Medicine and Health Sciences Commons^™

Prostate Cancer Microparticles As A Next Generation Screening Tool For Prostate Cancer, Khurram M. Siddiqui

Electronic Thesis and Dissertation Repository

Currently available screening tests for prostate cancer (PCa) are neither very sensitive nor specific. Microparticles (MP) are submicron tumor cell fragments released by PCa cells into the circulation and offer a possible means of sampling the tumor. We evaluated the utility of a MP blood test using nanoscale flow cytometry to distinguish patients with PCa from patients with benign prostatic hyperplasia (BPH). We used monoclonal antibodies against prostate specific membrane antigen, gastrin releasing peptide receptor and ghrelin peptide ligand.

We found higher but statistically insignificant, PSMA and Ghrelin dual +ve MP counts in the BPH group. Our results show that …

A Comparison Of Clinical Trial And Model-Based Cost Estimates In Glaucoma – The Case Of Repeat Laser Trabeculoplasty In Ontario, Omar Akhtar

Electronic Thesis and Dissertation Repository

Background and objective: For cost-effectiveness analyses (CEA) of glaucoma interventions to be of use they require valid and accurate cost and effectiveness data. Costs remain understudied relative to effectiveness. The impact of cost estimation methods on resultant estimates is unknown in glaucoma. Direct measurement of costs is labour-intensive and expensive. Decision-analytic modelling of costs using literature sources, expert opinion, institutional experience and assumptions provides a quicker, less laborious alternative to empirical costing. A lack of long-term effectiveness data in chronic diseases like glaucoma means that modelling is widespread and inevitable, both for CEAs and budget impact projections. The same problem …

Are Patients At The Centre Of Care?: A Qualitative Exploration Of Myotonic Dystrophy Type 1 (Dm1), Kori A. Ladonna

Electronic Thesis and Dissertation Repository

Health care for individuals living with myotonic dystrophy (DM1)—an uncommon, life-limiting neurological condition for which there are few treatments—may be challenged by patients’ symptoms including cognitive and behavioral impairments. Is patient-centered care—which incorporates the values, experiences and expertise of patients and their caregivers—feasible or achievable? Uncovering patients’ and their caregivers’ experiences of living with DM1, their health care expectations, and their health care providers’ (HCP) perspectives about care is essential for examining patient-centered care in this population. Therefore, the purpose of this research is to: (1) add patients’ and caregivers’ voices to the literature, (2) explore on-going care provision for …

Investigating Cortical Changes In Cervical Spondylotic Myelopathy Using Functional Magnetic Resonance Imaging, Proton Magnetic Resonance Spectroscopy And Diffusion Tensor Imaging, Izabela Kowalczyk

Electronic Thesis and Dissertation Repository

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in older adults. CSM can present abruptly with severe symptoms of neurological impairment or insidiously with a slow stepwise deterioration. There is no current imaging modality or biomarker that can help predict which patient will successfully respond to conservative versus surgical treatment. The goal of this thesis was to follow CSM patients longitudinally to assess how brain function, metabolism, and structure correlate to clinical outcomes in the context of recovering neurological function following surgery.

Chapter 1 of this thesis will provide a detailed literature review of the …

Comparison Of Housed And Homeless Patients With An Orthopedic Diagnosis, Susan M. Williams

Electronic Thesis and Dissertation Repository

Studies on homelessness have shown that people who are homeless are admitted to hospital more frequently, for longer periods of time, and at a younger age than people who are housed. Once admitted to hospital, discharge planning is difficult and resource intensive, often leading to discharge back to the streets or a shelter. This puts this population at risk for complications and readmission. Although people who are homeless are prone to orthopedic injuries, there is no research on the outcomes of patients who are homeless with orthopedic injuries. This retrospective, case control study, based on the social determinants of health, …

Cell Death Regulates Injury And Inflammation During Renal Allograft Transplantation, Arthur Lau

Electronic Thesis and Dissertation Repository

Renal transplantation invariably results in tissue injury resulting from ischemia reperfusion injury (IRI), inflammation, drug toxicity, and rejection. Tubular epithelial cells (TEC) comprise the majority of renal parenchyma and are susceptible to cell death and injury during diverse forms of inflammation, which has direct and indirect effects on long term allograft function. Renal TEC have the unique ability to attenuate inflammation and alloimmune injury through the expression of various mediators of cell death and inflammatory molecules. Inhibition of cell death pathways in renal allografts may influence outcomes of alloimmune responses and graft survival. In this body of investigation, alteration of …

A Health Promotion Perspective On Transitioning Into Retirement, Catherine P. Gelinas

Electronic Thesis and Dissertation Repository

The transitional stages towards retirement of those with chronic disorder(s) often present a diversity of additional challenges and people look at the measurement of their anticipated quality of life as a meaningful way of determining this successful adjustment. The overall objective of this research study was to understand transition into retirement considering the impact of comorbidity and associated socio-demographic factors have on the (physical and mental) health status. Quantitative data analysis of people (aged 50-65) with chronic upper extremity musculoskeletal disorders was used to inform health impacts in the group transitioning towards retirement; or who have selected or required early …

Investigation Of Β-Catenin-Mediated Regulation Of Igfbp-6 And The Roles Of Igfbp-6 And Igf-Ii In Dupuytren's Disease, Christina N. Raykha

Electronic Thesis and Dissertation Repository

Dupuytren’s Disease (DD) is a benign and heritable connective tissue fibrosis that affects the palmar fascia and typically results in permanent finger contracture(s). Similar to other fibroses, DD is characterized by increased fibroblast proliferation, myofibroblast differentiation and excess collagen deposition. Currently, there are no truly effective treatment options for connective tissue fibroses.

Increased levels of β-catenin, an intracellular trans-regulator of gene transcription, have been previously reported in DD. Genes that are associated with, and therefore potentially transcriptionally regulated by, β-catenin during DD development were identified in this thesis. One of these gene targets, IGFBP6, was shown to consistently be …

Overall Survival And Biochemical Failure-Free Survival Comparison Of Brachytherapy Treatment Options Versus External Beam Radiation Therapy For Both Low And Intermediate-Risk Prostate Cancer: A Propensity-Score Matched Analysis, Graham D. Smith

Electronic Thesis and Dissertation Repository

Purpose: This study compares overall survival (OS) and biochemical failure-free survival (bFFS) in low- and intermediate-risk prostate cancer patients that received brachytherapy [low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy with external beam radiation therapy (HDR-BT+EBRT)] versus external beam radiation therapy (EBRT) alone.

Materials/Methods: Patient data was obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated at four Canadian institutions. Propensity score (PS) matching was used to generate matched cohorts with balanced baseline prognostic factors.

Results/Conclusions: Final PS matches included two 1:1 intermediate-risk patient matches, LDR-BT vs. EBRT (total n = 254) and HDR-BT+EBRT vs. EBRT (total n=388), and …

Impacts Of Diabetic Neuropathy On The Human Neuromuscular System, Matti D. Allen

Electronic Thesis and Dissertation Repository

Diabetes mellitus (DM) imparts vascular and metabolic stressors that cause damage and dysfunction to the human nervous system. The disorder associated with this dysfunction is termed diabetic polyneuropathy (DPN). Although DPN has been associated with muscle weakness and atrophy, the extent of its impacts on the neuromuscular system is not well understood. The five studies presented in my thesis investigated how DPN affects the neuromuscular system in humans, from the motor neuron to skeletal muscle contractile properties, using a combination of electromyography (EMG), dynamometry and magnetic resonance imaging (MRI) techniques.

The purpose of Studies 1 and 2 was to determine …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

Probiotic Therapy For Heart Failure: Investigating The Potential Anti-Hypertrophic Properties Of Probiotics, Grace L. Ettinger

Electronic Thesis and Dissertation Repository

Heart failure patients face a five-year 50% mortality rate, due to impaired cardiac function and hypertrophy of the heart. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Considering the established cardiovascular benefits of some probiotics, including reduction of cholesterol and hypertension, it was hypothesized that probiotics can improve outcomes of heart failure. Probiotics or controls were administered orally to an animal model for heart failure. Those receiving probiotics showed a significant improvement in cardiac hypertrophy and an attenuation of heart failure compared to control. No changes in gut microbial composition occurred. …

Managing Uncertainty In Young-Onset Parkinson's Disease, Michael J. Ravenek

Electronic Thesis and Dissertation Repository

Typically considered a disease of old-age, Parkinson’s disease can affect those younger in life, i.e., before the age of 55, when it is referred to as young-onset Parkinson’s disease (YOPD). Using constructionist grounded theory, this research sought to understand how, and why, individuals with YOPD became informed about their disease over time. A total of 39 individuals, who self-identified as living with YOPD, took part in this study which was organized according to four cycles of data collection. These cycles utilized focus groups, in-depth interviews and a private online discussion board, supplemented by 14 autobiographies written by individuals living with …

Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver

Electronic Thesis and Dissertation Repository

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg^-1•min^-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO₂max, 60 min/day, 5 days/wk for 10 wk) improves vasa nervorum reactivity …

Analysis Of Invariant Natural Killer T Cells In Intra-Abdominal Sepsis, Ram Venkatesh Anantha

Electronic Thesis and Dissertation Repository

Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of circulating iNKT cells in their peripheral blood, as compared to non-septic patients. We therefore investigated iNKT cells in mice with intra-abdominal sepsis (IAS). Our data show that iNKT cells are …

Effects Of An Angiotensin Ii Type 1 Receptor Blocker On Cardiovascular Calcification, Zachary B. Armstrong

Electronic Thesis and Dissertation Repository

Aims: Three types of cardiovascular calcification are commonly found in humans: arterial calcification, intimal calcification, and calcific aortic valve disease. Very little is known about the mechanisms driving cardiovascular calcification despite serious clinical implications and a clear association with morbidity and mortality. Indeed, it is even unclear whether the same factors are involved in arterial, intimal, and valvular calcification. The objective of this study was to elucidate the effects of an angiotensin II type 1 receptor blocker (ARB) on the progression of cardiovascular calcification in male New Zealand White rabbits. Where appropriate, statins were examined in conjunction and in combination …

Cortisol And Testosterone In Hair As Biological Markers Of Systolic Heart Failure, Justin Chan

Electronic Thesis and Dissertation Repository

Congestive heart failure (CHF) is associated with increased stress and alterations in metabolism, favoring catabolism over anabolism. Hormonal profiles of patients with heart failure have been assessed using serum and saliva as matrices, which are only point measurements and do not provide long-term information. Scalp hair is a novel matrix that allows for measurement of hormones over a period of several months. We aimed to evaluate whether levels of cortisol and testosterone and their ratio (C/T) in hair correlate with severity of heart failure. We conducted a prospective study in ambulatory male patients with a left ventricular ejection fraction (LVEF) …

Effect Of Ascorbate On Coagulation And Fibrinolytic Factors In The Septic Microvasculature, Scott Swarbreck

Electronic Thesis and Dissertation Repository

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection.

We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate …

Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki

Electronic Thesis and Dissertation Repository

Indoleamine 2,3-dioxygenase-1 (IDO) is an immunosuppressive molecule expressed by most human tumours. IDO levels correlate with poor prognosis in cancer patients and IDO inhibitors are under investigation to enhance endogenous anticancer immunosurveillance. Little is known regarding the immune-independent functions of IDO relevant to cancer therapy. In this thesis I show, for the first time, that IDO mediates human tumour cell resistance, in a cell-autonomous fashion, to single and combination treatment with a diverse group of chemotherapy drugs and g radiation. These drugs include a PARP inhibitor (olaparib), a DNA cross-linking agent (cisplatin), a folate antimetabolite (pemetrexed), a nucleoside analogue (gemcitabine), …