Most HIV-1 infections worldwide are acquired sexually after exposure to semen. Research shows that co-infection with ulcer-causing sexually transmitted diseases, such as syphilis and herpes, increases the chance of HIV-1 transmission between sexual partners. Studies have also associated urethritis (inflammation of the urethra) with high levels of HIV in semen. Gonorrhea or chlamydia frequently cause urethritis in men, but recent studies suggest another sexually transmitted infection, Mycoplasma genitalium, is a cause of urethritis. Dr. Thomas Lampinen is investigating the association of Mycoplasma genitalium with urethritis and accumulation of HIV-1 in semen of young gay and bisexual men in BC. The study could identify Mycoplasma genitalium as a potentially treatable co-infection linked to the spread of HIV-1. The research has special urgency given recent recommendations to delay antiretroviral therapy, which will likely cause an increase in infectiousness among men with HIV-1.
Research Location: Providence Health Care
Mediator mobilization and release from neutrophil azurophilic granules in association with asthma and COPD
Asthma is the most common chronic respiratory disease in children, and accounts for 25 per cent of school absenteeism. Chronic obstructive pulmonary disease (COPD) generally affects people over 60, and includes emphysema and chronic bronchitis. The rate of both diseases is increasing worldwide, and while asthma symptoms can be treated, COPD has no cure. Neutrophils are the largest cell population among white blood cells and are a critical component of the immune system. Neutrophils contain toxins that enable them to kill bacteria. However, they are more aggressive in people with asthma and COPD and release more toxins, which may exacerbate lung damage. The way neutrophils release these toxins and the genes that may control their release are unknown. Dr. Salahaddin Mahmudi-Azer is researching the mechanism for toxin release and the genes controlling the process to develop new ways of treating asthma and COPD.
The development of a method to study biomechanics of bronchial smooth muscle obtained from endobronchial biopsy
Dr. Brent McParland believes the key to improving care for asthma lies in understanding the underlying mechanisms that cause airway narrowing. In asthma, the airways narrow too much and too easily when exposed to stimuli such as pollens and cat hair. The amount of airway smooth muscle (ASM) is increased in people with asthma, which should mean that asthmatic airways develop more force than non-asthmatic airways. Yet studies have not shown more force in asthmatic airways, as might be expected with more muscle. However, these studies did not assess the ability of the muscle to shorten, which causes the airway to narrow. Dr. McParland is developing a method of obtaining very small airway tissue samples from lung surgeries for use in measuring smooth muscle shortening. He will use the method to compare the airway smooth muscle in normal and asthmatic tissues. This research could result in a better understanding of the nature of exaggerated airway narrowing in asthma.
A postdoctoral program to enhance planning and quality improvement initiatives in mental health through the validation of administrative mental disorder diagnoses
While a number of significant improvements in treatment of mental disorders have been made in recent years, gaps remain. For example, major depression is identified in only 50 per cent of people with the disorder when they visit their family doctor, and only half of those people receive appropriate treatment. Initiatives to address these gaps include programs that provide public and physician education and increase connections between care providers. However, it’s unclear how successful these initiatives will be due to a lack of data on the prevalence of mental disorders and whether people improve as a result of these programs. Dr. Paul Waraich is evaluating whether data routinely collected from hospital and physician visits, as well as medication prescriptions, are of sufficient quality to be used to evaluate changes in the care of major depression and other mental disorders. The research could greatly improve understanding of whether new mental health care programs are effective.
Baseline HIV RNA and mortality after the initiaton of HARRT: Exploring the mechanism that explains the association
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.
Secondary prevention – the gap between evidence and practice
Cardiac disease remains the leading cause of death in Canada. A significant portion of cardiac health care resources are expended on acute interventions such as clot-busting drugs, angioplasty and bypass surgery. However, there is a lack of research on the use of proven strategies – known as secondary prevention – to prevent patients from experiencing subsequent coronary events such as a heart attack. Dr. Karin Humphries is a leading investigator in the area of cardiac health outcomes and the epidemiology of cardiovascular disease. Dr. Humphries is studying how BC patients with heart disease are monitored and how many are using aspirin, beta-blockers and cholesterol-lowering drugs as part of their efforts to reduce their risk of further coronary events. Eventually, she hopes to design a clinical trial to assess new approaches to increase the use of secondary prevention strategies.
Airway epithelial injury as a result of corticosteroid-induced apoptosis
In people living with asthma, the cells lining the airway are more sensitive to injury from allergens and other irritants. Researchers have found that these cells have an impaired ability to repair themselves following injury. Dr. Delbert Dorscheid is studying how the inhaled corticosteroids that asthmatics use to control their symptoms may actually contribute to ongoing breathing problems. While corticosteroid benefit asthmatics by suppressing the inflammation of the airway, Dr. Dorscheid’s research has shown that corticosteroid use also causes the death of cells lining the airway. In severe asthmatics, this may create a cycle of repeated injury and incomplete repair that results in permanent damage. Dr. Dorscheid’s is assessing the extent to which corticosteroids may cause permanent damage to airways and also clarifying the mechanisms by which these drugs cause cell death. His goal: the development of treatment options that will have fewer damaging side effects.
Contribution of granzyme B-induced cell death to atherosclerotic plaque rupture
Jonathan Choy brings previous research experience in the mechanisms of controlled cell death to his work at the Cardiovascular Research Laboratory in the McDonald Research Laboratories at St. Paul’s Hospital. His research focuses on atherosclerotic plaques in the vascular system—also known as hardening of the arteries—caused by a buildup of lipids on the innermost portion of the arteries. Advanced plaques tend to break down and rupture, and can lead to blood clots and heart attack. Jonathan is specifically studying the role of granzyme B—a protein normally used by the immune system to kill abnormal and infected cells—in causing plaque rupture. He is investigating whether granzyme B destroys structural cells in the plaques, thereby reducing the integrity of this part of the vessel wall. Understanding the processes that alter the structural integrity of the atherosclerotic plaques could enable control of some of the events that lead to heart attacks.
A cost-utility analysis of infliximab plus methotrexate versus methotrexate alone for the treatment of Rheumatoid Arthritis
The cornerstone of treatment for rheumatoid arthritis is early intervention with drug therapies. There are, however, limitations to the long-term effectiveness and safety of the conventionally-used drugs. While the use of new drug therapies, called biologicals, have yielded positive results in clinical trials, these drugs are many times more expensive than the traditional therapies for rheumatoid arthritis. Already a Doctor of Pharmacy, Carlo Marra is focusing his PhD studies in Health Care and Epidemiology on the long term costs and consequences (such as health-related quality of life) of using biological agents instead of traditional drug therapies. The potential of these drugs to reduce other direct and indirect health care costs and improve quality of life for patients with severe rheumatoid arthritis may, in fact, make them more-cost-effective over the long term. The results of this study could help inform drug therapy funding decisions by provincial drug plans.
The relationship between socioeconomic status and short-acting beta-agonist use by asthmatics in BC
Asthma is a chronic disease that affects approximately one in 20 Canadians. Research has shown an association between lower socioeconomic status and poorer outcomes for asthma patients, including more hospital admissions and emergency room visits and a greater likelihood of a fatal attack. Excessive use of short-acting bronchodilators, which help manage acute episodes of asthma, indicates inadequate asthma control and has been associated with poorer outcomes. Larry Lynd is investigating whether there is a relationship between lower socioeconomic status-measured by education, income, occupation and characteristics of residence-poor asthma control, and the overuse of bronchodilators. Confirming that relationship could determine whether inappropriate management of asthma is at least partially responsible for poorer outcomes. Larry hopes this research can lead to policies and strategies aimed at improving the management of asthmatics of lower socioeconomic status.