug choice.

Adolescent↗

Clearance of infection with Mycobacterium bovis BCG in mice is enhanced by treatment with S28463 (R-848), and its efficiency depends on expression of wild-type Nramp1 (resistance allele).

The mouse bcg host resistance gene is known to control the activation of host macrophages for killing of intracellular parasites like Leishmania donovani as well as intracellular bacteria, including Mycobacterium bovis BCG and Salmonella enterica serovar Typhimurium. The Nramp1 gene has been mapped to this locus and affects the efficiency of macrophage activation. It has been shown that imidazoquinoline compounds, including S28463, are able to improve the clearance of a number of intracellular pathogens such as herpes simplex virus 2, human papillomavirus, and Leishmania. The goal of this study was to determine whether S28463 is efficient against infection with another intracellular pathogen, M. bovis BCG, and to determine the molecular basis underlying this effect. To achieve this, B10A.Nramp1(r) and B10A.Nramp1(-/-) mice were infected with M. bovis BCG and treated with S28463. The bacterial content in the spleen from these mice was assayed by a colony-forming assay. In addition, in vitro experiments were performed using bone marrow-derived macrophage cell lines from these mice. These cells were treated with S28463 and/or gamma interferon (IFN-gamma), and nitric oxide (NO) production was measured. Our study was able to show that S28463 acts in synergy with IFN-gamma to increase the production of NO in vitro. We were also able to demonstrate that mice that carried the resistant allele of the Nramp1 gene and were infected with M. bovis BCG responded to treatment with S28463, resulting in a decreased bacterial load after 2 weeks of treatment. Mice that do not express the Nramp1 gene responded only to a very large dose of S28463, and the response was not as efficient as that observed in mice carrying a wild-type Nramp1 allele. Our data provide evidence for the potential of S28463 as an immunomodulator that may be helpful in designing efficient strategies to improve host defense against mycobacterial infection.

Alleles↗

Psychosocial factors at work, smoking, sedentary behavior, and body mass index: a prevalence study among 6995 white collar workers.

This cross-sectional study examined whether psychosocial factors at work were associated with smoking, sedentary behavior, and body mass index. The study population was composed of 3531 men and 3464 women employed as white collar workers in 21 organizations. Data were collected at worksites. Psychological demands and decision latitude at work were measured with the Karasek 18-item questionnaire. Smoking, sedentary behavior, and mean body mass index were compared by quartiles of decision latitude and psychological demands and by job strain categories. Prevalence of smoking, mean number of cigarettes smoked per day, prevalence of sedentary behavior, and mean body mass index were not consistently associated with decision latitude, psychological demands, or high job strain. However, prevalence of smoking was elevated in women belonging to the highest quartile of psychological demands (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0 to 1.6) and in the active job strain groups in both men (OR, 1.6; 95% CI, 1.2 to 2.1) and women (OR, 1.4; 95% CI, 1.0 to 2.0). Prevalence of sedentary behavior was elevated in men in the lowest quartile of decision latitude (OR, 1.3; 95% CI, 1.0 to 1.7), in the passive group (OR, 1.3; 95% CI, 1.0 to 1.5), and in the high strain group (OR, 1.2; 95% CI, 1.0 to 1.6). In women, this prevalence was elevated in the third quartile of psychological demand (OR, 1.3; 95% CI, 1.1 to 1.6). These results provide only partial support for an association between some psychosocial factors at work and the prevalence of smoking and sedentary behavior.

Adolescent↗

Appropriateness of omeprazole prescribing in Quebec's senior population.

BACKGROUND: Prescribing omeprazole for the treatment of digestive disorders accounts for an important part of the costs in Quebec's drug benefit plan. In July 1993, the Quebec drug program listed omeprazole, with restriction, in its formulary. On January 1, 1994, this restriction was lifted; since then, omeprazole has been listed in the regular provincial formulary. OBJECTIVE: To describe the appropriateness of initial omeprazole prescribing in the ambulatory senior population of Quebec in the 27 months after being listed without restriction. SUBJECTS AND METHODS: A retrospective population-based cohort study was performed using prescription and medical services claims databases of the Quebec drug program. Data were extracted for elderly patients who received their first omeprazole prescription between July 1, 1994 and March 31, 1996. RESULTS: Among the 47,140 first-time users of omeprazole identified, 7516 (15.9%) had had an endoscopy in the previous six months, 2308 (4.9%) were given an antimicrobial agent and omeprazole simultaneously, and 22,730 (48.2%) received omeprazole after prior use of an H2 receptor antagonist (H2RA) or a prokinetic drug. A total of 26,525 (56.3%) first-time users were prescribed omeprazole based on at least one of the three criteria listed above. Among these users, 729 (2.8%) received an H2RA concurrently with omeprazole. Altogether, 25,796 (54.7%) first-time users received omeprazole appropriately. CONCLUSIONS: Although reimbursement for omeprazole prescriptions has not been restricted in Quebec since January 1, 1994, it was prescribed appropriately for elderly patients in the majority of cases studied.

Aged↗

Billing for cognitive services: understanding Québec pharmacists' behavior.

BACKGROUND: There is growing evidence that pharmacists' interventions to solve drug-related problems are effective and cost-saving. Since 1978, under the Quebec provincial drug plan, payment for two cognitive services, the pharmaceutical opinion and the refusal to dispense a prescription, has been disbursed to community pharmacists. However, the number of claims for these services lags far behind expectations. OBJECTIVE: To identify factors influencing Quebec community pharmacists in the billing for a pharmaceutical opinion or for a refusal to dispense. METHODS: Questions on predisposing, enabling, and reinforcing factors potentially related to pharmacists' behavior were included in a self-administered questionnaire sent to all 3517 community pharmacists practicing in the province of Quebec during 1996. Using multivariate logistic regression, models were built to explain billing for an opinion and billing for a refusal. RESULTS: According to our models, the typical pharmacist who billed for opinions or refusals in Quebec is <45 years of age, has attended a continuing education program on this topic, and believes that billing for interventions is important. This typical pharmacist handles a mean daily volume of 100-250 prescriptions, uses a decision-support computer program, and has sufficient technical staff assistance. This pharmacist believes that interventions can be billed rapidly and are consistently paid by the province's drug plan. CONCLUSIONS: In order to increase the billing of pharmaceutical care in community pharmacies, tailored educational programs should be offered to pharmacists. There is also a need to improve working conditions in pharmacies.

Adult↗

Health-related quality-of-life measurement in hypertension. A review of randomised controlled drug trials.

In hypertension, tolerability of drug treatment is important because individuals may see the use of antihypertensive medications as more troubling than their seemingly symptomless disease. This may result in noncompliance and ineffectual long term treatment. In the past 15 years, new antihypertensive medications have been marketed on the basis of the advantages they offer with regard to adverse effects and the unavoidable impact of such adverse effects on a person's quality of life. When related to health, quality of life refers to the physical, psychological and social dimensions of health that are influenced by a person's experiences, beliefs, expectations and perceptions. To measure this concept, many instruments, either generic or specific, may be used. The purpose of this study is to describe, by way of a critical review of the literature, the instruments that are most often used in the measurement of health-related quality of life (HR-QOL) in people using antihypertensive drug treatments. We carried out a search of the literature published in English in the period January 1966 to July 2000, looking for randomised controlled trials of antihypertensive drugs. Using the Medline database, we included 77 papers in our review. Our main finding suggests that HR-QOL changes associated with antihypertensive treatment are measured with many different instruments. In almost all studies, at least 1 instrument specific to a health dimension was used, whereas not many used a generic instrument only. The most commonly measured HR-QOL dimensions were cognitive function, symptomatic well-being, sexual function, psychological well-being, sleep dysfunction, social participation and general health perception. Since the choice of dimensions to measure depends not only on the disease but also on the drug, this review adds further evidence that a generic instrument as well as a preference measurement should be added to a specific instrument.

Antihypertensive Agents↗

[International Prostate Symptom Scale. Evaluation of the usefulness of a French version].

OBJECTIVE: To evaluate the usefulness of a French-language version of the International Prostate Symptom Scale (I-PSS) by measuring, on this scale and on the quality of life index, the scores of patients with benign prostatic hyperplasia before and after prostate surgery. METHOD: The questionnaire was completed by 14 men, mostly between 60 and 80 years old, 24 hours before surgery and 1 month and 3 months after surgery. RESULTS: The French-language scale worked well. Scores changed from 19.1 before surgery to 7.5 3 months after surgery for prostate symptoms and from 8.5 to 4.5 for quality of life. CONCLUSION: This version of the questionnaire is a valid tool for evaluating prostate symptoms reported by French-speaking people.

Aged↗

[Accuracy of a self-administered questionnaire on the use of antibiotics].

BACKGROUND: To document the ambulatory use of drugs and the indications for that use, investigators often rely on self-administered questionnaires of questionable accuracy. The present study assessed the accuracy of a French Canadian self-administered questionnaire with regard to documenting current antibiotic drug use. METHODS: The information independently obtained from physicians and pharmacists was compared with the information reported by 340 patients. Patients were asked to participate in the study by their pharmacist at the time that their prescribed antibiotic was dispensed. The proportion of agreement between the data sources was calculated with regard to antibiotic regimen characteristics and indications for use and the nature of the treated infection. RESULTS: Self-reported information demonstrated a high level of agreement with data provided by physicians (k = 0.87) and pharmacists (k = 0.94), with regard to antibiotic names. Regarding the nature of the treated infection, the agreement between self-reported information and data obtained from physicians was substantial (k = 0.63). A total of 242 patients completed the questionnaire twice at two-week intervals. Test-retest reliability was high regarding both the antibiotic name (k = 0.72) and the nature of the treated infection (k = 0.86). CONCLUSIONS: The self-administered questionnaire assessed in this study can reliably and accurately document the name of antibiotics used and the nature of the treated infections. Further work is needed to improve the accuracy of the questionnaire with regard to other components of antibiotics use.

Adolescent↗

Electrophysiological evidence that a subset of midbrain dopamine neurons integrate the reward signal induced by electrical stimulation of the posterior mesencephalon.

This study was aimed at determining whether midbrain dopamine (DA) neurons are trans-synaptically activated by rewarding electrical stimulation applied near the midline in the posterior mesencephalon (PM), and in the affirmative, whether the increase in firing was proportional to the rewarding effectiveness of the stimulation. Experiments were performed on male Long-Evans rats trained to lever press to obtain 400 ms trains of cathodal rectangular pulses. Following the training period, curves relating the rates of responding to the stimulation frequencies were determined at two current intensities and reward thresholds were calculated for each animal. Each animal was then anesthetized with urethane (1.2 g/kg, i.p.) and firing rate of DA neurons were recorded before, during, and after each of 50 trains (1 train/3 s) of stimulation to the PM using stimulation parameters that either sustained near threshold responding (rewarding), or failed to sustain responding (non-rewarding), in the behavioral tests. A total of 24 DA cells were recorded from 13 behaviorally trained animals, and of these, 17 (71%) responded to rewarding stimulation by an increase in firing, five (21%) were unresponsive and two (8%) were inhibited. In 12 of the 17 cells that were activated, the increase in firing was proportional to the rewarding effectiveness of the stimulation rather than the total strength of the stimulation. These results provide evidence that a subset of midbrain DA neurons are trans-synaptically activated by rewarding PM stimulation and constitute a second, or subsequent, stage of the reward-relevant pathway that integrates the PM reward signal.

Action Potentials↗

Activation of neurotensin receptors in the prefrontal cortex stimulates midbrain dopamine cell firing.

The effects of medial prefrontal cortex microinjections of 3 nmol/0.5 microl of neurotensin-(1-13), the inactive fragment neurotensin-(1-8), or vehicle on the firing rate of midbrain dopamine neurons were studied in anesthetized rats. Twelve of 19 cells tested with neurotensin-(1-13) showed an average 20-25% increase in firing rate between 10 and 20 min after the injection. This effect was not mimicked by neurotensin-(1-8) (9 cells), nor by a control injection (10 cells) suggesting that it is mediated by high-affinity neurotensin receptors. These results suggest that activation of neurotensin receptors in the medial prefrontal cortex can modulate neural activity of a subpopulation of midbrain dopamine neurons.

Animals↗

Job strain and ambulatory blood pressure among female white-collar workers.

OBJECTIVES: The association between job strain and ambulatory blood pressure was studied among female white-collar workers. METHODS: This cross-sectional investigation studied 210 women in high- or low-strain jobs randomly selected from 3183 women of all ages, employed as white-collar workers. The women wore an ambulatory blood pressure monitor for 24 hours during a workday. Mean blood pressures were calculated. Psychological demands and decisional latitude were measured twice (14 months before and 7 days before the blood pressure measurement) with 2 scales recommended by Karasek. RESULTS: Significant differences in blood pressure were found according to current job strain among the women holding a university degree. Their mean blood pressures during work were significantly higher [8.0 mm Hg (1.1 kPa) systolic and 6.4 mm Hg (0.8 kPa) diastolic blood pressure] in the high-strain group than in the low-strain group. Statistically significant elevations in blood pressure over the 24-hour period were also found for women with a university degree. Cumulative exposure to high strain over 14 months was also significantly associated with high systolic blood pressure at work, in the evening, and over a 24-hour period irrespective of other factors related to blood pressure. Among the women without a university degree, the blood pressure differences observed between the job strain groups were less than 1 mm Hg (0.1 kPa) and not statistically significant. CONCLUSIONS: These results provide support for the effect of job strain on ambulatory blood pressure only among female white-collar workers holding a university degree.

Adolescent↗

Job strain and psychological distress in white-collar workers.

OBJECTIVES: In line with Karasek's job strain model, the objective of the study was to determine whether workers submitted to high job strain, a combination of high psychological demand and low decision latitude, develop more psychological distress than workers not submitted to high job strain. A second objective was to determine whether social support at work modifies the association between job strain and psychological distress. METHODS: The design was cross-sectional and included white-collar workers in the Québec city area. A self-administered 26-item questionnaire (the Job Content Questionnaire) measured psychological demand, decision latitude, and social support at work. Psychological distress was measured by the Psychiatric Symptom Index, a 14-item self-administered instrument. RESULTS: Among the 2889 participants, the prevalence of psychological distress was 27.8%. High job strain was present in 20.5% of the subjects. The crude odds ratio (OR) of high job strain with psychological distress was 3.52 [95% confidence interval (95% CI) 2.54-4.88]. The OR adjusted for age, gender, employment status, occupation, social support at work, nonwork social support, cynicism, hostility, domestic load, and stressful life events during the last 12 months was still significant (OR 2.45, 95% CI 1.66-3.62). CONCLUSIONS: Our results support the association between job strain and psychological distress. Social support at work, although significantly associated with psychological distress, did not modify the association between job strain and psychological distress.

Adolescent↗

[Validation of a French adaptation of the international prostatic symptom score].

OBJECTIVE: To evaluate the reliability and the validity of a French Canadian version of the International Prostatic Symptom Score. DESIGN: Between November 23, 1993 and April 8, 1994, a self-administered questionnaire was submitted to a group of men on two occasions at an interval of at least one week. This questionnaire was composed of seven questions designed to score the severity of prostatic symptoms and two questions designed to score quality of life. CONTEXT: Family medicine unit and prostatic cancer screening programme of the hormonal treatment clinic of the Laval University hospital centre. PARTICIPANTS: Men between the ages of 50 and 80 years presenting for prostatic cancer screening or for a family medicine visit were invited to participate. A total of 207 men answered the questionnaire on the first occasion and all but two answered the questionnaire on the second occasion. MAIN ASSESSMENT CRITERIA: The internal consistency of the scale, its test-retest stability, the correlation between the prostatic symptom index of the scale and the quality of life index and the urine output were estimated. RESULTS: The internal consistency of the scale has found to be good, with Cronbach's coefficient alpha equal to 0.82. Each question of the scale displayed a good test-retest stability, with coefficient Kappa varying between 0.41 and 0.66 according to the question. The correlation coefficient between the prostatic symptom index of the scale and the quality of life index was 0.75 (P < 0.001). An inverse linear relationship was observed between urine output and the prostatic symptom index, with a correlation coefficient of -0.289 (p < 0.001). CONCLUSION: The psychometric qualities of the adapted scale, evaluated during the present study, are similar to the qualities of the original English language I-PSS scale. The present French version of the scale constitutes a reliable and valid tool to assess the severity of prostatic symptoms in the Quebec male population.

Aged↗

Leisure physical activity and age at menarche.

Early menarche has been associated with higher risk of breast cancer. A prospective study of 2487 girls, has been conducted in Quebec City, Canada, to evaluate the relationship of exercise to menarche, taking personal and family characteristics into account. Weight, height, body mass index, and abdominal and supra-iliac skinfolds were inversely associated with age of menstruation. Mother's age at menarche was positively associated with age of menstruation. Age, mother's age at menarche, and weight-adjusted incidence density ratios (IDR) showed no association between energy expenditure and onset of menstruation. Girls who participated in dance, gymnastic figure skating, synchronized swimming, or diving competitions had a lower risk of reaching menarche at an early age (IDR = 0.71 (0.51-0.97)).

Adolescent↗