Martin G.,LOEX Inc |
Guerard S.,LOEX Inc |
Fortin M.-M.R.,LOEX Inc |
Rusu D.,Laval University |
And 3 more authors.
Laboratory Investigation | Year: 2012
Psoriasis, a chronic autoimmune-related skin disease, involves both immune and non-immune cells like T cells and keratinocytes. This study investigates the regulatory role of T cells-keratinocyte interactions during psoriasis on immune factors production. Cytokines and chemokines were evaluated by multiplex and ELISA assays in an in vitro model of co-culture of keratinocytes with T lymphocytes. Keratinocytes were from psoriatic skin lesions or healthy skin. T lymphocytes were from healthy volunteers. Psoriatic keratinocytes (PKs) alone generated concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1Β, IL-8, monocyte chemotactic protein (MCP)-1, interferon-γ-induced protein 10 kDa (IP-10) and vascular endothelial growth factor (VEGF) higher than those produced by healthy keratinocytes (HKs). In contrast, IL-1α and IL-Ra production was reduced in PKs. Normal T cells, which had no effect on HKs, increased the production of TNF-α, IL-6, GM-CSF, IL-8, MCP-1 and IP-10 by PKs, but did not influence PK production of IL-1Β, IL-1α, IL-Ra and VEGF. The most striking effects were obtained with PK-and IL-2-stimulated T lymphocytes: most of the above cytokines and chemokines were greatly upregulated, except IL-1Β and VEGF that were decreased or unchanged, respectively. In addition, fractalkine was overproduced in this latter condition only. Our results indicate (1) a functional interaction between keratinocytes and T lymphocytes that requires a direct cellular contact, and (2) a reciprocal influence that depends on cytokine and chemokine types. In conclusion, lesional keratinocytes from psoriasis vulgaris alter functions of normal T lymphocytes that conversely modulate these keratinocytes. © 2012 USCAP, Inc All rights reserved.
Perry J.J.,Ottawa Hospital |
Perry J.J.,University of Ottawa |
Sharma M.,McMaster University |
Sivilotti M.L.A.,Queen's University |
And 13 more authors.
Stroke | Year: 2014
Background and Purpose-The occurrence of a transient ischemic attack (TIA) increases an individual's risk for subsequent stroke. The objectives of this study were to determine clinical features of patients with TIA associated with impending (=7 days) stroke and to develop a clinical prediction score for impending stroke. Methods-We conducted a prospective cohort study at 8 Canadian emergency departments for 5 years. We enrolled patients with a new TIA. Our outcome was subsequent stroke within 7 days of TIA diagnosis. Results-We prospectively enrolled 3906 patients, of which 86 (2.2%) experienced a stroke within 7 days. Clinical features strongly correlated with having an impending stroke included first-ever TIA, language disturbance, longer duration, weakness, gait disturbance, elevated blood pressure, atrial fibrillation on ECG, infarction on computed tomography, and elevated blood glucose. Variables less associated with having an impending stroke included vertigo, lightheadedness, and visual loss. From this cohort, we derived the Canadian TIA Score which identifies the risk of subsequent stroke =7 days and consists of 13 variables. This model has good discrimination with a c-statistic of 0.77 (95% confidence interval, 0.73-0.82). Conclusions-Patients with TIA with their first TIA, language disturbance, duration of symptoms =10 minutes, gait disturbance, atrial fibrillation, infarction on computed tomography, elevated platelets or glucose, unilateral weakness, history of carotid stenosis, and elevated diastolic blood pressure are at higher risk for an impending stroke. Patients with vertigo and no high-risk features are at low risk. The Canadian TIA Score quantifies the impending stroke risk following TIA. © 2013 American Heart Association, Inc.
Zhao J.,University of Québec |
Dupre N.,Hopital de lEnfant Jesus |
Puymirat J.,Unite de recherche genetique humaine |
Chahine M.,University of Québec
Journal of Physiology | Year: 2012
M1476I, a French Canadian founder mutation of Na+ channel Nav1.4, causes potassium-aggravated myotonia, with cold-induced myotonia as the most distinctive clinical feature. Mexiletine, a class 1B local anaesthetic, relieves the myotonic symptoms of patients carrying the M1476I mutation. We used the patch-clamp method to investigate the functional characteristics of this mutation by heterologous expression in tsA201 cells. The M1476I mutation caused an increased persistent Na+ current, a 2- to 3-fold slower fast inactivation, a 6.4 mV depolarizing shift in the midpoint of steady-state inactivation, and an accelerated recovery from fast inactivation compared to the wild-type (WT) channel. Cooling slowed the kinetics of both channel types and increased the amplitude of the persistent current in M1476I channels. Mexiletine suppressed the persistent Na+ current generated by the M1476I mutation and blocked both WT and M1476I channels in a use-dependent manner. The inactivation-deficient M1476I channels were less susceptible to mexiletine during repetitive pulses. The decreased use-dependent block of M1476I channels might have resulted from the slower onset of mexiletine block, and/or the faster recovery from mexiletine block, given that the affinity of mexiletine for the inactivated state of the WT and mutant channels was similar. Increased extracellular concentrations of potassium had no effect on either M1476I or WT currents. These results indicated that cooling can augment the disruption of the voltage dependence of fast inactivation by M1476I channels. The therapeutic efficacy of mexiletine in M1476I carriers may be partly due to the open-channel block targeting the persistent Na+ currents generated by M1476I channels. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.
PubMed | Hopital de lEnfant Jesus, University Paris DescartesParis, French Institute of Health and Medical Research and Institut Universitaire de France
Type: | Journal: Frontiers in human neuroscience | Year: 2016
A major feature of the human cortex is its huge morphological variability. Although a comprehensive literature about the sulco-gyral pattern of the central region is available from post-mortem data, a reliable and reproducible characterization from in vivo data is still lacking. The aim of this study is to test the reliability of morphological criteria of the central region sulci used in post-mortem data, when applied to in vivo magnetic resonance imaging (MRI) data. Thirty right-handed healthy individuals were included in the study. Automated segmentation and three dimensional (3D) surface-based rendering were obtained from clinical 3D T1-weighted MRI. Two senior radiologists labeled the three sulci composing the central region (precentral [PreCS], central [CS] and postcentral [PostCS]) and analyzed their morphological variations using 47 standard criteria derived from Onos atlas based on post-mortem data. For each criterion, inter-rater concordance and comparison with the occurrence frequency provided in Onos atlas were estimated. Overall, the sulcal pattern criteria derived from MRI data were highly reproducible between the raters with a high mean inter-rater concordance in the three sulci (CS: = 0.92 in left hemisphere/ = 0.91 in right hemisphere; PreCS: = 0.91/ = 0.93; PostCS: = 0.84/0.79). Only a very limited number of sulcal criteria significantly differed between the in vivo and the post-mortem data (CS: 2 criteria in the left hemisphere/3 criteria in the right hemisphere; PreCS: 3 in the left and right hemispheres; PostCS: 3 in the left hemisphere and 5 in the right hemisphere). Our study provides a comprehensive description of qualitative sulcal patterns in the central region from in vivo clinical MRI with high agreement with previous post-mortem data. Such identification of reliable sulcal patterns of the central region visible with standard clinical MRI data paves the way for the detection of subtle variations of the central sulcation associated with variations of normal or pathological functioning.
PubMed | The Ottawa Hospital, Interventional Imaging, Ottawa Hospital Research Institute and Hopital de LEnfant Jesus
Type: | Journal: Journal of clinical epidemiology | Year: 2016
We derived and validated a method to screen all hospital admissions for 1 subarachnoid hemorrhage (SAH) by retrospectively implementing recognized diagnostic criteria.A screen for 1 SAH was developed using two previously created registries. Screen-positive cases underwent diagnosis confirmation with primary record review. A review of all patient hospital encounters with the diagnostic code for 1 SAH, and cross-referencing with an existing SAH registry was undertaken to identify missed cases.Three subscreens were combined to form the 1 SAH screen (sensitivity: 98.4% [95% CI: 91.7-99.7%], specificity: 93.4% [95% CI: 90.4-95.4%], n = 455 patients in validation sample). From 1,699 screen-positive admissions between July 1, 2002 and June 30, 2011, we identified 831 true cases of SAH of which 632 patients had 1 SAH from ruptured aneurysm/arteriovenous malformation (sensitivity: 96.5% [95% CI: 94.8-97.8%], specificity: 40.3% [95% CI: 38.1-42.6%]). A review of all encounters with a diagnostic code for 1 SAH yielded additional 22 true cases.When positive, our 1 SAH screen significantly increases the probability of this diagnosis in a particular hospitalization. The addition of patient hospitalizations encoded with the diagnostic code for 1 SAH improved sensitivity. Together, these methods represent the best way to retrospectively identify all cases of 1 SAH within an extensive sampling frame.
Efficacy and Tolerability of a 20-mg Dose of Methylphenidate for the Treatment of Daytime Sleepiness in Adult Patients With Myotonic Dystrophy Type 1: A 2-Center, Randomized, Double-Blind, Placebo-Controlled, 3-Week Crossover Trial
Puymirat J.,University of Québec |
Bouchard J.-P.,HOpital de lEnfant Jesus |
Mathieu J.,Neuromuscular Clinic
Clinical Therapeutics | Year: 2012
Background: Despite the fact that excessive daytime sleepiness (EDS) is one of the most common manifestations in patients with myotonic dystrophy type 1 (DM1), no treatment is yet available. Methylphenidate is being studied for prospective use in the treatment of EDS. Objective: The aim of this investigator-initiated study was to evaluate the efficacy and tolerability of a single 20-mg morning dose of methylphenidate for the treatment of EDS in adults with DM1. Methods: This randomized, double-blind, placebo-controlled, 3-week crossover trial was conducted at 2 sites in Quebec. French-Canadian patients with DM1 with an Epworth Sleepiness Scale score ≥10 were invited to participate in this crossover trial of 20 mg/d of methylphenidate versus placebo, with 3 weeks in each arm of the study separated by a 2-week washout period. The primary efficacy end points were the Daytime Sleepiness Scale and the Epworth Sleepiness Scale at week 3. Secondary end points included the energy/vitality scale of the RAND 36-Item Health Survey, the Profile of Mood States questionnaire, and the mean sleep latency test. Assessment of tolerability profile included a physical examination, measurement of blood pressure, standard 12-lead ECG, and laboratory tests. Adverse event assessments were recorded based on patient reporting at each visit on clinical report forms. Results: In a total of 24 patients (12 men, 12 women; mean [SD] age, 46  years), 17 completed the study. Treatment with methylphenidate showed a significant change in median scores on the Daytime Sleepiness Scale (-3.0 vs -0.5; . P = 0.003) and the Epworth Sleepiness Scale (-3.0 vs -1.5; . P = 0.039). The Profile of Mood States and the energy/vitality scale from the RAND 36-Item Health Survey showed no significant changes. Likewise, there was no significant change in mean sleep latency test results. One patient died during the trial, but the autopsy results eliminated methylphenidate as cause of death. Three patients discontinued methylphenidate due to treatment-emergent adverse events (1, diarrhea; 2, nervousness and irritability). Loss of appetite, nausea, and palpitations were the most common adverse events reported by more patients treated with methylphenidate than those receiving placebo. Conclusion: A single 20-mg dose of methylphenidate significantly reduced daytime sleepiness in this small selected population of patients with DM1. . ClinicalTrials.gov identifier: . NCT01421992. © 2012 Elsevier HS Journals, Inc.
PubMed | McGill University, CHU Sainte Justine, Laurentian University, University of Toronto and 4 more.
Type: | Journal: BMC hematology | Year: 2016
This study was undertaken to explore the longitudinal patterns of health-related quality of life (HRQoL) among youth and young adults with Hemophilia A (HA) over a 3-year period. This report presents the baseline characteristics of the study cohort.Males, 14 to 29years of age, with predominantly severe HA were recruited from six treatment centres in Canada. Subjects completed a comprehensive survey. HRQoL was measured using: the CHO-KLAT2.0 (youth), Haemo-QoL-A (young adults) and the SF-36v2 (all).13 youth (mean age=15.7, range=12.9-17.9years) and 33 young adults (mean age=23.6; range=18.4 -28.7years) with moderate (7%) and severe (93%) HA were enrolled. All were on a prophylactic regimen with antihemophilic factor (Helixate FS) during the study. The youth had minimal joint damage (mean HJHS=5.2) compared to young adults (mean HJHS=13.3). The mean HRQoL scores for youth were: 79.2 (SD=11.9) for the CHO-KLAT, and 53.0 (5.5) and 52.3 (6.8) for the SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores respectively. The mean HRQoL scores for young adults were: 85.8 (9.5) for the Haemo-Qol-A, and 50.8 (6.4) and 50.9 (8.8) for PCS and MCS respectively. PCS and MCS scores were comparable to published Canadian norms, however significant differences were found for the domains of Physical Functioning and Bodily Pain. The disease-specific HRQoL scores were weakly correlated with the PCS for youth (CHO-KLAT vs. PCS r=0.28, p=0.35); and moderately correlated for the MCS (r=0.39, p=0.19). Haemo-QoL-A scores for young adults were strongly correlated with the PCS (r=0.53, p=0.001); and weakly correlated with the MCS (r=0.26, p=0.13). Joint status as assessed by HJHS was correlated with PCS scores. A history of lifelong prophylaxis resulted in better PCS but worse MCS scores.Despite having hemophilia, the youth in this cohort have minimal joint disease and good HRQoL. The young adults demonstrated more joint disease and slightly worse HRQoL in the domains of physical functioning and pain. The data presented here provide new information to inform the selection of Health Related Quality of Life (HRQoL) instruments for use in future clinical trials involving persons with hemophilia.ClinicalTrials.gov : NCT01034904. Study funded by CSL Behring Canada.
PubMed | McMaster University, Ottawa Hospital Research Institute, Hopital de lEnfant Jesus, Laval University and Queen's University
Type: Journal Article | Journal: Cerebrovascular diseases extra | Year: 2014
Isolated dysarthria is an uncommon presentation of transient ischemic attack (TIA)/minor stroke and has a broad differential diagnosis. There is little information in the literature about how often this presentation is confirmed to be a TIA/stroke, and therefore there is debate about the risk of subsequent vascular events. Given the uncertain prognosis, it is unclear how to best manage patients presenting to the emergency department (ED) with isolated dysarthria. The objective of this study was to prospectively identify and follow a cohort of patients presenting to EDs with isolated dysarthria in order to explore their natural history and risk of recurrent cerebrovascular events. Specifically, we sought to determine early outcomes of individuals with this nonspecific and atypical presentation in order to appropriately expedite their management.Patients with isolated dysarthria having presented to 8 Canadian EDs between October 2006 and April 2009 were analyzed as part of a prospective multicenter cohort study of patients with acute neurological symptoms as assessed by emergency physicians. The study inclusion criteria were age 18 years, a normal level of consciousness, and a symptom onset <1 week prior to presentation without an established nonvascular etiology. The primary outcome was a subsequent stroke within 90 days of the index visit. The secondary outcomes were the rate of TIA, myocardial infarction, and death. Isolated dysarthria was defined as slurring with imprecise articulation but without evidence of language dysfunction. The overall rate of stroke in this cohort was compared with that predicted by the median ABCD2 score for this group.Between 2006 and 2009, 1,528 patients were enrolled and had a 90-day follow-up. Of these, 43 patients presented with isolated acute-onset dysarthria (2.8%). Recurrent stroke occurred in 6/43 (14.0%) within 90 days of enrollment. The predicted maximal 90-day stroke rate was 9.8% (based on a median ABCD2 score of 5 for the isolated dysarthria cohort). After adjusting for covariates, isolated dysarthria independently predicted stroke within 90 days (aOR: 3.96; 95% CI: 1.3-11.9; p = 0.014).The isolated dysarthria cohort carried a recurrent stroke risk comparable to that predicted by the median ABCD2 scores. Although isolated dysarthria is a nonspecific and uncommon clinical presentation of TIA, these findings support the need to view it first and foremost as a vascular presentation until proven otherwise and to manage such patients as if they were at high risk of stroke in accordance with established high-risk TIA guidelines.
Chaleat-Valayer E.,Center Medico Chirurgical Of Readaptation Des Massues |
Mac-Thiong J.-M.,University of Montréal |
Paquet J.,Hopital de lEnfant Jesus |
Berthonnaud E.,University of Lyon |
And 2 more authors.
European Spine Journal | Year: 2011
Introduction: The differences in sagittal spino-pelvic alignment between adults with chronic low back pain (LBP) and the normal population are still poorly understood. In particular, it is still unknown if particular patterns of sagittal spino-pelvic alignment are more prevalent in chronic LBP. The current study helps to better understand the relationship between sagittal alignment and low back pain. Materials and methods: To compare the sagittal spino-pelvic alignment of patients with chronic LBP with a cohort of asymptomatic adults. Sagittal spino-pelvic alignment was evaluated in prospective cohorts of 198 patients with chronic LBP and 709 normal subjects. The two cohorts were compared with respect to the sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), lumbar tilt (LT), lordotic levels, thoracic kyphosis (TK), thoracic tilt (TT), kyphotic levels, and lumbosacral joint angle (LSA). Correlations between parameters were also assessed. Results: Sagittal spino-pelvic alignment is significantly different in chronic LBP with respect to SS, PI, LT, lordotic levels, TK, TT and LSA, but not PT, LL, and kyphotic levels. Correlations between parameters were similar for the two cohorts. As compared to normal adults, a greater proportion of patients with LBP presented low SS and LL associated with a small PI, while a greater proportion of normal subjects presented normal or high SS associated with normal or high PI. Conclusion: Sagittal spino-pelvic alignment was different between patients with chronic LBP and controls. In particular, there was a greater proportion of chronic LBP patients with low SS, low LL and small PI, suggesting the relationship between this specific pattern and the presence of chronic LBP. © 2011 Springer-Verlag.
PubMed | Hopital de lEnfant Jesus
Type: Journal Article | Journal: Journal of rehabilitation medicine | Year: 2016
To determine the reliability of quantitative measures of the long head of the biceps tendon using an ultrasound-imaging system.Intra- and inter-rater reliability study.Thirty-one participants without shoulder pain.All participants took part in 3 ultrasound imaging sessions; they were assessed by 2 evaluators (inter-rater reliability), one of whom assessed them twice (intra-rater reliability). All measurements were taken at the widest identified part of the tendon using longitudinal and transverse views. Measurements of the long head of the biceps tendon included width, thickness and cross-sectional area. Intraclass correlation coefficients and minimal detectable change were used to characterize reliability.Intra- and inter-rater reliabilities were excellent for all measures when the mean of 2 measures were considered, except for inter-rater reliability of the width, for which it ranged from 0.76 to 0.86. Minimal detectable change ranged from 0.3 to 1.6 mm for width and thickness, and from 2.8 to 4.9 mm2 for cross-sectional area.Ultrasound measurement of the long head of the biceps tendon is a highly reliable method, except for the width. When measuring the long head of the biceps tendon, a mean of 2 measurements is recommended. Now that reliability has been shown in healthy individuals, the next step will be to determine the validity/reliability of these quantitative measures in symptomatic shoulders.