Before triple-drug antiretroviral therapy was developed to treat HIV, certain levels of HIV ribonucleic acid (RNA) in the blood were strongly associated with progression of the disease. However, there has been a great deal of uncertainty about the clinical relevance of HIV RNA levels since the therapy was introduced. Recent studies have produced conflicting results about the association of HIV RNA levels with survival or death for individuals with HIV. But these studies did not assess patient adherence to triple-therapy treatment. Dr. Evan Wood is using data from the BC Centre for Excellence in HIV/AIDS Drug Treatment Program to research the association between HIV RNA levels and survival after beginning triple-drug antiretroviral therapy. He is also investigating the relationship between HIV RNA levels and factors such as non-compliance with triple therapy treatment. The findings could be used to adapt provincial guidelines for HIV/AIDS treatment.
Year: 2003
Muscle metaboreflex during exercise in chronic obstructive pulmonary disease
Chronic Obstructive Pulmonary Disease is a progressive lung disease that causes breathing difficulties and chronic cough. Those affected often have weak arm and leg muscles that are easily fatigued, which can cause them to avoid exercise and adopt an inactive lifestyle. Dr. A. William Sheelâs research is directed at understanding how reduction in blood flow and oxygen during exercise leads to muscle fatigue and how different types of exercise affect the amount of fatigue. Results from his study will help explain why people with chronic lung disease become prematurely fatigued and could be used to design exercise rehabilitation programs to improve their health.
Obesity in the community: a comparison of the differential distribution of body fat in four distinct populations
Being overweight or obese, especially around the stomach, dramatically increases oneâs risk for health problems such as diabetes and heart disease. This is of great concern as the prevalence of obesity in Canada has steadily increased during the past 15 years. However, most of the research on obesity is based on populations with European origins; very little is known about the effects of being overweight in Aboriginal, Chinese and South Asian populations yet the rates of obesity in these populations are also increasing. Preliminary evidence suggests that at the same weight and stomach size, people of Aboriginal, Chinese or South Asian descent have a higher amount of body fat and greater risk for diabetes and heart disease compared to men and women of European descent. Therefore, using clinical targets for obesity developed from European populations may result in inappropriate screening for prevention of these diseases. Dr. Scott Learâs research involves recruiting 200 people from each of the Aboriginal, Chinese, South Asian and European communities to study the relationship between cultural background, body fat distribution and risk for diabetes and heart disease. Each participant will undergo a scan for stomach fat, overall body fat and risk factors. By improving understanding about the implications of excess body fat in these under-studied populations, the research could lead to guidelines for identifying people at risk for chronic disease, and contribute to prevention strategies targeted to these populations.
Modeling musculoskeletal diseases: from epidemiology to quality of life
Osteoarthritis (OA), which results in the breakdown of joint cartilage, is the most common form of arthritis. Despite much research on the condition, there is no primary prevention strategy for the disease. Macro-level studies evaluating different prevention and treatment strategies are also needed. In collaboration with colleagues in Canada, the US and Europe, Dr. Jacek Kopec is conducting three osteoarthritis studies. The first involves the development of a computer simulation model of OA. The model will synthesize data from different sources, creating the worldâs largest database simulating the nature history of OA. Results from this study will be used to assess prevention strategies and develop optimal treatments for the disease. The second study investigates whether or not moderate physical activity can cause OA. The third study focuses on patientsâ preferences about different treatment options for OA of the hip and knee. As part of the study Dr. Kopec is developing a questionnaire that can be adapted to individual respondents, making the assessment more precise and efficient than previous questionnaires. The studies as a whole could advance knowledge of osteoarthritis and improve treatment of the condition.
Dendritic cells in autoimmunity and cancer
Dendritic cells play a vital role in regulating the immune response. They are the only cells capable of activating T cells that have not previously been exposed to a particular antigen (immune threat) to recognize and mount an attack on these foreign proteins. This process ensures an appropriate immune response against potentially harmful antigens. Dendritic cells are also thought to have the ability to instruct the immune system to ignore certain antigens, establishing a state of immune tolerance in the body. When the balance between immune activation and immune tolerance is disrupted, the result may be the development of autoimmune disorders in which the immune system attacks body tissue or cancer in which tumour cell growth goes unchecked. Dr. Cheryl Helgason is studying the biology of dendritic cells and the mechanisms by which they interact with T cells to activate an immune response or to establish immune tolerance. Such research could suggest ways of manipulating immune function to develop new methods of treating cancers, autoimmunity and other diseases involving immune dysfunction.
Bioinformatic approaches to cancer research
Genes â the functional units of DNA â are involved in all aspects of normal human development and human disease. Although most cells have a core set of active genes, selective activation of other genes is necessary to produce different types of specialized cells, such as muscle cells, nerve cells and skin cells. Malfunction in the normal pattern of gene activation is implicated in many diseases, including cancer. Dr. Jones uses sophisticated computational techniques to analyze the activation of genes involved in the formation and development of mammalian organs and tissues and to explore genes that are activated in specific cell types such as muscle and neural cells. His goal is to develop software that will allow researchers to predict the behaviour of genes by indicating when they are switched âonâ or âoffâ. Besides improved understanding of normal growth and development, this research will help clarify the changes in activation patterns that give rise to cancer, potentially leading to new ways of detecting cancer risk and the earliest stages of cancer onset.
Genetic modifiers of pulmonary disease severity in cystic fibrosis
Cystic fibrosis is a severe genetic disorder caused by a single gene called the cystic fibrosis transmembrane regulator (CFTR). The disease is characterized by chronic and persistent respiratory infections, which progressively damage and eventually destroy lung function. Research has shown that cystic fibrosis patients with the same alteration in the CFTR gene may each follow a very different clinical course: with one patient having very mild lung disease and infrequent lung infections, while another will have frequent lung infections and significantly decreased lung function. Dr. Andrew Sandford is investigating genes other the CFTR gene that may play a role in causing lung disease to progress more quickly in some cystic fibrosis patients than in others. It is thought that cystic fibrosis patients may also have compromised immune function. For this reason, Dr. Sandford is looking for genes involved in fighting infections and in controlling the inflammatory response to the bacteria and viruses that attack the lungs.
Chronic psychological stress and immune system dysregulation
Research has shown that chronic stress negatively affects health. One model suggests that chronic stress suppresses immune function, leaving people more vulnerable to infectious diseases and cancers. However, it doesnât explain how stress affects conditions that result from over-activation of the immune system, such as autoimmune, arthritic and cardiovascular disorders. To investigate how stressors interfere with the immune system’s ability to turn itself off once activated, Dr. Miller is comparing the immune responses of two groups: parents with a severe chronic stressor (a child undergoing cancer treatment), and parents of healthy children. Results from the research could increase knowledge about the ways stressors affect health, including confirmation that one of the effects is interference with the immune systemâs ability to turn off responses against bacteria. As part of this study, Dr. Miller is also examining whether supportive personal relationships act as a buffer against chronic stress.
CHIPS (control of hypertension in pregnancy study): a pilot trial
Almost 10 per cent of women who become pregnant develop hypertension (high blood pressure). Experts agree that pregnant women with severe hypertension should receive blood pressure medication to protect them from stroke. However, it is not clear if or how much the medication would benefit pregnant women with mild to moderate hypertension. A complicating factor is that the medication may also contribute to poorer growth and lower birth weight in babies, placing them at increased risk for health problems as newborns, children and adults. According to a national survey, Canadian obstetricians are unsure about prescribing blood pressure medication to women with mild to moderate hypertension. To help clarify the issue, Dr. Laura Magee and her research team have designed a Control of Hypertension in Pregnancy Study (CHIPS), aimed at determining if it is better for the baby (i.e. better growth before birth and better health thereafter) to allow a motherâs blood pressure to be higher than normal during pregnancy or to prescribe blood pressure medication to lower it. To begin, Dr. Magee is conducting a pilot trial to assess whether or not physicians would adhere to the treatment protocols in a full trial and to confirm if sufficient patients could be enrolled. If the pilot study indicates that CHIPS is feasible, the full trial will be conducted at major maternity centres across Canada.
Regulation and role of granzyme B in Atheromatous Diseases
Atherosclerosis â hardening of arteries â is caused by buildup of plaque inside artery walls. This constricts blood flow and elevates blood pressure, and is the leading cause of heart attacks, stroke and lower limb loss due to poor circulation. There is evidence that immune cells provoke a tightly-regulated form of cell death known as apoptosis (programmed cell death) in atherosclerotic blood vessel walls, which contributes to progression of the disease. While the mechanisms are not clearly understood, the result is a change in the architecture of blood vessel walls that leads to additional plaque build-up and also to plaque instability. The latter increases the danger of pieces of plaque breaking off and potentially lodging in and blocking blood flow in smaller vessels. In previous work, Dr. David Granville and his research team have found that an enzyme used by the immune system to kill abnormal and infected cells is released in atherosclerotic blood vessels. Dr. Granville is studying the role of this enzyme â granzyme B â in vessel wall restructuring and cell death associated with atherosclerosis and transplant vascular disease. Findings from this research may reveal new opportunities for intervening to prevent or treat these vascular disorders.