Previous studies in this laboratory have demonstrated that low doses of some selective $ sigma$ ligands such as DTG act as "agonists" by potentiating the neuronal response of rat CA$ sb3$ dorsal hippocampus pyramidal neurons to NMDA. Other $ sigma$ ligands such as haloperidol act as "antagonists" by reversing this potentiation. At doses in between 1-1000 $ mu$g/kg, i.v., several selective $ sigma$ ligands and antidepressant $ sigma$ ligands present a bell-shaped dose-response curve, which effect cannot be explained by a rapid desensitization. These $ sigma$ ligands that behave as "agonists" at low doses act as "antagonists" at the dose of 1000 $ mu$g/kg, i.v. / To date, two subtypes of $ sigma$ receptors ($ sigma sb1$ and $ sigma sb2$) are acknowledged. However, data presented in this thesis have shown that pertussis pretreatment abolished the potentiation induced by JO-1784 but not that induced by (+)pentazocine. Moreover, the injection of colchicine in the dentate gyrus abolished the potentiation induced by JO-1784, but not that of (+)pentazocine. These data suggest that the subtype of $ sigma sb1$ receptor on which J0-1784 is acting is related to a G-protein and is located presynaptically whereas the subtype of $ sigma sb1$, receptor on which (+)pentazocine is acting is not related to a G-protein and is located postsynaptically. / Because progesterone possesses high affinity at the $ sigma$ receptors, we have determined the effects of neuroactive steroids on NMDA-induced excitation. Low doses of DHEA potentiated the NMDA response selectively and dose-dependently. Progesterone had no effect by itself but reversed, at low doses, the potentiation of the NMDA response induced by DHEA as well as those induced by selective $ sigma$ ligands. The degree of the potentiation induced by 1 $ mu$g/kg, i.v. of DTG is significantly greater in ovariectorized rats than in control rats. Moreover, in late pregnancy, ten-fold higher dose of DTG is required to obtain a selective potentiation of the NMDA response. Conversely, the potentiation of the NMDA response induced by DTG is greater at day 5 post-partum than in control rats. / The data presented in this thesis suggest that: (1) more than two subtypes of $ sigma$ receptors exist in the mammalian brain; (2) neuroactive steroids such as progesterone and DHEA modulate the NMDA response via $ sigma$ receptors.

Objective. In order to prevent the last stages of chronic venous insufficiency of the lower limbs, a case-control study was performed to identify and quantify demographic and clinical risk factors for venous ulcer disease. A particular attention was given to history of superficial as well as deep vein thrombosis. / Patients and method. Patients presenting to a participating vascular surgery department between January and December 1997 with a first open venous ulcer served as cases. Controls were sampled among patients with sub-acute conditions such as back pain, cold, headache/migraine, sore throat and mild ear infections and were matched on referral, age (+/-5 years), and gender. Subjects were eligible if they were 18 years or older and had a good understanding of English or French. They were excluded if they had non-palpable pedal pulse or any chronic active diseases such as cancer or AIDS. Cases' status were ascertained by participating vascular surgeons using a standardized and objective protocol. Data on risk factors were collected with a valid and reliable interviewer-administered questionnaire developed and tested for face validity and reliability before the beginning of the study. The questionnaire has 54 items and explores areas such as obesity, disease antecedents, services utilization, lifestyles, work history, as well as pregnancy and menopause status in women. Inter-rater reliability was high and above 75% for all 54 items. Leg circumferences were measured with a Leg-O-Meter and patients were asked to fill a quality of life questionnaire. / Results. The mean age of participants was 61 years for cases (n = 102) and 59 years for controls (n = 200). History of deep vein thrombosis (DVT) (OR = 17.6 [2.9, 106.8]95%), strenuous exercise (OR = 8.9 [1.1, 72.0]95%) and family history of venous insufficiency on the mother's side (OR = 6.8 [1.9, 24.3]95%) were found to be significant predictors of venous ulcers in matched multivariate logistic regression analysis adjusted for body mass index (kg/height (m2)), history of pulmonary embolism, cardiovascular diseases, hypertension, fracture, smoking history, work, number of physician visits in past year, and education. / Clinical implications. Venous ulcers are a major public health problem mostly because of the cost associated with treating them. Our study suggests that prevention and adequate treatment of DVT, and monitoring of family history and physical activity will lead to ulcer prevention. This is especially important since there are no effective treatments to prevent ulcer recurrence at the present time.

The objective of the present thesis was to conduct a comparative study between persons with idiopathic Parkinson's disease and similarly aged normal subjects, by examining their lower limb reflex responses to forward whole head-body tilts under different sensory conditions. / Tilts were applied with subjects (10 parkinsonian and 10 control) in standing, via a tilting apparatus through an axis collinear with the ankle joints. Vestibular input was manipulated by changing the acceleration of the tilt, visual input by the use or removal of a blindfold, and somatosensory input by the use of a compliant versus a firm support surface. / We found a consistently lower number of respondents in parkinsonian subjects under all the tilting conditions. These patients also demonstrated a higher proportion of absent or abnormal tilt-evoked responses, while exhibiting a significantly greater resting EMG activity in proximal limb muscles. / The most significant difference lies in the number of respondents between the two subject groups during the "eyes closed-compliant surface" tilting condition. The basal ganglia play a particular role in the weighing of appropriate versus inappropriate sensory inputs, in order to modify balance responses according to changes in environmental conditions.

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<p> The motivation for this work is a vision of widespread adoption of a priori quantitative epidemiological information for clinical decision-making, and can be seen as a quantitative large-scale extension of evidence-based medicine (EBM). Medical images can be seen as a spatially encoded map of physiological measurements that can be used to predict prognosis and to drive treatment plans. This paradigm can be very powerful and is driven by the recent big data revolution in computer science as well as the increasing availability of medical imaging modalities due to decreases in manufacturing costs. In order to achieve this overarching goal, three practical requirements must be reached and correspond to the parts of this thesis: Part A: Developing IT infrastructure and technology that enables the dataset to be properly collected and organized for analysis. Part B &amp; C: Generation of functional (Part B) and structural (Part C) medical imaging contrast that are optimized for analysis. Part D: Pattern recognition techniques (including both image processing and machine learning techniques) to mine information from the large imaging datasets generated. As part of the thesis, I discuss my contribution to IT infrastructure (Part A) by developing a Short Message Service (SMS)-based system to control the clinically used Picture Archival and Communication System (PACS) (Ch.2) as well as an imaging study tool that categorizes patient imaging data for use in retrospective studies(Ch.3). I then go on to detail my work with functional neuroimaging of obesity using functional magnetic resonance imaging (fMRI)(Ch.4) and (Ch.5). Chapters 6-9 details my efforts at studying abnormal aging versus normal aging using diffusion MRI as well as applications of diffusion MRI to surgical planning. Chapters 10 discusses my work integrating diffusion MR with FLAIR MRI to investigate the properties of white matter lesions and how it can be used in the clinical setting. Chapter 11 then moves on to talk about my work modifying standard brain parcellation techniques to allow them to work with aged brains with large infarcts. Chapters 6-11 altogether represent my efforts in structural neuroimaging using MRI (Part C). The thesis then closes with capstone work in development staging using hand x-rays using fuzzy logic (Ch. 12 &amp; 13). To close the work with Alzheimer's Disease (AD) and aging, we used machine learning techniques to predict disease progression based on a baseline MRI scan as well as higher order analysis of our diffusion MRI dataset by integrating MRI information with other clinical information such as neuropsychological tests, cardiovascular status. This is all in an effort to computationally explore the relationship between MRI measurements and clinical presentation of disease as measured by neuropsychological scores. Similarly with the Obesity work, we related fMRI activation differences between high and low calorie foods with non-imaging information such as insulin resistance (Ch. 16).</p>

<p> Physician assistant (PA) program directors perform an essential role in the initiation, continuation, and development of PA education programs in the rapidly changing environments of both health care and higher education. However, only limited research exists on this academic leader. This study examined the leadership roles of PA program directors in the context of full-range leadership theory. This theory distinguishes between transformational, transactional, and passive/avoidant behaviors of the program director from the perspectives of both leader and follower. This study also examined leadership outcomes. </p><p> Data were collected via an electronic survey (Multifactor Leadership Questionnaire) administered to PA program directors and other members in the same academic unit. The survey was deployed to 82 academic units. The response rates for completed MLQ surveys were 43.2% (54) for program directors and 24.6% (228) for others associated with the PA academic unit. </p><p> The results of this study indicated that program directors use transformational leadership factors frequently in the execution of their responsibilities, and those program directors perceive favorable outcomes with these behaviors. However, discrepancies existed between leader perceptions and the perceptions of individuals in the same academic unit in regards to leadership and outcomes, with program directors having more favorable perceptions. This research provides a foundation for future study of the PA program director and contributes towards professional development efforts and the measurement of associated outcomes.</p>

While the concept of medical futility has existed for as long as medicine has been practiced, it remains a controversial issue that has become more clouded as medicine has advanced. This thesis will explore futility in the most technologically rich and emotionally charged of settings, the intensive care unit. The complex interactions of biology, ethics and the law, with their competing and sometimes conflicting interests will be explored. Disputes between patients, families and health care workers over life-sustaining interventions occur most often in the ICU, and the factors that influence this dynamic, such as lack of communication, time constraints, media-driven misconceptions and value-conflicts, will be examined. Attempts to address futility through advance health directives and conflict resolution policies will be critiqued. But most importantly, this thesis will explain, by appealing to the proper goals of medicine, why limitations should be placed on end-of-life care, and why physicians have an important role to play in making these determinations.

The SF-36 scale is widely used to evaluate the quality of life among breast cancer patients, but provides an inadequate reflection of their quality of life; therefore, we aimed to set up a new scale, a breast cancer surgery quality of life (BCSQOL) scale and to assess its reliability and validity. The analysis review showed that 75% to 91% of surgically treated patients (59/79) found that the questionnaire items were an accurate reflection of their feelings and were clear. The validity coefficient analysis showed a highly correlated extent of commonality (alpha = 0.778) between BCSQOL and SF-36 and a significant strength of relationship (rho = 0.785). Strong to moderate correlation reliability coefficient analysis (alpha = 0.779--0.351) was observed for the association among all items of the scale. BCSQOL scale may help health care providers to better understand the health status of breast cancer subjects, rendering them more equipped to improve their quality of life.

The purpose of this prospective cohort study was to describe the profile and outcomes of geriatric trauma care patients treated in level I trauma centers in Quebec. The study also evaluated the quality of care provided to geriatric trauma patients and identified predictors of outcomes which focused on mortality. / A total of 4934 trauma patients over the age of 65 were admitted for the treatment of injuries in three level I trauma centers in Quebec. The majority of the patients were injured in falls and had a low injury severity score. Male gender, older age, thoracic and abdominal injuries, burns, and delayed emergency room stays were identified as significant predictors of mortality. Inferior quality of care was observed with increased age and fall-related injuries. / The observed association between longer emergency room stay and falls with increased risk of mortality along with inferior care for patients injured in falls would suggest that level I trauma centers are inefficient and potentially harmful in treating elderly trauma patients. Further studies would be helpful in confirming these conclusions.

Background. Concussion is an important public health problem. The difficulty in recognizing mild concussions and the significant risk for repeat injury make early detection critical to the management of the concussed athlete. Since the 1990s, the use of neuropsychological tests has helped to measure cognitive deficits from sports-related concussion more objectively. Given the cost and limited availability of these tests, more user-friendly tools are needed. / Objectives. (1) Develop and evaluate the capacity of a new user-friendly neurocognitive tool called the McGill ACE to detect concussion in college athletes. (2) Compare the sensitivity of the McGill ACE to a formal neuropsychological test battery (NHL battery) for detection of concussion. (3) Examine individual variations of post-concussion symptoms, in number and severity, when concussed athletes are compared to their own baseline result. (4) Evaluate whether the McGill ACE results differ according to gender. / Design. Prospective study. / Subjects. 313 athletes from the men's and women's varsity teams at McGill University: 144 football players, 75 ice hockey players, 65 soccer players, 19 basketball players, and 10 men's volleyball players. / Interventions. On the pre-season exam, each athlete underwent the McGill ACE evaluation for a baseline measurement. The football and men's ice hockey players were also evaluated with the NHL test battery before contact began. During the sports season, only the football and men's ice hockey players were evaluated with both test batteries within 3 days of a concussion. / Main results. The McGill ACE showed as significant sensitivity as the formal neuropsychological battery (the NHL battery) in detecting cognitive problems in a group of concussed college athletes. Post-concussion symptoms significantly increased their total score in number and severity after a concussion, and the appearance of some specific symptoms were significantly associated with a new concussive injury. Finally, this study confirmed gender differences on a test that may involve visual-spatial strategy. / Conclusion. The McGill ACE is a valid neurocognitive test to detect concussion and demonstrates the importance of evaluating PCS. This study underscored the importance of comparing the results of neurocognitive testing to each athlete's baseline result, and the even greater importance of such a comparison when men and women are included in the same group.