Thesis (M.S.)--University of Louisville, 2002. / Department of Pharmacology & Toxicology. Vita. "August 2002." Includes bibliographical references (leaves 26-29).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1974. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.D.)--University of Hong Kong, 1965. / Also available in print.

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Christopher J. McCarthy. Vita. Includes bibliographical references.

This thesis is composed of two studies. The principal aim of the first study, the Sites of Atheroma Study, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and plasminogen activator inhibitor - type I) were related to the angiographic site and severity of atherosclerosis in the arteries of the lower limb. The principal aim of the second study, the Prognostic Study of Intermittent Claudication, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and tissue plasminogen activator), were related to the future incidence of atherothrombotic events, and deterioration of peripheral arterial disease in subjects with intermittent claudication. The study samples in both studies consisted of men and women with ischaemic symptoms in the lower limb referred to the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. In the Sites of Atheroma Study, 192 patients referred for angiography were categorised by site and severity of peripheral atherosclerosis using the Bollinger angiographic scoring system. A clinical examination was conducted on each patient including the administration of a questionnaire and taking of a blood sample for the measurement of haemostatic factors. In the Prognostic Study, 607 patients with intermittent claudication who had had a comprehensive examination at baseline, including measurement of haemostatic factors, were followed up over six years to determine the incidence of fatal and non-fatal ischaemic heart disease and stroke and deterioration of peripheral arterial disease. Follow-up data were obtained from hospital records, general practitioners, self-administered questionnaires, the Information and Statistics division of the Common Services Agency and the Scottish National Health Service Central Registry. Results from the Sites of Atheroma Study indicated that 34 (17.7%) patients had predominantly aorto-iliac disease, 85 (44.3%) had femoro-popliteal disease and 73 (38.0%) had dual-site disease. There were no significant differences in the mean levels of the haemostatic factors between patients with disease affecting different sites. An independent relationship was found between nephelometric fibrinogen and between fibrin D-dimer and disease severity only in the femoro-popliteal arteries. On multiple regression, fibrinogen remained independently associated with disease severity in the femoro-popliteal arteries, when life-time smoking or current smoking were taken into account. There was no influence of current smoking on the association between fibrin D-dimer and disease severity but, on inclusion of life-time smoking, the association became non-significant. In the Prognostic Study of Intermittent Claudication, a total of 210 (34.6%) patients died during the six year follow-up period. Of these 90 (42.9%) died from ischaemic heart disease, 29 (13.8%) from stroke and 27 (12.9%) from other vascular causes, including cardiac arrhythmias and ruptured aneurysm. Ninety three (15.3%) patients had a non-fatal myocardial infarction and 79 (13.0%) had a fatal or non-fatal stroke. Forty five (7.4%) patients underwent investigations for peripheral arterial disease and 64 (10.5%) patients progressed to severe chronic leg ischaemia. A total of 203 (33.4%) patients did not have a vascular event or show any deterioration of limb ischaemia. Baseline median levels of plasma fibrinogen, fibrin D-dimer and von Willebrand Factor were significantly higher in patients who died from ischaemic heart disease compared to those who had no vascular events. Tissue plasminogen activator antigen levels were significantly elevated in patients who suffered a stroke. All the relationships between the haemostatic factors and vascular events became weaker and statistically non-significant in analysis adjusting for cardiovascular risk factors and baseline ischaemic heart disease. von Willebrand Factor levels were significantly raised in claudicants who developed severe chronic leg ischaemia (rest pain, ulceration and gangrene). In multivariate analyses adjusting for life-time smoking, fibrinogen became significantly associated with the risk of vascular intervention, and von Willebrand Factor was associated with the risk of severe chronic leg ischaemia. In conclusion, these results indicate that there may be a stronger relationship between chronic smoking and increased fibrin turnover than coagulation in symptomatic peripheral arterial disease. Increased coagulation and fibrinolytic activity may also contribute to thrombosis or progression of atherosclerosis in the coronary and cerebral arteries in claudicants. The effect that fibrinogen, fibrin D-dimer and other haemostatic factors may have on the progression of peripheral arterial disease was mostly independent of cigarette smoking.

Coronary heart disease (CHD) remains one of this country's leading cause of mortality. This study has concentrated on the development of a functional biscuit, which will reduce selected risk factors for heart disease, in particular elevated serum homocysteine. The developed biscuit contains vitamins Be, Bi 2, and folic acid, all of which have been shown to be important in homocysteine metabolism. There were a number of criteria that had to be met for the author to receive the full support of Burton's Foods: (1) The biscuit must remain commercially viable and be accepted by the consumer. (2) Enzymes should not be used in the preparation of the dough. (3) The jam could not be modified in any way. Without exception, these have been successfully achieved. Jammie Dodgers were selected as the control product for a number of reasons. They are one of the UK's best selling biscuits and are consumed by both children and adults. This makes the target number of consumers very large. In addition, the standard product is high in both fat and sugar, its modification into a health promoting biscuit was therefore technically challenging. The product resulting from this project is commercially viable; it is low in fat and sugar, contains the vitamins that will deliver the full RNI on consumption of just two biscuits daily, and is not significantly different to the control product. The product is also palatable. Clinical trials have demonstrated that following consumption of the product, serum homocysteine, an independent risk factor for coronary heart disease, has been significantly reduced. In addition, there appears to be a relationship with consumption of the modified biscuit and a fall in serum lipoprotein(a). It is possible to reduce selected mutable risk factors associated with heart disease, simply by the daily consumption of a product that is liked and consumed by a great number of people. As far as the author is aware, there has been no other development of this kind prior to this study, i.e. a biscuit that will reduce the risk of coronary heart disease by lowering serum homocysteine. This biscuit is therefore the first of its kind.

Low-fat, high-carbohydrate diets are recommended by various scientific bodies for the prevention of coronary heart disease. However, these diets increase postprandial lipaemia and so their net benefit for coronary heart disease risk has been the subject of vigorous debate. Exaggerated postprandial lipaemia has been implicated in the development of atherosclerosis. Previous research suggests that physical exercise improves triacylglycerol metabolic capacity. The present thesis investigated whether exercise, when simultaneously adopted with a high-carbohydrate diet, could prevent the augmentation of postprandial lipaemia observed with this dietary change.

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