peripheral arterial disease (PAD), a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy on the ability of plasma, from patients undergoing PTA, to stimulate SMCs in vitro. We aimed to investigate the effect of combination treatment on levels of circulating adhesion molecules and factors which mediate SMC proliferation in experimental models. We also sought to demonstrate any association between changes in measured markers and the development of restenosis or vascular events. Methods Fifty patients were randomised to receive clopidogrel or placebo, for thirty days, in addition to their daily 75mg aspirin. To measure proliferative capacity, diluted plasma was incubated with 24h-growth-arrested rat vascular SMCs, and Extracellular-regulated-kinase (ERK)1/2 activation was analysed by Western blotting at baseline, 1-hour pre-PTA, and at 1-hour, 24-hours and 30-days post-PTA. Plasma platelet-derived growth factor (PDGF-BB), soluble (s)E-selectin, sICAM-1 (intracellular adhesion molecule-1) and von Willebrand factor (vWF) were measured by ELISA (Enzyme-linked immunosorbent assay), at the same time-points. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and 1-hour post-PTA. Patients’ notes and all investigations were reviewed for 2 years post-PTA to record restenosis or vascular events. Results Samples were available for all 50 patients at baseline, 1-hour pre-PTA and 1-hour post-PTA timepoints. In this cohort ERK1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups. Those who developed a symptomatic restenosis had a significantly higher level of SMC activation at the 1-hour post-PTA time-point. There was a statistically significant decrease in PDGF-BB, and increase in vWF, following loading with clopidogrel. sICAM-1 levels significantly decreased in the aspirin/placebo group following PTA. ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel therapy post-PTA. Conclusions This is the first study to show in-vitro ERK1/2 activation (a marker of SMC proliferation) increases post-PTA. Patients developing a symptomatic restenosis had a significantly higher level of SMC activation at the 1-hour post-PTA time-point. Clopidogrel therapy had no significant effect on ERK1/2 activation, although it did reduce PDGF-BB in the larger cohort of patients. Further work is required to evaluate potential therapeutic treatments which may reduce peripheral PTA-induced smooth muscle cell activation.

by Cheng Sau-kwan. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 98-106). / LIST OF TABLES / LIST OF FIGURES / ACKNOWLEDGEMENTS / ABSTRACT --- p.1 / Chapter CHAPTER ONE --- p.3 / Chapter 1.1 --- Introduction --- p.3 / Chapter 1.1.1 --- Sources of homocysteine and origins of deficiency or excess in the human body --- p.3 / Chapter 1.1.2 --- Homocysteine metabolism --- p.4 / Chapter 1.2 --- Causes of and clinical syndromes in homocysteinaemia --- p.12 / Chapter 1.2.1 --- Deficiency of cystathionine β-synthase --- p.12 / Chapter 1.2.1.1a --- Homozygous homocysteinaemia --- p.13 / Chapter 1.2.1.1b --- Heterozygous hyperhomocysteinaemia --- p.17 / Chapter 1.2.2 --- "Deficiency of 5, 10 methylenetetrahydrofolate reductase" --- p.20 / Chapter 1.2.3 --- Defects of cobalamin synthesis --- p.21 / Chapter 1.3 --- Standardised oral methionine load test --- p.23 / Chapter 1.4 --- Treatment and prospects for homocysteinaemia --- p.25 / Chapter 1.4.1 --- Homozygous homocysteinaemia --- p.25 / Chapter 1.4.2 --- Heterozygous homocysteinaemia --- p.27 / Chapter 1.5 --- Pathogenesis of vascular disease in homocystinuria --- p.28 / Chapter 1.6 --- Aim of the study --- p.30 / Chapter CHAPTER TWO --- p.31 / Chapter 2.1 --- Patient's criteria --- p.31 / Chapter 2.2 --- Control' s criteria --- p.32 / Chapter 2.3 --- Exclusion criteria for patients and controls --- p.32 / Chapter 2.4 --- The methionine loading test and additional investigations carried out --- p.33 / Chapter 2.5 --- Statistics used for data analyses --- p.35 / Chapter CHAPTER THREE --- p.38 / Chapter 3.1 --- Sample collection --- p.38 / Chapter 3.2 --- Analytical methods for homocysteine determination --- p.39 / Chapter 3.2.1 --- Cyanide nitroprusside test --- p.39 / Chapter 3.2.2 --- Radioenzymic Assays --- p.40 / Chapter 3.2.3 --- Gas chromatography - Mass spectrometry --- p.41 / Chapter 3.2.4 --- HPLC with Electrochemical detection --- p.42 / Chapter 3.2.5 --- HPLC and postcolumn derivatization --- p.43 / Chapter 3.2.6 --- "Precolumn derivatization, HPLC and fluorescence detection" --- p.44 / Chapter 3.3 --- The method used in this study --- p.47 / Chapter 3.3.1 --- Materials --- p.48 / Chapter 3.3.2 --- Reagents --- p.49 / Chapter 3.3.3 --- Instrumentation --- p.49 / Chapter 3.3.4 --- Sample preparation --- p.50 / Chapter 3.3.4.1 --- Reduction --- p.50 / Chapter 3.3.4.2 --- Derivatization --- p.50 / Chapter 3.3.5 --- Chromatographic conditions --- p.51 / Chapter 3.3.6 --- Standard preparation --- p.51 / Chapter 3.4 --- Method Optimization --- p.52 / Chapter 3.4.1 --- Choice of reducing agent --- p.52 / Chapter 3.4.1.1 --- Dithiotreitol (DTT) --- p.52 / Chapter 3.4.1.2 --- Sodium borohydride --- p.53 / Chapter 3.4.2 --- Choice of precipitating reagent --- p.56 / Chapter 3.4.3 --- Optimization of chromatographic conditions --- p.56 / Chapter 3.4.3.1 --- "Flow rate, temperature and organic composition of mobile phase" --- p.56 / Chapter 3.4.3.2 --- pH of the mobile phase --- p.59 / Chapter 3.4.4 --- Confirmation of homocysteine peak --- p.60 / Chapter 3.5 --- Analysis of results --- p.60 / Chapter 3.6 --- Method validation --- p.60 / Chapter 3.6.1 --- Linearity --- p.60 / Chapter 3.6.2 --- Precision --- p.63 / Chapter 3.6.3 --- Recovery --- p.64 / Chapter CHAPTER FOUR --- RESULTS --- p.66 / Chapter 4.1 --- The pre- and post-methionine loading plasma homocysteine concentrations in patients and controls --- p.66 / Chapter 4.2 --- The frequency distributions of hyperhomocysteinaemia in patients and controls --- p.68 / Chapter 4.2.1 --- The distributions of homocysteinaemia in patients and controls --- p.68 / Chapter 4.2.2 --- The frequency distributions of fasting hyper-homocysteinaemia in patients and controls --- p.68 / Chapter 4.2.3 --- The frequency distributions of post-methionine hyperhomocysteinaemia in patients and controls --- p.73 / Chapter 4.2.4 --- The frequency distributions of the abnormal methionine tolerance in patients and controls --- p.75 / Chapter 4.3 --- "The frequency distributions of hypertension and hyperlipidaemia in controls and, including smoking,in patients without and with hyperhomocysteinaemia" --- p.77 / Chapter 4.3.1 --- The frequency distribution of hypertension and hyperlipidaemia in patients and controls --- p.77 / Chapter 4.3.2 --- "The frequency distributions of hyper-lipidaemia, hypertension, smoking and gender in patients with vascular disease with and without hyperhomocysteinaemia" --- p.79 / Chapter 4.4 --- "The comparison of the age, haematological and biochemical indices and the blood pressure between the patients and controls" --- p.81 / Chapter 4.4.1 --- The comparison of the patients' age at presentation and plasma lipids following recovery from the acute episode with those in controls at the time of methionine loading --- p.81 / Chapter 4.4.2 --- The comparison of the age at presentation and the plasma lipids in patients with and without hyperhomocysteinaemia --- p.83 / Chapter 4.4.3 --- "The comparison of the B12, serum folate and RBC folate in patients and controls at the time of presentation" --- p.84 / Chapter 4.4.4 --- "The comparison of the B12, serum folate and RBC folate levels in patients with and without hyperhomocysteinaemia and in controls" --- p.85 / Chapter CHAPTER FIVE --- DISCUSSION --- p.87 / REFERENCES --- p.98

Access to abstract permanently restricted to Ball State community only. / Access to thesis permanently restricted to Ball State community only. / School of Physical Education, Sport, and Exercise Science

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (M.D.)--Aberdeen University, 2008. / With: Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state / P. Collins ... et al. Platelets. 2006: 17(5), 311-317. With: A preliminary study on the effects of exercising to a maximum walking distance on platelet and endothelial function in patients with intermittent claudication / P. Collins ... et. Eur. J. Vasc. Endovasc. Surg. 2006: 31, 266-273. Includes bibliographical references.

Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.S.)--Springfield College, 2005. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Springfield College, 2005. / Includes bibliographical references.

The work presented includes over thirty peer reviewed published manuscripts based on studies undertaken during my surgical career. As Principal Investigator, I led the study conception/design/data acquisition/analysis/interpretation and was involved with writing the final drafts of all manuscripts prior to their formal submission to high impact factor peer-reviewed specialist journals. The thesis is divided into subsections reflecting my development and different interests within surgery. The subsections start with my learning basic research principles, moving onto clinical problem solving in general surgical dilemmas, followed by a collection of papers in my subspecialty of vascular surgery. The work culminates with a group of papers focused on aneurysmal disease, specifically, abdominal aortic aneurysms (AAA), the clinical impact of which has had a bearing on the introduction of a National AAA Screening Program in Wales in 2013. I conclude these sections with a collection of papers that reflect my long term commitment to surgical training both at regional level (as Secretary and Deputy Chairman to the Higher Surgical Training Committee and Chairman of the Basic Surgical Training Committee) and national level including my involvement with the Four Royal Colleges of Surgeons for the Intercollegiate Examinations in General Surgery. This examination is undertaken at completion of junior surgical training and used to confirm a doctor's competence for safe independent practice as a consultant. In conclusion, over forty years of academic research during my career as a vascular surgeon has provided unique insight into the pathophysiology, treatment and ultimately prevention of artherosclerotic disease. These findings have improved health policies in Wales and significantly reduced patient morbidity and mortality.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.