Triple combination antiretroviral therapy has greatly reduced the rate at which people with HIV infections progress to AIDS. However, the medications used in the therapy can be quite toxic, leading to serious liver, kidney, muscle and nerve problems and reducing the length of time patients are able to tolerate the treatment. Dr. HélÚne CÎté and colleagues at the BC Centre for Excellence in HIV/AIDS have developed a blood test to measure toxicity from antiretroviral therapy and are now assessing its effectiveness in detecting and monitoring toxicity levels. She is also investigating whether the test could predict complications from drug therapy before serious symptoms appear. If so, it could be used to tailor use of antiretroviral therapy and improve treatment outcomes. As part of the research, Dr. CÎté also is studying the effectiveness of the blood test in measuring toxicity of medications used for hepatitis C.
Research Pillar: Clinical
Translating mechanistic understanding of the systemic inflammatory response syndrome (SIRS) to clinical practice via genomics
Each year, about 75,000 patients in Canada will develop sepsis (severe infection). Although it is reversible, sepsis often causes death. Sepsis and a related condition, systemic inflammatory response syndrome (SIRS), lead to multiple organ dysfunction and are the most common reasons for admission to intensive care units. Using genetic information that became available after completion of the human genome project, Dr. Keith Walley is researching the genetic determinants of the acute inflammatory response and organ failure associated with sepsis. His aim is to clarify the genetic mechanisms which give rise to the inflammatory response and to apply this information to identify patients who are at risk for adverse outcomes based on their genotype (genetic make-up). His ultimate goal is individualized management of patients with sepsis, based on knowledge of the way their genotype will influence their susceptibility to and risk of developing life-threatening symptoms, as well as their ability to respond to treatment.
Postural Control in individuals with stroke
Every year about 50,000 Canadians will have a stroke, which is the number one cause of neurological disability leading to impaired balance and mobility. Those affected face a seven-fold increase in hip fractures because of falls due to poor balance. Unfortunately, there are very few community-based programs to help individuals with stroke improve or maintain mobility and balance, and a lack of research assessing the effectiveness of such programs. Dr. Janice Eng is investigating the effectiveness of a 12-week exercise program for improving balance and mobility in two groups of people with stroke: a group participating in an intensive exercise program, and another group doing arm exercises. Results of her research could assist in developing guidelines for community-based exercise programs to improve the health of people with stroke, and to reduce hospital admissions due to falls.
Improving psychosocial treatment adherence in young individuals presenting with a first psychotic episode
Research has shown that psychosocial treatments, such as cognitive-behavioural therapy, can reduce symptoms and improve overall well-being of people who are experiencing a first psychotic episode. Yet, studies also show that only about one-third of potential candidates for treatment agree to participate in and complete the therapy. Dr. Tania Lecomte is exploring why some individuals experiencing a first psychotic episode refuse or fail to adhere to treatment. Besides assessing whether or not motivation enhancement therapy improves adherence to treatment, she is also evaluating the impact on symptoms and patient well-being when they receive both motivation therapy and cognitive-behavioural therapy, or just the latter. If motivation therapy is shown to be effective, results from the study could help young people cope better with psychotic symptoms. Her research may also reveal new information about factors that motivate individuals with psychotic symptoms to seek help.
Retinoids in synovial sarcoma
Synovial sarcoma is a form of cancer occurring most commonly in the limbs of young adults. Patients are treated with aggressive surgery and radiation, but the disease often spreads and proves fatal. Current chemotherapy provides limited benefit, with serious side effects. Using gene microarrays, a new technology that allows scientists to monitor tens of thousands of genes simultaneously in tumour specimens, Dr. Nielsen helped discover a group of genes playing a central role in synovial sarcoma. These include several potential therapeutic targets, including the signalling pathway involving retinoic acid, a vitamin A derivative. Several existing and experimental drugs interfere with this pathway and have been successfully used to treat other cancers such as leukemia, but have not been tested in synovial sarcoma. Dr. Torsten Nielsen is using the gene expression profile of this cancer type to develop targeted therapies needed for its treatment.
Physical activity as primary prevention: evaluating novel interventions for child health
Physical activity can help prevent a host of chronic diseases, including osteoporosis and obesity, two major medical conditions that likely begin with childhood inactivity. But itâs estimated that three out of five Canadian youths between five and 17 years of age are not physically active enough to ensure optimal growth and development. Weight reduction programs targeting children who are already obese have largely been unsuccessful, which indicates the need for a stronger focus on developing more effective prevention strategies. Several studies have shown that school-based programs can effectively improve bone health. Dr. Heather McKay is evaluating the impact of innovative physical activity programs on bone health and weight of elementary school children, research that could lead to the development and implementation of public health programs to encourage physical activity and improve the health of Canadian children.
Trauma, dissociation and post traumatic stress disorder (PTSD) in violent offenders: The cycle of violence revisited
Research indicates that many violent crime offenders have been victims of violent crime. Many develop stress-related psychiatric disorders, such as Posttraumatic Stress Disorder, as a response to perpetrating or being victimized by violent crime. Barry Cooperâs earlier research focused on the development of Posttraumatic Stress Disorder symptoms and their effect on memory in victims of violent crimes. Now he is examining the complex factors that contribute to the development, severity, and maintenance of the condition in violent crime offenders. His research involves interviewing violent crime offenders incarcerated in BC and developing an extensive database detailing factors such as their personality characteristics, history of trauma, severity and type of violence, use of alcohol or other substances, and memories of their crimes and traumatic experiences. The results will help refine assessment techniques and treatment programs for violent offenders, leading to improved rehabilitation and a lower rate of violent offences.
Focused attention, exploration and heart rate at 8-months in relation to prematurity and maternal interaction
Premature infants spend critical periods of early development in neonatal intensive care. The stress and pain experienced as part of early medical care can lead to the disorganization of infant behaviour or physiologic states, which may reflect risk for adverse neurodevelopment. Research links early stress to changes in brain stress circuits and heart rate regulation and follow-up studies show that high-risk premature infants have a high incidence of attention related deficits. Julianne Petrie-Thomas is examining the complex relationships between behavioural and physiological regulation of attention by studying focused attention and patterns of heart rate in premature infants at 8-months compared with term-born controls. As the infantâs interactions with its mother play an essential role in the regulation of behavioural as well as internal physiological systems, she is also studying the effects of maternal-infant interaction on infantsâ behaviour and physiology. The findings could fill major gaps in understanding of how attention problems develop in premature infants and lead to interventions that significantly improve the developmental outcomes of these vulnerable babies.
Pharmacogenetics of codeine metabolism to morphine in pediatric dental patients
Pharmacogenetics-the study of how genetic makeup affects an individual’s response to drugs-fascinates Evan Kwong. The field addresses the underlying causes of why drugs may affect people differently, bringing the study of genetics into a practical, clinical setting. In the future, having access to a patient’s genetic profile could help clinicians more quickly and accurately select the right therapy. Evan’s research focuses on the common painkiller codeine, which produces pain relief as it is metabolized into morphine by a liver enzyme. A genetic variation in 25 to 40 per cent of people of Chinese descent appears to be associated with decreased function of this liver enzyme. Evan hopes to determine whether people who carry this genetic variation metabolize codeine less effectively. With that knowledge, clinicians could offer other drugs that will be effective.
Effect of a training program on postural reflexes in individuals with chronic stroke: A randomized controlled study
Stroke is the number one cause of neurological disability in Canada. Following a stroke, people may experience paralysis, or loss of motor function, in the muscles controlling one side of the body. As a result, people with stroke can have difficulty maintaining balance when standing or walking. In fact, the incidence of falls among people who have had a stroke has been reported as high as 73 per cent within a six-month period following the stroke. Daniel Marigold is conducting the first study to assess whether an exercise program can improve the reflexes that control balance in people with chronic stroke. He will measure postural reflexes before and after a 10-week training program to see if they improve. Study participants will stand on a large platform, which suddenly moves under their feet. A harness will prevent people from falling and electrodes will measure muscle activity. If this study shows improvement in postural reflexes with training, an exercise program could be implemented in the community to help people with chronic stroke.