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

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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.)

Mechanisms of postoperative junctional ectopic tachycardia: Chronotropic and inotropic regulation in the neonate heart

Date created: 
2005
Abstract: 

Junctional ectopic tachycardia (JET) is a common arrhythmia in postoperative pediatric patients after open-heart surgery for congenital heart defects. This arrhythmia is life-threatening and mechanisms of this arrhythmia are not yet clear. Isolated working hearts from neonate rabbits were administered P-adrenergic agonists alone or with antagonists under normal or ischemia-reperfusion stunned conditions. The effect of the sodium hydrogen exchanger inhibitor HOE642 on the recovery of ischemia-reperfusion stunned leA ventricle was tested, the potential for P-adrenergic agonist-induced arrhythmogenesis on the stunned neonate hearts was examined as well. We found that dopamine has a positive chronotropic, and a negative inotropic effect on the isolated neonate rabbit heart. Furthermore, dopamine has an arrhythmogenic effect on the ischemia-reperfusion stunned neonate myocardium. Finally, it was shown that HOE642 has a significant protective effect on contractile function in the neonate myocardium on recovery from ischemia-reperfusion stunning, but was not robust in its antiarrhythmic effect.

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

Improving the detection and triage of oral premalignant lesions in high-Risk clinics and community dental practices

Author: 
Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2009
Abstract: 

Oral cancer occurs at a cancer site that is easily examined; yet more than 40% of oral cancers are diagnosed at a late stage when the chance of death is high and treatment can be devastating. Although oral cancer screening is part of every oral health professional’s (OHP) training, it is often difficult for OHPs to differentiate high-risk oral premalignant lesions (OPLs) from benign reactive lesions. A primary goal of this thesis was to evaluate two approaches to enhancing visualization of clinical lesions: the application of toluidine blue (TB) stain, used to improve contrast of suspicious mucosal areas in normal tissue (Project 1), and fluorescence visualization (FV), used to identify an alteration to tissue optics that is associated with morphological and biochemical change seen in cancers and premalignant disease (Projects 2 and 4). A second goal was to develop and evaluate an educational strategy for oral cancer screening in community dental clinics aimed at strengthening conventional screening activities and providing a framework for integration and assessment of visualization techniques in community settings (Projects 3 and 4). Studies were conducted on patients within two settings: referral clinics of the BC Oral Cancer Prevention Program (Projects 1 and 2) and community dental clinics in the Vancouver lower mainland (Projects 3 and 4). Use of two settings is important: technology developed within high-risk referral settings needs to be re-evaluated in community clinics where the spectrum of disease is different and expertise is variable. Among key results of these studies were: a strong association between TB positive staining and increased (6-fold) cancer risk for OPLs; an association of FV and high-risk clinical, histological and molecular change; and; identification of barriers and facilitators for oral cancer screening in OHPs with evaluation of a triaging framework to support key decision points in community practices. In summary this thesis data supports the use of TB and FV visualization approaches in high-risk clinics to improve detection of OPLs. In addition, the community studies have produced a framework for transfer of new technology into general dental practice building upon an enhanced triage and referral system.

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

Upper trapezius recruitment with a repetitive upper limb task: comparison of female WADII subgroups and healthy controls

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2009
Abstract: 

Persistent neck pain in whiplash associated disorders (WAD) is a worldwide problem. In an effort to improve classification and management of people with WADII, surface EMG of upper trapezius of the dominant limb was compared between 10 healthy women and 19 women with persistent neck pain post motor vehicle accident, before, during, and after a repetitive upper limb task. Separate analyses were also performed with the WADII women grouped by level of disability (Neck Disability Index scores) as well as using a clinically focused system, the Sterling Classification System (WADIIA, WADIIB, WADIIC). Evidence of abnormalities of upper trapezius recruitment were present in the women with persistent neck pain and WADII, however, further research is indicated to understand the clinical implications of these changes and optimal intervention strategies.

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

Adaptive Tetrodotoxin-Resistance in Garter Snake Sodium Channels

Author: 
Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2009
Abstract: 

Tetrodotoxin (TTX) is a neurotoxin that specifically binds to voltage gated sodium channels (NaV). TTX binding physically blocks the flow of sodium ions through NaV, thereby preventing action potential generation and propagation. TTX has different binding affinities for different NaV isoforms. These differences are imparted by amino acid substitutions in positions within, or proximal to, the TTX binding site in the channel pore. The garter snake Thamnophis sirtalis has evolved TTX-resistance over the course of an arms race, allowing some populations of snakes to feed on tetrodotoxic newts, including Taricha granulosa. We tested the properties of NaV with TTX resistance found in garter snake populations. We observed some surprising changes in gating properties and ion selectivity of the TTX resistant NaV. These results suggest TTX resistance comes at a cost to performance caused by changes in the biophysical properties and/or ion selectivity of the TTX resistant

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