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 & Breast cancer. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

Abstract: Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma

Abstract: The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment (p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.

Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.

Abstract: 1. The effects of propofol (2,6 di-isopropylphenol) on responses to the selective glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, were investigated in cultured hippocampal neurones of the mouse. Whole cell and single channel currents were recorded by patch-clamp techniques. Drugs were applied with a multi-barrel perfusion system. 2. Propofol produced a reversible, dose-dependent inhibition of whole cell currents activated by NMDA. The concentration of propofol which induced 50% of the maximal inhibition (IC50) was approximately 160 microM. The maximal inhibition was incomplete leaving a residual current of about 33% of the control response. This inhibitory action of propofol was neither voltage- nor use-dependent. 3. Analysis of the dose-response relation for whole cell NMDA-activated currents indicated that propofol caused no significant change in the apparent affinity of the receptor for NMDA. 4. Outside-out patch recordings of single channel currents evoked by NMDA (10 microM) revealed that propofol (100 microM) reversibly decreased the probability of channel opening but did not influence the average duration of channel opening or single channel conductance. 5. Whole-cell currents evoked by kainate (50 microM) were insensitive to propofol (1 microM-1 mM). 6. These results indicate that propofol inhibits the NMDA subtype of glutamate receptor, possibly through an allosteric modulation of channel gating rather than by blocking the open channel. Depression of NMDA-mediated excitatory neurotransmission may contribute to the anaesthetic, amnesic and anti-convulsant properties of propofol.

Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant melanomas.

Abstract: Angiogenesis in malignant melanoma (MM) was evaluated by comparing mean vessel number (MVN) in Spitz's nevi (SN), thick and thin MMs that metastasized, and thick and thin MMs with > or = 10-year survival. Vessels were identified with antibodies against factor VIII-related antigen (FVIII) and CD34 in 37 MMs (17 or = 4.0 mm) with > or = 10-year follow-up and 10 SN from children ( or = 5.5 mm) and five pairs ( or = 5.5 mm, there was no correlation with MVN with either metastasis or death (FVIII P = 0.98; CD34 P = 0.85). Among the thin paired lesions, high MVN (FVIII = 46, CD34 = 39) was significantly related not only to metastasis (FVIII P = 0.04, CD34 P = 0.03) but also to death (FVIII P = 0.04, CD34 P = 0.05). MVN does not separate SN versus MM nor predict outcome in thick (> or = 4.0 mm) MMs; however, high MVN (> or = 42 average) is predictive of metastasis and death in MMs < or = 0.75 mm. Larger matched studies are indicated to confirm this observation.

Point-of-care ultrasonography for the diagnosis of acute cardiogenic pulmonary edema in patients presenting with acute dyspnea: a systematic review and meta-analysis.

Abstract: Objectives:Acute dyspnea is a common presenting complaint to the emergency department (ED), and point-of-care (POC) lung ultrasound (US) has shown promise as a diagnostic tool in this setting. The primary objective of this systematic review was to determine the sensitivity and specificity of