Introduction : La Fibrose Kystique (FK) est la maladie autosomique récessive la plus fréquente chez les Caucasiens et est due à une mutation du gène Cystic Fibrosis Transmembrane Regulator (CFTR), codant pour un canal chlore. La principale mutation est la délétion de l'acide aminé phénylalanine en position 508. En raison de l’augmentation de l'espérance de vie, de nouvelles complications telles que le diabète associé à la FK (DAFK) ont vu le jour. Le DAFK semble principalement dû à un défaut de sécrétion d'insuline. Des études ont montré que les femmes et les personnes homozygotes ΔF508 ont un risque plus élevé de développer le DAFK. Objectifs : Comparer la sécrétion d'insuline entre les hommes et les femmes FK selon leur génotype CFTR. Notre hypothèse était que les femmes FK présentaient une sécrétion d'insuline moins élevée que des hommes. Méthodes : Deux cents sujets adultes sans diabète connu ont été recrutés dans la clinique de FK du CHUM et inclus dans cette étude. Cent seize ont été revus après un suivi de 24 ± 10 mois. Leur génotype CFTR a été extrait à partir des dossiers médicaux. Tous les sujets ont subi une hyperglycémie provoquée par voie orale de 2-h (HGPO) afin de déterminer leur tolérance au glucose : normale (NGT), intolérance (IGT) ou DAFK. Des échantillons de sang ont été prélevés aux temps 0, 30, 60, 90, et 120 min de l’HGPO. À partir de ces derniers, la sécrétion d'insuline et la sensibilité à l’insuline des sujets ont été évaluées en utilisant les indices de Stumvoll et les aires sous la courbe de l’insuline durant l’HGPO. Résultats : Pour une excursion glycémique comparable, il y avait des différences significatives dans les concentrations d'insuline entre les hommes et les femmes et selon le génotype CFTR. Ainsi, les femmes et les sujets hétérozygotes avaient des concentrations d’insuline plus élevées que les hommes et les sujets homozygotes. Cela restait significatif quelle que soit leur tolérance au glucose. Le calcul du disposition index représentant la sécrétion d'insuline ajustée pour le degré de sensibilité à l’insuline a suggéré une sécrétion d'insuline plus élevée chez les femmes que les hommes. Le suivi prospectif nous a permis de déterminer que cette sécrétion plus élevée d’insuline était associée à une évolution plus favorable pour la tolérance au glucose. Fait intéressant, cette constatation n'était vraie que pour les femmes. Conclusion : Dans une vaste cohorte prospective observationnelle de patients FK sans diabète connu, nous avons démontré qu’en dépit d’un âge et d’une fonction pulmonaire semblables, les femmes présentaient une sécrétion d'insuline supérieure à celle des hommes et que cela pourrait avoir un effet protecteur, à court terme, chez celles-ci pour le développement du DAFK. / Introduction: Cystic Fibrosis (CF) is the most common autosomal recessive disease among Caucasians and is caused by a mutation in the gene encoding for a chloride channel, the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. The main change is the deletion of the phenylalanine amino acid at position 508. Due to increasing life expectancy, new complications such as CF related diabetes (CFRD) have emerged. CFRD seems mainly due to a defect in insulin secretion. Studies have shown that women and people with homozygous ΔF508 have a higher risk of developing CFRD. Objectives: To compare insulin secretion between men and women according to their CFTR genotype. Our hypothesis was that, in CF, women had a lower insulin secretion than men. Methods: Two hundred adult subjects without known diabetes were recruited from the CF clinic at the CHUM and included in this study. One hundred and sixteen were reviewed after a follow-up of 24 ± 10 months. Their CFTR genotype was extracted from medical records. All subjects underwent a 2-h oral glucose tolerance test (OGTT) to determine their glucose tolerance: normal (NGT), intolerance (IGT) or CFRD. Blood samples were collected at 0, 30, 60, 90, and 120 min of the OGTT. Insulin secretion and insulin sensitivity were evaluated using the Stumvoll indices and the area under the curve (AUC) of insulin during the OGTT. Results: For a similar glycemic excursion, there were significant gender differences in insulin concentrations and according to the CFTR genotype. Thus, women and heterozygous subjects had insulin concentrations higher than men and homozygous. This remained significant regardless of their glucose tolerance. The calculation of the disposition index, representing insulin secretion adjusted for the degree of insulin sensitivity, suggested a higher insulin secretion in women than in men. Prospective follow-up showed that higher insulin secretion was associated with more favorable evolution of glucose tolerance. Interestingly, this finding was only applicable for women. Conclusion: In a large prospective observational cohort of CF patients without known diabetes, we demonstrated that, despite similar age and pulmonary function, women had a higher insulin secretion than men and that this could have a protective effect for the development of CFRD.

Des décisions médicales en fin de vie sont souvent prises pour des patients inaptes. Nous avons souhaité connaître les argumentations éthiques entourant ces décisions difficiles. Notre objectif était de pouvoir comprendre et apprécier ces lignes d’argumentation. Pour atteindre cet objectif, nous avons répertorié et analysé les lignes argumentatives présentes dans des articles scientifiques, incluant les sections de correspondance et commentaires des journaux savants. Afin d’éviter que les résultats de notre analyse soient trop influencés par les caractéristiques d’un problème médical spécifique, nous avons décidé d’analyser des situations cliniques distinctes. Les sujets spécifiques étudiés sont la non-initiation du traitement antibiotique chez des patients déments souffrant de pneumonie, et l’euthanasie de nouveau-nés lourdement hypothéqués selon le protocole de Groningen. Notre analyse des lignes d’argumentation répertoriées à partir des débats entourant ces sujets spécifiques a révélé des caractéristiques communes. D’abord, les arguments avancés avaient une forte tendance à viser la normativité. Ensuite, les lignes d’argumentation répertoriées étaient principalement axées sur les patients inaptes et excluaient largement les intérêts d’autrui. Nous n’avons trouvé aucune des lignes d’argumentation à visée normative répertoriés concluante. De plus, nous avons trouvé que l’exclusion catégorique d’arguments visant l’intérêt d’autrui des considérations entrainait l’impossibilité d’ évaluer leur validité et de les exclure définitivement de l’argumentaire. Leur présence non-explicite et cachée dans les raisonnements motivant les décisions ne pouvait alors pas être exclue non plus. Pour mieux mettre en relief ces conclusions, nous avons rédigé un commentaire inspiré par les argumentaires avancés dans le contexte de l’arrêt de traitement de Terri Schiavo, patiente en état végétatif persistant. Nous pensons que l’utilisation d’un argumentaire qui viserait davantage à rendre les actions intelligibles, et sans visée normative immédiate, pourrait contribuer à une meilleure compréhension réciproque des participants au débat. Une telle argumentation nous semble aussi mieux adaptée à la complexité et l’unicité de chaque cas. Nous pensons qu’elle pourrait mieux décrire les motivations de tous les acteurs participant à la décision, et ainsi contribuer à une plus grande transparence. Cette transparence pourrait renforcer la confiance dans l’authenticité du débat, et ainsi contribuer à une meilleure légitimation de pratiques cliniques. / Medical decision making is often occurring at the end of life of inapt patients. We wished to learn about and appreciate the ethical arguments concerning these difficult decisions. Our objective was to understand and evaluate these lines of argument. To reach this objective, we have listed and analyzed lines of argument as they were presented in scientific articles, including the sections correspondence and commentary of scholarly journals. In order to avoid that our results are too much influenced by the specifics of one given clinical problem, we decided to analyze distinct clinical settings. The specific subjects studied are the non-initiation of antibiotic treatment for demented patients suffering from pneumonia, and active euthanasia of severely affected newborns following the Groningen protocol. Our analysis of the indexed lines of arguments from debates dealing with these specific subjects has revealed common characteristics. First, the issued argumentations had a strong normative tendency. Second, the indexed argumentation was principally oriented towards the patient himself, while largely excluding the interests of others. We found that none of the indexed normative lines of argument was compelling. Moreover, we found that the systematic exclusion of arguments based on the interests of others entailed the impossibility to evaluate them, and potentially to exclude them definitively from the considerations. It was thus also impossible to evaluate their potentially concealed persistence as a driving force motivating the decisions made. In order to illuminate these conclusions, we have written a commentary inspired by the lines of arguments evoked in the context of the treatment withdrawal of Terri Schiavo, a patient in persistently vegetative state. We believe that the use of lines of argument that render decisions intelligible, without however aiming at immediate normativity, could contribute to a better mutual understanding between the participants of such debates. Such argumentation also seems, in our opinion, more adapted to take the complexity and uniqueness of each single clinical case into account. We believe that such argumentation could better describe the respective motivations of the participants in the decision, and thus increase its transparency. Increased transparency would reinforce the confidence in the authenticity of the debate, and thus better legitimate clinical practice.

La problématique du consentement éclairé en santé mentale demeure au coeur des préoccupations des cliniciens, médecins spécialistes et médecins experts. Le travail auprès des cérébrolésés ou des patients souffrant de troubles mentaux graves, tout comme les questions qui me sont adressées depuis près de 20 ans par les médecins spécialistes, juristes ou résidents en psychiatrie, m’ont amenée à y réfléchir davantage. J’ajouterais que le constat personnel d’une compréhension des comportements, attitudes, motivations et jugements des patients vulnérables qui s’est modifiée au fil des ans, et le constat de l’importance de la notion du consentement vs le flou de sa définition et la fragilité des paramètres établis pour l’évaluer et la définir ont ravivé cette réflexion. La présente étude n’a aucunement pour but d’élaborer quelque règle de conduite que ce soit, ni de définir ce que devrait être le consentement éclairé en psychiatrie, mais plutôt d’explorer les dilemmes éthiques et les questionnements cliniques auxquels sont confrontés les médecins psychiatres afin de raviver une réflexion éthique qui semble s’estomper au profit de procédures juridiques et administratives. / In the mental health field, the topic of informed consent has always been among the most important problems to address for clinicians and psychiatrists. My clinical work with head injured patients and patients with severe mental health disorder, as well as all the questions addressed by physicians, residents or lawyers for the last decade lead me to think about it more deeply. Moreover, the personal observation of cognitively impaired patients and the fact that the concept of informed consent is so present compared to the lack of parameters to assess it has lead me to think about it otherwise. This study does not pretend to lead the actions or clinical behaviour, nor as it pretend to find a better definition of the concept of informed consent. It is only a way to explore some aspects of the complexity and clinical difficulties over the legal and administrative frame in which the medical field is evolving.

Les objectifs de cette étude étaient (1) de décrire la localisation et la sévérité des lésions d’ostéoarthrose (OA) chroniques acquises naturellement au niveau du grasset équin grâce à l’échographie (US), la radiographie (XR), la tomodensitométrie (CT) et l’évaluation macroscopique (ME), (2) de comparer la performance diagnostique de chacune des modalities d’imagerie avec ME et (3) d’évaluer quantitativement la densité osseuse sous-chondrale lors d’OA du grasset chez le cheval à la tomodensitométrie. Des évaluations post mortem radiographique, tomodensitométrique et échographique ont été réalisées sur 23 grassets cadavériques et comparées à l’évaluation macroscopique. Des associations significatives ont été notées entre le «osteophytes global score» de toutes les modalités (US, p=0.04; XR, p=0.005; CT, p˂0.0001) et ME. De plus, la tomodensitométrie a démontré la plus forte association. Les ostéophytes étaient principalement localisés au niveau de l’articulation fémorotibiale médiale et cette articulation présentait également les scores d’ostéophytes les plus sévères. Un patron spécifique d’ostéophytes associé à l’insertion de la capsule articulaire sur le condyle fémoral médial a été mis en évidence. La nouvelle projection radiographique (Ca10Pr5L-CrDiMO) a été utile dans la détection des ostéophytes de la région intercondylaire. Les grades d’ostéophytes (0-3) ne différaient pas significativement selon la modalité dans la majorité des sites. La faible sensibilité/spécificité a indiqué que la sclérose de l’os sous-chondral et l’applatissement des condyles fémoraux ne semblent pas être des indicateurs fiables d’OA du grasset équin. L’OA du grasset équin est associée à une réduction de la densité osseuse sous-chondrale et des sites spécifiques de résorption/kystes sous-chondraux ont été notés chez certains spécimens. / The objectives of this study were (1) to describe the location and severity of chronic naturally acquired OA lesions in the equine stifle using ultrasound (US), radiography (XR), computed tomography (CT) and macroscopic evaluation (ME), (2) to compare the diagnostic performance of each imaging modality with ME, (3) to quantitatively assess the subchondral bone mineral density in the equine stifle OA using CT. Radiographic, CT and US evaluation were performed on 23 horse cadaver stifles and compared with ME. Significant associations were found between osteophyte global score of all modalities (US, p=0.04; XR, p=0.005; CT, p˂0.0001) and ME, and CT showed the highest association. Osteophytes were predominantly located in the medial femorotibial (MFT) joint and this joint also had the most severe osteophyte scores. This study also highlighted a specific pattern of osteophytes associated with the insertion of the MFT joint capsule cranially on the medial femoral condyle (MFC). The previously unreported radiographic projection (Ca10Pr5L-CrDiMO) was particularly helpful in the detection of intercondylar region osteophytes. Osteophyte grade (0-3) at most sites did not significantly differ between modalities. Low sensitivity/specificity indicated that subchondral bone sclerosis and flattening of femoral condyles do not appear to be reliable radiographic or CT indicators of OA in the equine stifle. Equine stifle OA is associated with a decrease in bone mineral density and specific sites of focal subchondral bone resorption/cyst formation were found in some specimens.

Endothelial cells (EC) are essential regulator of vascular homeostasis through the generation and release of various bioactive agents, including nitric oxide (NO). NO modulates several vascular functions such as vascular tone and permeability, through the stimulation of soluble guanylate cyclase (sGC) leading to the production of cGMP. Conversely, phosphodiesterases (PDEs) are enzymes metabolizing cyclic nucleotides (cGMP and cAMP) and are therefore major regulatory players for cGMP and cAMP signalling pathways. Although ECs are the main source of NO, little is known on the endothelial NO-cGMP signalling pathway and cellular outcomes. It was then hypothesized that a specific population of cGMP-phosphodiesterases allows ECs to stabilize cGMP levels despite the elevated production of NO. Expression of cGMP-phosphodiesterases was initially studied in resistance mesenteric arteries from mice. PDE5 and PDE6 were both found at mRNA and protein levels in native arteries but PDE6 is not found in cultured ECs. Interestingly, subcellular distributions of both enzymes were distinct. PDE5 appeared to be homogeneously distributed whilst PDE6 catalytic subunits (PDE6 and PDE6) showed a preferential staining in the perinuclear region. These results suggest that PDE6 might be involved in the regulation of cGMP microdomains. Based on these findings, a mathematical model was developed. Simulations of dynamic cGMP levels in ECs support the notion of cGMP microdomains dependent on PDE6 expression and localization. In the absence of PDE6, application of NO either as a single bolus or repetitive pulses led to a homogeneous increase in cGMP levels in ECs despite PDE5 homogeneous distribution. However, PDE6 subcellular targeting to the perinuclear membrane generated a cGMP-depleted perinuclear space. The findings from this study provide the first evidence of the expression and specific intracellular distribution of PDE6 in native endothelial cells that strongly support their involvement in the generation of cGMP microdomains / Les cellules endothéliales (CEs) participent au maintien de l’homéostasie vasculaire en générant et libérant de nombreux agents bioactifs, incluant l’oxyde nitrique (NO). Le NO module plusieurs fonctions vasculaires telles que le tonus et la perméabilité vasculaire via la stimulation de la guanylate cyclase soluble (GCs) provoquant la formation de GMPc. D’autre part, les phosphodiestérases (PDEs) sont des enzymes métabolisant les nucléotides cycliques (GMPc et AMPc) et participent donc à des étapes essentielles du contrôle des voies de signalisation du GMPc et de l’AMPc. Bien que les CEs soient la source principale de NO, la voie de signalisation NO-GMPc endothéliale et les répercussions fonctionnelles demeurent méconnues. Nous avons alors émis l’hypothèse qu’une population spécifique de PDEs ciblant le GMPc (PDEs-GMPc) permettrait aux CEs de maintenir des niveaux de GMPc faible malgré l’importante production de NO. L’expression des isoformes de PDEs-GMPc dans les artères mésentériques de souris fut initialement déterminée. PDE5 et PDE6 furent détectées tant sous la forme d’ARNm que de protéines dans les artères natives alors que PDE6 est absente de lignées de CEs en culture. La distribution intracellulaire des deux enzymes est distincte. Alors que PDE5 est distribué uniformément dans le cytoplasme des cellules endothéliales, les sousunités catalytiques de PDE6 ( et ) sont préférentiellement présentes dans la région périnucléaire. Ces résultats suggèrent que PDE6 puisse être impliqué dans le contrôle de microdomaines de GMPc. Des simulations effectuées à l’aide d’un modèle mathématique développé sur la base de ces données sont en accords avec la notion selon laquelle l’expression et la distribution subcellulaire de PDE6 sont responsables de microdomaines de GMPc dans l’endothélium. En absence de PDE6, l’ajout de NO sous forme de bolus unique ou répétée mène à une augmentation homogène de la concentration cytoplasmique en GMPc malgré la présence de PDE5. Toutefois, la présence de PDE6 à la membrane péri-nucléaire crée un espace péri-nucléaire pauvre en GMPc. Les résultats de cette étude forment les premières évidences de l’expression et de la distribution intracellulaire hétérogène de PDE6 dans les cellules endothéliales natives et suggèrent leur implication dans la génération de microdomaines.

Master of Public Health / Department of Human Nutrition / Sandra B. Procter / Family meals and meals with caregivers can be sources of social support. Current literature indicates that social support is important for physical and psychological health and well-being. There has been no published research looking at the role of communal meals in collegiate dining centers as sources of social support. This study investigated the possibility that communal meals in a collegiate dining center and eating with other people in these settings may be related to perceived social support, academic success, frequency of family meals, and/or degree of involvement in college extracurricular activities. To investigate these relationships, first-year Kansas State University students living in the residence halls of the Derby Complex (Ford, Haymaker, Moore, and West Halls) were administered a survey about dining center usage habits. The survey included the previously tested Interpersonal Relationship Inventory Short Form by V.P. Tilden (n.d.) as a measure of perceived social support. Participants granted access to their first semester Kansas State University grade point average and semester dining center usage data. Surveys were completed online (n=216) and in paper format (n=89) for a total of 303 participants. There was no significant difference between the demographics of those that completed the online versus paper formats of the survey. Therefore, the online and paper formats of the survey were analyzed together. The data were analyzed for all participants and for males (n=94) and females (n=209) separately. Results revealed multiple significant relationships (p<0.05). Results related to grade point average and perceived social support revealed a significant positive relationship between frequency of eating in the dining center and grade point average for all participants combined. This relationship was also noted for males and females analyzed separately. Frequency of eating with others was found to be significantly positively correlated to perceived social support score for all participants combined, and for males and females analyzed separately. Frequency of eating with others was significantly positively correlated with grade point average for males alone and females alone, but not all participants combined. Further research is needed to determine if the relationships are causal and if so, the direction of causality in the relationships.

No description available.

No description available.

This qualitative research study examined the patient education experience from the point of view of health care professionals, namely doctors of chiropractic in the Greater Toronto Area practicing for up to ten years. Health care professionals’ views and beliefs of this important aspect of health care have not been well studied. Patient education is defined as, “the process by which patients learn or acquire knowledge about his/her health status or condition and may involve learning in the cognitive, affective, and/or psychomotor domains.” The study explored eight participants’ views on the nature of patient education in their early and current practices by examining their feelings, beliefs, and use of patient education, its role in their practices, as well as the perceptions of their roles as patient educators. Two semi-structured interviews were conducted with each of the participants. The transcribed interviews underwent detailed qualitative analysis to determine response trends and consensus. The key findings revealed that the participants felt that, while they were well prepared in their undergraduate curricula to diagnose and treat patients, they were not as well prepared to be effective patient educators when they entered practice. Early in their careers, they did not understand or appreciate patient education’s importance and value as a component of their practice. Over time, their beliefs and understanding of patient education changed and participants reported that with experience, they began to value patient education to a greater extent. Changing values reflected changing behaviours. For example, participants increased their time and efforts related to patient education with increased clinical experience. A variety of teaching aids were used with wall charts/posters, three dimensional anatomical models, printed materials and images from textbooks being among the most common. Most of the teaching described by the participants would be characterized as transmission with a one-way flow of information from the doctor to the patient. To a great extent, patient education involved speaking with individual patients. Participants reported encountering, throughout their careers, intrinsic and extrinsic barriers that interfered with the effectiveness of their patient education. The findings suggest that curricular planners for health care professional programs, and specifically for chiropractors, might consider developing content aimed at improving students’ patient education knowledge and skills.

Acute demyelination in children may be a monophasic illness or the sentinel attack of multiple sclerosis (MS) – a chronic inflammatory neurodegenerative demyelinating disease. MS risk is largely determined during childhood and vitamin D may protect against MS. The primary objective of this thesis was to evaluate vitamin D status in children presenting with acute demyelinating syndromes (ADS) as a potential contributor to MS outcome. The LIAISON “25 OH Vitamin D TOTAL” assay was validated to assess the biomarker of vitamin D status – serum 25-hydroxyvitamin D (25(OH)D) concentrations. Consecutive patients (<16 y) were enrolled at presentation with ADS and prospectively evaluated at 23 Canadian centres. MS was defined by a second clinical demyelinating event or by MRI evidence of new lesions over time. Cox proportional hazards regression models assessed risk of MS outcome as a function of serum 25(OH)D tertiles, accounting for factors associated with either MS risk or vitamin D status – age, sex, season, and HLA-DRB1*15 status. Of 211 children with 25(OH)D measured in sera obtained a median of 9 days from onset (interquartile range, 5 – 17 d; maximum 36 days), 20% (n = 41) were diagnosed with MS after 3.7 mos. (3.1 – 7.3 mos.). Risk of MS was lower in children with 25(OH)D levels in the highest tertile (≥ 74 nmol/L) at ADS versus those in the lowest tertile (<50 nmol/L) (HR 0.41; 95% CI 0.18 to 0.97, adjusted model). Children with higher circulating 25(OH)D concentrations at ADS have a lower risk of MS. Further evidence for a role of vitamin D insufficiency during childhood and adolescence contributing to MS risk comes from three MS patients with suboptimally managed pseudo-vitamin D deficiency rickets. Finally, a sun exposure questionnaire was validated in the latter part of this thesis for use in future research into determinants of vitamin D status and their association with risk of MS.