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