Obstruction of the urinary tract activates apoptotic pathways in collecting duct cells and leads to loss of renal parenchyma prior to surgical intervention. It has been suggested that development molecular programs may be reactivated to offset acute organ damage. One such molecule, Pax-2, is expressed throughout the fetal collecting duct and was recently shown to suppress apoptosis during kidney development. / We hypothesized that during urinary tract obstruction (UTO), PAX-2 expression is reactivated in the mature kidney, partially suppressing apoptosis; and that mice with PAX-2 mutations will have increased susceptibility to parenchymal damage during UTO. / Wildtype (C3H) and heterozygous PAX-2 mutant mice (C3H/ PAX-21Neu) underwent unilateral ureteral ligation or sham operation at six weeks of age. Kidneys were removed, weighed and assayed for Pax-2 reactivation following 5, 10 and 15 days of UTO. Kidneys were then screened for apoptosis by TUNEL staining, and the novel anti-cleaved spectrin assay. / Pax-2 protein expression fell to nearly undetectable levels in the first weeks of life but was sharply reactivated in collecting duct cells of wildtype, but not in PAX-21Neu mutant mice with 10 days of UTO. Wildtype mice with UTO had increased TUNEL, cleaved spectrin and reduced kidney weight after 10-15 days UTO. Mutant mice had exaggerated increases in TUNEL staining, cleaved spectrin and parenchymal loss in the obstructed kidney. / In conclusion, we have shown that PAX-2 is highly expressed in the fetal kidney but is normally down regulated in the postnatal period; it is rapidly reactivated in collecting duct cells during UTO. Mice with genetically limited PAX-2 expression have heightened susceptibility to apoptosis and renal parenchymal loss following acute UTO.

Introduction. Total hip arthroplasty (THA) has been well documented to enhance patient function, but patient outcome is dependent on preoperative status. The exact timing of surgery to optimize patient outcome after THA remains unknown. This study determines the ideal timing for surgery to obtain the best possible functional outcome. / Methods. Prospective, multicenter, cohort studies of 175 hybrid THAs. General health (SF-36) and disease specific (WOMAC and Harris Hip Score (HHS)) questionnaires were used to determine preoperative and 2 year final outcomes. Student's t-test, 95% confidence intervals, receiver operator characteristic curves, simple regression analysis and probability were measured. / Results. All functional scores were improved significantly postoperatively (p<0.001). Patients with a HHS ≥ 65 preoperatively had a 100% probability of having an excellent result postoperatively. A preoperative HHS value of 34 and preoperative WOMAC (physical function) value of 50 were the best cutoff points to attain a significantly better postoperative functional outcome.

Current therapies do not prevent the devastating complications associated with type 1 and 2 diabetes. Novel therapies seek to restore a functional beta-cell mass through stimulating endogenous beta-cell mass expansion. Whilst there is considerable evidence that the beta-cell mass is under homeostatic regulation in the normal pancreas, it is unclear if such regulation exists in the context of induced beta-cell mass expansion. The aim of this study was to demonstrate that beta-cell mass expansion resulting from the induction of islet cell neogenesis is subject to long-term homeostatic control in the normoglycemic mouse adult pancreas. / A pentadecapeptide fragment of Islet Neogenesis Associated Protein (INGAP 104-118) was administered daily to adult C57BL/6J mice for 12 weeks. Four animals from the INGAP104-118 treatment group and control group were sacrificed each week. The pancreas was removed from each mouse and stained for insulin. beta-cell mass was calculated as the organ weight multiplied by the percent of insulin+ area of total tissue area. Contrary to our expectations, there was no change in the total beta-cell mass in INGAP104-118-treated animals compared to control. Reanalysis of the stained tissue sections was preformed, and insulin+ structures were classified as being: (1) a duct islet, (2) a cluster of insulin+ cells, or (3) a mature islet. The density (#/mm2) of duct islets, clusters, and total structures in INGAP 104-118-treated animals was significantly increased; conversely, the density of mature islets was significantly decreased. The increase in cluster density suggests that INGAP104-118 induced neogenesis in the pancreas of treated animals. Poisson regression revealed 9th order polynomial time trends in the structure densities. Though these time trends differed between the classes of structures, they were identical in INGAP104-118 and control animals for each class of structure, suggesting an external stimulus was acting equally on both groups. / While this study did not determine if there is homeostatic regulation of induced beta-cell mass expansion, it did reveal important aspects for the design of a future study to address this issue. The definitions for structure classification must be well-established and rates of beta-cell replication should be determined.

The introduction of minimally invasive surgery has resulted in revolutionary changes in the process of surgery. As a consequence, surgeons have had to adopt an entirely new skill set, one which requires additional training. To this end, surgical simulators have been developed, (physical simulators and virtual reality based simulators). We endeavored to validate the LapSim virtual reality simulator and assess its potential in the learning and acquisition of basic and complex laparoscopic skills. A series of studies were undertaken to provide evidence for the simulator's validity. They include the formulation of metrics, transference of basic skills to more complex laparoscopic tasks, and the transference of skills acquired using the simulator to the in vivo model. Through these studies, it is demonstrated that the virtual reality simulator is effective in enhancing laparoscopic skills in novices in both in vitro and in vivo environments.

Despite more conservative surgical treatment for breast cancer, lymphedema and arm dysfunction remain sources of significant morbidity. The study for this thesis was conducted to explore methods for defining and identifying lymphedema and arm dysfunction after treatment for breast cancer. / In order to establish cut-points in the differences in the sizes of arms to define the presence of lymphedema among women previously treated for breast cancer, the distributions of the differences in the sizes of arms, using measures of circumference and volume, among 40 women with no history of breast cancer were determined. The selected cut-points in the differences were defined as the mean plus one, two, or three standard deviations. / A questionnaire (referred to as the Lymphedema Identification Tool) based on self-reported symptoms was developed to identify women with lymphedema. The Lymphedema Identification Tool and the 'Disabilities of the Arm, Shoulder and Hand' (DASH) questionnaire were sent to 596 women previously treated for stage I or II breast cancer and 50 women attended an evaluation session. At this evaluation session, measurements of the sizes of their arms were made and the Lymphedema Identification Tool and the DASH were repeated. This allowed for the evaluation of test-retest reliability, internal consistency reliability, and criterion validity of the Lymphedema Identification Tool. / From these measurements and responses to the questionnaires, the association between arm dysfunction, as assessed by the DASH questionnaire, and the presence of lymphedema, as determined by the measurements of arm sizes and by women's self-report was determined. In addition, through the development of logistic regression models, the Lymphedema Identification Tool, the DASH questionnaire, age at diagnosis, and body mass index were found to predict the presence of lymphedema, as defined by the measurements of arms. / Lymphedema appears to be a condition associated with a spectrum of symptoms and functional impairment varying from mild to severe. This thesis, even though results are preliminary, suggests a methodology for identifying lymphedema and arm dysfunction.

Our ongoing hypothesis is that skeletal muscle satellite cells can be injected into injured myocardium with the intent of myocardial repair. In early experiments tritiated thymidine was used to label the satellite cells prior to injection into the injured myocardium. Tritiated thymidine however was not seen in the retrieved heart specimens. This gave rise to the criticism that there was no definitive proof that cardiac tissue fibres originating in the injured myocardium were a result of the satellite cell implantation. It was felt that tritiated thymidine was an inadequate label possibly due to a dilutional effect. It was also thought that the cryo-injury was too severe to allow for a sufficient micro environment for cell growth. The purpose of the present study was to develop an appropriate labelling technique that would confirm without doubt that the satellite cells injected indeed led to myocardial regeneration. (Abstract shortened by UMI.)

The purpose of the project described in this thesis is to provide intraoperative feedback to the neurosurgeon using the equipment comprising a typical IGNS environment. The project accomplishes this task through the use of physically based, deformable models. The major objectives for this mode of intraoperative feedback are to provide useful visual and quantitative feedback to the neurosurgeon about the progress of tissue resection during a surgical procedure using the equipment available in a typical IGNS environment and to be simultaneously being unobtrusive to the surgeon's work. / An overview of the current state of IGNS is presented, followed by a logical association between current work and the significance of the project developed for this thesis. The mathematics of deformable models as a means for providing intraoperative feedback are developed and a thorough description of the work completed for this thesis is presented. A series of increasingly realistic validation studies that were undertaken for the project are described, followed by a discussion of the use of the software in intraoperative applications. Finally, conclusions are made as to the utility of the project as a viable means of providing intraoperative feedback and future work is extrapolated from the project. (Abstract shortened by UMI.)

Transformed fatigue resistant skeletal muscle has been proposed as a potential power source for totally implantable ventricular assist systems (VAS). The goal of this study was to determine the optimal latissimus dorsi muscle (LDM) configuration capable of obtaining maximum power output. A device was designed to measure the power output and performance characteristics at varying levels of preload from each of four in situ configurations in Watts/kg of muscle(W/kg). Eight LDMs were acutely measured and revealed peak power output as follows: Sub-Dorsi (compliance chamber between LDM and chest wall): 8.3 +/- 1.6 W/kg; Circular (chamber in skeletal muscle ventricle): 16.4 +/- 6.2 W/kg; Linear-Origin (measurements from LDM thoracolumbar origin): 47.1 +/- 4.4 W/kg; Linear-Insertion (measurements from LDM humeral insertion): 59.9 +/- 12.1 W/kg, (ANOVA, p < 0.0001). A linear oriented LDM is capable of generating maximal power output comparable to current VAS requirements. Confirmation of these findings in mansformed, conformed, fatigue-resistant muscle will provide information essential for the optimal design of muscle powered ventricular assist systems.

Physicians have traditionally withheld opioid analgesics from patients with acute abdominal pain due to concerns of masking physical findings. No study has examined morbidity and mortality after narcotic administration. The purpose of this study was to determine: (1) frequency of abdominal pain requiring narcotic analgesics, and (2) rate of serious outcomes, (death, infection, perforation, obstruction or hemorrhage of abdominal organs), in order to assess the feasibility of a randomized clinical trial on the safety of narcotics. Of 860 patients with acute abdominal pain, 477 (55%) completed a pain questionnaire, and 321 met study criteria for need of narcotic analgesia (37.3%). Of these, 36 (11.2%) experienced a serious outcome as assessed by telephone contact 2 to 3 weeks after initial visit. The overall rate of serious outcomes was 67 of 860 (7.8%). A clinical trial using serious outcomes as the primary endpoint is possible, but would need to randomize approximately 3200 patients.

This thesis explores the scope of physicians' legal and ethical duties of disclosure in an era marred by decreasing available medical resources. Using three hypothetical case scenarios, it examines the scope of physicians' obligations to disclose information about medical interventions that patients might wish to consider but that are not available in their immediate community. / The legal analyses focus on Canadian and Quebec law. Discussion of the ethical considerations centres on the concept of 'benefit' and issues of 'communication' and 'trust' in the physician-patient relationship. It integrates, as well, empirical knowledge about patients' desire for information and participation in decision-making. The thesis demonstrates the broad scope of the legal and ethical disclosure obligations that physicians owe patients, regardless of conditions of economic scarcity. It further highlights areas where law and ethics would suggest different conclusions with respect to disclosure obligations.