31 results on '"Godbout C"'
Search Results
2. Morphological Features of Synthesized Ectomycorrhizae of Alnus crispa and A. rugosa
- Author
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Godbout, C. and Fortin, J. A.
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- 1983
3. Independent validation of the Sleep Apnoea Quality of Life Index
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Lacasse, Y, Godbout, C, and Sériés, F
- Published
- 2002
4. Health-related quality of life in obstructive sleep apnoea
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Lacasse, Y., primary, Godbout, C., additional, and Series, F., additional
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- 2002
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5. Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor.
- Author
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Cao, J, O'Donnell, D, Vu, H, Payza, K, Pou, C, Godbout, C, Jakob, A, Pelletier, M, Lembo, P, Ahmad, S, and Walker, P
- Abstract
A cDNA encoding a thyrotropin-releasing hormone (TRH) receptor expressed in the pituitary was previously cloned (De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899; De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) J. Biol. Chem. 267, 25703-25708; Duthie, S. M., Taylor, P. L., Anderson, J., Cook, J., and Eidne, K. A. (1993) Mol. Cell Endocrinol. 95, R11-R15). We now describe the isolation of a rat cDNA encoding a novel subtype of TRH receptor (termed TRHR2) displaying an overall homology of 50% to the pituitary TRH receptor. Introduction of TRHR2 cDNA in HEK-293 cells resulted in expression of high affinity TRH binding with a different pharmacological profile than the pituitary TRH receptor. De novo expressed receptors were functional and resulted in stimulation of calcium transient as assessed by fluorometric imaging plate reader analysis. The message for TRHR2 was exclusive to central nervous system tissues as judged by Northern blot analysis. Studies of the expression of TRHR-2 message by in situ hybridization revealed a pattern of expression remarkably distinct (present in spinothalamic tract, spinal cord dorsal horn) from that of the pituitary TRH receptor (present in hypothalamus, and ventral horn of the spinal cord, anterior pituitary). Therefore, we have identified a novel, pharmacologically distinct receptor for thyrotropin-releasing hormone that appears to be more restricted to the central nervous system particularly to the sensory neurons of spinothalamic tract and spinal cord dorsal horn, which may account for the sensory antinociceptive actions of TRH.
- Published
- 1998
6. MORPHOLOGICAL FEATURES OF SYNTHESIZED ECTOMYCORRHIZAE OF ALNUS CRISP A AND A. RUGOSA*
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GODBOUT, C., primary and FORTIN, J. A., additional
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- 1983
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7. Methods for synthesizing ectomycorrhizas and their effect on mycorrhizal development
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Godbout, C., Fortin, J. A., and Piche, Y.
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- 1983
8. Developing a living lab in ethics: Initial issues and observations.
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Racine E, D'Anjou B, Dallaire C, Dumez V, Favron-Godbout C, Hudon A, Montreuil M, Olivier C, Quintal A, and Chenel V
- Abstract
Living labs are interdisciplinary and participatory initiatives aimed at bringing research closer to practice by involving stakeholders in all stages of research. Living labs align with the principles of participatory research methods as well as recent insights about how participatory ways of generating knowledge help to change practices in concrete settings with respect to specific problems. The participatory, open, and discussion-oriented nature of living labs could be ideally suited to accompany ethical reflection and changes ensuing from reflection. To our knowledge, living labs have not been explicitly trialed and reported in ethics literature. In this discussion paper, we report and discuss four initial issues that marked the process of setting up a living lab in ethics: (1) determining the goals and expected outcomes of an ethics living lab; (2) establishing operational procedures; (3) selecting communities and defining pilot projects; and (4) adopting a lens to tackle emerging questions and challenges. We explain these four issues and present the paths taken based on the novel and specific orientation, that is, living ethics, at the basis of this project. In alignment with living ethics and É-LABO, we approach challenges as learning opportunities to ask not only "how" questions but also "why" questions. We hope that this discussion paper informed by our experience helps to clarify the theoretical, methodological, and practical approaches necessary to successfully adopt and employ living labs in ethics., (© 2023 The Authors. Bioethics published by John Wiley & Sons Ltd.)
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- 2024
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9. Medical assistance in dying for people living with mental disorders: a qualitative thematic review.
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Favron-Godbout C and Racine E
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- Humans, Canada, Medical Assistance, Morals, Mental Disorders, Psychotic Disorders, Suicide, Assisted
- Abstract
Background: Medical assistance in dying (MAiD) sparks debate in several countries, some of which allow or plan to allow MAiD where a mental disorder is the sole underlying medical condition (MAiD-MD). Since MAiD-MD is becoming permissible in a growing number of jurisdictions, there is a need to better understand the moral concerns related to this option. Gaining a better understanding of the moral concerns at stake is a first step towards identifying ways of addressing them so that MAiD-MD can be successfully introduced and implemented, where legislations allow it., Methods: Thus, this article aims (1) to better understand the moral concerns regarding MAiD-MD, and (2) to identify potential solutions to promote stakeholders' well-being. A qualitative thematic review was undertaken, which used systematic keyword-driven search and thematic analysis of content. Seventy-four publications met the inclusion criteria., Results: Various moral concerns and proposed solutions were identified and are related to how MAiD-MD is introduced in 5 contexts: (1) Societal context, (2) Healthcare system, (3) Continuum of care, (4) Discussions on the option of MAiD-MD, (5) MAiD-MD practices. We propose this classification of the identified moral concerns because it helps to better understand the various facets of discomfort experienced with MAiD-MD. In so doing, it also directs the various actions to be taken to alleviate these discomforts and promote the well-being of stakeholders., Conclusion: The assessment of MAiD-MD applications, which is part of the context of MAiD-MD practices, emerges as the most widespread source of concern. Addressing the moral concerns arising in the five contexts identified could help ease concerns regarding the assessment of MAiD-MD., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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10. Chronic noncancer pain management: Integration of a nurse-led program in primary care.
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Assefa M, LeClerc I, Muggah E, Deonandan R, Godbout C, and Finestone HM
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- Humans, Adolescent, Adult, Analgesics, Opioid therapeutic use, Pilot Projects, Nurse's Role, Primary Health Care, Chronic Pain drug therapy
- Abstract
Problem Addressed: Chronic noncancer pain is often excessively managed with medications (most notably opioids) instead of nonpharmacologic options or multidisciplinary care-the gold standards., Objective of Program: To offer an effective alternative to pharmacologic management of chronic noncancer pain in primary care., Program Description: Patients 18 years of age or older with chronic noncancer pain were referred by family physicians or nurse practitioners in a family health team (outpatient, multidisciplinary clinic) in Ottawa, Ont. A registered nurse used the Pain Explanation and Treatment Diagram with patients, taught self-management skills (related to habits [smoking, consumption of alcohol, diet], exercise, sleep, ergonomics, and psychosocial factors), and referred patients to relevant resources., Conclusion: A nurse-led chronic pain program, initiated without extra funding, was successfully integrated into a primary care setting. Among the participating patients in the pilot project, outcomes related to pain intensity, pain interference with daily living, and opioid use were encouraging. This program could serve as a model for improving chronic noncancer pain management in primary care., (Copyright © 2023 the College of Family Physicians of Canada.)
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- 2023
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11. Circulating microRNA expression signatures accurately discriminate myalgic encephalomyelitis from fibromyalgia and comorbid conditions.
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Nepotchatykh E, Caraus I, Elremaly W, Leveau C, Elbakry M, Godbout C, Rostami-Afshari B, Petre D, Khatami N, Franco A, and Moreau A
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- Humans, Chronic Disease, Biomarkers, Fatigue Syndrome, Chronic diagnosis, Fatigue Syndrome, Chronic genetics, Fibromyalgia diagnosis, Fibromyalgia genetics, Circulating MicroRNA genetics, MicroRNAs
- Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and fibromyalgia (FM) are two chronic complex diseases with overlapping symptoms affecting multiple systems and organs over time. Due to the absence of validated biomarkers and similarity in symptoms, both disorders are misdiagnosed, and the comorbidity of the two is often unrecognized. Our study aimed to investigate the expression profiles of 11 circulating miRNAs previously associated with ME/CFS pathogenesis in FM patients and individuals with a comorbid diagnosis of FM associated with ME/CFS (ME/CFS + FM), and matched sedentary healthy controls. Whether these 11 circulating miRNAs expression can differentiate between the two disorders was also examined. Our results highlight differential circulating miRNAs expression signatures between ME/CFS, FM and ME/CFS + FM, which also correlate to symptom severity between ME/CFS and ME/CFS + FM groups. We provided a prediction model, by using a machine-learning approach based on 11 circulating miRNAs levels, which can be used to discriminate between patients suffering from ME/CFS, FM and ME/CFS + FM. These 11 miRNAs are proposed as potential biomarkers for discriminating ME/CFS from FM. The results of this study demonstrate that ME/CFS and FM are two distinct illnesses, and we highlight the comorbidity between the two conditions. Proper diagnosis of patients suffering from ME/CFS, FM or ME/CFS + FM is crucial to elucidate the pathophysiology of both diseases, determine preventive measures, and establish more effective treatments., (© 2023. The Author(s).)
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- 2023
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12. The induced membrane technique in animal models: a systematic review.
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Sun H, Godbout C, Hali K, Momic J, Schemitsch EH, and Nauth A
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Objectives: The induced membrane technique (IMT) is a 2-stage surgical approach that has become increasingly popular to manage bone defects. Preclinical investigations have been conducted to better understand and define several aspects of this technique. This review summarizes the literature regarding the IMT performed in animal models and identifies potential future directions., Data Sources: Biosis Citation Index, Ovid Embase, and Ovid MEDLINE databases were searched from inception up to June 23, 2021 for articles related to the IMT., Study Selection: Animal studies involving the use of the IMT for segmental defects in long bones were selected. Only full-length original research articles published in English or French were included., Data Extraction: Two authors extracted the data from the selected studies and a third author verified the accuracy of the information., Data Synthesis: Information concerning the animal model, the surgical procedures, and the outcome measures were recorded for each study and compiled., Conclusions: Forty-seven studies were included in this review. Twenty-nine studies (62%) performed both stages of the technique, but only 8 (17%) reported on radiographic union rates explicitly and 5 (11%) included biomechanical testing. A large proportion of the preclinical literature on the IMT has failed to report on radiographic union as an outcome. While studies reporting membrane properties are valuable, they may not provide information that translates into clinical practice or further clinical research if the ultimate outcome of bony healing is not considered. Future animal studies of the IMT should consider this in their study design., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)
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- 2022
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13. Assessing infant cognition in field settings using eye-tracking: a pilot cohort trial in Sierra Leone.
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Leppänen JM, Butcher JW, Godbout C, Stephenson K, Hendrixson DT, Griswold S, Rogers BL, Webb P, Koroma AS, and Manary MJ
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- Adult, Child, Child, Preschool, Cohort Studies, Humans, Infant, Prospective Studies, Reproducibility of Results, Sierra Leone, Cognition, Eye-Tracking Technology
- Abstract
Objectives: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone., Design: Prospective dual cohort study nested in a cluster-randomised trial., Setting: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM)., Participants: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control., Interventions: Infants with MAM were provided with supplementary feeding., Outcome Measures: The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children., Results: Infants exhibited consistent orienting to targets on a computer screen (>95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls., Conclusions: The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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14. Treating high-risk moderate acute malnutrition using therapeutic food compared with nutrition counseling (Hi-MAM Study): a cluster-randomized controlled trial.
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Lelijveld N, Godbout C, Krietemeyer D, Los A, Wegner D, Hendrixson DT, Bandsma R, Koroma A, and Manary M
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- Female, Food, Humans, India epidemiology, Infant, Male, Rural Population, Counseling, Infant Nutrition Disorders diet therapy, Nutrition Therapy, Nutritional Status
- Abstract
Background: There is a lack of consensus on what is the most appropriate treatment of moderate acute malnutrition (MAM)., Objectives: We aimed to determine if provision of ready-to-use-therapeutic food (RUTF) and antibiotics to "high-risk" MAM (HR-MAM) children in addition to nutritional counseling would result in higher recovery and less deterioration than nutrition counseling alone., Methods: At the 11 intervention clinics, HR-MAM children were given RUTF and amoxicillin along with standard nutrition counseling, for 2-12 wk. All others received 6 wk of nutrition counseling alone. HR-MAM was defined as midupper arm circumference (MUAC) <11.9 cm, weight-for-age z score (WAZ) <-3.5, mother not the main caregiver, or a child <2 y old not being breastfed. Outcomes were compared using intention-to-treat analysis., Results: Analysis included 573 children at the intervention sites and 714 children at the control sites. Of the intervention group, 317 (55%) were classified as HR-MAM. Short-term recovery was greater at the intervention sites [48% compared with 39% at week 12; risk difference (rd): 0.08; 95% CI: 0.03, 0.13]. The intervention group had lower risk of deteriorating to severe acute malnutrition (SAM) (18% compared with 24%; rd: -0.07; 95% CI: -0.11, -0.04), lower risk of dying (1.8% compared with 3.1%; rd: -0.02; 95% CI: -0.03, -0.00), and greater gains in MUAC and weight than did children at the control sites. However, by 24 wk, the risk of SAM was similar between the 2 arms (31% compared with 34%; rd: -0.03; 95% CI: -0.09, 0.02). Control group data identified recent illness, MUAC <12.0 cm, WAZ <-3, dropping anthropometry, age <12 mo, being a twin, and a history of previous SAM as risk factors for deterioration., Conclusions: Provision of RUTF and antibiotics to HR-MAM children improved short-term recovery and reduced short-term risk of deterioration. However, recovery rates were still suboptimal and differences were not sustained by 6 mo post enrollment.This trial was registered at clinicaltrials.gov as NCT03647150., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
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- 2021
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15. Effect of electroencephalography-guided anesthesia on neurocognitive disorders in elderly patients undergoing major non-cardiac surgery: A trial protocol The POEGEA trial (POncd Elderly GEneral Anesthesia).
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Morisson L, Laferrière-Langlois P, Carrier FM, Pagé G, Godbout C, Fortier LP, Ogez D, Létourneau G, Jarry S, Denault A, Fortier A, Guertin MC, Verdonck O, and Richebé P
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- Aged, Anesthetics, Inhalation administration & dosage, Blood Pressure, Elective Surgical Procedures, Electroencephalography, Humans, Oximetry, Postoperative Complications, Prospective Studies, Sevoflurane administration & dosage, Anesthesia, General adverse effects, Neurocognitive Disorders etiology
- Abstract
Introduction: The number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth., Objective: The objective of this trial is to investigate-in patients ≥ 70 years old undergoing major non-cardiac surgery-the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform)., Material and Methods: This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8-1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups., Study Registration: NCT04825847 on ClinicalTrials.gov., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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16. Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology.
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Nepotchatykh E, Elremaly W, Caraus I, Godbout C, Leveau C, Chalder L, Beaudin C, Kanamaru E, Kosovskaia R, Lauzon S, Maillet Y, Franco A, Lascau-Coman V, Bouhanik S, Gaitan YP, Li D, and Moreau A
- Subjects
- Biomarkers blood, Fatigue Syndrome, Chronic etiology, Female, Humans, Male, Middle Aged, Severity of Illness Index, Circulating MicroRNA blood, Fatigue Syndrome, Chronic diagnosis, Fatigue Syndrome, Chronic genetics
- Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease, rooted in multi-system dysfunctions characterized by unexplained debilitating fatigue. Post-exertional malaise (PEM), defined as the exacerbation of the patient's symptoms following minimal physical or mental stress, is a hallmark of ME/CFS. While multiple case definitions exist, there is currently no well-established biomarkers or laboratory tests to diagnose ME/CFS. Our study aimed to investigate circulating microRNA expression in severely ill ME/CFS patients before and after an innovative stress challenge that stimulates PEM. Our findings highlight the differential expression of eleven microRNAs associated with a physiological response to PEM. The present study uncovers specific microRNA expression signatures associated with ME/CFS in response to PEM induction and reports microRNA expression patterns associated to specific symptom severities. The identification of distinctive microRNA expression signatures for ME/CFS through a provocation challenge is essential for the elucidation of the ME/CFS pathophysiology, and lead to accurate diagnoses, prevention measures, and effective treatment options.
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- 2020
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17. Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model.
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Bates BD, Godbout C, Ramnaraign DJ, Schemitsch EH, and Nauth A
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The repair of segmental bone defects remains a significant challenge for orthopaedic surgeons. Endothelial progenitor cells (EPCs) have successfully promoted the repair of acute defects in animal models; however, the ability of EPCs to induce the repair of chronic nonhealing defects, such as those often encountered clinically, has not been investigated. Therefore, the purpose of this study was to investigate the ability of EPCs delivered in delayed fashion to induce the repair of nonhealing defects in a clinically relevant model. In order to simulate delayed treatment, 5 mm segmental defects in Fischer 344 rat femora were treated with bone marrow-derived EPCs on a Gelfoam scaffold at 3 weeks post creation of the defect. At ten weeks posttreatment, 100% of EPC-treated defects achieved union, whereas complete union was only achieved in 37.5% of defects treated with Gelfoam alone. Furthermore, significant increases in ultimate torque ( p = 0.022) and torsional stiffness ( p = 0.003) were found in EPC-treated defects compared to controls. Critically, no differences in outcomes were observed between acute and delayed EPC treatments. These results suggest that EPCs can enhance bone healing when applied in an acute or delayed fashion and that their use may represent a clinically translatable therapy for bone healing in humans.
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- 2017
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18. Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair.
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Cadby JA, Buehler E, Godbout C, van Weeren PR, and Snedeker JG
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- Adipogenesis, Animals, Biomarkers, Cell Culture Techniques, Cell Differentiation, Cell Movement, Cell Proliferation, Colony-Forming Units Assay, Gene Expression Profiling, Gene Expression Regulation, Horses, Myofibroblasts cytology, Myofibroblasts metabolism, Osteogenesis, Stem Cells cytology, Tendon Injuries genetics, Tendon Injuries metabolism, Tendons metabolism, Tendon Injuries therapy, Tendons cytology, Wound Healing physiology
- Abstract
The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in peritenon cells. Cells from the peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the peritenon have substantial potential to influence tendon-healing outcome, warranting further scrutiny of their role.
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- 2014
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19. The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.
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Godbout C, Follonier Castella L, Smith EA, Talele N, Chow ML, Garonna A, and Hinz B
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- Actins chemistry, Animals, Biomechanical Phenomena, Cell Adhesion, Extracellular Matrix metabolism, Myofibroblasts metabolism, Rats, Stress, Mechanical, Calcium Signaling, Intracellular Space metabolism, Mechanical Phenomena, Myofibroblasts cytology
- Abstract
Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.
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- 2013
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20. Molecular mechanism by which a potent hepatitis C virus NS3-NS4A protease inhibitor overcomes emergence of resistance.
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O'Meara JA, Lemke CT, Godbout C, Kukolj G, Lagacé L, Moreau B, Thibeault D, White PW, and Llinàs-Brunet M
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- Antiviral Agents pharmacology, Cell Line, Cloning, Molecular, Crystallography, X-Ray methods, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Models, Chemical, Models, Molecular, Molecular Conformation, Protease Inhibitors pharmacology, Sulfonamides chemistry, X-Rays, Carrier Proteins chemistry, Drug Resistance, Viral, Hepatitis C drug therapy, Viral Nonstructural Proteins chemistry
- Abstract
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms.
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- 2013
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21. Direct optical measurements of the evolving spatio-temporal charge density in ultrashort electron pulses.
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Morrison VR, Chatelain RP, Godbout C, and Siwick BJ
- Abstract
The temporal evolution of the charge density distribution in femtosecond laser produced electron pulses was studied using electron-laser pulse cross correlation techniques and compared to analytical predictions and simulations. The influence of propagation time and weak magnetic focusing were both investigated. Our results show that ultrashort electron pulses develop a relatively uniform internal charge density as they propagate, which is in good agreement with analytical predictions, and that weakly focusing an ultrashort electron pulse results in an increased internal charge density towards the leading edge of the pulse.
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- 2013
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22. Hypoxia impairs skin myofibroblast differentiation and function.
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Modarressi A, Pietramaggiori G, Godbout C, Vigato E, Pittet B, and Hinz B
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- Animals, Cell Differentiation physiology, Cell Division physiology, Cells, Cultured, Fibroblasts cytology, Humans, Hypoxia metabolism, Hypoxia physiopathology, Ischemia metabolism, Ischemia pathology, Ischemia physiopathology, Oxygen pharmacology, Rats, Skin injuries, Skin metabolism, Skin pathology, Subcutaneous Tissue physiology, Wounds and Injuries metabolism, Wounds and Injuries physiopathology, Fibroblasts metabolism, Hypoxia pathology, Oxygen metabolism, Wound Healing physiology, Wounds and Injuries pathology
- Abstract
Ischemic wounds are characterized by oxygen levels lower than that of healthy skin (hypoxia) and poor healing. To better understand the pathophysiology of impaired wound healing, we investigated how switching from high (21%) to low (2%) oxygen levels directly affects cultured skin myofibroblasts, essential cells for the normal wound repair process. Myofibroblast differentiation and function were assessed by quantifying α-smooth muscle actin expression and cell contraction in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2% oxygen is perceived as hypoxia and significantly reduced myofibroblast differentiation and contraction despite high levels of the profibrotic transforming growth factor-β1. Analysis of α-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded α-smooth muscle actin disassembly from stress fibers after switching from 21 to 2% oxygen. These effects were reversible by restoring high oxygen conditions and by applying mechanical stress. We suggest that mechanical challenge is a clinical relevant strategy to improve ischemic and chronic wound healing by supporting myofibroblast formation.
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- 2010
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23. A new lock-step mechanism of matrix remodelling based on subcellular contractile events.
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Castella LF, Buscemi L, Godbout C, Meister JJ, and Hinz B
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- Actins metabolism, Animals, Calcium Signaling, Cell Differentiation, Cells, Cultured, Focal Adhesions metabolism, Models, Biological, Myocardial Contraction, Rats, rho-Associated Kinases metabolism, Extracellular Matrix metabolism, Fibroblasts physiology, Fibrosis physiopathology, Muscle Cells physiology, Stress Fibers metabolism
- Abstract
Myofibroblasts promote tissue contractures during fibrotic diseases. To understand how spontaneous changes in the intracellular calcium concentration, [Ca(2+)](i), contribute to myofibroblast contraction, we analysed both [Ca(2+)](i) and subcellular contractions. Contractile events were assessed by tracking stress-fibre-linked microbeads and measured by atomic force microscopy. Myofibroblasts exhibit periodic (approximately 100 seconds) [Ca(2+)](i) oscillations that control small (approximately 400 nm) and weak (approximately 100 pN) contractions. Whereas depletion of [Ca(2+)](i) reduces these microcontractions, cell isometric tension is unaffected, as shown by growing cells on deformable substrates. Inhibition of Rho- and ROCK-mediated Ca(2+)-independent contraction has no effect on microcontractions, but abolishes cell tension. On the basis of this two-level regulation of myofibroblast contraction, we propose a single-cell lock-step model. Rho- and ROCK-dependent isometric tension generates slack in extracellular matrix fibrils, which are then accessible for the low-amplitude and high-frequency contractions mediated by [Ca(2+)](i). The joint action of both contraction modes can result in macroscopic tissue contractures of approximately 1 cm per month.
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- 2010
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24. Stereoselective synthesis of (+)-euphococcinine and (-)-adaline.
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Arbour M, Roy S, Godbout C, and Spino C
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- Alkaloids chemistry, Bridged-Ring Compounds chemistry, Carbon chemistry, Cyanates chemistry, Cyclization, Isocyanates chemistry, Nitrogen chemistry, Piperidines chemistry, Stereoisomerism, Substrate Specificity, Alkaloids chemical synthesis, Bridged-Ring Compounds chemical synthesis, Piperidines chemical synthesis
- Abstract
We describe the syntheses of (+)-euphococcinine and (-)-adaline, two naturally occurring alkaloids containing a quaternary carbon bearing a nitrogen atom. Key features of the syntheses are a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration.
- Published
- 2009
- Full Text
- View/download PDF
25. Sterically biased 3,3-sigmatropic rearrangement of chiral allylic azides: application to the total syntheses of alkaloids.
- Author
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Lauzon S, Tremblay F, Gagnon D, Godbout C, Chabot C, Mercier-Shanks C, Perreault S, DeSève H, and Spino C
- Subjects
- Allyl Compounds chemical synthesis, Amino Acids chemical synthesis, Animals, Azides chemical synthesis, Heterocyclic Compounds chemical synthesis, Piperidines chemical synthesis, Quinolines chemical synthesis, Stereoisomerism, Alkaloids chemical synthesis, Allyl Compounds chemistry, Azides chemistry
- Abstract
We describe a tandem Mitsunobu/3,3-sigmatropic rearrangement of allylic azides on a chiral auxiliary system that favors one regioisomer thanks to its exceptional steric bias. The sequence may be completed by the oxidative cleavage of the auxiliary or by a ring-closing metathesis reaction that produces a carbo- or heterocycle directly and a recyclable form of the chiral auxiliary. Applications of the methodology to the total synthesis of (+)-coniine, (+)-lentiginosin, and (+)-pumiliotoxin C are reported.
- Published
- 2008
- Full Text
- View/download PDF
26. Early voluntary exercise does not promote healing in a rat model of Achilles tendon injury.
- Author
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Godbout C, Ang O, and Frenette J
- Subjects
- Animals, Disease Models, Animal, Male, Physical Exertion, Rats, Rats, Wistar, Stress, Mechanical, Treatment Outcome, Volition, Exercise Therapy methods, Macrophage Activation immunology, Mechanotransduction, Cellular immunology, Neutrophil Activation immunology, Tendon Injuries immunology, Tendon Injuries therapy, Wound Healing immunology
- Abstract
Mechanical stress is an important modulator of connective tissue repair. However, the effects on tendon healing are very poorly defined, preventing optimal use of mechanical stress. We hypothesized that early voluntary exercise initially retards tendon repair but results in a faster recovery rate at longer term. Male Wistar rats were injured by a collagenase injection in the Achilles tendon, and exercise was voluntarily performed on a running wheel. We observed the persistent presence of neutrophils in injured tendons of rats that began exercise immediately after the trauma [injured + early exercise (Inj+EEx)]. Early exercise also increased the concentration of ED1(+) macrophages in injured tendons after 3 and 7 days compared with ambulatory injured rats (Inj). Similar results were obtained with the subset of ED2(+) macrophages in the tendon core 3 days after the collagenase injection. Furthermore, collagen content returned to normal values more rapidly in the Inj+EEx tendons than in the Inj group, but this was not associated with an increase in cell proliferation. Surprisingly, Inj+EEx tendons roughly displayed lower stiffness and force at rupture point relative to Inj tendons at day 28. Injured tendons of rats that began exercise only from day 7 had better mechanical properties than those of early-exercised rats 28 days postinjury. We speculate that the persistence of the inflammatory response and undue mechanical loading in the Inj+EEx tendons led to fibrosis and a loss of tendon function.
- Published
- 2006
- Full Text
- View/download PDF
27. Periodic direct current does not promote wound closure in an in vitro dynamic model of cell migration.
- Author
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Godbout C and Frenette J
- Subjects
- Animals, Cells, Cultured, Fibroblasts ultrastructure, Image Processing, Computer-Assisted, Microscopy, Rats, Video Recording, Cell Movement, Electric Stimulation, Fibroblasts physiology, Models, Biological, Wound Healing physiology
- Abstract
Background and Purpose: A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration., Methods and Results: Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC., Discussion and Conclusion: Contrary to the authors' expectations, they found that periodic DC did not promote wound closure, a finding that emphasizes the need to clarify the complex effects of electrical fields on migrating cells.
- Published
- 2006
- Full Text
- View/download PDF
28. Ti-catalyzed reactions of hindered isocyanates with alcohols.
- Author
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Spino C, Joly MA, Godbout C, and Arbour M
- Abstract
Highly hindered and sensitive isocyanates react with alcohols under mild catalysis by titanium tetra-t-butoxide to give high yields of the corresponding carbamates.
- Published
- 2005
- Full Text
- View/download PDF
29. Macrophages, not neutrophils, infiltrate skeletal muscle in mice deficient in P/E selectins after mechanical reloading.
- Author
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Frenette J, Chbinou N, Godbout C, Marsolais D, and Frenette PS
- Subjects
- Animals, Leukocyte Count, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Muscle Fibers, Skeletal pathology, Muscle, Skeletal pathology, Myositis immunology, Myositis pathology, Myositis physiopathology, Stress, Mechanical, Weight-Bearing, E-Selectin genetics, Hindlimb Suspension physiology, Macrophages cytology, Muscle, Skeletal immunology, Muscle, Skeletal physiopathology, Neutrophils cytology, P-Selectin genetics
- Abstract
Our objective was to test the hypothesis that endothelial selectins, P and E selectins, are necessary for leukocyte migration after muscle injury from unloading/reloading. Mice hindlimbs were suspended for 10 days followed by reloading periods of 6 or 24 h after which the soleus muscle was dissected. Light microscopic observations showed that macrophages, but not neutrophils, were able to invade soleus muscles in mice deficient in P/E selectins (P/E-/-) during reloading periods. The recruitment efficiency of neutrophils after 6 and 24 h of reloading was minimal in P/E-/- mice relative to unloaded animals. The recruitment of macrophages in the soleus muscle was preserved in P/E-/- mice. The concentration of macrophages increased by 8.1-fold compared with unloaded muscles in double-mutant mice after 24 h of reloading. The accumulation of macrophages in reloaded muscles did not lead to fiber necrosis. Together, these findings indicate that macrophages can invade skeletal muscle through cellular mechanisms that do not involve P/E selectins during skeletal muscle reloading.
- Published
- 2003
- Full Text
- View/download PDF
30. Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors.
- Author
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Liu HX, Brumovsky P, Schmidt R, Brown W, Payza K, Hodzic L, Pou C, Godbout C, and Hökfelt T
- Subjects
- Analgesics, Non-Narcotic administration & dosage, Analgesics, Non-Narcotic pharmacology, Animals, Causalgia chemically induced, Causalgia drug therapy, Cold Temperature adverse effects, Dose-Response Relationship, Drug, Galanin administration & dosage, Galanin chemistry, Galanin therapeutic use, Galanin toxicity, Ganglia, Spinal chemistry, Ganglia, Spinal drug effects, Hindlimb innervation, Hyperesthesia chemically induced, Hyperesthesia drug therapy, Hyperesthesia etiology, Infusion Pumps, Implantable, Male, Models, Animal, Nerve Tissue Proteins agonists, Pain Threshold drug effects, Peptide Fragments chemistry, Protein Isoforms agonists, Rats, Rats, Sprague-Dawley, Receptors, Galanin, Receptors, Neuropeptide agonists, Sciatic Nerve injuries, Sciatica drug therapy, Sciatica etiology, Spinal Cord chemistry, Stress, Mechanical, Substrate Specificity, Analgesics, Non-Narcotic therapeutic use, Causalgia physiopathology, Galanin pharmacology, Galanin physiology, Hyperesthesia physiopathology, Nerve Tissue Proteins physiology, Peptide Fragments pharmacology, Protein Isoforms physiology, Receptors, Neuropeptide physiology, Sciatica physiopathology, Spinal Cord physiopathology
- Abstract
Galanin is a 29-aa neuropeptide with a complex role in pain processing. Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in studies of a rat neuropathic pain model (Bennett). The results show that in normal rats mechanical and cold allodynia of the hindpaw are induced after intrathecal infusion of low-dose galanin (25 ng per 0.5 microl/h). The same effect is seen with equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and GalR2 receptors. In allodynic Bennett model rats, the mechanical threshold increased dose-dependently after intrathecal injection of a high dose of AR-M961, whereas no effect was observed in the control or AR-M1896 group. No effect of either of the two compounds was observed in nonallodynic Bennett model rats. These data indicate that a low dose of galanin has a nociceptive role at the spinal cord level mediated by GalR2 receptors, whereas the antiallodynic effect of high-dose galanin on neuropathic pain is mediated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain.
- Published
- 2001
- Full Text
- View/download PDF
31. How family physicians distinguish acute sinusitis from upper respiratory tract infections: a retrospective analysis.
- Author
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Little DR, Mann BL, and Godbout CJ
- Subjects
- Acute Disease, Adult, Anti-Bacterial Agents therapeutic use, Chi-Square Distribution, Diagnosis, Differential, Diagnostic Techniques, Respiratory System, Female, Humans, Logistic Models, Male, Predictive Value of Tests, Radiography, Regression Analysis, Respiratory Tract Infections drug therapy, Retrospective Studies, Sinusitis drug therapy, Transillumination, Family Practice, Practice Patterns, Physicians', Respiratory Tract Infections diagnosis, Sinusitis diagnosis
- Abstract
Background: The purpose of our study was to examine how physicians diagnose sinusitis in practice. We addressed three specific questions: (1) what clinical factors do physicians look for in evaluating and caring for patients with suspected sinusitis, (2) to what extent do physicians use transillumination and radiograph evaluations in diagnosing sinusitis, and (3) how does the diagnosis of sinusitis influence the decision to prescribe antibiotic therapy?, Methods: We conducted a retrospective review using charts from 25 local family physicians who volunteered to participate in the study. After selecting a random sample of charts of adult patients treated for sinusitis and for upper respiratory tract infection (URI) by each physician, we reviewed the charts to determine the nature of the information collected to differentiate between sinusitis and URI., Results: Rhinorrhea, sinus tenderness, visualization of purulent secretions, and a history of sinusitis were significant predictors of the diagnosis of sinusitis. Antibiotics were prescribed for 98.4% of patients with sinusitis and 13.1% of patients with URI., Conclusions: This sample of physicians based the diagnosis of sinusitis on three prominent clinical findings, which were also significant factors in diagnosing sinusitis in previous studies. The history of sinusitis might influence patient and physician expectations for the diagnosis.
- Published
- 2000
- Full Text
- View/download PDF
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