Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 3 uppsatser.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, 2005. / Bibliyografya var.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, 2006. / Bibliyografya var.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (Ph.D.)--Drexel University, 2008. / Includes abstract and vita. Includes bibliographical references (leaves 102-122).

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

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

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.

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.