The isolated perfused working heart was used to study hypertensive- diabetes induced alterations in cardiac function at 6 and 12 weeks after the induction of diabetes. There was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats at 6 weeks after diabetes induction. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-week study. Successful induction of diabetes was confirmed by the presence of hyperglycemia, hypoinsulinemia, glycosuria and increased haemoglobin glycosylation in all three diabetic groups. However, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups, associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats and could explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than is seen with either disease alone and is associated with a significant mortality. The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). When hydralazine was administered for a 6-week period to the diabetic rats, their blood lipids were not significantly different from that of non-diabetic rats despite a low serum insulin. In contrast, blood lipids were elevated in the diabetic rats that were not treated with hydralazine; these animals also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement which could be partly explained by their normal thyroid status in contrast to the untreated diabetic animals which were slightly hypothyroid. Blood pressure was elevated only in the untreated diabetic animals. Thus hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats. To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week male and female rats. Significantly lower values for +dP/dt occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats. / Pharmaceutical Sciences, Faculty of / Graduate

The purpose of this study was to review the evidence linking maternal and paternal lifestyle habits in the preconception and prenatal period to adverse reproductive outcomes; to determine either the proportion of reproductive casualties which could be attributed to lifestyle risk, thus be amenable to prevention, or the information required to estimate the preventable portion of lifestyle-related reproductive casualties; and to examine a method for surveillance of reproductive health in the community which would provide the basis for a comprehensive information system suited to the needs of the research, planning, preventive medicine and health promotion communities. As a means of managing the size of the study report, only a representative set of lifestyles (smoking, alcohol consumption and nutrition) and research literature (major cohort and case-control studies in human populations) was reported in detail. A method was developed to review and describe the degree to which the evidence meets established criteria for causal association. The most recently available prevalence data for determining smoking, alcohol and nutritional risk, and incidence data for seven reproductive outcomes (infertility, spontaneous abortion, stillbirth, infant mortality, congenital anomalies, fetal growth and morbidity) in the British Columbia population were used to calculate the preventable portion of reproductive casualties in this community. A review of the variables required, compared with the data available, provided the basis for recommendations regarding a reproductive health information system to support community surveillance, evaluation and research. The study supports the conclusion that there is evidence of a causal link between exposure to lifestyle risks and the majority of adverse reproductive outcomes selected as indicators of reproductive health. The calculation of the preventable portion (etiologic fraction) of lifestyle-related reproductive casualties in British Columbia suggests the preventable portion associated with single lifestyle risk variables may be in the range of 10-50 percent. A more extensive and up-to-date set of population data for British Columbia is required to determine an accurate estimate. The benefits to be derived from an improved information system were detailed in the study. Reproductive health data collected for British Columbia is primarily outcome oriented with very little input data on which to base rational planning decisions for the improvement of reproductive health outcomes. The study recommends that a more comprehensive reproductive health information system, with an integrated, linked data base, be considered a high priority by government and all institutions, agencies and individuals working to improve reproductive health outcomes in British Columbia. The potential to improve reproductive health is significant enough to warrant action at the clinical and community level, but additional data are required to plan cost-effective intervention strategies, to monitor improvements in reproductive health, and to support applied research initiatives. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

Contexte : L'obésité est considérée par l'OMS comme une « épidémie » mondiale en raison de l'essor de sa prévalence et de ses conséquences sur la santé. Chez les patientes enceintes, son impact semble tout aussi préoccupant et sa prévalence en France atteint actuellement 10%. Certaines complications de l'obésité chez la femme enceinte ont été peu étudiées et notamment le lien particulier avec la macrosomie fœtale.Objectifs : Mieux appréhender la prise en charge des patientes enceintes obèses et de certaines complications qui en découlent.Méthodes : Trois séries de données différentes ont servi pour répondre à différentes questions sur la thématique de l'obésité et de la macrosomie. 1) Une évaluation de la faisabilité et de la qualité d'une échographie obstétricale du 2ème trimestre chez les patientes obèses a été réalisée via une étude mono centrique avec recueil prospectif des données. 2) Une étude des facteurs de risques de complications maternelles en cas d'accouchement d'un enfant macrosome, indépendamment de l'obésité maternelle et du poids de naissance de l'enfant a été menée sous la forme d'une étude prospective de cohorte d'enfant de plus de 4000g dans deux maternités d'Ile de France. 3) Enfin, une comparaison de la relation entre les complications maternelles de la grossesse et /ou néonatales et l'obésité a été menée entre la France (4 maternités de type III) et le Québec (données issues d'une étude randomisée dans toute la province) entre 2009 et 2011 via une étude comparative de deux échantillons transversaux de femmes enceintes (26 973 accouchements en France et 83 545 accouchements au Québec). Résultats : 1) Une échographie du deuxième trimestre de la grossesse chez une population obèse est possible, avec un taux de réussite en une fois de 70,4 %, (versus 82% ; p=0,08). Les facteurs d'amélioration de ce taux étaient : passer plus de temps lors de l'échographie (p=0,03), déplacer le fœtus de sorte que son dos soit en position latérale ou postérieure (p=0,01), et échographie réalisée par des échographistes expérimentés (p=0,03). Néanmoins, la qualité des images reste significativement moins bonne dans la population obèse (p=0,001). 2) La survenue de complications maternelles lors de la tentative d'accouchement vaginal d'un enfant de plus de 4000 g est de 6%. Les facteurs de risque de complications maternelles, outre le poids de naissance de l'enfant (p=0,004, Risque attribuable (RA)=10%), sont l'origine asiatique de la mère (p=0,04 ; RA=3%), une durée longue du travail (>10h) (p=0,02 ; RA=12%), et une césarienne au cours du travail (p=0,004 ; RA=17%). Les patientes multipares ayant déjà accouché par voie vaginale d'un enfant macrosome avaient un risque diminué de complications maternelles (p=0,03). 3) La prévalence de l'obésité était de 9,1% en France et 16,8% au Québec (p<0,001). L'obésité était associée de manière statistiquement significative (p<0,0001), à la fois en France et au Québec, à un risque accru de diabète gestationnel, de troubles hypertensifs de la grossesse, de prééclampsie, de mort fœtale in utero, d'accouchement par césarienne et de macrosomie. L'association était différente en France et au Québec (p interaction <0,005), pour la survenue du diabète gestationnel, de complications hypertensives de la grossesse et pour la macrosomie, avec une augmentation plus importante des complications avec l'IMC au Québec par rapport à la France.Conclusion : La compréhension de certaines complications inhérentes à l'obésité (complications médicales de la grossesse, faisabilité et qualité du dépistage échographique, complications obstétricales) est améliorée par les résultats de cette thèse. / Background: According to WHO, obesity is considered as an "epidemic" condition due to the global growth of its prevalence and its impact on patient health. For pregnant patients, its impact seems equally worrying and its prevalence is now reaching 10% in France. Some complications of obesity in pregnant women have been little studied and particularly the special link with fetal macrosomia.Objectives: To better understand care and obstetric outcome of obese pregnant patients as well as some of their complications such as fetal macrosomia.Methods: Three different sets of data were used to deal with questions regarding obesity and macrosomia. 1) Assessment of feasibility and quality of second trimester ultrasound scan in obese patients was performed through a mono centric case-control study with prospective data collection. 2) A study of risk factors for maternal complications in case of the delivery of a macrosomic child, regardless of maternal obesity and child's birth weight, was conducted as a prospective cohort study including children with birthweight above 4000g in two “Ile de France” maternity wards. 3) Finally, a comparison of the relationship between maternal and/or neonatal complications of pregnancy and obesity was conducted in France (4 type III maternity wards) and in Quebec (data from a randomized study throughout the province) between 2009 and 2011 through a comparative study of two cross-sectional samples of pregnant women (26,973 births in France and 83,545 births in Quebec).Results: 1) Second trimester ultrasound scan in obese pregnant women is feasible, with a success rate of 70.4% (versus 82%; p=0.08). Factors of improvement were: to spend more time at ultrasound (p=0.03), to move the fetus so that its back is in lateral or posterior position (p=0.01) and when ultrasound was performed by experienced sonographers (p=0.03). However, the quality of the image remains significantly lower in the obese population (p=0.001). 2) The occurrence of maternal complications, when attempting vaginal birth of a child of more than 4000g, was 6%. Beyond childbirth weight (p=0.004, attributable risk (AR) = 10%), the risk factors of maternal complications were Asian ethnicity (p=0.04; AR=3%), prolonged labor (> 10h) (p=0.02; AR=12%), and caesarean section during labor (p=0.004; AR=17%). Multiparous women with a previous vaginal delivery of a macrosomic child had a lower risk of maternal complications (p=0.03). 3) The prevalence of obesity was 9.1% in France and 16.8% in Quebec (p <0.001). Obesity was significantly (p <0.0001) associated with, both in France and in Quebec, an increased risk of gestational diabetes, hypertensive disorders of pregnancy, preeclampsia, stillbirth, cesarean delivery and macrosomia. The strength of the association was different in France and Quebec (p of interaction <0.005) for the occurrence of gestational diabetes, hypertensive complications of pregnancy and macrosomia, with a larger increase in complications with body mass index in Quebec compared to France.Conclusion: Understanding some inherent complications of obesity (medical complications of pregnancy, feasibility and quality of ultrasound screening, obstetric complications) is enhanced by the result of this work.

Les endofuites sont des complications évolutives des traitements endovasculaires des anévrysmes de l'aorte abdominale sous rénale et exposent au risque persistant d'évolution vers la rupture en maintenant une pression positive au sein du sac anévrysmal théoriquement exclu de la circulation générale par l'endoprothèse. Différents types d'endofuites sont décrits selon leur origine et mécanismes d'action. Les endofuites de type 2, définies par une circulation rétrograde au sein du sac anévrysmal depuis les artères mésentérique inférieure ou lombaires pose un problème de prise en charge thérapeutique. A travers la modélisation chez l'animal d'anévrysmes traités par endoprothèses et sièges d'endofuites de type 2, cette étude expérimentale établit qu'une seule de ces endofuites suffit pour créer une pression positive anévrysmale. Elle établit également la faisabilité d'un traitement coelioscopique des endofuites de type 2 permettant une baisse significative de cette pression tout en offrant une alternative thérapeutique peu invasive.

No description available.

The literature is replete with reports of osteoporosis in rheumatoid arthritis, but the mechanism of bone loss remains obscure. This is probably due to the overlap with bone loss of aging and the menopause, whose exact mechanisms are also poorly understood. Against this background, a study was designed to evaluate generalised bone loss in young, premenopausal (if female), patients with rheumatoid arthritis. The protocol was designed to record demographic data, as well as information pertaining to the disease. Cortical bone mass was measured at the metacarpals and left femur, using an automated, computer-controlled technique. Trabecular bone was evaluated at the left femur (Singh index) as well as at the 3rd lumbar vertebra (Saville index). Bone kinetics were studied by the measurement of urinary excretion of calcium, phosphate and hydroxy-praline (resorption) and serum alkaline phosphatase (formation). Disease activity was measured clinically and with laboratory indices. Physical activity was indirectly measured by quantitating the disability, using the Keitel function test as well as a modified health assessment questionnaire (HAQ). The radiograph of the right wrist was scored by the Larsen index. The carpometacarpal ratio was also calculated from the radiograph. Numerous statistical techniques were applied in the analysis of the data. Healthy volunteers were used as controls. Patients with SLE were also studied, in order to compare the 2 inflammatory diseases. Patients with RA had generalised cortical bone loss (metacarpal and femur) (p &lt; 0.001). Trabecular bone measurements were not significantly different from normals, using the crude radiographic techniques. Duration of disease was the most important clinical determinant of this bone loss. The relative contributions of disease activity and lack of physical activity to the loss of bone could not be adequately separated using conventional statistical techniques. Corticosteroid therapy did not promote metacarpal bone loss in these subjects, but may have contributed to thinning of the femoral cortex. Nonsteroidal anti-inflammatory drugs and disease modifying agents did not seem to influence the extent of the bone loss. Nutritional status and skinfold thickness did not correlate with bone mass. Dietary factors played no role in the genesis of bone loss, but may have had some effect on disease activity. Metacarpal measurements showed a sensitivity of 80% and specificity of 85% in discriminating between osteopaenic and normopaenic groups with RA. Osteopaenia could not be adequately predicted in the absence of metacarpal measurements. Metacarpal bone loss in RA was due to endosteal resorption, while in SLE it was due to periosteal resorption. The semi-automatic technique for measurement of metacarpal bone mass showed good reproducibility among 5 observers and at 2 different centres. The pathogenesis of bone loss in RA was multifactorial, the largest contribution probably coming from a humoral factor in the circulation, closely related to disease activity. Ionised calcium was elevated in 55% of RA patients, but only 5% of SLE patients. Serum PTH levels were normal in 99% of the RA subjects. Elevations in alkaline phosphatase. (25%) probably reflected disease activity rather than increased bone formation. Factor analysis of 27 variables showed that disease activity was central to the development of OP in RA. CS therapy tended to be used in the presence of active disease. Disability was not an important determinant of bone loss in RA, but may be a useful measure of activity of the disease. This study did not evaluate the relationships with sex hormonal status or vitamin D metabolism. Future research should aim at cohort analysis at 2 different periods, in order to improve our understanding of the pathogenesis of bone loss in RA.

The purpose of this study was to analyze and record the characteristics of grandparents who are raising school-aged children as they relate to how the United States is responding to their needs and the needs of their grandchildren. The researcher sought to determine the characteristics of grandparent-headed households with no parent present in regards to housing, nutritional assistance, transportation, employment, age of children in the household, language spoken in the home, and family type, as measured by the 2010 United States Census Bureau. This study was conducted using a quantitative, descriptive research design. The data used for this study were indirect estimates produced by statistical model-based methods using sample survey, decennial census, and administrative data sources compiled by the United States Census Bureau. The Census Bureau collects data about American families for the nation, states and communities, and data related to socioeconomic status, family composition, and language spoken were used to more fully understand characteristics of households where grandparents are raising grandchildren outside of the traditional 1-2 parent American households. Participants included the 92 grandparent-headed households from among the 15,482 participants in the American Community Survey, which included 556 households where grandparents were living with grandchildren. To address the research questions, descriptive statistics were used, including frequencies and percentages. The statistical package SPSS was used to analyze the data. The results of this study revealed that of the grandparents who lived with their grandchildren where there was no parent present, 100% lived in housing units, 75% participated in the yearly food stamp/supplemental nutrition assistance program, 36% had no transportation, 26% were female householders who were unemployed and did not have a husband living in the household, 74% had related children who were 6-17 years old in the household, 51% lived in homes where only English was spoken, and 53% resided in homes where there was a married couple, while 39% of them were in homes with female householders with no husband present.

The prevalence of diabetes is increasing rapidly around the world. People with diabetes are 2–4 times more likely to die from cerebro and cardio-vascular causes than people with no history of diabetes, even after controlling for other risk factors. Atherosclerosis, the underlying cause of most cardiovascular disease (CVD), is accelerated in people with diabetes, but several clinical trials have questioned the efficacy of glucose lowering therapies. A better understanding of the molecular pathways by which diabetes accelerates atherosclerosis will expand the scope of current targets and strategies for more effective therapies. In this thesis we investigate a novel mechanism and establish and characterize new hyperglycemic mouse models for the study of diabetic atherosclerosis. Firstly, we investigate the effects of hyperglycemia on the vasa vasorum, the microvascular network that surrounds and supplies large vessels, and correlate those effects to the development of atherosclerosis. In normoglycemic ApoE-/- mice, the vasa vasorum expands as atherosclerotic lesions grow. However, in hyperglycemic ApoE-/- mice there is no significant neovascularization of the vasa vasorum despite the enhanced atherosclerotic development. We hypothesize that the ability of hyperglycemia to disrupt vasa vasorum neovascularization may promote the development and progression of atherosclerosis in diabetes. Secondly, we establish, characterize and manipulate a new model of hyperglycemia-induced atherosclerosis: the ApoE-/-:Ins2+/Akita mouse. We describe sex-specific differences of the ApoE-/-:Ins2+/Akita mouse model. Male ApoE-/-:Ins2+/Akita mice develop chronic hyperglycemia and accelerated atherosclerosis. Castration slows atherosclerosis in ApoE-/-:Ins2+/Akita mice but enhances it in normoglycemic controls. Female ApoE-/-:Ins2+/Akita mice are only transiently hyperglycemic but still present with accelerated atherosclerosis. Ovariectomized ApoE-/-:Ins2+/Akita mice are chronically hyperglycemic and show indications of advanced atherosclerosis. Lastly, we investigate the effects of a western-type diet on the hyperglycemic ApoE-/-:Ins2+/Akita mice. We demonstrate the pernicious phenotype of the mice leading to a significantly shortened lifespan correlated with massive atherosclerosis that extends to the aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries. In conclusion we provide insights for a new mechanism by which hyperglycemia may accelerate atherosclerosis and possible role of the vasa vasorum in the progression of atherosclerosis in hyperglycemic mice. We also establish new mouse models that illuminate the action of sex hormones on pancreatic beta-cell function and the vasculature. These models will provide a test bed to further study sex hormone effects, as well as the diabetic pathways that promote atherosclerosis. / Thesis / Doctor of Philosophy (PhD)

L'objectif général de cette thèse était de comparer les effets d'une division de l'attention sur la combinaison de la locomotion en contournant des obstacles fixes et mobiles entre des participants ayant un traumatisme craniocerebral (TCC) et des participants sains. Une approche biomécanique a été utilisée pour analyser les altérations fonctionnelles qui ont été soulevées chez des adultes ayant un TCC de grade modéré ou sévère et des athlètes d'élite présentant un TCC de grade léger (TCCL). Des enfants sains ont aussi été étudiés afin de mieux comprendre les altérations fonctionnelles présentes à la suite d'une division d'attention dans des environnements complexes mais écologiques. Les adultes ayant un TCC ont démontré des temps de réaction de réponse plus longs, ont fait plus d'erreurs dans la réponse à la tâche d'interférence, avaient une vitesse moyenne de marche plus lente, une vitesse maximale de marche plus lente et démontraient aussi plus de dégagement minimal face aux obstacles que les adultes sains du groupe-contrôle. Ils ont également plus de difficulté à effectuer deux tâches ou plus simultanément. Il semble aussi que les déficits des fonctions executives, plus particulièrement au niveau de la planification, sont évidents chez des adultes avec un TCC modéré ou sévère mais aussi chez les athlètes ayant un TCCL. La planification et la navigation sont deux aspects importants dans le sport et pour les athlètes qui ont déjà eu un TCCL Cet aspect est primordial pour éviter de se mettre dans des situations à risque potentiel d'autres blessures à la tête. De plus, il a été démontré que même si les athlètes ne présentaient aucun symptôme et que leur résultats aux tests neuropsychologiques étaient revenus au niveau d'avant leur blessure, ils présentaient tout de même des altérations fonctionnelles plus de 30 jours suivant cette blessure. Une partie de cette thèse a été faite auprès d'enfants sains pratiquant le hockey sur glace. La vitesse maximale de patinage a diminué avec l'ajout de la tâche d'interférence visuelle et plus d'erreurs ont été commises lors de l'ajout du maniement du bâton.

Cette étude de cohorte vise à évaluer l’hypothèse qu’une malrotation postopératoire du tibia engendre des problèmes fonctionnels. Les patients adultes ayant subi un enclouage centro-médullaire d’une fracture isolée de la diaphyse tibiale (2003-2007) à l’Hôpital de l’Enfant-Jésus ont été identifiés à l’aide des codes ICD-10. Parmi les 100 patients admissibles sur les 288 identifiés, 70 ont accepté de participer à l’étude. Une tomodensitométrie a été effectuée afin d’évaluer le degré de rotation tibiale. Le test fonctionnel Lower Extremity Functional Score (LEFS) a été complété. Les résultats ont été comparés entre les patients avec malrotation radiologique (≥10°) (groupe AM) et sans malrotation (<10°) (groupe SM). Le score LEFS était comparable dans les 2 groupes (groupe AM : 71 pts vs. groupe SM: 73 pts) (p=0,41). Malgré son incidence élevée, la malrotation du tibia suite à un enclouage centro-médullaire verrouillé de la diaphyse tibiale semble ne pas avoir d’impact fonctionnel significatif à moyen terme.