College of Medicine - B.Sc. (Med) Projects

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Open Access
Regulatory Mechanisms Underlying Biological Control Activity of Pseudomonas chlororaphis PA23.
(FEMS Microbial Ecology, 2010) Selin, Carrie Lynn; Cardona, Sylvia (Microbiology) Fernando, Dilantha (Plant Sciences) Mulvey, Micheal (Medical Microbiology) Loper, Joyce (Oregon State University); DeKievit, Teri (Microbiology)
Biological control is an intriguing alternative to the use of chemical pesticides as it represents a safer, more environmentally friendly approach to managing plant pathogens. Pseudomonas chlororaphis strain PA23 was isolated from soybean root tips and it was found to be an excellent antagonist of sclerotinia stem rot. Our studies have shown that pyrrolnitrin (PRN) is the key metabolite required for S. sclerotiorum inhibition, while phenazine (PHZ) is important for biofilm establishment. For this reason, research efforts were directed towards elucidating the mechanisms governing PA23-mediated antibiotic production. To determine how these compounds were regulated, QS-deficient strains and an rpoS mutant were generated. The QS-deficient strains no longer inhibited the fungal pathogen S. sclerotiorum in vitro and exhibited reduced PRN, PHZ and protease production. Analysis of transcriptional fusions revealed that RpoS has a positive and negative effect on phzI and phzR, respectively. In a reciprocal manner, RpoS is positively regulated by QS. Characterization of a phzRrpoS double mutant showed reduced antifungal activity as well as PRN and PHZ production, similar to the QS-deficient strains. Furthermore, phzR but not rpoS was able to complement the phzRrpoS double mutant for the aforementioned traits, indicating that the Phz QS system is a central regulator of PA23-mediated antagonism. GacS/GacA, PsrA, RpoS and the PhzI/PhzR QS are members of a complex regulatory hierarchy that influence secondary metabolite production in PA23. An additional system, termed Rsm, was identified, adding yet another layer of complexity to the regulatory network. The Rsm system in PA23 appears to be comprised of a single small non-coding regulatory RNA termed RsmZ, and two RNA binding proteins RsmA and RsmE. We discovered that the expression of rsmZ, rsmA and rsmE all require GacA. In addition, both PsrA and QS were shown to positively regulate rsmZ transcription. For rsmE, GacA may indirectly regulate expression through PsrA, RpoS and QS, as all three regulators control rsmE transcription. Furthermore, we believe that the positive effects of PsrA and QS on rsmE transcription are likely mediated through RpoS as only RpoS show direct activation of rsmE in an E. coli background.
Open Access
Characterization of the expression of CD184/CXCR4, CD44/H-CAM, CD49d/VLA-4 and CD26/DPPIV on CD34+ hematopoietic stem ells collected from different sources
(2012-03-12) Charette, Miranda; Medicine; Dr. Donna Wall (Departments of Pediatrics and Child Health, Internal Medicine, and Immunology. Director, Manitoba Blood and Marrow Transplant Program) and Dr. David Szwajcer (Department of Internal Medicine, Medical Oncology and Hematology.
Not available.
Open Access
Mental Health Issues Associated with Foot Complications of Diabetes Mellitus
(2012-03-12) Hoban, Christopher; Medicine; Dr. John Embil (Medical Microbiology).
Diabetes mellitus (DM) is a chronic disease associated with severe multi-system complications including, but not exclusive to, peripheral neuropathy, peripheral vascular disease, renal and cardiovascular disease. Diabetic peripheral vascular disease and neuropathy often result in foot ulcers and Charcot arthropathy that can be complicated by infection, amputation and increased morbidity and mortality. Diabetic patients, especially those with severe functional impairment, have more frequent symptoms of psychological depression then the general population, which is further increased if the patient concurrently has a diabetic foot ulcer. Currently, there is limited information available on the effect of diabetic foot complications on other mental health issues, including tlle sphere and extent of anxiety disorders, co-morbid alcohol and substance abuse disorders, suicidality, and perceived need for mental health treatment. There is also a gap in ilie knowledge on ilie physical, emotional, and psychological stress that is placed on the caregiver, frequently being spouses and extended family members, for a patient with DM and DM foot problems. Therefore, the goal of this research was to evaluate diabetic patients with and without diabetic foot problems, and caregivers of patients with diabetic foot problems. The student will use patient interviews, and a series of psychological outcomes surveys to explore the impact that this disease has on the popUlation and ilieir caregivers. The objectives for the student would be gain knowledge of evidenced based medicine, biostatistics and epidemiological skills to evaluate the impact this disease has on select patient populations.
Open Access
Comprehensive Primary Health Care in the Island Lake Communities: What does it mean and how does it look?
(2012-03-12) Scramstad, Carly; Medicine; Dr. Marcia Anderson DeCoteau (Department of Community Health Sciences).
Introduction: As part of a global project on Comprehensive Primary Health Care (CPHC), this project was designed to identify the health beliefs and values of the residents of Garden Hill First Nation and to design a governance model for a CPHC system that would best reflect these health beliefs and values. Methods: The study had three components: First, a research agreement that appropriately recognized and respected the communities’ rights to own, control, access and possess the knowledge generated through the research was negotiated and signed. A literature review was performed to identify any previous articles on First Nations’ conceptualizations of health and on CPHC, especially in a First Nations’ context. Lastly, community level data gathering was in the form of modified focus group activities for youth (age 19-29), adults and elders. The focus groups were recorded and transcribed, and analyzed by three members of the research team for major themes. Results: The following themes were identified as either components of, barriers to, or conditions necessary for health: healthy and affordable food, physical activity, healthy body weights, being clean (personal hygiene, environmental cleanliness), mental health, substance abuse, prenatal health, parenting, link to the land, traditional food, traditional medicine, water, housing, expense of basic necessities, community perspective, community participation/ engagement, community independence, community leadership responsibilities, advocacy, equity, and safe and accessible health care. Of the five criterion of a CPHC system, the third tenet regarding the improvement of social and environmental factors that impact on health was the most significantly emphasized.
Open Access
Defining Neurodevelopmental Domains in Children with Prenatal Solvent Exposure
(2012-03-12) Bulman, Carolyn; Medicine; Dr. A. Hanlon-Dearman (MB FASD Centre, Winnipeg Children's Hospital) and Dr. T. Benoit (MB FASD Centre).
Organic solvents are inexpensive and commonly available substances of abuse that are found in accessible items such as spray paint, lacquer and glues, and which are often abused by young people in poverty. Solvents are highly lipophilic and can cross the plancenta resulting in fetal exposure. Case reports have suggested that children exposed in utero to solvents have developmental and/or physical features similar to those seen in children with a diagnosis of Fetal Alcohol Spectrum Disorder. This study will describe in detail the developmental and behavioral profile of children with prenatal solvent exposure. The student will use the database at the Manitoba FASD Centre and conduct a retrospective quantitative and qualitative chart review. The objective was to complete a chart review on a large clinical cohort of solvent exposed children with regards to dysmorphology, medical comorbidity and neurodevelopmental characteristics.
Open Access
Fish Oil Mediated Cardiovascular Complications in ApoEKO Mice
(2012-03-12) Du, Xiaozhou; Medicine; Dr. Mohammed Moghadasian (Human Nutritional Sciences) and Dr. Davinder S. Jassal (Department of Internal Medicine).
BACKGROUND: Atherosclerosis is the principle cause of cardiovascular disease. Due to their spontaneous development of atherosclerosis, apolipoprotein E knockout mice (ApoEKO) are one of the best studied animal models of atherosclerosis. Although previous reports have evaluated the effects of omega-3 fatty acids in the prevention of cardiovascular disease, little is known on their effects in the setting of ApoE deficiency. OBJECTIVE: To assess the cardiovascular effects of omega-3 fatty acid supplementation (fish oil, flaxseed oil, and designer oil) in ApoEKO mice maintained on a high fat diet. METHODOLOGY: A total of 40 six-week old ApoEKO mice were randomized into 4 treatment groups. All animals were fed a Western-type diet reconstituted with either safflower oil (control), fish oil, flaxseed oil or designer oil. In vivo cardiac function was assessed weekly using echocardiography. Blood pressure and plasma lipid levels were serially measured. Cardiac remodeling was examined using histological analysis and biochemical assessment of a cardiac biomarker: brain natriuretic peptide (BNP). RESULTS: Echocardiography demonstrated increased ventricular wall thickness in the fish oil treated mice, as compared to the control group (p<0.05). Blood pressure increased over time in the fish oil treated mice (p<0.05). Relative to control, the fish oil group also showed increased plasma triglycerides (p<0.01), and decreased plasma total cholesterol (p<0.05). Furthermore, ventricular BNP expression was elevated in the fish oil treated mice (p<0.05). Flaxseed oil and designer oil produced similar cardiovascular effects as the control diet. CONCLUSION: A high fat diet supplemented with fish oil leads to adverse cardiovascular effects in ApoE deficient mice.
Open Access
Social Perspective-Taking Abilities in Children with Autism Spectrum Disorder (ASD)
(2012-03-12) Leibl, Marli; Medicine; Dr. Albert Chudley (Department of Biochemistry and Medical Genetics) and Dr. Ana Hanlon- Dearman (Department of Pediatrics and Child Health).
Approximately 80% of children with autism spectrum disorders (ASDs) fail to perform perspective taking as measured by false belief (FB) tests that require speech. Since children with ASDs exhibit a range of verbal abilities, it is possible that children with limited speech may be successful on false belief tests that do not require vocal responses. The present study examined the performance of children on three false belief tests that require different verbal skills. Eighteen children with ASDs (ages 5 years to 11 years 11 months) and eighteen typically developing children (ages 3-5 years 11 months)were tested on: (a) two standard FB tests that require children to answer questions vocally and a nonvocal Guesser-Knower (GK) test designed to evaluate whether children are able to discriminate the relationship between seeing and knowing. Results indicate that: (a) performance did not differ significantly among the three different tests; (b) in the ASD population, children with higher expressive language scores outperformed those with lower expressive language scores on all tests.
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Phenotypic and genotypic evaluation of a large Manitoban kindred with hereditary xerocytosis
(2012-03-12) Houston, Brett; Medicine; Dr. Ryan Zarychanski (Department of Internal Medicine) and Dr. Donald Houston (Department of Internal Medicine).
The hereditary stomatocytoses are a group of heterogeneous conditions associated with chronic red cell haemolysis for which the causative genetic mutations are not known. We investigated 137 members of a large Manitoban kindred with phenotypic findings consistent with hereditary xerocytosis. The objectives of this study were to systematically characterize the disease phenotype and to define the chromosomal region carrying the disease locus. The mode of inheritance was autosomal dominant. Affected family members were found to have wellcompensated haemolysis, associated with an elevated MCHC, decreased osmotic fragility, decreased haptoglobin, and increased indirect hyperbilirubinemia. Cholelithiasis and progressive iron loading were common, despite normal haemoglobin levels. Quantitative erythrocyte morphologic evaluation revealed increased schistocytes, target cells, reticulocytes, and eccentrocytes in affected individuals; stomatocytes were however not increased. Using DNA linkage analysis, we confirmed the localization of the disease phenotype to chromosome 16q, and we refined the candidate region to 16q24.2 – 16qter, a 2.4 million base pair interval containing 51 known or predicted genes. Exome sequencing, and subsequent bioinformatic analysis identified a single gene mutation within a red cell membrane mechanosensitve ion channel that was present in all affected family members, but in no unaffected individual. Functional studies are necessary to clarify the influence of the identified mutation with regard to erythrocyte structure and function.
Open Access
Anti-estrogen Use, Estrogen Receptor Expression, Smoking Patterns, and Survival of Women with Non-Small-Cell Lung Cancer: A Manitoba Perspective
(2012-03-12) Lother, Sylvain; Medicine; Dr. Gary Harding (CancerCare Manitoba) and Dr. Marshall Pitz (CancerCare Manitoba).
Lung cancer is the leading cause of cancer death worldwide. Gender differences in lung cancer outcomes are known. When compared to men, women have significantly better survival and women are more likely to develop lung cancer when nonsmokers. Research suggests estrogen plays a key role in the risk of development and outcomes of lung cancer. Accordingly, anti-estrogen use should also influence survival in female non-small cell lung cancer (NSCLC) patients. In this study we compared mortality among anti-estrogen users and non-users. METHODS: This population-based study had a retrospective study design. Using the Manitoba Cancer Registry (MCR) we identified all women diagnosed with NSCLC from 2000-2007. The Drug Program Information Network (DPIN) was accessed to establish patients that received anti-estrogens. Demographic data (e.g. smoking patterns, stage, histology) was gathered by chart review. Mortality rates for anti-estrogen users and non-users were compared using Kaplan-Meier survival functions and Cox regression models. RESULTS: 2320 women fit our patient criteria, of which 156 had received prior anti-estrogens. A positive smoking history was documented in 88%, 62% being former vs. 26% current smokers. A history of 30+ packyears was seen in 55%. Exposure to anti-estrogen was associated with a significantly decreased mortality (HR 0.718, p = 0.0031). Overall survival with anti-estrogen vs. none resulted in median survival of 1.89 vs. 0.93 years, respectively (p < 0.0001). CONCLUSIONS: Our results demonstrate that anti-estrogens are associated with decreased mortality from NSCLC. These findings supplement and reinforce past evidence that estrogen plays a key factor in the biology and outcomes of NSCLC.
Open Access
Role of Glia Maturation Factor beta (GMFj3) in Differentiation of the Childhood Cancer Neuroblastoma
(2012-03-12) Richards, Ceri; Medicine; David D. Eisenstat (Departments of Pediatrics and Child Health).
Background: Neuroblastoma (NB), the second most common solid tumor of the peripheral nervous system, accounts for 10% of pediatric cancers. Most children present with advanced stage disease with very poor survival rates. 13-cis retinoic acid (RA), a differentiating factor, is a component of NB treatment following surgery, radiation and chemotherapy. Glia Maturation Factor beta (GMFj3) was initially characterized as a factor that caused process extension and reduced cell proliferation when added to glioblastoma cells. GMFB as an actin depolymerizing factor (ADF) may modify cell morphology by interacting with the peripheral actin cytoskeleton localized within the distal axon. GMFi3 is highly expressed in neuronal tumor-derived cell lines, especially NB. Results: GMFJ3 phosphorylation was shown to decrease with RA treatment of NB cell lines. GMFJ3 was hypophosphorylated in adult mouse brain tissues. GMFJ3 transfection showed modest increases in differentiation in NB cell lines as demonstrated in a neurite extension assay. A possible GMF-j3 dimer is formed with dephosphorylation of NB cells and in more differentiated mouse tissues. A MYCN-amplified NB cell line has increased GMFJ3 expression. Conclusions: Our results are consistent with the role of GMFJ3 as an ADF, since ADFs function when dephosphorylated. These experiments support a relationship between GMFJ3 phosphorylation and differentiation of NB cell lines. Examination of the role of GMFi3 as an ADF in NB differentiation may ultimately contribute towards novel biological therapies directed against this highly malignant childhood tumor.
Open Access
Long-term follow-up of ACL reconstruction: Insight into the natural history of altered biomechanics of the knee joint
(2012-03-12) Gourlay, Robert; Medicine; Dr. Peter MacDonald (Department of Surgery) and Dr. Jeff Leiter (Department of Surgery).
The goal of ACL reconstruction is to restore stability to the knee joint and prevent the onset of osteoarthritis. Little is known of the long-term natural history of a knee joint that has undergone ACL reconstruction. Our study set out to investigate changes in the knee joint following ACL reconstruction. This retrospective study examined 68 participants who had received a semitendinosus/gracilis autograft ACL reconstruction a mean 14.6 years prior. Clinical evaluation involved radiographic analysis, IKDC knee examination form, instrumented laxity testing with the KT-1000 arthrometer, Tegner Activity Scale, Lysholm Knee Score, ACL QOL outcome questionnaire, and knee flexor/extensor strength testing using the Biodex III dynamometer. We observed increased incidence of OA in the reconstructed knee compared to the contralateral knee, especially in the medial compartment. Tegner Activity Score was reduced from the pre-injury level. We also report a significant decrease in knee extensor strength in the reconstructed knee compared to the contralateral knee. In conclusion, the semitendinosus/gracilis hamstring autograft showed an increased incidence of OA compared to contralateral knee, but a very good clinical outcome in the majority of patients.
Open Access
Outcome of patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphomas (DLBCL) that are receiving upfront therapy in the hospital setting compared with patients diagnosed and treated in the outpatient setting
(2012-03-12) Shaffer, Seth; Medicine; Dr. Morel Rubinger (Internal Medicine).
Study Aim: To establish the characteristics of patients with DLBCL that requires up-front in-hospital therapy, as well as their outcome post-therapy. Comparison of characteristics and outcomes with a concurrent cohort of outpatient managed group was made. Methods: Retrospective chart review over 5 years for newly diagnosed patients with DLBCL admitted to a teaching hospital and concurrently for patients that were managed as outpatients. The study included 46 in-patients and 96 outpatients. Patients considered eligible for R-CHOP were those from age 18-80, as patients above age 81 were initially not eligible to receive Rituximab. Results: There were 38 in-patients eligible to receive R-CHOP, with 28 receiving R-CHOP, 3 R-CVP and 7 palliation. There were 77 outpatients eligible to receive R-CHOP, with 64 receiving R-CHOP, 12 R-CVP and 1 palliation. Patients with higher IPI (3 or more) correlated with a higher need for hospitalization (p<0.001). Patients from rural setting were also more likely to be hospitalized (p=0.043). Overall survival post-diagnosis for patients eligible to receive R-CHOP was lower for in-patients compared to the outpatient group (p=0.0002). At 3 years the overall survival was 60.5% for in-patients and 77.7% for outpatients. There was no significant difference in survival between in-patients and outpatients that completed R-CHOP treatment (p=0.1120). For patients with IPI of 3 or higher that completed therapy no significant difference in survival between treatment groups was noted (p=0.53). Conclusions: In-hospital patients with DLBCL eligible to receive R-CHOP had inferior outcomes compared with the outpatient group. Comparing patients that completed chemotherapy from either group, no survival differences were seen. Same applies to patients that finish therapy and have high IPI. Ability to complete R-CHOP chemotherapy in due time led to similar outcomes for either group.
Open Access
Supportive care in the management of severe pneumonia in Nigerian children
(2012-03-12) Daodu, Oluwatomilayo (Tito); Medicine; Dr. Maryanne Crockett (Department of Pediatrics and Child Health) and Dr. Adegoke Falade (Department of Pediatrics and Child Health).
According to 2008 estimates, about 177,000 children under the age of five years died of pneumonia in Nigeria, which was the third commonest cause of the 1 million deaths in Nigerian under-5s. Detecting hypoxemia with the use of simple pulse oximeters and providing immediate, cost- effective oxygen treatment may be effective in decreasing the mortality due to childhood pneumonia in Nigeria. During the period .June I, 2010 through August 31, 2010 children aged between 2 and 59 months with severe and very severe pneumonia were enrolled and treated with standard therapy as well as supplemental oxygen via oxygen concentrator or cylinder at University College Hospital, Ibadan. There were no significant differences found in the socio-demographic data (age, sex, socioeconomic class) between the oxygen concentrator and cylinder groups (p>O.1 for each variable). Forty-five out of80 patients (56%) admitted were hypoxic (Sp02 < 90%). Twenty-three were commenced on oxygen therapy via oxygen concentrator and 22 via oxygen cylinder. The majority of patients (98%) recovered without sequelae (44). 6 patients experienced complications during admission and one child died. There were no significant differences found in the outcome parameters between the two groups (p>0.05) except a decrease in the days to resolution of nasal flaring in the oxygen concentrator group (p<0.05)The data that has been gathered in this study suggests that the use of oxygen concentrators as a mode of oxygen delivery for hypoxemic children with pneumonia is as effective as the use of oxygen cylinders.
Open Access
Temporal Dystrophic Remodeling within the Intrinsic Cardiac Nervous System of the Streptozotocin Diabetic Rat Model
(2012-03-12) Menard, Chantalle; Medicine; Dr. Rakesh Arora (Surgery) and Dr. Paul Fernyhough (Pharmacology).
There is significant evixdence to support the existence of “diabetic cardiomyopathy,” described as heart failure (HF) in diabetic individuals in the absence of obstructive coronary disease and hypertension. The underlying pathogenesis is only partially understood, but alterations in the autonomic nervous system’s (ANS) control of cardiac function have been implicated. An important component of the cardiac ANS is the intrinsic cardiac nervous system (ICNS). The ICNS behaves as a neuronal modulator of cardiac function, and has been called the “little brain on the heart”. While there have been several investigations into the effects of diabetes on extracardiac neurons, little is known about the alterations that occur in the ICNS. It is proposed that high glucose concentrations induce toxicity via oxidative stress, resulting in neuronal dystrophy and dysfunction. Our first aim was therefore to confirm that a process of dystrophic remodeling occurs within the ICNS of diabetic hearts. Our second aim was to examine the role of oxidative stress in the pathogenesis of neuronal dystrophy. Our preliminary data indicated that neuronal dystrophy occurs in the ICNS neurons of streptozotocin (STZ)-diabetic rats, and accumulates temporally within the disease process. It was also determined that an increase in reactive oxygen species (ROS) occurs in the neuronal processes of diabetic rats, indicating an association between oxidative stress and the development of a dystrophy. While our preliminary work provides novel insight for diabetes and cardiac research, more investigations are needed to further examine neuronal dysfunction and cell death, and to prove a causative role for oxidative stress in the development of dystrophy.
Open Access
Carboplatin and Paclitaxel versus Doxorubicin and Cisplatin for Carcinosarcoma of the Uterus: A historical cohort with control based on FIGO 2009 criteria from the University of Manitoba
(2012-03-12) Barnard, Alicia; Faculty of Medicine; Dr. Shaundra Popowich (Section of Gynecology Oncology at CancerCare Manitoba), Dr. Erin Dean (Section of Gynecology Oncology at CancerCare Manitoba) and Dr. Robert Lotocki (Section of Gynecology Oncology at CancerCare Manitoba)
Objectives: To compare two different chemotherapy adjuvant treatment regimens currently and previously used at CancerCare Manitoba for endometrial carcinosarcoma. Methods: This is a retrospective analysis of 60 patients diagnosed with primary endometrial carcinosarcoma at CancerCare Manitoba from 1998-2008. The demographic characteristics, malignancy stage, presence of recurrent disease, and treatment type(s) utilized were studied. 37 patients were found to have received either carboplatin/paclitaxel or doxorubicin/cisplatin for carcinosarcoma, and were further analyzed to determine if there was a statistically significant difference in progression-free survival and overall survival between the two treatments. Kaplan-Meier curves were used to display progression-free survival and overall survival. Results: 60.4% of patients presented with low-stage disease. No statistically significant difference in progression-free survival or overall survival between the two cohorts was found. Recurrence rate was 31.7%. The mean time to recurrence in the combined cohorts was 23.2 months. 16.7% of the patients had or were currently being treated with tamoxifen. 73.7% of patients having recurrence did not undergo lymph node dissections and 100% of patients with local recurrence were treated with vaginal vault brachytherapy. Conclusions: Due to the rarity of this malignancy, multi-centre studies are warranted based on the data collected as sample sizes were too small for statistical significance. Further investigations towards optimizing treatment and understanding disease associations should be performed in the future to help better manage these patients and improve survival.
Open Access
The impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies
(2012-03-12) Davie, Sophie; Medicine; Dr. Hilary Grocott (Anesthesia).
Cerebral oximetry is a non-invasive technology using near-infrared spectroscopy (NIRS) to measure regional cerebral oxygen saturation (rSO2). Although NIRS cerebral oximetry is being increasingly used in many clinical settings, inter-device technologic differences suggest potential variation in the ability to accurately acquire brain oxygenation signals. The primary objective of this study was to determine if NIRS-derived rSO2 measurements accurately account for oxygen saturation contamination from extracranial tissue. Twelve healthy volunteers had three (the FORE-SIGHT, INVOS, and EQUANOX) NIRS devices randomly applied to the forehead. After this, a circumferential pneumatic head cuff was positioned such that when inflated, hypoxia-ischemia would be produced in the scalp extracranial tissue beneath the NIRS cerebral oximeters. Comparisons among the three devices were made of the NIRS measurements prior to and following hypoxia-ischemia produced in the scalp tissue with inflation of the head cuff. The induction of extracranial hypoxia-ischemia resulted in a significant reduction in rSO2 measurements in all three NIRS devices studied. At 5 minutes post-inflation of the pneumatic head cuff, the INVOS demonstrated a 16.6± 9.6% decrease from its baseline (p = 0.0001), the FORE-SIGHT an 11.8± 5.3% decrease from its baseline (p = 0.0001) and the EQUANOX a 6.8± 6.0% reduction from baseline (p = 0.0035). Therefore, extracranial contamination appears to significantly affect NIRS measurements of cerebral oxygen saturation. Although the clinical implications of these apparent inaccuracies require further study, it suggests that the oxygen saturation measurements provided by cerebral oximetry do not solely reflect that of the brain alone.
Open Access
Dynamic Novel Cardiac Imaging Parameters in Home Nocturnal Hemodialysis
(2012-03-12) Zhu, Mike; Medicine; Dr. Paul Komenda (Nephrology) and Dr. Davinder Jassal (Department of Internal Medicine).
BACKGROUND: Most patients on dialysis have left ventricular hypertrophy (L VH) as seen on cardiac imaging. Nocturnal home hemodialysis (NHD) may produce regression of L VH and may also improve other cardiac and non-cardiac parameters. OBJECTNE: To evaluate whether NHD improves cardiac parameters as assessed by cardiac imaging, and to explore whether this improvement correlates with any of the other measures of health we used. METHODS: TIns observational cohort study involved information from cardiac imaging, medical history, clinical examination, lab data, and quality of life data from five patients, collected when they began NHD and again at one-year follow-up. RESULTS: Left ventricular mass index (LVMI) decreased for all patients at follow-up from 35±2g/m2 at baseline to 33±2g/m2 at 12 months (p
Open Access
Chromosome territory position of chromosome X and 11 is non-random and cell-type specific in mouse cells of B cell lineage
(2012-03-12) Kuzyk, Alexandra; Medicine; Dr. Sabine Mai (Department of Biochemistry and Medical Genetics).
The interphase nucleus of a cell is organized into non-random, cell-type specific chromosome territolies (CTs). In lymphocytes, a gene-density correlated radial arrangement has been identified, with gene-dense CTs located more in the nuclear interior and gene-poor CTs located towards the periphery. However, other factors such as chromosome size, transcription and interactions of the nuclear membrane and matrix are also involved in the final ammgement of CTs within a nucleus. In this project, the CTs of chromosome 11 and X were studied in five different cell types of mouse B cell lineage: diploid preB cells, primary B cells of [T38HxBALB/c]N wild-type mice, primary B cells of [T38HxBALB/c]N with rcpT(X;l1) mice, primary B cells of BALB/c mice and a Wehi 231 mouse B lymphoma line. These two chromosomes have not been studied before in the mouse. 3D FISH experiments that labeled the CTs of chromosome 11 and X with chromosome-specific paints were carried out for each cell type. The karyotype regarding these two chromosomes and specificity of the chromosome paints was first confim1ed through 2D FISH experiments. The radial distance from the centre of each CT to the centre of the nucleus was measured lIsing AxioVision 4.8 software. The results show a non-random, statistically significant and cell-type specific nuclear distribution of these two chromosomes. Altered nuclear positions of translocation chromosomes in normal healthy mice and as a result of tumorigenesis were observed in the primary B cells of [T38HxBALB/c]N with rcpT(X;l1) mice and in the Wehi 231 mouse B lymphoma line, respectively.
Open Access
The role of tissue Doppler imaging using transesophageal echocardiography in the non-invasive assessment of left ventricular filling pressures during cardiac surgery
(2012-03-12) Nepomuceno, Roman G.; Medicine; Dr. Davinder S. Jassal (Internal Medicine) and Dr. Scott Mackenzie (Anesthesia).
Background: Cardiac surgical patients often require invasive pulmonary artery catheters (PAC) to determine left ventricular filling pressures (LVFP) in order to guide fluid management. Tissue Doppler imaging (TDI) as derived by transthoracic echocardiography (TTE), non-invasively assesses pulmonary capillary wedge pressure (PCWP), which is a surrogate for LVFP. With the use of TDI as derived by TTE, the ratio of transmitral inflow to mitral annular velocity during early diastole (E/E’) correlates with PCWP. However, little is known on the role of TDI using intra-operative transesophageal echocardiography (TEE) in the assessment of LVFP during cardiac surgery. Objective: To determine if TDI indices obtained by intra-operative TEE during cardiac surgery accurately estimates PCWP using PAC as the gold standard. Methods: Patients undergoing cardiac surgery were prospectively enrolled at a single tertiary care centre. Conventional and novel echocardiographic parameters were evaluated using intra-operative TEE with concurrent invasive PAC monitoring before and after cardiopulmonary bypass (CPB). Results: The study population included 34 patients (26 males, mean age 649 years). The correlation between E/E’ using TEE and PCWP was poor to modest at best. Pre-CPB, the correlation ratio between mean E/E’ and PCWP was r=0.23. Post-CPB, the correlation ratio between mean E/E’ and PCWP was r=0.42. Conclusion: Intra-operative TEE was unable to accurately assess LVFP in patients undergoing cardiac surgery. The PAC continues to be the gold standard in the assessment of LVFP for this patient population.
Open Access
Population Outcomes in Primary Central Nervous System Lymphoma: Provincial Experience and National Survey
(2012-03-12) Penden, Kirstie; Medicine; Dr. David Szwajcer (Internal Medicine).
Introduction: Primary central nervous system lymphoma (PCNSL) is rare and carries a poor prognosis. A retrospective review of Manitoba data for patients diagnosed with PCNSL spanning 1998-2008 was undertaken along with a national survey of PCNSL management. The study’s goal was to benchmark provincial metrics for diagnostic work-up and patient outcomes in PCNSL. Materials and Methods: A retrospective chart review was carried out, and data involving diagnostic workup, treatment, and outcome were collected. A mailed survey regarding PCNSL diagnosis and therapeutic practices was distributed to adult neuro oncology centres in Canada. Results: The age adjusted rate of PCNSL in Manitoba was 0.8 cases per 100,000. Comparing diagnostic tests obtained by Manitobans with PCNSL between 1998-2003 and 2004-2008, the proportion of patients receiving the appropriate testings increased. Curative intent treatment utilizing high-dose methotrexate was offered to 12/72 (17%) patients, and conferred a median overall survival (OS) of 33 months. Non-curative intent therapy or palliation was offered to 83% of patients, who achieved a median OS of 2 months. No significant survival difference was found between patients receiving non-curative chemotherapy or radiotherapy. National survey results demonstrate significant variation in the management of patients with PCNSL across Canada. Discussion: The proportion of patients receiving appropriate diagnostic testing has increased over time. Patients considered for non-curative intent therapy have suboptimal responses and may benefit from novel treatment approaches or more aggressive palliation. National variation in PCNSL management offers an opportunity to develop a national consensus.