Osteoarthritis (OA) is a painful, debilitating disease affecting approximately three million Canadians, most commonly at the knee. In addition to joint cartilage damage, the disease is also marked by changes in the underlying bone. It has been suggested that changes in bone stiffness, thickness and density influence and accelerate the breakdown of cartilage and the development of OA. In order to verify this (i.e. understand when during the disease process these changes occur and assess their impact on the timing and extent of damage to the bone or cartilage) there is an urgent need to develop a tool that can reliably assess bone and cartilage simultaneously. The aim of James Johnstonâs research is to understand early onset and progression of osteoarthritis and to develop diagnostic tools for its early detection. Johnston has already developed a novel method of matching bone to cartilage that can be used to assess cartilage and underlying bone simultaneously in any joint. He is now working on a method to investigate relationships between bone (thickness, density) and cartilage (thickness, biochemistry) using magnetic resonance imaging (MRI), computed tomography (CT) and three-dimensional assessments. He will then link information gained through these imaging methods with physical stiffness measures to determine how these properties are affected at early and late stages of OA, compared to healthy subjects. This research will improve understanding of how OA develops, and contribute to the development of methods for the early detection and treatment of the disease.
Research Pillar: Clinical
The effect of reward expectation and dopamine release on the mechanism of the placebo effect in Parkinson's disease
Parkinsonâs disease (PD) is the second most common neurodegenerative disorder and affects about 100,000 Canadians. It occurs when cells that produce dopamine in the brain die. Without enough dopamine to send signals to the striatum, an area of the brain that controls movement, people with Parkinsonâs develop tremors, stiffness and balance problems. Patients take medication to replace the missing dopamine, but this often produces troubling side effects. Interestingly, a significant placebo effect can occur in patients with Parkinsonâs, with patents showing an improvement in symptoms due to their belief that a particular treatment will be beneficial. Sarah Lidstone is expanding on her earlier MSFHR-funded research to study how patientsâ expectations for an improvement in symptoms actually produce measurable improvement. Using positron emission tomography (PET), a powerful brain scanning technique, Sarah has shown that patients with Parkinsonâs disease release dopamine in the brain when given a placebo they thought was medication. Dopamine is also released in the same brain areas when people anticipate receiving a reward such as money or food, a response also generated in drug addiction. Sarah is examining whether the placebo mechanism in Parkinsonâs taps into the same process as reward anticipation. If so, this research could lead to better treatments for the disorder. It could also inform treatment for drug addiction and other conditions influenced by a placebo effect or dopamine, including pain management, depression and obsessive-compulsive disorder.
Links between Patellofemoral Biomechanics and Osteoarthritis
One in ten Canadians suffers from osteoarthritis, an incurable disease that causes pain and limits motion in joints. It occurs most often in the knee joint; the patellofemoral joint, which is located at the juncture of the kneecap and thigh bone, is involved in half of these cases. Emily McWalterâs research is focused on improving the diagnosis and treatment of patellofemoral osteoarthritis. It is widely believed that biomechanical factors, such as abnormal joint motion and excessive force exerted on bone and cartilage are related to the onset and progression of osteoarthritis. While treatment focuses on correcting abnormal joints through surgery or physiotherapy, these treatments do little to slow progression of the disease. Thatâs likely because the procedures do not correct all of the biomechanical factors contributing to the damage. With recent advances in MRI imaging, itâs now possible to study biomechanical factors and cartilage degeneration simultaneously. Emily McWalterâs research is focused on developing better methods of detecting and identifying the causes of cartilage degeneration earlier. She is currently working to develop and validate a tool that can estimate the pressure that develops on the surface of cartilage, with a view to using this information to determine if areas under abnormal levels of pressure are at greater risk for degeneration. If successful, this tool will be a valuable asset in understanding the onset and development of patellofemoral osteoarthritis and in assessing the effectiveness of surgeries and other biomechanics-based treatment strategies.
Action Schools! BC: The effect of a school based physical activity model on risk factors for cardiovascular disease in Aboriginal children
Cardiovascular disease (CVD) is a chronic condition that can lead to heart attack and stroke. CVD costs the BC health care system approximately $2.5 billion a year. Sadly, the onset of cardiovascular disease often starts in childhood. About 50 per cent of North American children exhibit one or more risk factors for CVD and many children and adolescents exhibit multiple risk factors. These statistics are worrisome because the severity of CVD increases with the number of risk factors, and risks during childhood tend to track into adulthood. As a result, these children are susceptible to developing cardiovascular disease as adults. Previous research has linked higher levels of physical activity during childhood to a lower risk for CVD as adults. Lindsay Nettlefold is examining the prevalence of CVD risk factors in children and whether differences exist between girls and boys and between children of different ethnicity. She is also studying whether a school-based physical activity program can reduce the level of risk factors for cardiovascular disease in children. The goal to develop an effective program that could be used to improve cardiovascular health in children will prove beneficial in helping to prevent the development of disease later in life.
Acute exercise in individuals with spinal cord injury: friend or foe?
Individuals with spinal cord injury often have cardiovascular complications, such as fainting and dramatic increases in blood pressure. These conditions lead to a decrease in quality of life and significant treatment costs. Although these cardiovascular problems have been well documented, little is known about their causes following spinal cord injury. Jessica Scottâs research builds on her MSFHR-funded Masterâs work that investigated whether a sudden drop in blood pressure following exercise predisposes people with high blood pressure to lose consciousness. While exercise can help reduce or reverse cardiovascular disease in people with spinal cord injury, the striking decrease in blood pressure that occurs after vigorous short-term exercise may in fact be dangerous. Loss of consciousness associated with physical exercise may be the first indication of a dangerous underlying cardiovascular condition. Scott is researching the connection between this sudden drop in blood pressure with the predisposition to lost consciousness following exercise in individuals with spinal cord injury. She aims for the research to contribute to development of an intervention program to improve post-exercise tolerance in individuals with spinal cord injury. The findings may also help in assessing post-exercise tolerance in other cardiovascular diseases such as chronic heart failure.
eVENT: An expert system for detecting ventilatory events during anesthesia
Despite the best intentions of clinicians many patients suffer adverse events during their medical care. As technology becomes more sophisticated and the amount of information generated increases, the risk that something goes wrong or is missed increases. The technology, work environment and clinical work flow needs to be designed to mitigate these risks. Technology has the potential to help clinician’s with tasks that humans do not perform well, such as vigilance, and reduce risk to patients.
Dr. J Mark Ansermino is a pediatric anesthesiologist with a background in health informatics and a particular interest in patient safety. He and his team are developing an expert system that automatically detects important changes in a patient’s status in the operating room. The clinician must divide his or her time between keeping an eye on the monitors, attending to the patient, and other tasks such as teaching students and giving drugs. Important events or evolving conditions can be missed. The technology will assist the busy clinician with attending to the huge amount of information generated by the monitors and bringing the important changes to the attention of the clinician. The system can also offer advice on what should be done about these changes and information on current treatment guidelines, providing the clinician with a recommended course of action in real time.
The current emphasis is on developing rules for a few dangerous events that affect breathing. This will be expanded to address other anesthesia-related events in the operating room. In this research, the system will be evaluated in both simulated and real clinical settings to determine if it is possible for clinicians to identify and respond to critical events more rapidly and reliably. This expert system will lend itself to promoting better decision making by both less skilled or experienced anesthesiologists during training or in situations where advanced training is not available.
Molecular Imaging of Cancer with Positron Emission Tomography
Recent developments in imaging devices provide researchers with powerful tools to detect cancers and explore the impact of therapy on tumour cells. This research program plans to leverage the strengths of positron emission tomography combined to computed tomography (PET/CT) to characterize and rapidly assess response to therapy in 3 common cancers (breast, prostate, and lymphoma) and combine this information with other predictors of aggressiveness and treatment failure. PET/CT imaging is a powerful technique that combines the strenghts of a PET scanner (which can measure tumor receptors and metabolic activity) with those of a CT scanner (which provides detailed images of a patient’s anatomy). The combination of both approaches could rapidly identify patients that are likely to fail conventional therapy and offer them alternatives that are better suited to the nature of their cancer. The research program is designed around 3 core themes. The first research them focuses on the development of methods to predict the outcome of patients with breast cancer who are treated with chemotherapy or hormone therapy. We will pursue ongoing work to develop animal models of breast cancer and imaging methods to monitor response of these tumors to chemotherapy and hormone therapy. We will also conduct clincial studies to correlate the results of imaging studies performed with PET/CT with outcome and response to therapy. The second theme focuses on the development of new probes that target specific proteins that are overexpressed at the surface of breast and prostate tumors. These probes might eventually be translated into clinical studies as breast and prostate cancer diagnostic agents for use with PET/CT, or even for therapy by tagging them with radioisotopes that can destroy tumor cells by proximity. The last theme proposes practical research studies of immediate clinical interest. We will assess the accuracy of PET/CT imaging in staging prostate cancer (with 2 radiopharmaceuticals designed to assess tumor lipid synthesis and bone turnover). We will also extend to the Vancouver site an ongoing study that assesses PET/CT imaging to predict the early response to chemotherapy in large cell lymphoma.
Population-Based Genetic Studies of Cancer and Healthy Aging
The number of elderly Canadians is increasing as the baby boomers age. Insight into how to promote healthy aging, coupled with advice that can be provided to our population as it ages, will influence Canada’s healthcare costs, as well as the quality of life of a large segment of our population. Cancer and aging are intimately connected. Cancer incidence rises with age, and this increase accelerates dramatically over 60 years of age. Cancer and other aging-associated diseases like cardiovascular disease are thought to result from the interaction of numerous genetic and environmental or lifestyle factors. Population-based studies that use large groups of affected and unaffected individuals are now the preferred method to study the genetics of complex diseases. This program has clinical relevance and involves close collaboration with clinical experts to study healthy aging and two specific cancers, non-Hodgkin lymphoma and cervical cancer. The overall objective is to discover genetic factors that contribute to susceptibility to cancer or confer long-term good health. The program will use state-of-the-art genetic analysis methods, and over the next 5 years will expand these projects and add additional types of cancer. This coordinated study of cancer and healthy aging is a unique and innovative approach by which we will increase our understanding of the connection between cancer and aging and benefit from new knowledge regarding the basis of common aging-associated diseases like cancer. This research will lead to development of clinically useful markers that will help individuals avoid developing diseases as they age.
Novel Antimicrobial Surface Coatings for Urologic Devices
Health Issue:Urinary catheters provide drainage of the bladder to an external collecting device and are the most commonly placed medical devices. Ureteral stents provide drainage of urine from the kidney to the bladder and are used in the treatment of kidney stones. Both of these devices are foreign bodies in the urinary tract and allow bacteria to adhere and result in urinary tract infections and encrustations leading to device blockage and malfunction. Catheter and ureteral stent-associated infections prolong hospital stay, result in greater health care costs and may result in blood-borne bacterial infections possibly resulting in death. Antibiotics may be given for the duration that the drainage devices remain in the body, but there is great concern that the overuse of antibiotics will lead to the development of antibiotic resistant bacteria, or superbugs. Novel ways to reduce catheter and stent related infections would certainly improve patient care and decrease costs to the health care system without inducing resistant superbugs. Project Objective: To develop and test a novel peptide (protein) coating on urinary devices to reduce device-related urinary tract infection. Work to Undertake: Urinary catheters and stents will be coated with this novel peptide and evaluated for their ability to resist infection and encrustation using test tubes, bacterial cultures, and animals. Ultimately, human trials will be required. Unique to this research program/proposal of research: This novel peptide coating was discovered at the University of British Columbia by two researchers and is already being applied to artificial joints and implants used in orthopaedics. This will be the first use of this novel, promising technique in protecting urologic devices from infection and encrustation.
Use of the skin immune system and dendritic cells to alter systemic immunity
The skin is the largest organ of the human body and represents the body’s primary interface with the external environment. As such, the skin is challenged by a broad range of factors and conditions. These include both endogenous (genetic, immunologic, and systemic) and exogenous (solar radiation, allergens, irritants, pollutants, and microbes) factors. As a result, the skin is a major site for disease including inflammation and cancer. Dendritic cells are immune cells that begin and coordinate immune responses. The skin is one of the largest repositories of these dendritic cells. Thus, in addition to being a direct target for inflammation, the skin is one of the prime sites where systemic immune responses begin. The proposed program includes four primary themes. The first three themes revolve around the use of the skin immune system (and skin dendritic cells) to modify immune responses (The skin immune system in the induction of immune responses; The skin immune system in the reduction of immune responses and; The skin immune system in disease pathogenesis). The final theme involves the use of pharmaceutical agents to modulate the activity of nonskin derived dendritic cells. The skin offers a unique opportunity to observe and manipulate dendritic cells and thereby the immune system. The focus on the skin as an organ to manipulate immune responses is innovative. This program will lead to a better understanding of the role of the skin immune system in systemic as well as local autoimmune disease (examples include lupus, psoriasis and type 1 diabetes). Further, the program will lead to cost effective strategies to treat and prevent human disease with anticipated improvements in vaccine delivery and efficacy and novel methods to control autoimmune disease.