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.

Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome

Abstract: Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT-PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders.

Does Inclusion of a Placebo Arm Influence Response to Active Antidepressant Treatment in Randomized Controlled Trials? Results From Pooled and Meta-Analyses

Abstract: OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

Assessing Individual Risk for Prostate Cancer

Abstract: Purpose To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC. Patients and Methods We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score ≥ 7). Results Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio,...

Association of Diet-Induced Hyperinsulinemia With Accelerated Growth of Prostate Cancer (LNCaP) Xenografts

Abstract: Background Prior research suggested that energy balance and fat intake influence prostate cancer progression, but the influence of dietary carbohydrate on prostate cancer progression has not been well characterized. We hypothesized that hyperinsulinemia resulting from high intake of refined carbohydrates would lead to more rapid growth of tumors in the murine LNCaP xenograft model of prostate cancer. Methods Athymic mice were injected subcutaneously with LNCaP human prostate cancer cells and, when tumors were palpable, were randomly assigned (n = 20 per group) to high carbohydrate – high fat or low carbohydrate – high fat diets. Body weight and tumor volume were measured weekly. After 9 weeks, serum levels of insulin and insulin-like growth factor 1 (IGF-1) were measured by enzyme immunoassay. AKT activation and the levels of the insulin receptor in tumor cells were determined by immunoblotting. The in vitro growth response of LNCaP cells to serum from mice in the two treatment groups was measured based on tetrazolium compound reduction. All statistical tests were two-sided. Results After 9 weeks on the experimental diets, mice on the high carbohydrate – high fat diet were heavier (mean body weight of mice on the high carbohydrate – high fat diet = 34 g versus 29.1 g on the low carbohydrate – high fat diet, difference = 4.9 g, 95% CI = 3.8 to 6.0 g; P = .003), experienced increased tumor growth (mean tumor volume in mice on high carbohydrate – high fat diet = 1695 versus 980 mm 3 on low carbohydrate – high fat diet, difference = 715 mm 3 , 95% CI = 608 to 822 mm 3 ; P <.001), and experienced a statistically significant increase in serum insulin and IGF-1 levels. Tumors from mice on the high carbohydrate – high fat diet had higher levels of activated AKT and modestly higher insulin receptor levels than tumors from mice on the low carbohydrate – high fat diet. Serum from mice on the high carbohydrate – high fat diet was more mitogenic for LNCaP cells in vitro than serum from mice fed the low carbohydrate – high fat diet. Conclusion A diet high in refined carbohydrates is associated with increased tumor growth and with activation of signaling pathways distal to the insulin receptor in a murine model of prostate cancer.