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.
Year: 2007
Mechanism of androgen regulated expression of SESN1, a potential tumor suppressor
Male sex hormones (androgens) regulate tumour growth in prostate cancer. The only effective treatment for advanced prostate cancer is the removal of androgens using medication, or the surgical removal of the testes — treatments that cause impotence and a decreased sex drive. The results are usually temporary since some tumour cells survive, become independent of androgens, and continue to grow. Prostate cancer cells depend primarily on the androgen receptor, which encodes genetic information, for growth and survival. Gang Wang is studying how the androgen receptor decreases the expression of the SESN1 gene — a gene that may inhibit the growth of prostate tumour cells. Wang believes the SESN1 gene is no longer repressed when patients receive hormone therapy. This would explain the initial suppression of prostate cancer cells seen in these patients and the subsequent reappearance of cancer cells which later follows. Wang will confirm if the androgen receptor begins lowering the gene following therapy, allowing the cancer cells to grow. If so, the SESN1 gene could be a promising therapeutic target for treating prostate cancer.
The Genetics of Asthma, Atopy and Allergic Diseases
My research focuses on trying to identify why some children get asthma and others do not. By identifing specific environmental and genetic risk factors and determining how they work together to predispose children to developing asthma and other allergic diseases we can design better treatments. Studies have found a 1-in-5 risk of developing asthma if one parent has asthma. The odds rise to 2 out of 3 if both parents have asthma. However, in itself, a genetic predisposition does not ensure that asthma will develop. Asthma and allergic disease are the result of both genetics and the environment. The interaction between a genetic disposition and environmental factors is key in the development of – or in protecting against- asthma. I will use information from 250 French Canadian Asthma Families and two additional birth cohorts, and information from the town of Busselton Australia in my research. Home visits were conducted for all the families and children to collect information on environmental factors such as family history, number of children, parental occupations, daycare, pets, dust samples, infections, hospitalizations and medication usage. After reviewing the literature we have found 162 genes which may predispose children to developing asthma and we will be looking at these genes in conjuction with other environmental factors to try and better understand why some children develop asthma and others do not. Using statistical models we will look at what genetic and environment factors best explain why some children develop asthma and others do not. We will then do further laboratory experiments to try and identify these factors work together.
Optimal, evidence-based use of vaccines
Immunization is one of the most powerful tools available in medicine. The number of available vaccines expands each year, reducing infection and disease. Optimal use of these new products can be hampered by gaps in understanding the disease epidemiology, vaccine effectiveness or longevity of protection provided. These gaps also affect decision-making related to resource allocation and prioritization of immunization programs. Dr. Jan Ochnio is working to close these gaps by gathering missing evidence to facilitate vaccine use in several viral and bacterial infections. As a MSFHR Scholar, Ochnio investigated the risk of hepatitis A for children in specific areas of the province. Now, his research is focusing on two areas: investigations of hepatitis A virus infections using population-based assays and saliva/mail-based surveys, and optimizing prevention of meningococcal infections by measuring the levels and duration of protection offered by the various meningococcal immunization schedules in Canada. A better understanding of the most efficient strategies for using vaccines could lead to substantial savings in health care by omitting unnecessary doses and the related costs of providing these doses. Ochnio’s findings will be shared with public health policy experts to be used in finely-tuned vaccination programs and policies that will provide optimal protection for Canadians.
Structural analysis of the molecular machinery involved in protein secretion, membrane protein assembly and protein processing
The ability for proteins to travel across cell membranes is critical to the life of all cells, yet research shows that bacterial cells differ from human cells in some of the components necessary for this movement to occur. In previous work supported by an MSFHR Scholar award, Dr. Mark Paetzel uncovered the three-dimensional structure of proteins that make up the molecular machinery involved in this movement in bacterial cells. Now a Senior Scholar, Dr. Paetzel will continue this work with the goal of learning more about these structures in order to determine how to inhibit the movement of proteins across cell membranes in bacteria. He will use X-ray crystallography to investigate the proteins involved in protein targeting, translocation, and membrane protein assembly in bacteria. Dr. Paetzel is also investigating a particular enzyme that functions at the membrane surface — one that causes the cleaving of interior peptide bonds in a protein. Understanding how to inhibit this enzyme and its role in bacterial cell movement could lead to the development of a novel class of antibiotics — a strategy that is required to meet the ever-increasing challenge of antibiotic resistance.
Detecting, Treating and Preventing Drug-Related Morbidity
In Canada, 7.5 per cent of hospital admissions are complicated by an adverse event related to medical care that leads to death, disability, or a prolonged hospital stay. Adverse drug related events (ADREs) represent the most common cause of preventable non-surgical adverse events, with up to 130,000 patients in British Columbia (BC) presenting to Emergency Departments with a symptomatic ADRE. However, there are currently no efficient screening strategies for ADREs. This team is working to develop and evaluate a clinically effective, resource-efficient screening strategy. Once the strategy has been proven effective in an Emergency Department setting, the team aims to adapt it for use in community-based practice, and determine its cost effectiveness in comparison to the current standard of care.
Team in Child and Adolescent Healthy Body Weights
At least one in four BC children and youth is overweight or obese, and many of these young people are already developing serious diseases, such as hypertension and type 2 diabetes. Preventative and therapeutic measures have not succeeded in curbing the prevalence of overweight and obese children and youth in BC and Canada. This award supports the development of a multidisciplinary team bringing together clinical, social and basic researchers. The team aims to study determinants of childhood and adolescent overweight at individual, family, community and population levels, and to develop targeted interventions that will result in sustainable outcomes and healthy body weights.