Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Characterization of Submicron Phase-change Perfluorocarbon Droplets for Extravascular Ultrasound Imaging of Cancer

Abstract: Because many tumors possess blood vessels permeable to particles with diameters of 200 nm, it is possible that submicron perfluorocarbon droplets could constitute a novel extravascular ultrasound contrast agent capable of selectively enhancing tumors. Under exposure to bursts of ultrasound of sufficient rarefactional pressure, droplets can undergo vaporization to form echogenic microbubbles. In this study, phase-change thresholds of 220-nm–diameter droplets composed of perfluoropentane were studied in polyacrylamide gel phantoms maintained at temperatures of 21–37°C, exposed to high-pressure bursts of ultrasound with frequencies ranging from 5–15 MHz and durations of 1 μs to 1 ms. The thresholds were found to depend inversely and significantly ( p p In vivo experiments in a mouse tumor model demonstrated that intravenously injected droplets can be converted into highly echogenic microbubbles 1 h after administration.

Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart.

Abstract: Aims Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized 13C magnetic resonance (MR), in which 13C-labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non-invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non-invasive hyperpolarized [13C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease. Methods and results Dilated cardiomyopathy (DCM) was induced in pigs (n = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine-MRI assessed cardiac structure and function; hyperpolarized [2-13C]pyruvate was administered intravenously, and 13C MRS monitored [13C]glutamate production; 31P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1-13C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)-mediated pyruvate oxidation via [13C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [13C]glutamate production decreased by 51%. After clinical features of DCM appeared, end-diastolic volume increased by 40% and [13C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two-fold, and phosphorylated Akt decreased by half. Peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1 gene expression decreased by a half and a third, respectively. Conclusion Despite early changes associated with cardiac energetics and 13C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized 13C MR may be important to characterize metabolic changes that occur during heart failure progression.

Management of Skin Rash during egfr-Targeted Monoclonal Antibody Treatment for Gastrointestinal Malignancies: Canadian Recommendations

Abstract: The epidermal growth factor receptor (egfr) is often overexpressed or dysregulated in a variety of solid tumours, including gastrointestinal (gi) malignancies. Agents targeting the egfr-mediated signalling pathway are increasingly part of the therapeutic armamentarium for the treatment of advanced lung, head-and-neck, and colorectal carcinoma. The egfr inhibitors (egfris) approved in Canada include the tyrosine kinase inhibitors erlotinib and gefitinib (in selected cases), and the monoclonal antibodies (mAbs) panitumumab and cetuximab. Although egfris have been proven effective in the treatment of a variety of malignancies, the entire class of agents is associated with a high prevalence of dermatologic side effects, most commonly skin rash. This reversible condition requires intervention in approximately one third of patients. A proactive, multidisciplinary approach to management can help to improve skin rash and optimize clinical outcomes by preventing egfri dose reduction or discontinuation. In addition, effective management and patient education may help to alleviate the significant social and emotional anxiety related to this manageable side effect, thus resulting in improved quality of life. The present article focuses on egfr-targeted mAbs for the treatment of gi malignancy, addressing the pathophysiology, clinical presentation, and incidence of skin rash caused by this class of agents. Recommendations aimed at establishing a framework for consistent, proactive management of skin rash in the Canadian setting are presented.

Silent stroke and carotid stenosis.

Abstract: Silent cerebral infarction is often found on computed tomographic scan in patients with asymptomatic carotid stenosis, but its relation to the arterial stenosis is uncertain.We compared computed tomographic scans and carotid Doppler in 115 patients with asymptomatic carotid stenosis, 203 with carotid transient ischemic attacks and carotid stenosis, and 63 with transient ischemic attacks but without carotid stenosis. There was no group with normal carotid arteries for comparison.Lesions seen on CT scan were most common in the transient ischemic attack with carotid stenosis group (47%) compared with the other groups (30%, 19%) (p less than 0.001). Cerebral infarcts ipsilateral to the carotid stenosis were found in 10% of patients with mild (35-50%) stenosis, 17% in moderate (50-75%) stenosis, and 30% with severe (greater than 75%) carotid stenosis (p less than 0.001). In patients with asymptomatic carotid stenosis, 68% of infarcts were ipsilateral to the stenosis; in those with transient ischemic attacks an...