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Menon B.K.,University of Calgary | Goyal M.,University of Calgary | Goyal M.,Seaman Family Research Center
Expert Review of Cardiovascular Therapy | Year: 2011

Stroke is the third leading cause of death and a leading cause of severe long-term disability worldwide. It costs the world's economy billions of dollars each year in physician services, hospital costs, lost wages and decreased productivity. Rapid advances in medical technology have resulted in an explosion of treatment strategies in the management of acute ischemic stroke. Each clinical scenario presents unique challenges related to risks and benefits of therapy. In this article, we review the evolution of endovascular therapy in acute ischemic stroke, discuss the latest advances, challenges and controversies in the field and speculate on the future of this therapy. © 2011 Expert Reviews Ltd. Source


Doiron A.L.,University of Calgary | Doiron A.L.,Seaman Family Research Center | Clark B.,University of Calgary | Rinker K.D.,University of Calgary
Biotechnology and Bioengineering | Year: 2011

Nanoparticles are increasingly important in medical research for application to areas such as drug delivery and imaging. Understanding the interactions of nanoparticles with cells in physiologically relevant environments is vital for their acceptance, and cell-particle interactions likely vary based on the design of the particle including its size, shape, and surface chemistry. For this reason, the kinetic interactions of fluorescent nanoparticles of sizes 20, 100, 200, and 500nm with human umbilical vein endothelial cells (HUVEC) were determined by (1) measuring nanoparticles per cell at 37 and 4°C (to inhibit endocytosis) and (2) modeling experimental particle uptake data with equations describing particle attachment, detachment, and internalization. Additionally, the influence of cell substrate compliance on nanoparticle attachment and uptake was investigated. Results show that the number of binding sites per cell decreased with increasing nanoparticle size, while the attachment coefficient increased. By comparing HUVEC grown on either a thin coating of collagen or on top of three-dimensional collagen hydrogel, nanoparticle attachment and internalization were shown to be influenced significantly by the substrate on which the cells are cultured. This study concludes that both particle size and cell culture substrate compliance appreciably influence the binding of nanoparticles; important factors in translating in vitro studies of nanoparticle interactions to in vivo studies focused on therapeutic or diagnostic applications. © 2011 Wiley Periodicals, Inc.. Source


Eesa M.,University of Calgary | Almekhlafi M.A.,University of Calgary | Almekhlafi M.A.,King Abdulaziz University | Mitha A.P.,University of Calgary | And 3 more authors.
Neuroradiology | Year: 2012

Introduction: Timely recanalization during endovascular procedures for acute ischemic stroke can be challenging in cases with large clot burden, such as those encountered in the terminal internal carotid T- or L-type occlusion. Methods: A novel but simple technique to achieve fast reduction in clot burden in stroke patients with occlusion of the internal carotid artery termination is described where manual suction using a 60-ml syringe applied through an 8-F balloon guide catheter positioned in the cervical carotid vasculature with proximal flow arrest allows subsequent revascularization of the residual middle cerebral artery clot. Results: The use of manual suction through a balloon-tipped guide catheter in internal carotid artery L- or T-type occlusion is illustrated. This resulted in a significant reduction of the clot burden and facilitated further interventions leading to full recanalization. Conclusion: Manual suction using a 60-ml syringe through a ballon guide catheter is a useful and feasible technique that facilitates thrombectomy of large burden cerebral clots. © 2012 Springer-Verlag. Source


Evans A.,Sunnybrook Health science Center | Demchuk A.,Seaman Family Research Center | Symons S.P.,Sunnybrook Health science Center | Dowlatshahi D.,Seaman Family Research Center | And 3 more authors.
Stroke | Year: 2010

Background And Purpose-: Mural thickening and permeability changes in patients with amyloid angiopathy (CAA) and chronic hypertension are implicated in the pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign, contrast extravasation on CT angiography, predicts hematoma expansion and is presumed to represent acute vessel damage. We hypothesize that the Spot sign is more common in patients without multiple prior chronic microbleeds. Methods-: A retrospective study was conducted of 59 patients presenting within 6 hours of primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT angiography spot sign presence was documented blinded to MRI. Hematoma expansion was defined as >6 mL or 30% enlargement. The Boston criteria were applied to microbleed interpretation dichotomizing subjects into probable and negative CAA. Basal ganglia, thalamic, and brain stem microbleed location were interpreted as chronic hypertensive pattern. Univariate logistic regression and ordinal logistic regression analysis identified significant predictive factors between spot-positive and -negative patients or microbleed pattern. Results-: The incidence of spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and CAA-positive patients, respectively (P=0.01). CAA-negative patients had higher baseline National Institutes of Health Stroke Scale (P=0.039), larger follow-up hematoma volume (P=0.02), and poorer Rankin score (P=0.049) than chronic hypertensive or CAA-positive patients. After age adjustment, spot-positive (P=0.023), age-related white matter change (P=0.041), number of microbleeds (P<0.0001), and modified Rankin score (P=0.027) remained significantly different between groups. Conclusion-: Boston criteria-defined CAA-negative status demonstrates the highest risk of spot positivity compared with patients with probable CAA and chronic hypertension. © 2010 American Heart Association, Inc. Source


Fluck D.,ETH Zurich | Fluck D.,University of Calgary | Fluck D.,University of Zurich | Beaudin A.E.,University of Calgary | And 9 more authors.
Frontiers in Physiology | Year: 2014

Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older = 106 ± 17%, p < 0.001) and systemic (young = 59 ± 9% and older = 80 ± 9%, p < 0.001) augmentation indices (AI) were higher in the older group. CBF responses to VS (PCA: p < 0.026) and hypercapnia (PCA: p = 0.018; MCA: p = 0.042) were lower in the older group. A curvilinear model fitted to cerebral AI and age showed AI increases until ~60 years of age, after which the increase levels off (PCA: R2 = 0.45, p < 0.001; MCA: R2 = 0.31, p < 0.001). Finally, MCA, but not PCA, hypercapnic reactivity was inversely related to cerebral AI (MCA: R2 = 0.28, p = 0.002; PCA: R2 = 0.10, p = 0.104). A similar inverse relationship was not observed with the PCA blood flow response to VS (R2 = 0.06, p = 0.174). In conclusion, older subjects had reduced neurovascular- and hypercapnia-mediated CBF responses. Furthermore, lower hypercapnia-mediated blood flow responses through the MCA were associated with increased vascular stiffness. These findings suggest the reduced hypercapnia-evoked CBF responses through the MCA, in older individuals may be secondary to vascular stiffening. © 2014 Flück, Beaudin, Steinback, Kumarpillai, Shobha, McCreary, Peca, Smith and Poulin. Source

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