Thesis (doctoral)--University of Lund, 1981. / Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1988.

Thesis (M.S.)--Ball State University, 2009. / Title from PDF t.p. (viewed on June 07, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 132-143).

Cardiovascular disease (CVD) causes 45% of on-duty firefighter fatalities, a high fraction even when compared to the risk of CVD found in other first-responder professions like police work and emergency medical services. Monitoring and managing firefighter cardiac health is important for both individual health and public safety. In our study, we are interested in assessing the utility of the most commonly used risk assessment scoring, known as the Framingham Risk Score, in evaluating the atherosclerotic risk in asymptomatic firefighters. To this end we determined FRS for 159 male firefighters from Gwinnett County, Georgia, and compared their risk categorization against their known atherosclerotic burden as determined by CIMT and CAC. While the 20% FRS threshold, corresponding to medium risk, had a high specificity for both CAC and CIMT, it also had a low sensitivity (17% and 40%, respectively), indicating that a large percentage of individuals with clinically significant atherosclerosis are being misclassified. By adjusting the FRS threshold downward, we were able to raise the sensitivity greatly with only a modest loss of specificity. Following percutaneous transluminal coronary angioplasty for the treatment of coronary artery disease, stents are commonly implanted at the treatment site to prevent recoil and negative remodeling. To combat in-stent restenosis, an arterial healing response that results in luminal loss in stented arteries, anti-restenotic drugs like sirolimus (SES) and zotarolimus (ZES) are commonly eluted by stents to suppress cell proliferation at the treatment site. While comparative studies have revealed significant difference between bare metal stents (BMS), SES, and ZES in both clinical and histological arterial response, the molecular basis of these differences remains poorly understood. We conducted a comparative gene expression profiling study using microarrays to examine differences in gene expression and pathway function in coronary arteries exposed to ZES, SES, and BMS in a porcine animal model. These molecular profiles suggest a model of delayed restenosis, resulting from a drug-induced suppression of inflammatory responses and proliferative processes, rather than an elimination of restenosis. microRNAs play a regulatory role in metastasis-related epithelial to mesenchymal transitions and mesenchymal to epithelial transitions in ovarian cancer cells. We previously showed that over-expression of miR-429 in ovarian cancer cells drove a transition from mesenchymal phenotypes to epithelial phenotypes both in morphology and expression of markers like ZEB1, ZEB2, and E-cadherin. Our study represents the first time course analysis of miR-429-induced MET in ovarian cancer cells. We transfected Hey cells with miR-429 and assayed gene expression over the course of 144 hours at regular intervals. The cell morphology and gene expression of our transfected cells changed to become more epithelial-like at 24 and 48 hours and then became more mesenchymal-like by 144 hours. By 144 hours the average gene expression levels for 98.6% of our genes were not significantly different from the levels they started from at 0 hours when we adjusted for baseline expression changes observed in our negative control treated cells. This suggests the use of microRNAs as cancer therapies and driving cancer cells to a more drug susceptible state.

Orientador: Winston Bonetti Yoshida / Resumo: Objetivo. A presente revisão se propõe a comparar a eficácia e segurança da angioplastia com stent versus angioplastia percutânea transluminal nas lesões sequenciais através dos desfechos: taxa de abertura do vaso (TICI 2b/3), evolução neurológica (mRs < 2) e taxa de hemorragia sintomática (hematoma grau II). Método. Utilizando como base de dados o PubMed, Scopus, Embase, SciELO/LILACS e outros, a presente revisão sistemática foi realizada até setembro de 2017 com base no PICO: (P) Pacientes com oclusão sequencial da carótida na fase aguda do AVCi tratados ou não com fibrinolítico endovenoso, (I) Angioplastia com stent, (C) Angioplastia percutânea transluminal, (O) TICI, mRs e hemorragia sintomática. As seguintes palavras chaves foram utilizadas: Stroke, Carotid Artery Injuries, Angioplasty, Stent and Safety. Aos artigos encontrados, os critérios de seleção do PRISMA foram aplicados, sendo realizada a análise qualitativa através do cheklist do NIH for before-after studies with no control group e a análise quantitativa através do programa Statdirect. Resultados. Identificados 228 artigos que após ajustes e exclusões restaram 29 para a análise qualitativa e quantitativa. TICI após CAS 0,76 (95% CI = 0,72 a 0,79); I2 = 36,9% versus PTA 0,71 (95% CI = 0,61 a 0,81); I2= 28,5%. mRs < 2 em 90 dias após CAS 0,47 (95% CI = 0,43 a 0,51) ); I2 = 3% versus PTA de 0,46 (95% CI = 0,36 a 0,57) ); I2 = 18,7%. Taxa de hemorragia sintomática após CAS 0,08 (95% CI = 0,06 a 0,10); I2 = 5,3%) ver... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: Compare carotid angioplasty and stent (CAS) versus percutaneous transluminal angioplasty (PTA) measuring the efficacy and safety through Thrombolysis in Cerebral Infarction scale (TICI 2b/3), modified Rankin scale (mRs <2) and symptomatic haematoma (PH2). Method: Using the PubMed and others database, we searched for articles publish until setember 2017. The PRISMA criteria was used and rigorous eligibility were applied. The article quality was assessed by a checklist of “Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group published" by NIH and proportional meta-analysis was performed by Statdirect software. Results: 228 articles were identified from the databases, after adjustments due to duplicates and submitted to the eligibility criteria, 29 articles with 1339 patients remained for the qualitative and quantitative analysis. TICI 2b/3 value after CAS was 0,76 (95% CI = 0,72 to 0,79); I2 = 36,9% versus PTA 0.71 (95% CI = 0.61 to 0.81); I2= 28,5%, mRs < 2 in 90 days after CAS 0.47 (95% CI = 0.43 to 0.51) ); I2 = 3% versus PTA 0.46 (95% CI = 0.36 to 0.57) ); I2 = 18,7% and symptomatic haematoma 0,08 (95% CI = 0,06 to 0,10) ); I2 = 5,3% versus PTA 0,06 (95% CI = 0,02 to 0,13); I2 = 35,5% showed no statistical difference. Other analyses of subgroups were done, including the effect of tPA with antiplatelet drugs. Conclusion: CAS is effective and safe when compared to PTA in the outcomes TICI 2b/3, mRs < 2 and PH2. A randomized clinical ass... (Complete abstract click electronic access below) / Doutor

abstract: ABSTRACT Despite significant advancements in drug therapy, cardiovascular disease (CVD) is still the leading cause of death in the United States. Given this, research has begun to seek out alternative approaches to reduce CVD risk. One of these alternative approaches is Vitamin D supplementation. Current research has shown a link between Vitamin D status and CVD risk in both healthy and diseased populations. Among the possible mechanisms is a positive effect of Vitamin D on vascular endothelial function, which can be measured with noninvasive techniques such as flow-mediated dilation (FMD) of conduit vessels using high-resolution ultrasound. This dissertation is comprised of two studies. The first examines whether Vitamin D supplementation can improve FMD in older adults within a time period (two weeks) associated with peak increases in plasma Vitamin D concentrations after a single-dose supplementation. The second examines the effect of Vitamin D supplementation in people with Rheumatoid Arthritis (RA). The reason for looking at an RA population is that CVD is the leading cause of early mortality in people with RA. In the first study 29 Post-Menopausal Women received either 100,000 IU of Vitamin D3 or a Placebo. Their FMD was measured at baseline and 2 weeks after supplementation. After 2 weeks there was a significant increase in FMD in the Vitamin D group (6.19 + 4.87 % to 10.69 + 5.18 %) as compared to the Placebo group (p=.03). In the second study, 11 older adults with RA were given 100,000 IU of Vitamin D or a Placebo. At baseline and one month later their FMD was examined as well as plasma concentrations of Vitamin D and tumor necrosis factor-alpha; (TNF-alpha;). They also filled out a Quality of Life Questionnaire and underwent a submaximal exercise test on the treadmill for estimation of maximum oxygen uptake (VO2max). There was no significant change in FMD in Vitamin D group as compared to the Placebo group (p=.721). Additionally, there was no significant improvement in either plasma Vitamin D or TNF-alpha; in the Vitamin D group. There was however a significant improvement in predicted VO2max from the submaximal exercise test in the group receiving Vitamin D (p=.003). The results of these studies suggest that a single 100,000 IU dose of Vitamin D can enhance FMD within two week in older adults, but that a similar dose may not be sufficient to increase FMD or plasma Vitamin D levels in older adults with RA. A more aggressive supplementation regimen may be required in this patient population. / Dissertation/Thesis / Ph.D. Exercise and Wellness 2012

abstract: Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 &mu;M) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 &mu;M). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia. / Dissertation/Thesis / M.S. Nutrition 2012

Background: Coronary Artery Bypass Grafting (CABG) surgery is one of the most commonly performed surgical procedures to improve the symptoms of coronary artery disease. The Long Saphenous Vein (LSV) is typically used as a graft to bypass the blocked coronary arteries. The traditional way of harvesting the LSV is to make a long skin incision in the patient's leg. This technique has a high rate of incidence of wound complications and postoperative pain and poorer patient satisfaction. Endoscopic Vein Harvesting (EVH) techniques, introduced more than a decade ago, reduce these complications and improve quality of life. Findings regarding the safety and efficacy of EVH techniques and the quality of the vessel harvested by this technique are contradictory. Adoption of EVH techniques is still inconsistent globally and it is not completely accepted by all cardiac centres. Many studies are available in the literature measuring either histological outcome or clinical outcome in relation to different harvesting techniques. However, there remains no definitive randomised data available directly correlating harvesting-induced vein damage with clinical outcome. The aim of this Vein Integrity and Clinical Outcome (VICO) randomised trial was designed to assess the direct relationship between the histological damage caused during different methods of vein harvesting and clinical outcome post coronary artery bypass surgery. Methods: 100 patients were randomised in each group: Group 1 consists of closed tunnel CO2 endoscopic vein harvesting (EVH) (CT-EVH) and Group 2 consists of open tunnel CO2 EVH (OT-EVH) with the control Group 3 consists of standard open vein harvesting (OVH) with a total of 300 patients in this study. All the veins were harvested by an experienced practitioner who has performed &gt;2000 OVH and &gt;250 EVH. 1cm x 3 segments from three different parts of the vein were obtained for all patients (n=900). The histological levels of damage (endothelial and muscular layers) of the harvested vein and post clinical outcome for Major Adverse Cardiac Events (MACE) were measured using validated measuring tools. Health economic (cost effectiveness, EQ-5D) and health-related quality of life (SF-36) data were also recorded to assess the impact of these surgical techniques. Results: The level of endothelial disruption was greatest in the OT-EVH group in the proximal, distal and random samples (all p < 0.001). Internal muscle migration was greatest in OT-EVH compared to the other groups for proximal, distal and random samples (all p < 0.001). Smooth muscle circular layer detachment was observed on a much greater scale in the endoscopic groups compared to OVH in proximal (p=0.008), distal (p < 0.001) and random (p=0.001). Smooth muscle longitudinal layer detachment was consistent between groups in proximal (p=0.113) and distal (p=0.380) samples but was greater in endoscopic groups compared to OVH (p=0.012). Secondary clinical outcomes demonstrated no significant differences in composite MACE scores at 3, 6, 12, 18 and 24 months. The quality adjusted life in years (QALYs) gain per patient was: 0.11 (p < 0.001) for closed tunnel CO2 EVH and 0.07 (p=0.003) for open tunnel CO2 EVH compared with open vein harvesting. The likelihood of being cost-effective, at a pre-defined threshold of £20,000 per QALYs gained was: 75% for closed tunnel EVH, 19% for open tunnel EVH and 6% for open vein harvesting. Conclusion: In this study, open vein harvesting was associated with better preservation of vein layers in non-distended proximal samples than endoscopic vein harvesting. Both EVH groups displayed some degree of histological damage; OT-EVH was associated with more endothelial disruption. Clinical outcomes suggest that histological findings do not directly contribute to MACE outcomes. Gains in health status were observed and cost-effectiveness was better with CT-EVH compared with the other two surgical techniques. These results suggest that EVH can be utilised safely, but with careful selection of patients.

Made available in DSpace on 2014-06-11T19:25:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-31Bitstream added on 2014-06-13T20:53:03Z : No. of bitstreams: 1 freschi_l_me_botfm.pdf: 749128 bytes, checksum: 75984be6da9edf1d52a38b056eecc519 (MD5) / Universidade Estadual Paulista (UNESP) / A doença arterial coronariana (DAC) é uma das principais causas de óbito e de perda de qualidade de vida ao longo do tempo. Seu tratamento pode ser clínico ou por meio de técnicas como a angioplastia percutânea ou a revascularização cirúrgica do miocárdio. Multidimensional, a DAC exerce fortes impactos físicos, emocionais e sociais. Por isso, além das avaliações clínicas, são indispensáveis as informações sobre a qualidade de vida e funcionalidade dos pacientes para uma análise mais precisa de suas condições após o tratamento. O objetivo deste estudo foi avaliar a percepção da qualidade de vida e a funcionalidade em pacientes com DAC nos momentos antes da revascularização cirúrgica ou da angioplastia, na alta hospitalar e 60 dias após a intervenção. Foram avaliados 90 pacientes divididos em grupos por procedimento. Utilizou-se uma ficha com perfil demográfico, questionário genérico de avaliação da qualidade de vida “The Medical Study 36-item Short-Form Health Survey” (SF-36) e escala de “Medida de Independência Funcional” (MIF). Observou-se, no perfil demográfico, a predominância do gênero masculino (58,9%), escolaridade com o ensino fundamental incompleto (64,4%) e índice de massa corporal (IMC) acima do ideal (37,8% sobrepeso e 25,6% obesidade). O grupo de angioplastia apresentou os melhores escores de qualidade de vida antes do procedimento nos domínios “aspectos físicos”, “dor”, “vitalidade”, “aspectos sociais” e na questão de avaliação da saúde anterior. Na alta isso se manteve com o acréscimo do domínio “capacidade funcional”. No momento 60 dias após o procedimento, a angioplastia obteve melhores escores em “aspectos físicos” e “aspectos sociais”. Na comparação entre os momentos, os domínios “capacidade funcional” e “dor” pioraram na alta para o grupo cirurgia, e melhoraram após 60 dias... / Coronary artery disease (CAD) is a leading cause of death and loss of quality of life over time. The treatment is clinical in early stages of disease or the technique is percutaneous angioplasty or coronary artery bypass grafting. The DAC is a multidimensional disease, which has strong physical, emotional and social impacts. Besides to clinical assessments, information about the quality of life and functionality of patients are essential for a more precise analysis of their condition after treatment. The aim of this study was to evaluate the perceived quality of life and functionality in patients with CAD in the moments before surgical revascularization or angioplasty, at discharge and 60 days after the intervention. We evaluated 90 patients divided into groups by procedure. We used a form with demographic profile, generic questionnaire for assessing quality of life The Medical Study 36-item Short-Form Health Survey (SF-36) and scale of Functional Independence Measure (FIM). It was observed in the demographic, the predominance of males (58.9%), schooling and incomplete primary education (64.4%) and body mass index (BMI) above the ideal (37.8% overweight and 25.6% obese). The angioplasty group had the best scores of quality of life before the procedure in the domains physical aspects, pain, vitality and social aspects and the issue of evaluation of previous health. These results remained at hospital discharge with the addition of domain functional capacity. At present 60 days after the procedure, angioplasty had higher scores in physical aspects and social aspects. Comparing the times, the domains physical functioning and pain got worse at the group of discharge for surgery and improved after 60 days for both groups. In the domains general health and vitality, both groups improved in the third stage of evaluation. Angioplasty only group showed improvement... (Complete abstract click electronic access below)