This thesis addresses aspects of hypothalamic, pituitary, ovarian and uterine function in post pubertal women following treatment for cancer in childhood. The effect of low dose cranial irradiation (18-24 Gray) on gonadal function was evaluated in long-term survivors of childhood leukaemia. Tracking of urine luteinising hormone (LH), oestrone and pregnandiol demonstrated reduced LH secretion throughout the cycle and particularly during the LH surge, short luteal phases and decreased oestrone production. These data indicate that treatment for childhood leukaemia results in a subtle ovulatory disorder in some patients, probably related to cranial irradiation. Women treated for childhood cancer, who have progressed spontaneously through puberty and have regular menstrual cycles, may still be at risk of an early menopause. Ovarian reserve was assessed in women with regular menstrual cycles and women with a history of regular cycles who were using the oral contraceptive pill (OCP), for contraception. They were investigated before and 24 hours after an injection of follicle stimulating hormone (FSH). Women with regular cycles had significantly higher basal FSH, and lower anti-Mullerian hormone levels, and reduced ovarian volume. Women on the OCP had a reduced inhibin B response to FSH and lower antral follicle counts. Therefore, both groups showed hormonal and biophysical evidence of partial loss of ovarian reserve. Radiotherapy to the abdomen carries a high risk of ovarian failure. The effect on the uterus is less well documented. Ovarian and uterine function were evaluated in women who had received total body irradiation in childhood (14.4 Gray). In women with ovarian failure, uterine function was evaluated before and after 3 months of physiological sex steroid replacement (pSSR). At baseline, uterine artery blood flow and thickening of the endometrial were not detectable. After 3 months of pSSR neither blood flow or endometrial thickness were different from controls. Uterine volume remained smaller, and there was a correlation with age at irradiation. Endometrial samples were obtained and the histology and histochemistry of the endometrium were normal compared with controls. Hormone replacement therapy and achieves physiological sex steroid concentrations improves uterine size, blood flow and endometrial development. For those young women that have ovarian failure there is no good evidence as to the optical method of pubertal induction and subsequent cyclical hormone replacement therapy. UK practice was evaluated by postal questionnaire sent to all British Endocrinologists who were members of the European Society for Paediatric Endocrinology.

This thesis examines the association between diet and PCa in Scottish men, based on the PCANDIET study: A population based case-control study of PCa in relation to inherited susceptibility and diet. Data on the habitual diets of 433 cases diagnosed with PCa and 483 controls were collected using a validated food frequency questionnaire. Significant odds ratios (Ors) (adjusted for energy intake, age, family history of PCa, Carstairs deprivation index, smoking and EI: BMR ratio) for highest intake versus lowest intake (reference) categories were observed for cholesterol (OR 1.57 95%CI, 1.04-2.37); red meat (OR 1.64, 95%CI 1.09-2.48); vegetables (OR 0.62, 95%CI 0.41-0.93); consumption of alcohol (OR 0.62, 95%CI 0.42-0.90), total alcohol (OR 0.66, 95%CI 0.44-0.99); wine (OR 0.38, 95%CI 0.19-0.74) and spirits (OR 0.48, 95%CI 0.29-0.79). Significant associations were also observed for protein (OR 2.34, 95%CI 1.13-4.87) and red meat (OR 3.74, 95%CI 1.70-8.15) within younger subjects, and for selenium (OR 0.61, 95%CI 0.37-0.99), vegetables (OR 0.60, 95%CI 0.36-0.99), wine (OR 0.21,95%CI 0.8-0.52) and spirits (OR 0.49, 95%CI 0.26-0.91) within older subjects. These results suggest that cholesterol and red meat are both associated with a 60% increase in PCa risk, whereas vegetables and alcohol are associated with a 40% reduction in PCa risk. The results also suggest that protein and red meat are associated with over a two-fold and three-fold increase in PCa risk respectively in younger men. Whereas, selenium and vegetables are associated with 40% reduction in PCa risk in older men, in addition to a further reduction in risk of PCa associated with wine and spirit is (80% and 50% respectively).

No description available.

Inpatient multidisciplinary care of patients with active rheumatoid arthritis has been shown to be clinically effective in a number of studies in both the UK and North America, but it is unfortunately expensive because of high fixed costs such as hospital overheads and ward running costs. Multidisciplinary care comprises several elements including bed rest, withdrawal from domestic pressures, medication, education and physical therapy, but the individual contribution of each element to the overall clinical benefit remains uncertain. Day care, by eliminating some of the high fixed costs and overheads yet preserving all of the clinical elements of inpatient care, could be a more efficient method of managing patients with active rheumatoid arthritis. The original work described in this thesis addresses this issue. A pilot study of day-patient versus inpatient care was performed on twenty patients. This confirmed the acceptability of day-patient care and the practicality of the trial design. It also provided some preliminary economic data which suggested that day care may be substantially cheaper (40%) than conventional inpatient care. The pilot study was not powered to address the question of whether clinical outcome of day-patient therapy was equivalent to inpatient care. A larger prospective randomised clinical and economic evaluation of 118 patients was therefore undertaken. The aim was to test the hypothesis that the clinical outcome of inpatient and day care management of patients with uncomplicated active rheumatoid arthritis is equivalent and that there is no difference in the use of resources. The study demonstrated that the day-patient and inpatient care are clinically equivalent for patients with active rheumatoid arthritis. The overall resource costs of day-patient care are slightly lower than those of inpatient care. Day care is associated with lower hospital costs but higher transport costs. Clinical benefit from either form of management is short lived. The background to this work and the implications of the results are discussed.

The major sources of infection for Legionnaire's Disease, identified by study of outbreaks, are hot water systems and cooling towers. However, most cases are not part of outbreaks and, for these, the source of infection is rarely traced. The principal aim of this study was to help understand the source of non-outbreak infection by examining the epidemiology of the disease in Scotland. Of the recognized cases which met the study case-definition, 366 were ill between 1978 to 1986 giving a mean annual incidence rate of 7.9 per million. The annual incidence varied in Scotland (range 3.1 to 20.2) and within health boards. Geographical variations were demonstrated by health board, by city and within cities, particularly for non-travel infection. For example, the cumulative incidence rate per million for non-travel, non-outbreak disease in Greater Glasgow Health Board (GGHB) was 130 compared to 45 for the whole of Scotland, and 11, 33 and 50 in Tayside, Lanarkshire and Lothian Health Boards respectively. Of 16 postcode sectors with a high incidence of disease in Scotland, 14 were in GGHB. In GGHB, the residence of non-travel, non-outbreakcases (but not of travel-related ones) was clustered in central areas. Previously unrecognised clustering was also found in other health boards. These variations were not fully explained by differences in the population's exposure to diagnostic tests, as indicated by the number of serology tests requested by Scottish hospitals; the diagnostic service and approach of bacteriology laboratories; and the approach of hospital consultants to the diagnosis of Legionnaires' Disease. Differences in host susceptibility, as reflected by socio-economic status and the incidence of other respiratory disease, were small and did not explain the variation. In the City of Glasgow, many cooling towers were not maintained in accord with recommendations and posed a theoretical risk of infection. The location of residence of non-travel cases was associated with the location of premises with cooling towers, the incidence of non-travel Legionnaires' Disease being more than three times higher in areas of Glasgow within 0.5 kilometres of a cooling tower than in areas more than one kilometre away. The best explanation for these observations is that cooling towers were a major source of non-travel, non-outbreak infection. Hence, for the investigation and prevention of such infection, the emphasis should be on cooling tower maintenance. Close surveillance of apparently sporadic disease is recommended as the basis for disease control and future research.

Epidemiology, clinical presentation, natural history, pathological features and treatment of cutaneous malignant melanoma have been studied in the British Columbia Cancer Agency [BCCA]. A retrospective review of 891 patients registered between 1972 and 1981 is presented. Age standardised incidence rates have increased significantly. Predominant primary sites were trunk for males and lower limb for females. Dominant growth patterns were superficial spreading [65%], nodular [25%], lentigo maligna [5%] and acral-lentiginous melanoma [2%]. Median primary tumor depth at presentation were 1.45mm for males and 1.10mm for females. No T 1 tumors were staged beyond the local area. Fifteen year survival was 55.5% for males and 70.3% for females. Multivariate analyses of prognostic factors in 556 clinical stage 1 patients showed that micrometer depth, pathological ulceration, primary site and type of initial surgery were principal prognostic factors. Elective lymph node dissections [ELND] were undertaken in 232 patients. Nodes examined after ELND were positive pathologically in 36 [16%] patients. Survival after ELND was compared with a concurrent group of patients not undergoing ELND and with other series. Multivariate analysis did not show ELND to be of independent significance. Survival after therapeutic LND was comparable with previous series. Adjuvant therapy with BCG and levamisole for 3 years was investigated in 76 patients from British Columbia as part of a National Cancer Institute of Canada Clinical Trials Group Study involving 543 patients. All patients were clinically disease-free after standard surgery for high risk primary or recurrent regional melanoma. Patients who received Levamisole alone experienced 30% fewer deaths than no immunotherapy control patients. Survival was worst in older patients in the control group and levamisole appeared to abolish the adverse prognostic significance of age.

No description available.

One hundred and twenty three patients who were awaiting angiography for the investigation of chest pain were contacted by post and invited to participate in the study. Subjects were required to keep a chest pain diary for 14 days, and complete 5 self-report questionnaires examining physical and psychological aspects of their pain. Of the total sample of 123 patients who proceeded to angiogram, 72 (58.5%) were subsequently found to have Coronary Artery Disease (CAD) and 51 (41.5%) were found to have Normal Coronary Arteries (NCA). Seventy-two patients agreed to take part, 48 with CAD and 24 with NCA. This represents a return rate of 66.7% for CAD patients and 47% for NCA patients. Comparison of the NCA and CAD cohorts using chi-squared and t-tests for independent samples revealed the main factors found to be significantly associated with a finding of NCA were : age (young), sex (female), non-elevated cholesterol, pain at rest, pain provoked by stress, wakening pain, relief by GTN after more than 5 minutes, and high levels of bodily awareness. Using these factors, a logistic regression was run. From this, factors which were found to be useful in discriminating between CAD and NAC patients were age, sex, somatic awareness and wakening pain. There was also found to be a lesser but consistent association with rest pain, anxiety and depression. These variables were found to correctly classify 85% of cases. The classification of cases differed between groups with 64% of NCA cases correctly classified, and 91.5% of CAD cases correctly classified. When the discriminatory power of this predictive equation was tested prospectively on a new sample of 74 patients (phase two) it was found to correctly predict 97.8% of the CAD cases and 58.3% of the NCA cases for an overall success rate of 89.5%. The implications of the results for the management of patients with chest pain and Normal Coronary Arteries are discussed.

In today's medicine, arguably the main objective is to provide the highest possible quality of medical care to patients. The provision of high-quality medical care is usually associated with the patients being monitored within medical establishments by specialist practitioners. However, there is a considerable number of medical conditions for which expert medical personnel is limited, or patients may be forced to be away from such experts for long periods of time. One of the most common cases where patients are forced to stay away from expert medical help for long periods of time is that of people suffering from spinal injury. Spinal injury affects tens of millions of people around the world, and has very severe consequences to patients; these include paralysis (of legs and, possibly, arms as well), loss of sensation, incontinence, etc. However, the medical centres around the world that can provide specialised care to such patients is very small, and they are concentrated in a very small number of areas around the globe. Therefore, providing efficient, quality care to patients suffering from spinal injury is a very important issue in the medical community. This observation has led us to the design and development of a Decision Support System that will act as a consultation and caring tool for such patients. The resulting system, called Dimitra-PRO, is based on probabilistic tools (more specifically, Bayesian Networks) to deliver a diagnosis about the possible conditions such patients may suffer from, given the symptoms they exhibit. Prior information is extracted from all possible sources of domain knowledge (literature, questioning experts and personal experience), and is modelled appropriately. In the context of this work, an important breakthrough in the applicability of Bayesian Networks (BNs) in real-world scenarios has also been made. So far, BNs have limited support for representing continuous random variables; if any are used, they are required to follow a Gaussian distribution in order to perform exact inference in a BN, otherwise discretisation is applied. In this thesis, we show that it is now possible to use any function that can be used as probability distribution function for nodes, without applying any kind of approximation, to perform exact inference in Bayesian Networks containing a random mixture of discrete and continuous nodes. BNs are now capable of modelling dependencies between discrete and continuous variables without the need to apply discretisation for continuous variables. By applying this paradigm in the case of Dimitra-PRO, it is experimentally demonstrated that the proposed method for representing continuous random variables in BNs outperforms discretisation of these nodes, thus enabling us to deliver a more accurate prognosis about the patients' condition-which, in turn, satisfies our demand for providing the highest possible quality of care to them.

No description available.