Self-management has emerged as an approach to enhance quality of care for patients suffering from long term conditions, and to control costs of health services. So far, however, the effects of this approach as adopted by the Saudi healthcare system in the early 1990s remain uncl…
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Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite successful ocular treatment, about 50% of patients succumb to metastatic dissemination, which occurs haematogenously and mainly affects the liver. On the basis of clinical, histopathological and gen…
Chronic lymphocytic leukaemia (CLL) is a lymphoid malignancy which despite advances in the treatment options available is still incurable. Characterised by the gradual accumulation of CD5+ B cells, the paradigm that this is due to failed apoptosis has been challenged and a signi…
I have explored the infection of human cells by the gammaretroviruses XMLV (xenotropic murine leukaemia virus) and FeLV (feline leukaemia virus). For XMLV the main aim was to assess the risks and consequences of contamination of human-mouse xenografts. For FeLV, the aim was to e…
Prostatic diseases are common; benign prostate hyperplasia (BPH) is almost ubiquitous in elderly men and 899,000 men were diagnosed with prostate cancer worldwide in 2008. The incidence of both is increasing and expected to continue to rise. Therefore, prostatic diseases represe…
Obesity is known to be associated with obstructive sleep apnoea (OSA) and Type 2 diabetes mellitus (T2DM). The effect of OSA in very severely obese individuals is not well documented. In this thesis, I compared the effect of OSA in South Asians and white Europeans, examined the …
ESBL prevalence is increasing globally and travellers visiting South Asia have high rates of acquisition of CTX-M-producing-E. coli (CTX-M-EC). A prospective observational cohort study of volunteers traveling from the UK to South Asia was undertaken to determine the mechanism of…
Tolerance of the semi-allogeneic fetus presents a significant challenge to the maternal immune system. The effect of pregnancy on maternal cellular immunity was established by assessing maternal effector and regulatory T-cell subsets during human pregnancy. This demonstrated tha…
In this thesis high intensity focused ultrasound (HIFU) is utilized for cancer treatment (thermal mode) and treatment of ischaemic stroke (mechanical mode). These two applications were investigated in vitro and in vivo models. MRI was utilized to monitor the lesions created by H…
Subclinical thyroid dysfunction (SCTD), characterised by abnormal serum thyrotrophin concentrations (TSH) with normal free thyroxine (FT\(_4\)), is regularly encountered in primary care. The clinical manifestations of SCTD are not well established, particularly in older individu…
Duchenne muscular dystrophy (DMD) is a muscle-wasting disease caused by the loss of sarcolemmal protein dystrophin. In DMD and the mouse model of the disease mdx, there is an increase in an associated protein, caveolin-3. In this study, mdx mice with deficiencies in caveolin-3 w…
The work in this thesis describes a series of studies utilising diverse data sources which were analysed using a number of regression methods (logistic, linear, Cox, Poisson), to address the factors associated with normal and abnormal pregnancy outcome. A series of maternal char…
Human African trypanosomiasis and leishmaniasis are caused by parasites belonging to the genera Trypanosoma and Leishmania, respectively. Significant numbers of people are affected by these diseases worldwide, which are fatal if untreated. Animals can also be infected, posing ag…
The purpose of this study was to investigate ROCK2 activation in squamous cell carcinogenesis and assess its co-operation with rasHa and fos oncogene activation together with loss of PTEN mediated AKT regulation. The analysis of ROCK deregulation with these genes in the MAP Kina…
Pancreatic cancer is common and aggressive: the main type is pancreatic ductal adenocarcinoma (PDAC). It is the fifth most common cause of cancer death in the UK with an overall five year survival of only 2-3%. Establishing the diagnosis of PDAC is important for optimal patient …
The platelet receptor CLEC-2 is the only known endogenous ligand for the transmembrane receptor podoplanin, which is expressed on lymphatic endothelial cells (LEC) as well as a number of other cell types. Both CLEC-2 and podoplanin are required for normal lymphangiogenesis as mo…
In this thesis I have explored different components of the pathogenesis of several related EBV associated cancers. In the first part of the thesis I focus on the microenvironment of two of these cancers, nasopharyngeal carcinoma (NPC) and diffuse large B cell lymphoma (DLBCL). O…
This thesis presents a qualitative study of genetic counselling. Using a combination of semi-structured interviews and conversation analysis, it focuses on the role, function and structure of genetic counselling and on its status as medical or counselling work. Semi-structured i…
Clostridium difficile, a Gram positive, anaerobic, spore-forming bacterium is the commonest cause of hospital acquired infection in the UK. The organism initiates infection through spore formation and attachment, germination in the gut and then the production of two potent cytot…