The Physicians’ Services Incorporated Foundation This site is primarily for individuals with an interest in the research programs of the Foundation

Report on Granting Activities

May 1 to Agust 31, 2008

The Foundation approved grants with a total value of $1,056,000 in the second quarter of 2008, for the following projects:

Dr. M. Bhandari
McMaster University

Fixation using alternative implants for the treatment of hip fractures (FAITH): An Ontario pilot study, a multi-centre randomized pilot trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures.

Hip fractures are associated with a 30% mortality rate and occur in 36,000 Canadians annually, and the number of hip fractures is likely to exceed 88,000 in Canada over the next forty years. Experimental data suggests that cancellous screws offer greater preservation of blood supply, while sliding hip screws provide greater bio-mechanical stability to bending stresses. While both arguments are persuasive, the impact of these biologic alterations on outcomes are important to patients and offer more compelling guidelines for clinical practice.

The objective of this study is to assess the feasibility of conducting a large definitive trial investigating the revision surgery rate and quality of life when cancellous screws versus sliding hip screws fixation is performed in patients over 50 years of age with a femoral neck fracture.

M. M. Flavin
Queen's University

Negative effect of high temperature on brain inflammatory response - a key factor in the cause of Cerebral Palsy.

Cerebral Palsy (CP) is linked to chorioamnionitis (ChA), a peri-natal infection of fetal membranes, which is usually accompanied by maternal fever. Strong epidemiological links between maternal fever and CP also exist. These investigators have recently carried out experiments showing that hyperthermia, a surrogate for fever, alters the intensity of the brain's inflammatory response.

The goal of this study is to determine if fever amplifies brain inflammatory response of the fetus to infection, and whether this results in brain damage. This study will clarify if hyperthemia, in a setting of inflammation, contributes to brain cell death during late fetal brain development.

Dr. R. McManus
Dr. D. Somerset
University of Western Ontario

Vitamin D and cytokine levels in women with and without gestational diabetes.

Pregnancy, and particularly gestational diabetes (GDM), are insulin resistant states; adipocytokines, inflammatory cytokines, and vitamin D (VITD) are of interest for developing associations with insulin resistant states. Evolving evidence also suggests associations between VITD repletion status and various cytokine patterns.

The objectives of this study include assessing VITD and cytokine levels in maternal serum, arterial and venous cord blood in pregnancies with and without GDM, and to seek relationships between VITD, cytokine levels, maternal and fetal outcomes.

Documentation between VITD and cytokine levels in GDM may provide insights into linkages between insulin resistance and chronic inflammation, while also identifying potential VITD intervention studies.

Dr. C. Cardella
Toronto General Hospital

Down-regulation of allosensitized B cells.

A large number of patients across Canada are unable to receive a successful organ transplant because of high levels of a destructive antibody in their circulation. This destructive antibody remains elevated in blood for years and reduces access to transplantation. It responds poorly to treatment, can damage the transplanted organ, and reduces the likelihood of a successful transplant. New information on the control and down-regulation of this destructive antibody is needed.

The specific aim of this study is to demonstrate that a regulatory antibody can be produced in the laboratory and in animals, and that this regulatory antibody will neutralize the effect of the destructive antibodies.

Control of this destructive antibody will lead to successful kidney transplantation in persons who are currently denied the opportunity of receiving a transplant, while also reducing the adverse effects of the destructive antibody on transplanted organs.

Dr. C. Craven
Toronto Rehabilitation Institute

Chronic pain and fractures after spinal cord injury (SCI): impact on costs of care and quality of life.

Spinal cord injury (SCI) is a major catastrophic life event that affects an individual's ability to move around their home/community, manage their bladder and bowel functions, blood pressure, body temperature, and ability to eat and breathe independently. Secondary Health Conditions (SHC) are common after SCI and incur costs to the patient (indirect) and healthcare system (direct), while also affecting the person's Quality of Life (QOL).

The objectives of this study include determining the affect of SHC on QOL among a group of people with chronic SCI, while also identifying and prospectively quantifying the associated indirect/direct costs of specific SHC (fractures and chronic pain) in 2008. The goal of this study is to minimize the economic burden of SHC and improve QOL after SCI.

Dr. M. Fehlings
M. Shoichet, Ph.D
Toronto Western Hospital

Neuroprotection of the injured spinal cord using an anti-apoptotic molecule delivered through a novel bioengineered drug delivery system.

Spinal cord injury (SCI) is devastating for the affected individual and a major financial burden for society. Current therapies for SCI are minimally effective, thus improved treatments are required. The mechanism of SCI involves a primary injury followed by biochemical processes that cause delayed cell death (apoptosis). These investigators have previously shown that activation of a 'death receptor' on nerve cells (FasR) appear to be a key cause of apoptosis after SCI; moreover, data suggests that administration of a soluble form of FasR (sFasR) can inhibit FasR activation, reduce apoptosis of nerve cells and improve neurological recovery.

This study will further examine the hypothesis that inhibition of FasR mediated apoptosis by sFasR, when delivered in a clinically relevant post-injury time window, will promote functional and neuroanatomical recovery after SCI.
The objectives of this study are to optimize the drug delivery system for sFasR, determine the most effective and clinically relevant time window for administration, and elucidate the mechanism by which sFasR is neuroprotective.

Dr. K. Boutis
Hospital for Sick Children

Implementation of the Low Risk Ankle Rule.

Ankle injury is a very common injury in children; each year approximately 35,000 children present to Ontario emergency departments (ED) with this problem, and 90% of these children receive x-rays of the injured ankle, even though only 12% of these x-rays show a break in the bone. Research has created specific rules that doctors can use to help determine which children really require x-rays. Unfortunately, even though these rules have been proven to safely reduce x-rays by as much as two-thirds, most doctors are not using these rules.

This study will be the first to put the best paediatric ankle x-ray rule, the Low Risk Ankle Rule, into physician practice in EDs. The main goal of this study is to determine how much the ankle x-ray rates can be reduced in EDs that use this rule regularly versus those that do not. If this study shows that doctors can safely use this rule and reduce the number of ankle x-rays, this will lessen unnecessary potentially harmful radiation exposure in children, and children will spend less time in the ED, thereby saving health care system resources.

Dr. Y. Yinon
Dr. J. Kingdom
Mount Sinai Hospital

Understanding the mechanisms for increased cardiovascular risk in women with a history of severe pre-eclampsia - An assessment of postpartum endothelial function.

Women with a history of pre-eclampsia or intra-uterine growth restriction (IUGR) face increased risk for the future development of hypertension and cardiovascular disease. The underlying mechanism that places women with such a history of increased risk remains unknown.

The aim of this study is to examine whether endothelial function is impaired in postpartum women with a history of pre-eclampsia or IUGR. These investigators will also determine the correlation between impaired vascular dilation and biochemical markers such as microalbuminuria and elevated circulatory levels of serum anti-angiogenic factors (sFlt-1 and sEng). The findings of this study may introduce new measures to predict future cardiovascular disease in women with a history of pre-eclampsia/IUGR, and then translate into early interventions for the prevention of negative cardiovascular outcomes.

Dr. I. Awad
Sunnybrook Health Sciences Centre

Femoral nerve block: Anatomical insertion point - A prospective randomised double-blind controlled trial.

Nerve blocks are an effective way to control pain after surgery. Two major nerves provide sensation to the knee: the femoral nerve provides sensation to the front of the knee, and the sciatic nerve provides sensation to the back of the knee.

This study attempts to address a belief that has not been evaluated scientifically, yet is accepted by practitioners and teachers of regional anesthesia. Does needle insertion at the inguinal crease with stimulation of sartorius muscle cause an equivalent block to the classical method with stimulation of the quadriceps femoris muscle, for femoral nerve blockade?

Dr. J. Snowdon
Dr. T. Childs
Queen's University

Investigation of the miRNA expression profiles of endometrial carcinoma.

MicroRNAs are small regulatory molecules present in the cells of animals, which have been implicated in the development of several human cancers.

This study will examine the expression profiles of microRNAs in endometrial cancer, of which endometrioid adenocarcinoma, also known as type 1 endometrialcarcinoma, is the most common. This study will assist with characterizing the molecular events leading to development of endometrial carcinoma. These investigators may be able to identify unique microRNA expression profiles that can be used to distinguish endometrial cancer from normal tissue, while also hoping to identify potential therapies or novel molecular markers that could be used to diagnose endometrial cancers at an earlier stage.

Dr. D. Yu
Dr. S. Vanner
Queen's University

Comparison of lactulose hydrogen breath test with scintigraphic oro-cecal transit study for detection of bacterial overgrowth in IBS.

Recent studies suggest that most patients with Irritable Bowel Syndrome (IBS) have undiagnosed intestinal bacterial overgrowth (SIBO), as determined by lactulose hydrogen breath test (LHBT). Treatment with antibiotics dramatically improves their symptoms. The reliability of LHBT for diagnosing SIBO is controversial, yet this test continues to be recommended and widely used. Surprisingly, as many as 90% of community gastroenterologists in the United States are currently prescribing antibiotics for patients with IBS, based on the finding on a LHBT, despite concerns about its accuracy.

To gain a more accurate understanding between the association of SIBO and IBS, it is important to employ complimentary investigations to better determine if rises in hydrogen in the LHBT, currently used as a diagnostic test for IBS, could be secondary to a colonic site of hydrogen production, as opposed to the small bowel as currently proposed.

The goal of this study is to determine the validity of the LHBT for diagnosing small bowel bacterial overgrowth, by determining whether changes in this test occur before of after the test meal reaches the large bowel. The investigators hypothesize that abnormalities in the LHBT in IBS patients are due to interaction with cecal bacteria and not small bowel bacteria.

Dr. P. Szmitko
Dr. S. Verma
St. Michael's Hospital

Role of the tumor suppressor gene BRCA1 in adverse cardiac remodeling: In Vivo integrative studies in cardiac specific BRCA1 knockout mice.

Heart attacks are a leading cause of death globally; they occur when the blood and oxygen supply to a part of the heart is blocked. Heart cells in the damaged areas consequently adapt or die, potentially resulting in heart failure and ultimately death. Understanding the signaling pathways governing cardiomyocyte death may offer therapeutic strategies to limit myocardial injury, cardiac morbidity and mortality.

The pathophysiological stressors of an evolving heart attack promote signaling pathways, which lead to myocardial cell apoptosis. DNA damage is the hallmark of apoptotic cell death. These investigators plan to determine if BRCA1, a gene that promotes DNA repair, can protect heart function by reducing heart cell injury and apoptosis. This is the first project aimed at studying how the breast cancer gene BRCA1 may be involved in cell adaptations and survival following heart injury. This work will improve the understanding of how and why heart disease occurs and will hopefully pave the way for better therapeutic drug designs.

Dr. K. Levitt
Dr. S. Verma
St. Michael's Hospital

ACE2 and atherosclerosis.

The renin-angiotensin system (RAS) is a clinical mediator of cardiovascular disease, and an established target in the treatment of hypertension, after heart failure. Angiotensin-II (AngII), the main effector molecule of the RAS, is a potent proinflammatory and proatherosclerotic molecule, and plays an important role in the development and progression of cardiovascular disease. Recent evidence suggests that the protein angiotensin converting enzyme 2 (ACE2) may be involved in regulating the activities of AngII.

These investigators hypothesize that since ACE2 is found in blood vessels, it may participate in regulating blood vessel function. The results of this study may aid in the development of novel ACE2-based treatment strategies in the treatment of cardiovascular diseases.