Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1963. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

OBJECTIVES: The association between bicuspid aortic valves and aortic aneurysms has been well documented. In order to better understand this association, this study sought to accomplish two goals. The first was to determine if there was any correlation between specific bicuspid aortic valve phenotypes and aortic aneurysms. The second goal was to determine if the association between bicuspid aortic valve disease and aortic aneurysms has a genetic or hemodynamic cause. METHODS: For the non-genetic portion of the study, we used echocardiogram and surgical records to classify the phenotypes of the aortic valve and the aorta of 434 patients. We then evaluated the correlation between valve morphotype and aortic aneurysm phenotype. For the genetic portion, we used a genome wide association study on 452 patients to find genes that could potentially be responsible for aortic aneurysms. These were then compared with genes suspected of causing bicuspid aortic valve to determine if there is a common genetic link between the two disorders. RESULTS: We observed a significant association between bicuspid aortic valve and aortic aneurysms; however we did not find any significant association between the different bicuspid aortic valve phenotypes and aortic aneurysm phenotypes. For the genome wide association study, we identified genes that could potentially be responsible for causing aortic aneurysms; however, none of the suspected markers were considered statistically significant. Also none of the identified genes matched to the genes suspected of causing bicuspid aortic valve. CONCLUSION: While the results were not as expected, the study provided us with information to better understand the relationship between bicuspid aortic valves and aortic aneurysms. According to the results of the current study, patients with bicuspid aortic valve are more likely to develop an aortic aneurysm but specific phenotype has no effect on where the aneurysm occurs in the aorta. The increased frequency of aortic aneurysms in bicuspid valve patients is most probably due to a combination of altered hemodynamics and genetic effects. In order for this information to be useful in the clinical setting, the methods of this study should be repeated in a larger cohort to make sure the results are accurate.

Thesis (doctoral)--Universitetet i Lund.

AAA disease remains a common and life threatening condition, predominantly affecting men of retirement age. Whilst clinical studies have done much to predict the course of this disease, understanding the pathogenesis has been complicated by both a multi-factorial aetiology as well as several poorly defined stages to the disease (formation, growth and rupture). Evidence points to a considerable inheritable component to this condition, but as yet, associations with identified genetic variants are few and weak. This thesis describes the current understanding of the molecular mechanisms behind AAA pathogenesis, concentrating on aneurysm formation and growth. A meta-analysis of published candidate gene studies identified three genes with small but significant effects on risk of developing AAA (ACE, MTHFR and MMP9) and none with a significant effect on AAA growth. Further examination of five genes connected the Renin-Angiotensin System, using three distinct case control series, demonstrated the strongest reported association to date with AAA disease risk, with AGTR1+1166A>C. (OR 1.55 [1.30-1.83, p=5x10-7]). An interest in the role of the TGF-β pathway in AAA formation and growth has developed from the recent illumination of the mechanism behind aneurysm aetiology in Marfan syndrome. Haplotype analysis was used to investigate five genes coding for TGF-β and its binding protein (LTBP). Variants in TGFB3 and LTBP4 were significantly associated with altered AAA growth. The importance of inflammatory process was also supported by observations made in a very large longitudinal data set of AAA growth. Anti-inflammatory drugs, together with anti-platelet drugs and drugs used in diabetes, were significantly associated with decreased AAA growth independent of confounding factors. In conclusion, this thesis demonstrates; a role for the RAS in AAA formation; TGF-β in AAA growth; and anti-inflammatory drugs as potentially disease modifying. In addition, observations have also been made concerning a two tier effect illuding to the nature AAA progression.

No description available.

No description available.

Abdominal aortic aneurysms are common and responsible for many deaths. They are treated increasingly by EndoVascular Aneurysm Repair (EVAR) rather than conventional surgery. Approximately 25% of EVAR patients require re-intervention to prevent aneurysm enlargement which can rupture despite previous repair. All EVAR patients undergo life-long surveillance for complications such as stent-graft migration or endoleak. Computed Tomography (CT) has been the ‘gold-standard’ for surveillance accounting for 65% of EVAR costs, and exposes patients to cumulative radiation and nephrotoxic contrast. Duplex Ultrasound Scanning (DUS) has been proposed as an alternative for surveillance with lesser cost and patient risk. However, clinical studies have reported varying results. The addition of microbubble contrast significantly improves endoleak detection rates, making it comparable with CT. The physical properties that affect endoleak detection with DUS have not been determined. It is also unknown specifically which endoleaks’ detection are improved by Contrast Enhanced Aortic Duplex UltraSound Scanning (CEADUSS). To investigate the physical properties of endoleaks, I constructed an EVAR phantom model with a simulated endoleak of variable velocity (fast/slow), position (near/far) and plane (anterior/lateral/posterior). Preliminary studies investigated the behavior of microbubble contrast in the phantom system, and then laboratory experiments tested subjects over 36 variable endoleaks using DUS and CEADUSS. These laboratory experiments were translated clinically with a pilot study of CEADUSS in 10 patients with endoleaks on CT not detected by DUS, undefined endoleak type or origin, or a sac enlargement with no endoleak present. My experiments reveal an insight into factors influencing ultrasound endoleak detection. With this knowledge, the use of these modalities for surveillance protocols can be increased, reducing current CT burden, radiation and nephrotoxic contrast exposure, and overall EVAR cost. Clinical assessment of an endoleak, specifically noting physical characteristics (plane, position and velocity) will improve detection and surveillance.