Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved.

Thesis (M.Res.(Med.))--University of Hong Kong, 2007.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph.D.)--Baylor University, 2008. / In abstract "CD14highCD16+" the "high" is superscript. Includes bibliographical references (p. 360-379).

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008.

Introdução: A prolactina (PRL) exerce efeitos imunoestimulatórios in vitro e in vivo, porém a literatura é controversa quanto ao papel deste hormônio na atividade do Lúpus Eritematoso Sistêmico (LES). A macroprolactina possui menor atividade biológica in vivo e poderia explicar os resultados díspares. Objetivos: avaliar a prevalência de hiperprolactinemia e macroprolactinemia em pacientes lúpicas; analisar a correlação entre a atividade do LES e PRL, e interferência da macroprolactina nesta associação. Casuística e Métodos: Em 73 mulheres com LES ativo foi dosada a PRL pelo Immulite 2000®, e a macroprolactina pelo método do Polietilenoglicol (momento 1); em 62 destas pacientes foi colhida uma segunda amostra com a menor atividade do LES ao longo do tratamento (momento 2). Os controles foram 29 mulheres hígidas no menacme (grupo C) e 34 gestantes no terceiro trimestre (grupo G). Resultados: Houve 15 casos (20,55%) de hiperprolactinemia nas lúpicas, e nenhum entre as mulheres hígidas (p = 0,005). Todas as gestantes apresentaram hiperprolactinemia. A concentração de PRL foi maior (Med = 11,70 ng/ml) (p = 0,01) no LES do que no grupo C (Med = 8,81ng/ml), e correlacionou-se com a atividade da doença pelo SLEDAI (r = 0,41; p = 0,0003) no momento 1. No LES muito ativo os níveis de PRL foram maiores do que na doença inativa (Med = 17,10 ng/ml vs. Med = 8,36 ng/ml) (p< 0,01), e moderadamente ativa (Med = 7,75 ng/ml) (p < 0,05). Dentre as lúpicas hiperprolactinêmicas, 04 casos (26,7%) foram devidos à macroprolactina, e nas gestantes, 02 casos (5,9%). O LES foi tão ativo na macroprolactinemia quanto nos casos pela forma monomérica, porém a correlação entre PRL e SLEDAI foi maior para a PRL livre (r = 0,44; p = 0,0001). O tratamento das pacientes lúpicas hiperprolactinêmicas resultou em diminuição da concentração de PRL (Me momento 1 = 56,71 ± 43,87 ng/ml vs. Me momento 2 = 18,68 ± 24,20 ng/ml) (p = 0,015). Conclusões: pacientes lúpicas apresentam hiperprolactinemia mais frequentemente do que mulheres hígidas, e a PRL correlaciona-se com a atividade do LES. A macroprolactinemia não é marcador de doença inativa/pouco ativa. / Introduction: Prolactin (PRL) is a hormone with widespread influences in the cells of the immune system, which have been demonstrated by several in vitro and in vivo studies. However, the role of this hormone in the pathogenesis of Systemic Lupus Erythematosus (SLE) is controversial within the medical literature. The potentially lower biological activity of macroprolactin could explain the disparity of the results. Methods: PRL levels were determined by chemo luminescence method (Immulite 2000®) in 73 women with active SLE (group L), while the screening for macroprolactinemia was determined by the polyethylene glycol precipitation method (first moment). Sixty two of these patients had their PRL levels determined in a second occasion, when the disease was inactive or with the lowest activity observed after treatment (second moment). The control groups were 29 healthy women (group C) and 34 third-trimester healthy pregnant (group P). The levels of PRL were correlated with the SLE Disease Activity Index (SLEDAI). Results: In the study group there were 15 (20.55%) cases of hyperprolactinemia, while in the group C there were none (p = 0,005). All pregnant women presented hyperprolactinemia. Prolactin levels were higher in group L (Med = 11,70 ng/ml) then in group C (Med = 8,81ng/ml) (p = 0,01) and correlated with the SLEDAI in the first moment (r = 0,41; p = 0,0003). We also detected that PRL levels were higher at highly active SLE (SLEDAI ¡Ý 11) than when the disease was inactive (SLEDAI = 0) (Med = 17,10 ng/ml vs. Med = 8,36 ng/ml) (p< 0,01) or moderately active SLE (6 ¡Ü SLEDAI ¡Ü 10) (Med = 7,75 ng/ml) (p<0,05). In the 15 patients of group L with hyperprolactinemia, there were 04 cases of macroprolactinemia (26.7%), while 02 subjects in group P presented it (5.9%). SLE was as active in the patients with hyperprolactinemia caused by the monomeric form of the hormone, as in the ones with macroprolactinemia. The correlation of the PRL levels and the SLEDAI was, nevertheless, stronger for free PRL (r = 0,44; p = 0,0001). The SLE treatment in the hyperprolactinemic patients reduced PRL levels from 56,71 ng/ml (sd = 43,87) to 18,68 ng/ml (± 24,20) (p = 0,015). Discussion: the frequency of hyperprolactinemia is higher in SLE than in the general population, and the levels of PRL correlate with the activity of the disease. Macroprolactin is also associated to active SLE.