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Biomedical subjects

A Cartier

Publications and source records attributed to A Cartier.

At least 19 recordsLinked to original sources
PubMed2006

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations.

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils 250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.

Adult↗
PubMed2005

Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast.

BACKGROUND: Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma. METHODS: A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%. RESULTS: Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not. CONCLUSIONS: Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.

Acetates↗
PubMed2004

Differential regulation of MHC class-I-restricted and unrestricted cytotoxicity by the Us3 protein kinase of herpes simplex virus-1.

Modulation of cytotoxic responses by viral immunoevasins plays an important role in the establishment of latent and persistent viral infections. Together with MHC class-I-restricted CD8T-lymphocytes, non-MHC-restricted natural killer (NK) and lymphokine-activated killer (LAK) cells participate in this anti-viral control. The Us3 protein kinase of herpes simplex virus-1 (HSV-1) inhibits CD8T-cell cytotoxicity, which correlates with the inhibition of granzyme-B (GrB)-induced activation of pro-apoptotic Bid. We have investigated the effect of Us3 on NK and LAK cytotoxicity, because these effectors are believed to share common mechanisms for inducing cell death. We show that, in contrast to their lower sensitivity to CD8T-cell lysis, HSV-1-infected cells are lysed by NK cells or LAK cells as efficiently as the uninfected controls. Both CD8T and NK/LAK effectors were dependent on the activity of GrB and were efficiently blocked by means of treatment with a GrB inhibitor. However, unlike CD8T cells, LAK cells and NK cells failed to induce Bid cleavage, suggesting that various GrB downstream targets be involved in the induction of cell lysis. This finding explains their various sensitivities to viral modulation, which is likely to be important for the respective role of MHC-restricted and non-restricted effectors in the control of HSV-1 infection.

CD8-Positive T-Lymphocytes↗
PubMed2004

Exaggerated bronchoconstriction due to inhalation challenges with occupational agents.

Inhalation challenges with occupational agents are used to confirm the aetiology of occupational asthma. It has been proposed that using closed-circuit equipment rather than the realistic challenge method would improve the methodology of these tests. Changes in forced expiratory volume in one second (FEV1) were examined in 496 subjects with "positive specific inhalation challenges", i.e. changes in FEVI of > or = 20% after exposure to an occupational agent, including 357 subjects exposed by the realistic method, 108 using the closed-circuit method and 31 by both methods. For immediate reactions, 18 of 95 (19%) showed changes in FEV1 of > or = 30% with the closed-circuit method, whereas a significantly larger proportion, i.e. 77 of 200 (38.5%), showed such changes using the realistic method. As regards nonimmediate reactions, changes in FEV1 of > or = 30% occurred in 16 of 43 (37%) cases with the closed-circuit method as compared to a larger proportion, i.e. 87 of 180 (48%) cases, using the realistic method. This favourable effect was significantly more pronounced in workers with higher levels of bronchial hyperresponsiveness to methacholine. It is concluded that, for agents that can be generated using the closed-circuit method, use of such apparatus results in a smaller proportion of exaggerated bronchoconstriction than does the realistic method, this being particularly true for low-molecular weight agents.

Administration, Inhalation↗
PubMed2003

The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B.

The Us3 kinase is part of the antiapoptotic arsenal that salvages herpes simplex virus (HSV)-1-infected cells from damage caused by different stimuli. We demonstrate that Us3 protects HSV-1-infected cells from lysis by MHC class I-restricted CD8T cells without affecting antigen presentation. Expression of Us3 was associated with inhibition of caspase activation and reduced cleavage of the proapoptotic protein Bid. Recombinant granzyme B (GrB) failed to cleave Bid in cytosolic extracts from Us3 positive cells, while recombinant Bid served as substrate for Us3 phosphorylation, suggesting that modification of Bid by Us3 blocks its processing by GrB. Our data illustrate a new strategy of viral escape, where modification of a cellular proapoptotic substrate may prevent lysis of the infected cells without affecting other T-cell functions.

Antigen Presentation↗
PubMed2003

Effect of age on the conformity rate to short-acting beta-agonist use criteria in asthma.

STUDY OBJECTIVES: Assess compliance to asthma guidelines and influence of age concerning inhaled short-acting beta2-agonist (SABA) utilization in 5 to 45-year-old asthmatic subjects in the province of Quebec. DESIGN: Population-based retrospective drug utilization review using a computerized database of claims submitted to a private prescription drug insurance plan. PATIENTS: Subjects who received at least one outpatient prescription of SABA (age range, 5 to 45 years) for the treatment of asthma between January 1996 and December 1997. MEASUREMENTS: Percentages of patients whose use was appropriate according to the criteria regarding the average daily dose of SABA. Use was considered appropriate if the consumption rate corresponded to a maximum of two puffs per day (Salbutamol equivalent) in subjects who did or did not use inhaled corticosteroids (ICS) at an estimated maximum dose of 800 mcg/day of Beclomethasone (BDP) equivalent for the 5 to 11-year-olds and 1000 mcg/day for the 12 to 45-year-olds. RESULTS: In 1996, use was found to be appropriate for 74.4% of the 394 patients who received an SABA without ICS as compared with 70.7% for 593 patients in 1997. If we consider those who received an ICS at low to moderate doses, appropriate use was found for 51% of the 375 patients in 1996 and 57.6% for 254 patients in 1997. If we exclude patients who did not renew their SABA, appropriate use drops to 46.3% for 1996 and 34.3% for 1997 for the group who receive SABA without ICS (29.4% and 37.6%, respectively, for those with ICS). There is a relationship between age and appropriateness; the percentage of appropriateness was higher for the younger ones (5 to 14-year-old group; 83% in 1996 and 86% in 1997 for the patients who received a SABA without IS and 58.5% in 1996 and 73% in 1997 for the patients who received a SABA using ICS (p < 0.05). CONCLUSION: Our results indicate that adherence to asthma guidelines concerning SABA is poor. SABA are still overused, particularly among ICS users, which might be explained by undertreatment or poor compliance. Appropriate SABA use was significantly more common among younger groups (p < 0.05). This can be explained by better treatment in that age group, better compliance or less severe asthma.

Administration, Inhalation↗
PubMed2002

A proposed 3D structure for crotamine based on homology building, molecular simulations and circular dichroism.

Crotamine, isolated from the venom of the South American rattlesnake Crotalus durissus terrificus is a strongly basic 42-amino acid polypeptide belonging to the small basic myotoxin family. As no tridimensional structure is available for this myotoxin subfamily, despite its important pharmacological interest, we propose in this paper a theoretical 3D model for crotamine. Starting from a homology modelling procedure, followed by intensive molecular dynamics (MD) simulations in water and complementary CD experiments, the designed 3D model is the first example of a tridimensional structure in this family of small basic myotoxins. Crotamine, therefore, belongs to a newly identified structural family presenting a common fold also found in beta-defensin and antopleurine-B. The proposed 3D model will be used for future calculations about crotamine aggregation and interaction with membranes.

Amino Acid Sequence↗
PubMed2002

Interpretation of occupational peak flow records: level of agreement between expert clinicians and Oasys-2.

BACKGROUND: Oasys-2 is a validated diagnostic aid for occupational asthma that interprets peak expiratory flow (PEF) records as well as generating summary plots. The system removes inconsistency in interpretation, which is important if there is limited agreement between experts. A study was undertaken to assess the level of agreement between expert clinicians interpreting serial PEF measurements in relation to work exposure and to compare the responses given by Oasys-2. METHOD: 35 PEF records from workers under investigation for suspected occupational asthma were available for review. Records included details of nature of work, intercurrent illness, drug therapy, predicted PEF, rest periods, and holidays. Simple plots of PEF and the Oasys-2 generated plots were available. Experts were advised that approximately 1 hour was available to review the records. They were asked to score each work-rest-work (WRW) period and each rest-work-rest (RWR) period for evidence of occupational effect. At the end of each record scores of 0-100% were given for evidence of "asthma" and "occupational effect" for the whole record. Kappa values were calculated for each scored period and for the opinions on the whole record. The scores were converted into four groups (0-25%, 26-50%, 51-75%, 76-100%) and two groups (0-50% and 51-100%) for analysis. This is relevant to scores produced by Oasys-2. Agreement between Oasys-2 scores and each expert was calculated. RESULTS: 24 of 35 records were analysed by seven experts in the allotted time. For whole record occupational effect, median kappa values were 0.83 (range 0.56-0.94) for two groups and 0.62 (0.11-0.83) for four groups. For asthma, median kappa values were 0.58 (0-0.67) and 0.42 (0.15-0.70) for two and four groups respectively. For all WRW and RWR periods kappa values were 0.84 (0.42-0.94) and 0.70 (0.46-0.87) respectively. Agreement between Oasys-2 and individual experts showed a median kappa value of 0.75 (0.50-0.92) for two groups and 0.50 (0.39-0.70) for four groups. Kappa values for the median expert score v Oasys-2 were 0.75 for two groups and 0.67 for four groups. Agreement was poor for records with intermediate probability, as defined by Oasys-2. CONCLUSION: Considerable variation in agreement was seen in expert interpretation of occupational PEF records which may lead to inconsistencies in diagnosis of occupational asthma. There is a need for an objective scoring system which removes human variability, such as that provided by Oasys-2.

Asthma↗
PubMed2002

Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum eosinophilia and their response to inhaled corticosteroids.

Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum eosinophilia has been suggested as a predictor of the response to inhaled corticosteroids in asthma. This study sought to investigate the proportion of steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (< or = 1%) and to examine whether sputum eosinophilia could predict the response to inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics who had not been treated with oral or inhaled corticosteroids for at least 3 months were investigated. The evaluation included a spirometry, methacholine inhalation challenge and sputum induction on two occasions, one at baseline and the other after 1 month of treatment with 250 microg twice-daily fluticasone propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46 completed the two visits. Patients with baseline sputum eosinophils < or = 1% (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline characteristics of these two groups were similar. After 1 month of treatment, respiratory symptoms, quality of life, forced expiratory volume in one second (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both groups. The absence of sputum eosinophilia does not seem to be an indicator of poor response to inhaled corticosteroid treatment in steroid-naive asthmatics. However, this finding needs to be investigated further in a double-blind, placebo-controlled study, entirely designed to answer this question.

Administration, Inhalation↗
PubMed2002

Molecular pharmacophore determination of lipid lowering drugs with the receptor mapping method.

Hypolipidemic pharmacophoric moieties of statins, fibrates, ACAT inhibitors and beta-sitosterol analog series were identified by computational modeling, and compared with the computed structure of new potential glycyrrhetinic acid derivatives lipid-lowering drugs. Their electronic and geometric domains, similar to those of fibrates, suggest a fibrate -like mechanism matching biochemical data.

Computational Biology↗
PubMed2001

Changes in sputum cell counts after exposure to occupational agents: what do they mean?

BACKGROUND: Exposure to occupational agents can induce eosinophilic inflammation in subjects with occupational asthma (OA). It might also induce nonspecific changes in airway inflammation in subjects without OA. OBJECTIVES: We sought to investigate the changes in airway inflammation induced by exposure to occupational agents in subjects with and without OA and to determine which changes in sputum eosinophil numbers and bronchial responsiveness to methacholine should be regarded as clinically significant for predicting a 20% fall in FEV(1). METHODS: We performed specific inhalation challenges (SICs) in 3 groups of subjects: subjects reporting a history consistent with OA with a positive SIC response (n = 17); subjects reporting a history consistent with OA with a negative SIC response (n = 14); and asthmatic subjects without any history of OA (n = 10). Induced sputum and methacholine challenges were performed at the end of the control day and again at the end of the last day of exposure; the last day of exposure was always performed in the laboratory. RESULTS: There was an increase in median sputum eosinophil and neutrophil numbers in subjects with positive SIC responses. Cell counts remained unchanged after exposure in asthmatic subjects without OA. A combination of a greater than 0.26 10(6)/mL increase in sputum eosinophil numbers and a decrease in the concentration of methacholine inducing a 20% fall in FEV(1) of at least 1.8-fold compared with baseline values predicted a 20% fall in FEV(1) in 96% (95% CI, 70%-99%) of patients. CONCLUSION: Exposure to occupational agents per se does not induce airway inflammation. Changes in both sputum eosinophil counts and methacholine responsiveness are satisfactory predictors of a significant bronchial responsiveness to occupational agents.

Adult↗
PubMed2001

Effectiveness and safety of salmeterol in nonspecialist practice settings.

STUDY OBJECTIVES: To evaluate the effectiveness and safety of inhaled salmeterol in patients managed in nonspecialist practice settings. DESIGN: A randomized, double-blind, 6-month, parallel-group study involving 253 centers. SETTING: Primarily nonspecialist practices (n = 232). PATIENTS: A total of 911 subjects (417 men; 494 women) who met American Thoracic Society asthma criteria were enrolled and randomized to treatment with either twice-daily salmeterol aerosol (50 microg; n = 455) or matching placebo twice daily (n = 456). Both groups were allowed to take salbutamol as needed. All subjects were previously treated with anti-inflammatory maintenance therapy that was continued throughout the study. MEASUREMENTS AND RESULTS: The primary outcome variable was the proportion of subjects with serious asthma exacerbations defined as an exacerbation requiring hospitalization, emergency department visit, or use of prednisone during the treatment period. A total of 712 subjects competed the study. There was no significant difference in the proportion of subjects experiencing serious exacerbations between the salmeterol and placebo groups (20.8% vs 20.9%, respectively; p = 0.935; power > 88%). Peak expiratory flow was significantly higher in the salmeterol group (398 L/min vs 386 L/min for placebo; p < 0.01). Median daily use of salbutamol was two inhalations for the salmeterol group and three inhalations for placebo (p < 0.001). The proportion of subjects sleeping through the night was significantly higher in the salmeterol group (74%) as compared to placebo (68%; p = 0.028). CONCLUSIONS: Salmeterol treatment is effective in subjects typically cared for in the primary-care setting and does not increase the frequency of severe exacerbations.

Acute Disease↗
PubMed2001

Ambulatory use of inhaled beta(2)-agonists for the treatment of asthma in Quebec : a population-based utilization review.

STUDY OBJECTIVES: To assess whether the utilization of inhaled short-acting beta(2)-agonists (ISAB) and inhaled long-acting beta(2)-agonists (ILAB) for the treatment of asthma was appropriate according to the 1996 Canadian Asthma Consensus Conference recommendations. DESIGN: Population-based retrospective drug utilization review using pharmacists' billing data of the Prescription Drug Insurance Plan administered by the Quebec health insurance board. However, the database used did not contain complete patient clinical information to accurately assess severity of asthma. SETTING: Province of Quebec, Canada. PATIENTS: Persons who received at least one outpatient prescription of ISAB (age range, 5 to 45 years) or ILAB (age range, 12 to 45 years) for the treatment of asthma between August 1997 and April 1998. MEASUREMENTS: Percentages of patients whose use was appropriate according to three criteria regarding the average daily dose of ISAB (criterion 1), the renewal interval of ILAB (criterion 2), and the concomitant daily use of corticosteroids for the expected length of utilization of ILAB (criterion 3). RESULTS: Overall proportions of appropriate use according to criterion 1 were as follows: 75% (without inhaled corticosteroids [ICS]) and 84% and 43% (with one or more than one prescription of ICS, respectively). Appropriateness was slightly higher for female patients, younger patients (5 to 18 years old), and those treated by pediatricians. However, appropriateness was only 9% among patients who received at least two prescriptions of ISAB during the study period. The proportion of appropriate use was 19% according to criterion 2 and 15% according to criterion 3; there were few differences by gender or by age, but the appropriateness according to criterion 2 was somewhat higher for patients of respirologists. CONCLUSION: Compared to the 1996 Canadian asthma consensus conference recommendations, ISAB are overused, ICS are underused, and ILAB are often used improperly. Close collaboration between health professionals and patients is essential to improve the pharmacotherapy of asthma.

Administration, Inhalation↗
PubMed2000

Frequency and determinants of exaggerated bronchoconstriction during shortened methacholine challenge tests in epidemiological and clinical set-ups.

The European Respiratory Society guidelines on bronchial provocation testing have proposed time-saving procedures, which may lead to unwanted exaggerated responses. The frequency and determinants of exaggerated bronchoconstriction in response to methacholine inhalation testing in clinical and epidemiological settings have not been assessed. The authors evaluated: 1) the prevalence of exaggerated bronchoconstriction, 2) its relation to time-saving measures (starting methacholine concentration and skipping concentrations); and 3) associations between such reactions and risk factors, respiratory symptoms and/or lung function parameters. Clinical (n=408) and epidemiological (n=711) groups were included. Exaggerated bronchoconstriction was defined as either a fall > or =20% following saline or a > or =30% fall in forced expiratory volume in one second (FEV1) after methacholine inhalations. Cases were compared with two groups of subjects: 1) with measurable bronchial responsiveness (MBR); and 2) without MBR. In the epidemiological group, 84 subjects (12%) presented exaggerated bronchoconstriction. Skipped concentrations accounted for an exaggerated bronchoconstriction in 18 of these. In the clinical group, 41 subjects (10%) experienced exaggerated reactions. Skipped concentrations accounted for an exaggerated bronchoconstriction in five of these. The provocative concentration of methacholine causing a 20% fall in FEV1 values were marginally lower in subjects with exaggerated bronchoconstriction. Questionnaire analysis in epidemiological subjects showed some symptoms of asthma and rhinitis to be more prevalent in cases than in subjects without MBR. In conclusion, methacholine inhalation tests with time-saving measures result in a 10% risk of exaggerated bronchoconstriction as defined in this study and bronchial responsiveness is more prominent in subjects with exaggerated bronchoconstriction.

Adult↗