Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Bone Marrow-Derived Cell Accumulation in the Brain in a Murine Model of Alzheimer’s Disease

Date created: 
2013-08-09
Abstract: 

One difficulty in treating some neurological disorders is that many pharmaceuticals cannot cross the blood brain barrier to reach affected areas. Human and animal studies have shown that bone marrow transplantation can result in the engraftment of donor-derived cells in the central nervous system (CNS) under certain conditions. Understanding these conditions will allow us to optimize recruitment of bone marrow-derived cells (BMDCs) to the CNS and, in the future, use these cells as vehicles for gene delivery. Using a triple transgenic mouse model of Alzheimer’s Disease (AD), I studied accumulation of amyloid-β, a pathological characteristic of AD, and association of BMDCs with amyloid-β. There were difficulties in maintaining chimerism after bone marrow transplantation in these mice. Reconstitution was achieved by depleting natural killer cell activity in the host, suggesting that hybrid resistance may be present.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charles Krieger
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Design, implementation and evaluation of a reduced cardiac rehabilitation program

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2013-02-28
Abstract: 

Background: Cardiac rehabilitation remains under-utilized and novel modes of cardiac rehabilitation delivery are needed to address this concern. Purpose: To compare a reduced cardiac rehabilitation program (rCRP) with the standard program (sCRP) in regards to change in exercise capacity and ischemic heart disease risk factors, at program completion and at one-year follow-up. Methods: This was a randomized controlled non-inferiority trial. Secondary prevention patients at low and moderate risk were randomized to either the sCRP (n=60) or to the rCRP (n=61). While the sCRP entailed 32 on-site exercise sessions, the rCRP consisted of 10 sessions throughout the four-month program duration. Mixed model analyses of variance were used to test for non-inferiority of the rCRP and repeated measured ANOVA to assess within-group comparisons. Results: Baseline data were similar between groups. The rCRP was non-inferior to the sCRP group in regards to exercise capacity at four and 16 months (group estimate=5.25, 95% CI 15.51-26.00 seconds, p=0.62). Exercise capacity improved at program completion for the sCRP and rCRP groups; 524 ± 168 to 630 ± 150 seconds and 565 ± 183 to 655 ± 196 seconds, p< 0.01, respectively, and remained higher than baseline at 16 months; 524 ± 168 to 604 ± 172 seconds and 565 ± 183 to 640 ± 192 seconds, p< 0.01, respectively. The rCRP was non-inferior in regards to HDL-C, triglycerides, TC/HDL-C ratio, fasting glucose, blood pressure, body mass index, waist circumference and waist to hip ratio changes. The rCRP had a higher attendance rate than the sCRP group (97.3 ± 62.6 % vs 70.5 ± 22.0 %, p=0.002) and was non-inferior in terms of self-reported physical activity (group estimate=1.02, 95% CI 0.86-1.21, p=0.8105). These improvements were maintained at one-year follow-up. Conclusion: While it utilized less hospital resources, rCRP was “not worse” than the sCRP in terms of exercise capacity and ischemic heart disease risk factor changes as well as program adherence for low and moderate risk patients. Further research is needed to assess if the rCRP helps overcome current CRP utilization barriers.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Scott Lear
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.

Design and fabrication of a positioning system for an intravascular electrode system

Author: 
Date created: 
2012-03-06
Abstract: 

Precise placement of intravascular leads is a vital requirement for transvascular neurostimulation as it determines the nerve selectivity and efficiency of stimulation. With the previous positioning method relying on ruler measurements, an electronic position sensor system was designed to minimize placement time, increase accuracy, reproducibility and allow for integration into a control unit system. To keep track of each electrode array, the developed sensor uses one linear membrane potentiometer for each lead. A plastic bead is fitted on each lead and as the bead is lightly squeezed into the membrane potentiometer, the potentiometer resistance changes proportionally to a bead position. The electrode position can therefore be inferred from this measurement. This system is simple, inexpensive and provides an absolute position measurement. This concept is also expected to be easily made into commercial product because of its compact and intuitive nature.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Andy Hoffer
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

The effects of ambient lighting on mobility deficits in older adults with age-related macular degeneration

Date created: 
2013-06-11
Abstract: 

Age-related macular degeneration (AMD) is characterized by loss of central vision. This eye disease restricts mobility and increases the risk for falls. We sought to determine how changes in ambient light affect performance on essential mobility tasks in this population. Subjects had to step to stationary and moving targets and negotiate a sidewalk curb. In each task, lighting simulated an office environment, a moonlit night, and a sudden light reduction. Older adults with AMD were less accurate and more variable in their ability to step to targets compared to controls. A similar result was evident with curb negotiation. Importantly, both groups had greater difficulty with poor lighting. This was most evident when lighting was suddenly reduced and was exacerbated with AMD. Understanding AMD-specific mobility deficits and the influence of lighting will help design rehabilitation programs and better environments to reduce falls, improve mobility, and enhance these individual’s quality of life.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Dan Marigold
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Cardiovascular responses to orthostasis: methods, assessments, and their association with falls in older adults in long-term care

Date created: 
2013-06-03
Abstract: 

Background: Orthostatic hypotension (OH) refers to a significant decline in blood pressure that occurs upon assuming an upright posture and represents an intrinsic risk factor for falls in older adults. Methods: Beat-to-beat blood pressure and cerebral blood flow velocity responses were assessed during a passive seated orthostatic stress test (PSOST). In healthy controls, PSOST responses were compared to head up tilt (the ‘gold-standard’). In a cohort of long-term care residents, data from PSOST were compared to falling history.Results: Hemodynamic and cerebrovascular responses were similar between head up tilt and PSOST in healthy controls, except for the delayed systolic blood pressure decline. Older adult fallers had greater delayed systolic blood pressure declines and maximum cerebral blood flow velocity declines compared to non-fallers.Conclusions: PSOST may be a good surrogate for head up tilt in some population groups. We identified novel cardiovascular differences for falling risk in long-term care residents.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Victoria Claydon
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Transplanted Haematopoietic Cells Populate The Murine CNS In The Absence Of Irradiation

Date created: 
2013-03-08
Abstract: 

Currently, there are no effective treatments available for patients suffering from amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. Experiments in rodents and humans with neurodegenerative diseases have shown that after bone marrow transplantation following irradiation-induced myeloablation, donor cells can be found in the central nervous system (CNS). Previous work indicates that irradiation itself may be essential for bone marrow-derived cell (BMDC) entry into the CNS. Here we attempted to determine whether myelosuppressive regimens other than irradiation will potentiate BMDC accumulation in the CNS. Transgenic mice over-expressing human mutant superoxide dismutase-1 (mSOD) develop motor neuron loss resembling amyotrophic lateral sclerosis (ALS). We treated control and mSOD mice with the chemotherapeutic agent, Busulfex (BU), and transplanted with GFP+ BM. Sub-myeloablative doses of 60-100 mg/kg BU induced ≥80% blood chimerism in these animals. In addition, GFP+ cells were observed in the spinal cords of both control and mSOD mice. Greater numbers of GFP+ cells were detected in mSOD spinal cords at disease end-stage compared to controls. Histological analysis of BMDCs revealed that a large fraction of donor cells acquired the stellate morphology and immunophenotype characteristic of parenchymal microglia. These data demonstrate that BU alone can be used to achieve high level BM chimerism in mice and lead to accumulation of BMDCs in the spinal cord. These protocols could be adapted for use in humans with neurodegenerative diseases such as ALS.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charles Krieger
Fabio Rossi, Jonathan Choy
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Molecular assessment of former cancer sites predicts second oral malignancy

Author: 
Date created: 
2005
Abstract: 

Clinicopathological criteria currently used to identify lesions at risk for second oral malignancy (SOM) have severe limitations. This thesis investigated the value of loss of heterozygosity (LOH) as a risk-predictor for SOM. Eighty-nine patiknts with a history of oral cancer in longitudinal follow-up were used. Each patient had one sample (biopsy or brushing) analyzed for LOH using 19 markers on 7 chromosome arms. Within the follow-up period (mean 65 months), 28% developed SOMs. Brushing served as a valid DNA source for LOH analysis. An increased frequency of LOH observed at several loci was noted in samples from the SOM group compared with the non-SOM: 3p (P = 0.003), 4q (P = 0.045), 9p (P < 0.0001), 17p (P = 0.001), multiple LOH (P < 0.0001), and LOH at 3p &/or 9p (P < 0.0001). The latter pattern was associated with a 21.4-fold increase in SOM risk. In conclusion, LOH analysis could identify high-risk lesions for SOM using either biopsies or brushings.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

The etiology and natural history of type 2 diabetes

Author: 
Date created: 
2005
Abstract: 

Type 2 diabetes is a complex disorder characterized by progressive defects in nearly every aspect of metabolic regulation. Despite this complexity, traditional in vivo methodologies have limited experimental examination to a small number of metabolic indices at one or two points in time. As a result the etiology and natural history of this disease remain unclear and much debated. This thesis takes a two pronged approach to this problem. First, a mathematical model is developed to incorporate experimental data from different sources into an integrated representation of metabolic regulation. Bifurcation and simulation analysis of this model are used to investigate mechanisms of metabolic regulation as well as the pathogenesis of type 2 diabetes. Second, new experimental methodologies are developed that greatly improve the practicality of estimating several key metabolic indices in vivo. Applying these methodologies to animal models of type 2 diabetes allowed us to perform a fully dynamic and integrative analysis of the pathogenesis of type 2 diabetes in two commonly used animal models. Overall, data from this thesis suggests that the etiology of type 2 diabetes lies in two distinct abnormalities; rapid development of insulin resistance coupled to impaired P-cell mass adaptation.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
Dissertation (Ph.D.)

Effect of base of support size on ability to recover balance

Author: 
Date created: 
2005
Abstract: 

Humans' ability to recover balance should depend on the size of the base-ofsupport (BOS) between the feet and ground. To test this hypothesis, I conducted experiments where subjects (n=15) were released suddenly from an inclined position by means of a tether and electromagnet, and recovered upright stance using the feet-in-place ankle strategy or mixed (hiplankle) strategy. I varied the size of the available BOS by adjusting the length of a block that the subject stood upon. I found that the maximum angle where subjects were able to recover balance (THETA - MAX) declined from 8.8 to 7.3 deg when BOS decreased from 100% to 75%, and from 7.3 to 5.0 deg when BOS decreased from 75% to 50%. THETA - MAX was 19% larger for the mixed than ankle strategy. However, recovery strategy did not influence the effect of BOS on THETA - MAX. These results confirm that BOS size strongly influences ability to recover balance.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Lumbar mechanics from ultrasound imaging

Date created: 
2005
Abstract: 

Using ultrasound, the feasibility of estimating lumbar mechanics in-vivo was evaluated. In Experiment 1, images were obtained while subjects were seated with the pelvis fixed and pulled on an anchored cable by isometrically contracting trunk muscles at different force levels. Linear regression identified ultrasound measurements which were correlated with trunk force. In Experiment 2, the cable was released and the trunk was rapidly displaced by shortening springs during the isometric contraction. Ultrasound images of the transverse processes of the L1-L2 vertebrae were acquired during this displacement for the purposes of estimating L1 -L2 joint stiffness. Results suggest that ultrasound is more suitable for estimating lumbar mechanics in the coronal plane than the sagittal plane. A linear trend was found between changes in thickness of some muscles and trunk force and with changes in muscle activity. Displacement of the vertebrae during perturbation occurred too quickly to be tracked by conventional ultrasound.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)