Approximately 1,050 new spinal cord injuries occur every year in Canada, primarily in young people. There are currently approximately 40,000 Canadians living with a spinal cord injury (SCI). As a physician and neuroscientist, Dr. Brian Kwon is actively involved in discovering new ways to improve the prognosis of those with SCI. Experimental treatments that have shown tremendous benefits in animal models of spinal cord injury have not translated in human clinical trials. This discrepancy suggests important differences in the biological responses to spinal cord injury between humans and animals. Within minutes of a spinal cord injury occurring, the spinal cord swells at the injury site. This swelling reduces blood flow and oxygen to the spinal cord tissue and can subsequently result in further secondary damage. Dr. Kwon is researching whether draining some of the cerebrospinal fluid (CSF) that surrounds the spinal cord will reduce the pressure on the cord, restoring blood flow and minimizing the risk for secondary damage. In a clinical trial of patients enrolled at Vancouver General Hospital within 48 hours of their SCI, CSF samples will be taken and measured for proteins that regulate inflammation. This biochemical evaluation will offer the first human description of how these inflammatory proteins are expressed following injury, leading to new biomarkers or indicators of injury severity to assist with further research. The expression proteins will be compared with the expression of proteins in animal models to determine differences in response between humans and animals. Ultimately, these insights will assist researchers in developing therapies to improve the lives of patients with spinal cord injuries.
Research Location: Vancouver Coastal Health Research Institute
Genetics of alopecia areata
Alopecia areata (AA) is a common autoimmune disease leading to extensive hair loss in men, women and children. About 640,000 Canadians (one out of 50) will develop AA. There is no cure, and treatment options are minimal. While, in general, the condition is not life threatening, hair loss can be psychologically devastating, particularly for women and children. Using a rat model, Dr. McElwee has identified several areas on chromosomes where genes coding for AA susceptibility are present. Now further work is required to determine the specific genes involved and what they do. Once these genes are identified in the rat model, the next step is a large scale study to identify corresponding genes in AA-affected humans. A more comprehensive understanding of the structure and function of these genes in comparison to corresponding genes in non-affected individuals will lead to a better understanding of how AA develops. In the long run, the goal is to explore the development of treatments which specifically target and ameliorate the affects of underlying genetic flaws that give rise to the disorder.
Novel strategies for treatment of PTEN deficient prostate cancer
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men of the Westernized world. While early stage disease is frequently curable with surgery or radiotherapy, limited treatment options are currently available for approximately one-third of patients who clinically present with locally advanced or metastatic disease resulting in a poor prognosis for patients with advanced disease. One treatment option that is currently being used for advanced PCa is a medical procedures designed to block androgenic steroids to induce death of prostate cancer since prostate cancer cells typically require these hormones for their growth and integrity. While this treatment is often effective with a response rate of up to 80%, within 1-3 years the tumours inevitably recur as hormone-refractory variants, a condition for which there is no current effective therapy. Thus if we are to have an impact on survival rates of patients with PCa, new therapeutic strategies are required for treating advanced disease. Up to 50% of advanced prostate cancers have acquired mutations in a gene called PTEN that essentially inactivated it. Inactivation of PTEN in prostate cancer is correlated with a poor prognosis. Loss or inactivation of this gene makes prostate cancer cells more resistant to different forms of therapy including chemo-, radiation and hormone-therapy. The development and progression of cancer is dependent on the deregulation of the intricate balance in the rates of cell growth and death. The proposed project addresses how loss of the PTEN gene confers cell with a survival advantage and resistance to therapies. Under ordinary conditions, PTEN keeps growth of normal cells in check by serving as a brake to inhibit cell growth. When PTEN is mutated in cancer, the brakes fail and this confers uncontrolled growth and increased resistance of the cancer cells to chemotherapy and hormone ablation therapy. My lab is actively working on how loss of PTEN protects prostate cancer cells from death signals and we are looking for different ways to block the effects of inactivating PTEN. Results of this study will be directly relevant to development of new therapies aimed at treating the subset of advanced prostate cancers that have lost PTEN.
Early diagnosis of compartment syndrome following tibial fractures using Intra-Compartmental Pressure Monitoring, near infra-red spectroscopy and plasma ischemic markers
Fractures of the main bone in the lower leg, known as the tibia, cause local bleeding, and tissue swelling within the compartments of the leg. In some patients, pressure within the compartments rises sufficiently high to prevent blood flow and cuts of the oxygen supply to intracompartmental muscles, nerves and other tissues. This condition is known as acute compartment syndrome. It is a surgical emergency and requires immediate identification and surgical treatment to save the function and viability of the lower leg. Delay in diagnosing this condition exposes the patient to increased risk of local muscle loss and a wide range of severe complications which requires multiple surgical procedures, prolonged hospitalization and even amputation of the affected limb. At the present time, diagnosis of acute compartment syndrome is mainly based on the clinical observation which is not always reliable and early. Measurement of intra-compartmental pressure can help to confirm the diagnosis but requires an invasive procedure which has some drawbacks. It is believed that direct monitoring of muscle oxygenation may provide early and precise diagnosis of this condition. Near infrared spectroscopy (NIRS) is a noninvasive and continuous method for monitoring tissue oxygenation. Babak Shadgan, a sport medicine researcher, is studying whether careful monitoring of lower leg muscle oxygenation in fractured leg patients who are in a higher risk of acute compartment syndrome may allow for an early diagnosis of this critical condition. If effective, this new method would improve speed and accuracy of diagnosis, leading to improved care for patients and substantial health care cost-savings.
Wheelchair use by nursing home residents: An exploration of the relationship between wheelchair use, activity participation and quality of life
It’s been estimated that more than half of nursing home residents use wheelchairs as their primary means of mobility. But little research has examined wheelchair use within facility settings. A few studies have shown that nursing home residents experience a variety of wheelchair-related problems, such as wheelchair discomfort, immobility, poor posture, and dysfunctional wheelchairs. As well, rather than facilitating independence, wheelchairs may be used as restraints. William Mortenson is conducting a two-phase study on wheelchair use in nursing homes. In the first phase, Mortenson will explore the overall impact of wheelchairs and wheelchair seating on nursing home residents through interviews and observations. In the second phase, he will identify factors that predict wheelchair mobility and investigate the relationship between wheelchair use, activity participation and quality of life amongst nursing home residents. He has three goals for the study: to improve understanding of how the nursing home setting influences the availability of wheelchair equipment and impacts the use of wheelchairs; to improve opportunities for residents to access wheelchairs; to support lobbying for better funding for wheelchairs and wheelchair services. He also hopes his research will ultimately contribute to the health and quality of life of facility residents through the development of an intervention program, which could improve wheelchair-related institutional policies and practices for this increasing segment of the population.
Evaluating the contribution of bone micro-architecture, density and bone strength to fracture at clinically relevant sites using a novel instrument:An Xtreme CT study
Osteoporosis is a chronic condition whereby bones become fragile and individuals are predisposed to fracture. Osteoporosis may occur in all older people but it most frequently affects post-menopausal women. Worldwide, more than nine million osteoporosis-related fractures occur annually. Older Canadians sustain more than 24,000 hip fractures annually — which levies a substantial physical, emotional and economic burden on individuals and the health care system. By 2040, this number is expected to increase to 90,000 at a cost of $2.4 billion. The likelihood of a person sustaining a fracture is related to their bone strength and their propensity to fall. Bone strength is related to bone’s material and structural properties. Currently, DXA (dual-energy x-ray absorptiometry) is the most commonly used diagnostic tool to measure bone health. However this technology has limitations in that it provides a two-dimensional (2-D) representation of bone, a 3-D structure. Further, DXA does not capture the nuances of bone geometry and structure that underpin bone strength. Recently, a high resolution imaging system (the Xtreme CT scanner) was developed that is able to assess bone mass, geometry and bone microarchitecture. The extent to which this novel technology is able to predict bone failure is currently unknown. Thus, Sarah Braid will utilize state-of-the-art imaging techniques (X-treme CT and pQCT) to evaluate bone strength and its components – and most importantly – link these evaluative tools with the susceptibility of a bone to fracture. The results of her research will enhance our ability to assess fracture risk so as to prevent fractures in vulnerable populations in future.
Seniors at high risk of falls: Clinical and economic studies
Falls among older people are a major health problem. In Canada, hospital emergency departments report that 86 per cent of seniors’ injury-related admissions are due to falls, and individuals who present to an emergency department after one fall are at particularly high risk of falling again and incurring significant injuries. Current practice guidelines encourage a sophisticated and costly program to prevent subsequent (secondary) falls, including referrals to physiotherapy, ophthalmology, family practice and occupational therapy. However, despite the proven effectiveness of this approach, current “real life” practices throughout BC do not generally follow these guidelines, and the outcomes – both physical and economic – have not been studied in a Canadian context. Working within VGH’s Falls Prevention Clinic, Jennifer Davis is conducting the first Canadian randomized controlled trial to compare secondary falls and fall rate between seniors receiving “gold standard” care at the Clinic versus those receiving the standard of care with their GP. She will also detail health resource utilization for all study participants in order to analyze the cost-effectiveness of the Clinic intervention versus the standard of care.
Characterization of oligodendrocyte abnormalities in schizophrenia
Schizophrenia is a severe psychiatric illness affecting approximately one per cent of Canadians. While the causes are not yet fully understood, it is thought that the symptoms of this disorder may arise from abnormalities in nerve fibre connections between different brain regions. Mounting evidence suggests that a contributing factor may be abnormalities in myelin, the fatty insulating substance that surrounds nerve fibres and speeds up the transmission of nerve impulses. Studies have shown reduced density of oligodendrocytes, the brain cells that produce myelin, and altered expression of several proteins found specifically in myelin—suggesting a possible source for impaired transmission of nerve impulses between brain regions. Through a series of investigations Dr. Clare Beasley is examining the role of oligodendrocytes in schizophrenia. She will characterize oligodendrocyte alterations in the brain in schizophrenia and examine their relationship with myelin proteins and lipids. By better understanding the connection between abnormalities in these myelin-producing cells and the symptoms of schizophrenia, she hopes to shed light on the cause of this devastating disorder.
A prospective exploration of associations among cognitive dietary restraint, cortisol excretion, ovarian function and bone health in premenopausal women
About 16 per cent of Canadian women over age 50 have osteoporosis – a condition with low bone density that increases their risk of fracture. Osteoporosis costs the health system $1.3 billion annually, and both prevalence and costs are expected to rise in the next two decades as the population ages. Optimizing peak bone mass during women’s younger years is key to preventing osteoporosis. In western culture where thinness is idealized, many women experience body dissatisfaction. In response, women attempt to control their body size and weight, typically through diet and/or exercise. The eating attitudes of many women are characterized by high levels of cognitive dietary restraint (CDR) – the perception that one is constantly monitoring and attempting to limit food intake in an effort to control weight. While the adverse consequences of clinical eating disorders (e.g. anorexia nervosa) are well-recognized, the potential health effects of subtle disturbances of eating attitudes, such as high levels of CDR, are only beginning to receive researchers’ attention. Jennifer Bedford is studying whether these eating attitudes affect young women’s bone density. Previous research in the area suggests that women with high CDR have higher levels of the stress hormone, cortisol, which may negatively affect bone density directly by disrupting bone and calcium metabolism. It also affects bone indirectly by disturbing the menstrual cycle hormones, resulting in disturbances in ovarian function. Jennifer is conducting the first prospective study to examine the relationships between eating attitudes, cortisol levels, ovarian function and bone density in young women. The findings should lead to health and nutrition education strategies to inform young women of the potential health effects of their attitudes about food, eating and their bodies.
The organization and utilization of chronic pain health services for Aboriginal and Anglo-Canadians
Chronic pain is a relatively common phenomenon that typically results in considerable health services use as well as significant hardship for the sufferer. Experts generally agree that chronic pain is often poorly managed leading to poor quality of life for the sufferer. Additionally, most experts suggest that access to appropriate chronic pain expertise is a major contributor to poor outcomes in the sufferer despite the existence of a variety of pain management programs/services. Because poorly managed chronic pain is so common, a critical look at chronic pain management services is warranted. Canadian health services must meet the needs of diverse Canadian populations and specialized services have been developed for some ethno-cultural groups. While all Canadian people may experience difficulties accessing health services, some are at a special disadvantage due to unfamiliarity or lack of comfort with our current system. Aboriginal-Canadians, who have historically had difficulties with access to the health care system, have been identified as a population at a special disadvantage. In this study I will speak with Aboriginal and Anglo-Canadian chronic pain sufferers and their health care providers. In addition I will observe how patients and the health professionals who look after them interact with one another. I will also examine materials that are written about current pain management programs and services. This study will lead to recommendations for improvements in the health services for chronic pain for these two populations.