Diabetes mellitus has been associated with both clinical and experimental cardiac dysfunction. Diabetic cardiomyopathy which is characterized by depressed cardiac contractility is accompanied by a variety of biochemical changes in Ca⁺⁺ metabolism. This cardiomyopathy may occur in the presence of normal coronary arteries and normal blood pressure. However, some studies have shown that hypertension is more prevalent among diabetics and can aggravate the cardiovascular abnormalities associated with diabetes. To understand the mechanisms of diabetic cardiomyopathy and consequences of combined hypertension and diabetes, experiments were designed to measure cardiac tissue responses to various inotropic agents in experimental diabetes. Six weeks following streptozotocin (STZ) administration, Wistar, spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats exhibited the 'classical signs' of diabetes which included: hyperglycemia, hypoinsulinemia, hyperlipidemia (except in WKY), and hypothyroidism. Decreased basal atrial rate and increased basal developed force (BDF) suggest a depressed SA node function and an alteration of Ca⁺⁺ utilization by diabetic ventricles. Decreased post quiescent potentiation (PQP) values (except in WKY) in ventricular tissues suggest a diminished amount of releasable Ca⁺⁺ from sarcoplasmic reticulum (SR). Decreased post stimulation potentiation (PSP) values in SHR papillary muscles (PM) are probably suggestive of a depressed sarcolemmal Na⁺-Ca⁺⁺ exchange function in this tissue. Diabetic rats show subsensitivity to β-adrenergic stimulation in ventricular tissues, supersensitivity and hyperresponsiveness to Ca⁺⁺ and α-adrenergic stimulation (except in WKY) in ventricular tissues and left atria (LA) and supersensitivity to BAY K 8644 in SHR LA and hyperresponsiveness to verapamil in ventricular strips. These alterations may be attributed to a change in receptor number and/or a post receptor alteration. Ryanodine decreased the PQP of Wistar and SHR PM and SHR LA in both controls and diabetics. It especially abolished PQP in SHR diabetic tissues, but had no effect on WKY tissues, which may suggest a difference in the SR function in these tissues. SR with impaired Ca⁺⁺ uptake may contribute to these phenomena in diabetic rats. Ryanodine also diminished (PQP + BDF) of SHR LA and (PQP/BDF) of Wistar and SHR PM, ˙but had no effects on control and other diabetic tissues. It appears that ryanodine has some influence on the Na⁺-Ca⁺⁺ exchange generated by sarcolemma (SL) of certain diabetic tissues. Further experiments are required to clarify this. SHR diabetic rats had greater changes in most of the measurements such as hyperlipidemia, depressed PQP and PSP values, and altered drug responses. This model exhibited very high mortality as compared to Wistar and WKY diabetic rats. As has been shown previously, the combination of hypertension and diabetes exerts a synergistic effect on the cardiac dysfunction in this model, and that altered lipid metabolism, SL and SR function are all involved in the development of cardiomyopathy. WKY diabetic rats, on the other hand, exhibited no significant changes in blood lipids, or in response to phenylephrine or to Ca⁺⁺ (LA) stimulation. Lack of change in these factors may explain the relatively normal cardiac function of this model as measured previously. / Pharmaceutical Sciences, Faculty of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / Complications following intestinal ostomy surgery can diminish quality of life for individuals living with an ostomy, resulting in physical and psychosocial limitations. Risk factors contributing to ostomy complications are not well established in the literature. The purposes of this study were to: 1) identify risk factors contributing to the development of fecal ostomy complications; 2) describe the incidence and severity of early fecal ostomy complications; and 3) estimate the reliability and validity of two newly developed instruments, Ostomy Risk Factor Index (ORFI) and Ostomy Complication Severity Index (OCSI). Using a prospective longitudinal design, 71 adult patients who had undergone ostomy surgery were recruited from three acute care settings. Data were collected through self-administered surveys, medical record review, and direct observation prior to discharge and at 30 to 60 days post-operatively. Data were analyzed using descriptive statistics, analysis of variance, chi-square tests, correlation, and multiple regression. Psychometric properties of the Ostomy Risk Factor Index and the Ostomy Complication Severity Index were examined using content validity indices, Cohen coefficient kappa, Pearson correlation coefficient, and intra-class correlation. Two risk factors were found to be predictive of ostomy complications scores, stoma/abdomen characteristics (p= .007) and BMI (p= .002). Ostomy complications and ostomy adjustment were significantly inversely correlated (r= - 0.27, p=.04) and stoma care self-efficacy and ostomy adjustment were significantly correlated (r= .599, p= .01). The ORFI and OCSI demonstrated acceptable content validity (CVI= 0.9). ORFI demonstrated acceptable inter-rater reliability for 10 of the 14 items (k= 1.0) and excellent intraclass correlation of total scores between raters (r= .998, p= .001). The OCSI demonstrated acceptable inter-rater reliability for all of the items (k= .71- 1.0) and excellent intra-class vii correlation of total scores between raters (r= .991, p= .000). The OCSI demonstrated acceptable internal consistency (Cronbach's alpha .68). In conclusion, this study provides new knowledge regarding risk factors, incidence and severity of ostomy complications, and provided support for the validity and reliability of two new instruments for the researcher and practitioner to reliably identify and describe important contributors (risk factors) and outcomes (complications) that affect care of the patient with an ostomy.

No description available.

Au cours des dernières années, on a vu une augmentation radicale de la proportion de gens avec un indice de masse corporelle (IMC) dit extrême. Au Canada, de 1978 à 2004, la proportion de patients avec une obésité sévère de classe II (IMC > [ou égal à] 35 kg/m²) a plus de doublée (2,3% à 5,1%) et celle de classe III (IMC > [ou égal à] 40 kg/m²) triplée (0,9% à 2,7%). Ces patients à haut risque de maladies cardiovasculaire sont de plus en plus représentés en chirurgie cardiaque. En 2008, la "Society of Thoracic Surgeons" rapportait qu'environ 14% des patients opérés en chirurgie cardiaque avaient un IMC supérieur à 35 kg/m². Le présent projet traite du risque de complications associées l'obésité sévère en postopératoire de chirurgie coronarienne isolée et de remplacement valvulaire isolé. Il a pour but primaire de préciser si l'obésité sévère a un impact en ce qui a trait à la morbidité et mortalité postopératoire de ces chirurgies. Il a par également comme objectif de préciser la relation entre le tour de taille et le risque de complications dans ces deux populations chirurgicales. Nous avons montré que le risque de mortalité postopératoire en chirurgie coronarienne et valvulaire isolée n'est pas augmenté chez une population de patient avec une obésité sévère en comparaison avec des patients avec un IMC normal. Par contre, les patients en chirurgie coronarienne sont plus à risque de développer de la fibrillation auriculaire, de se faire réintuber, de présenter des embolies pulmonaires, de présenter des complications rénales, de développer des infections de plaies, une médiastinite et une septicémie. Les patients en chirurgie valvulaire isolée présentent quant à eux un risque accru d'insuffisance rénale nécessitant une thérapie de remplacement rénal, un taux plus élevé de médiastinite, de septicémie et d'infection de cathéter. Enfin, le tour de taille ne semble pas être un meilleur prédicteur de complications en chirurgie coronarienne ou valvulaire isolée. Par contre, en chirurgie coronarienne, le tour de taille pourrait sélectionner un groupe à plus faible risque de mortalité et de saignement postopératoire.

Pregnancy loss, the demise of a pregnancy at any time between implantation and delivery, is a common event in women’s lives, affecting approximately one in three pregnancies. Pregnancy loss often causes profound psychological distress to women, their partners, and their families. However, despite its frequency and troubling nature, relatively little is known about the natural history of pregnancy loss, especially the multitude of signs and symptoms that precede a loss and distinguish it from an ongoing healthy pregnancy. One of the challenges in describing the natural history of pregnancy loss is that most losses occur very early, before entry to clinical care, necessitating the use of preconception cohort studies. Few such studies have ever been conducted worldwide. This dissertation aimed to describe the natural history of early pregnancy loss at <20 weeks gestation for the first time using a unique preconception cohort with daily prospective follow-up from the start of the pregnancy attempt through seven weeks post-conception. To accomplish this goal, three specific aims were undertaken. First, a systematic literature review was conducted to synthesize the existing literature on the relationships between the signs and symptoms and pregnancy loss. Two analytic aims were then undertaken to delineate thoroughly the relationships between prospectively ascertained signs and symptoms—namely, vaginal bleeding, lower abdominal cramping, nausea and vomiting (hereafter referred to as “signs and symptoms”)—and subsequent early pregnancy loss. The first analytic aim used a fixed covariate and fixed effect survival analytic approach to estimate the cumulative incidence of early pregnancy loss by the presence of individual, combinations, and patterns of signs and symptoms and the associations between signs and symptoms and the cumulative incidence of pregnancy loss. The second analytic aim used a time-varying covariate and time-varying effect survival analytic approach to estimate the weekly associations between signs and symptoms and pregnancy loss to determine if these relationships were consistent or divergent across gestational ages. The results of the first and second analytic aims were then compared to gain a more complete understanding of the natural history of early pregnancy loss. The literature review revealed a dearth of studies on the signs and symptoms of pregnancy loss. Two preconception and 16 pregnancy cohort studies were identified. The literature suggested that vaginal bleeding, particularly heavy vaginal bleeding, was associated with an increased risk of pregnancy loss while vomiting, and in some studies nausea, was associated with a decreased risk of pregnancy loss. However, reliance on care-seeking cohorts, maternal retrospective reports of signs and symptoms after pregnancy loss, and retrospective recall of signs and symptoms over long periods (e.g., entire trimesters) may have biased the observed associations between signs and symptoms and pregnancy loss leading to incorrect inferences regarding the relationships between signs and symptoms and pregnancy loss. The two analytic aims addressed the data gaps identified in the literature review. The preconception cohort design with prospective daily follow-up from the beginning of the pregnancy attempt facilitated the ascertainment of pregnancies at the earliest stages of gestation and losses prior to clinical care entry through the use of urine-based home pregnancy testing. The daily reporting of multiple signs and symptoms in the first five weeks after a positive home pregnancy test, or approximately two to seven weeks post-conception, allowed for a full description of the relationships between signs and symptoms of pregnancy loss without recall bias. Data for the two analytic aims come from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, a population-based cohort with preconception recruitment of couples in 16 counties in Michigan and Texas followed for 12 months of trying for pregnancy and then through pregnancy loss or delivery for couples achieving an hCG pregnancy. 501 couples entered the study, and 347 achieved a pregnancy during the study period. Three hundred forty-one singleton pregnancies comprise the study population for the two analytic aims in this dissertation. Overall, 95 (28%) pregnancies in the study population ended in a pregnancy loss. Lower abdominal cramping, nausea, and vomiting were often reported during the early pregnancy period; vaginal bleeding was less common. The results of the fixed covariate fixed effect survival analysis from the first analytic aim demonstrated that vaginal bleeding, particularly heavy bleeding and bleeding accompanied by lower abdominal cramping, was associated with an increased risk of pregnancy loss. In contrast, the presence of vomiting, but not nausea alone, during the early pregnancy period was associated with a lower risk of loss. Analyses in the second analytic aim using weekly time-varying covariates and time-varying effects of signs and symptoms on pregnancy loss revealed some new findings. The first week after a positive pregnancy test appeared to be a vulnerable period. Vaginal bleeding and lower abdominal cramping were associated with an increased risk of loss in the first week but not in later weeks; conversely, nausea and/or vomiting were associated with lower risk of pregnancy loss but only after the first week. The observed weekly variations in the signs and symptoms of pregnancy loss may reflect changes in maternal adaptation to pregnancy across gestation. Overall, relatively little is known about the biological processes underlying healthy and unhealthy adaption to pregnancy as well as how embryo quality may affect these adaptive processes. More work is required from basic scientists, clinicians and epidemiologists to better understand the causes of signs and symptoms and their relationships to pregnancy loss, including genetic and environmental factors and their interactions. In the meantime, prognostic models developed from data in this dissertation using time-varying signs and symptoms may be useful to women and their health care providers for identifying pregnancies at increased risk for pregnancy loss. These models could prompt women to seek medical care when concerning patterns of signs and symptoms arise.

Objectif : To determine the frequency and the nature of complications and sequelae of serogroup B and serogroup C meningococcal disease, during a recrudescence caused by a virulent clone of serogroup C, serotype 2a Neisseria meningitidis. To evaluate the quality of life of survivors. Methods. The study population included all cases of culture-proven serogroup B and C meningococcal disease reported in the province of Quebec, Canada, between 1 January 1990 and 31 December 1994. Complications and sequelae were assessed by review of medical files, postal questionnaires, and telephone interviews. Results. There were 167 cases of serogroup B and 304 cases of serogroup C infection. The largest number of cases was observed in the under 1 year age group for serogroup B and in the 10-19 year age group for serogroup C. Fatality rates were 7% for serogroup B and 14% for serogroup C. %). Only 3% of survivors of serogroup B cases had physical sequelae. 15% of survivors of serogroup C infection had one or more significant physical sequelae (skin scars 12%, amputations 5%, significant sensorineural hearing loss 2%, renal failure 1%, other sequelae 4%. Among cases without identified physical sequelae who completed the questionnaire, 19% reported a reduction in their quality of life attributable to the disease. Conclusions. These results confirm the gravity of disease caused by serogroup C, serotype 2a Neisseria meningitidis and support vaccination for control of outbreaks and epidemics of disease caused by this particular strain.

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Master / Master of Public Health