Parker K.,Queen Elizabeth Health science Center |
Hanada E.,Dalhousie University |
Adderson J.,Queen Elizabeth Health science Center
Gait and Posture | Year: 2013
Gait temporal-spatial variability and step regularity as measured by trunk accelerometry, measures relevant to fall risk and mobility, have not been well studied in individuals with lower-limb amputations. The study objective was to explore the differences in gait variability and regularity between individuals with unilateral transtibial amputations due to vascular (VAS) or nonvascular (NVAS) reasons and fall history over the past year. Of the 34 individuals with trans-tibial amputations who participated, 72% of the 18 individuals with VAS and 50% of the 16 individuals with NVAS had experienced at least one fall in the past year. The incidence of falls was not significantly different between groups. Variability measures included the coefficient of variation (CV) in swing time and step length obtained from an electronic walkway. Regularity measures included anteroposterior, medial-lateral and vertical step regularity obtained from trunk accelerations. When controlling for velocity, balance confidence and time since amputation, there were no significant differences in gait variability or regularity measures between individuals with VAS and NVAS. In comparing fallers to nonfallers, no significant differences were found in gait variability or regularity measures when controlling for velocity and balance confidence. Vertical step regularity (p=0.026) was found to be the only significant parameter related to fall history, while it only had poor to fair discriminatory ability related to fall history. There is some indication that individuals who have experienced a fall may walk with decreased regularity and this should be explored in future studies. © 2012.
Burns A.M.,Dalhousie University |
Green P.J.,Dalhousie University |
Pasternak S.,Queen Elizabeth Health science Center
Journal of Cutaneous Pathology | Year: 2012
A 59-year-old female with rheumatoid arthritis on etanercept therapy presented with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non-necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4-month follow-up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid-like disease. We present this case to promote the recognition of TNFα inhibitor-induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas. Copyright © 2012 John Wiley & Sons A/S.
Khaperskyy D.A.,Dalhousie University |
Hatchette T.F.,Dalhousie University |
Hatchette T.F.,Queen Elizabeth Health science Center |
McCormick C.,Dalhousie University |
McCormick C.,Beatrice Hunter Cancer Research Institute
FASEB Journal | Year: 2012
An important component of the mammalian stress response is the reprogramming of translation. A variety of stresses trigger abrupt polysome disassembly and the accumulation of stalled translation preinitiation complexes. These complexes nucleate cytoplasmic stress granules (SGs), sites of mRNA triage in which mRNAs from disassembling polysomes are sorted and the fates of individual transcripts are determined. Here, we demonstrate that influenza A virus (IAV) actively suppresses SG formation during infection, thereby allowing translation of viral mRNAs. Complete inhibition of SG formation is dependent on the function of the viral nonstructural protein 1 (NS1); at late times postinfection, cells infected with NS1-mutant viruses formed SGs in a double-stranded RNA-activated protein kinase (PKR)-dependent fashion. In these cells, SG formation correlated with inhibited viral protein synthesis. Together, these experiments demonstrate the antiviral potential of SGs and reveal a viral countermeasure that limits SG formation. © FASEB.
Wood L.,Queen Elizabeth Health science Center
Expert Opinion on Pharmacotherapy | Year: 2012
Introduction: Over the past decade, a greater understanding into the molecular pathogenesis of renal cell carcinoma (RCC) has led to major advances in treatment options. Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) that targets a number of receptors, including vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR). Sunitinib was one of the first targeted agents studied in metastatic RCC (mRCC) and is currently used worldwide in the management of mRCC. Areas covered: This drug evaluation addresses the preclinical and clinical development of sunitinib. It provides an in-depth discussion of the Phase II data that led to its approval in mRCC and the subsequent Phase III clinical trial comparing sunitinib to interferon-α. More recent data from the large international expanded access trial, in non-clear cell carcinoma patients, different dosing schedule studies and safety issues are also discussed. Finally, areas for the future use of sunitinib, including in the adjuvant setting, are reviewed. Expert opinion: Since the FDA approved sunitinib for advanced RCC in January 2006, much more has been learned about its efficacy and tolerability. Over the past decade of its clinical use, it has become clear that expertise is required when prescribing sunitinib, in terms of maximizing dose, anticipating and managing side effects, and assessing responses. In the future, a better understanding of sunitinib's role compared with other VEGF TKIs and mTOR inhibitors, and in other roles such as the adjuvant setting or in non-clear cell pathology, will become evident. © 2012 Informa UK, Ltd.
Herman C.R.,Queen Elizabeth Health Science Center
Journal of cardiothoracic surgery | Year: 2013
Quality improvement initiatives in cardiac surgery largely rely on risk prediction models. Most often, these models include isolated populations and describe isolated end-points. However, with the changing clinical profile of the cardiac surgical patients, mixed populations models are required to accurately represent the majority of the surgical population. Also, composite model end-points of morbidity and mortality, better reflect outcomes experienced by patients. The model development cohort included 4,270 patients who underwent aortic or mitral valve replacement, or mitral valve repair with/without coronary artery bypass grafting, or isolated coronary artery bypass grafting. A composite end-point of infection, stroke, acute renal failure, or death was evaluated. Age, sex, surgical priority, and procedure were forced, a priori, into the model and then stepwise selection of candidate variables was utilized. Model performance was evaluated by concordance statistic, Hosmer-Lemeshow Goodness of Fit, and calibration plots. Bootstrap technique was employed to validate the model. The model included 16 variables. Several variables were significant such as, emergent surgical priority (OR 4.3; 95% CI 2.9-7.4), CABG + Valve procedure (OR 2.3; 95% CI 1.8-3.0), and frailty (OR 1.7; 95% CI 1.2-2.5), among others. The concordance statistic for the major adverse cardiac events model in a mixed population was 0.764 (95% CL; 0.75-0.79) and had excellent calibration. Development of predictive models with composite end-points and mixed procedure population can yield robust statistical and clinical validity. As they more accurately reflect current cardiac surgical profile, models such as this, are an essential tool in quality improvement efforts.
Stueck A.E.,Queen Elizabeth Health science Center |
Wanless I.R.,Queen Elizabeth Health science Center
Hepatology | Year: 2015
Repair of cirrhotic livers occurs, in part, by repopulation with hepatocytes through the stem/progenitor pathway. There remain many uncertainties regarding this pathway. Hepatocyte "buds" occurring in broad septa are hypothesized to be the anatomic manifestation of this pathway. Our purpose was to define a morphologic sequence of bud maturation to allow a quantitative measure of the importance of the stem/progenitor pathway in humans. Histologic sections from 37 liver resection specimens were stained with trichrome, epithelial cell adhesion molecule (EpCAM), K19, CD34, glutamine synthetase (GS), and Ki-67. Specimens were stratified by etiology (10 biliary, 22 nonbiliary, five controls) and stage. Buds were defined as clusters of hepatocytes within septa. Five levels of bud maturation (0-4) were defined by the progressive increase in hepatocyte progeny relative to cholangiocytes. Level 0 single-cell buds are K19+/GS+/EpCAM+/Heppar1-. In level 1, the progeny are morphologically hepatocytes (K19-/GS+/EpCAM+/Heppar1+). In level 2-4 buds, hepatocytes increase and become progressively GS- and EpCAM-. Associated endothelium is CD34+ in level 1-2 buds and becomes CD34- near hepatic veins in level 3-4 buds. Progeny of the bud sequence may represent up to 70% of hepatocytes (immaturity index of 70%). In biliary disease, bud number is reduced in association with duct loss and cholestatic destruction of nascent buds. Conclusions: The stem/progenitor pathway, manifested anatomically by the bud sequence, is a major mechanism for repopulation of cirrhotic livers. The bud sequence reveals some critical features of hepatic morphogenesis, including that 1) the majority of distal cholangiocytes have stem-like properties, and 2) availability of bile ducts and/or venous drainage are limiting factors for regeneration. © 2015 by the American Association for the Study of Liver Diseases.
Kanellakos G.W.,Queen Elizabeth Health science Center
Anesthesiology Clinics | Year: 2012
This article describes the perioperative risks of pregnant patients with anterior mediastinal masses, and demonstrates the importance of a multidisciplinary approach for the management of high-risk patients. Mediastinal mass syndrome is defined as immediate right heart failure secondary to vascular compression when positive pressure ventilation is initiated. Greater emphasis on the potential for cardiovascular collapse (versus respiratory collapse) challenges the conventional teaching of risks associated with mediastinal masses in the adult population. © 2012 Elsevier Inc.
Parkash R.,Queen Elizabeth Health science Center |
Tang A.S.L.,Royal Jubilee Hospital |
Sapp J.L.,Queen Elizabeth Health science Center |
Wells G.,University of Ottawa
Journal of Cardiovascular Electrophysiology | Year: 2011
Review of the Catheter Ablation Technique in AF. Background: Several randomized controlled trials (RCTs) have been published to investigate the optimal techniques for atrial fibrillation (AF) ablation. Many of these are small in number and include both paroxysmal and persistent AF; however, the techniques for each of these types of AF may differ. Method and Results: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for RCTs evaluating AF ablation for either paroxysmal or persistent AF. The primary endpoint was freedom from AF after a single procedure. A total of 35 unique randomized controlled trials were found to fulfill the criteria. A significant degree of heterogeneity was present given the differing sample sizes, populations studied, and outcomes. Radiofrequency ablation (RFA) was found to be favorable in prevention of AF over antiarrhythmic drugs (AADs) in either paroxysmal (5 studies, RR 2.26; 95% CI 1.74, 2.94) or persistent AF (5 studies, RR 3.20; 95% CI 1.29, 8.41). When comparing specific techniques, wide-area PVI appeared to offer the most benefit for both paroxysmal (6 studies, RR 0.78; 95% CI 0.63, 0.97) and persistent AF (3 studies, RR 0.64; 95% CI 0.43, 0.94). CFE ablation provided only benefit for persistent AF when combined with antral PVI (4 studies, RR 0.55; 95% CI 0.34, 0.87). Conclusions: Despite significant methodological limitations, it appears that additional ablations beyond PVI are necessary for persistent AF but not proven for paroxysmal AF. The optimal technique for persistent AF, however, deserves a further study, in the setting of a large, randomized controlled trial. © 2011 Wiley Periodicals, Inc.
Kelly R.,Queen Elizabeth Health Science Center |
Buth K.J.,Queen Elizabeth Health Science Center |
Legare J.-F.,Queen Elizabeth Health Science Center
Journal of Thoracic and Cardiovascular Surgery | Year: 2012
Objective: The objective of this study was to examine the effect of arterial grafting on long-term coronary artery bypass grafting mortality. Methods: Consecutive coronary artery bypass grafting surgeries performed at a single tertiary care center between 1995 and 2007 were reviewed. Long-term survival was compared among patients according to the type of arterial grafts used: no internal thoracic artery, single internal thoracic artery, single internal thoracic artery with other arterial graft, or bilateral internal thoracic artery. Cox proportional hazard models were generated to examine the association of arterial grafting with mortality. Results: A total of 8264 isolated coronary artery bypass grafting operations were performed and followed for a median time of 4.7 years (interquartile range, 2.1-7.5). A single internal thoracic artery was used in the majority of patients (79%), multiple arterial grafts were used in 24% of patients, and bilateral internal thoracic artery grafts were used in 13% of patients. Patients who received multiple arterial grafts were more likely to be younger, to be male, and to undergo non-urgent surgery. After adjusting for these differences, patients who received bilateral internal thoracic artery grafts were found to have a significant survival advantage when compared with all other patients, including those who received a single internal thoracic artery plus other arterial grafts (hazard ratio, 0.818; confidence interval, 0.672-0.996). Survival at 10 years was 71% for patients with bilateral internal thoracic artery grafts compared with 66% for patients with single internal thoracic artery grafts and 58% for patients with no internal thoracic artery graft. Patients with bilateral internal thoracic artery grafts had significantly better freedom from readmission for acute coronary syndrome (hazard ratio, 0.802; confidence interval, 0.668-0.963). Conclusions: After adjusting for relevant clinical differences, only multiple arterial grafting using the bilateral internal thoracic artery was able to offer a long-term survival advantage over single internal thoracic artery grafting in patients undergoing coronary artery bypass grafting. Copyright © 2012 by The American Association for Thoracic Surgery.
Fleming K.E.,Queen Elizabeth Health science Center |
Wanless I.R.,Queen Elizabeth Health science Center
Liver International | Year: 2013
Background & Aims: In normal human liver, glutamine synthetase (GS) is expressed in a rim of hepatocytes surrounding hepatic veins. GS expression is decreased in cirrhosis and increased in chronic hepatitis, focal nodular hyperplasia, peritumoural hyperplasia and some hepatocellular neoplasms. For the non-neoplastic conditions, there is limited information available on histological pattern of altered GS expression and the mechanisms of these changes. Methods: We examined GS expression in 58 large specimens and 45 needle biopsies with a variety of non-neoplastic human liver conditions and in 12 normal control livers. Expression was correlated with clinical and histological disease states. Results: We identified four patterns of GS expression: (i) Loss of normal perivenular expression was seen in states of chronic congestion, severe cirrhosis and zone 3 necrosis. (ii) Diffuse expression was seen in states with active hepatocellular injury and correlated with Ki-67 expression. (iii) Interface expression was seen in feathery degeneration of chronic cholestasis. (iv) GS expression in activated hepatocyte progenitor cells (HPCs) associated with small ducts and ductules was seen in fulminant hepatic failure and in early and late chronic liver disease and rarely in normal livers. Conclusions: Glutamine synthetase expression is increased in regenerating hepatocytes and in early HPCs prior to morphological evidence of hepatocellular differentiation. This may be the earliest marker of HPCs yet demonstrated. Loss of expression may be a reflection of disrupted endothelium-hepatocyte contact in hepatic vein walls caused by congestive injury as found in congestive heart failure and advanced cirrhosis. © 2013 John Wiley & Sons A/S.