Total hip and knee replacement are increasingly common elective surgical procedures in the UK, performed primarily for the relief of osteoarthritis in the majority of cases. Research has shown that individual psychological variables play a part in determining outcomes following these procedures. The literature review systematically examined the role played by patient expectations in outcomes following total hip and knee replacement. In addition, it examined the way in which both expectations and outcomes were conceptualised and measured in the literature. Finally, it sought to determine the theoretical underpinnings of expectations research. With the exception of one study, results showed that expectations do influence outcome. Weaknesses were identified in respect to the inconsistent approach used to measure both outcomes and expectations. A lack of theoretical underpinning of expectations was noted. Expectations may have implications for informing surgical selection and prognosis. Suggestions for future research in this area were made. The empirical study examined the role that hope might play in determining outcomes following primary total knee replacement for osteoarthritis. Much previous research in this area has been conducted from a deficit model of health. In contrast, hope is a positive psychological construct, which identifies and builds on individuals’ strengths. Pre-operative hope did not, as expected, directly influence outcome after surgery. It was found however, to be a significant unique predictor of pre-operative psychological morbidity and physical function, accounting for 9% and 10% of variance respectively. Both depression and function have been shown to influence outcome in this population. It could be argued that the pre-operative period is when the impact of osteoarthritis is most significant. Hope may be an important factor in delivering effective condition management at this time. Suggestions for future research and possible interventions based on these findings were advanced.

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The basis of the work in this thesis is an assessment of renal preservation techniques. The first chapter comprises a review of the pathophysiology of ischaemic injury and the role of hypothermic preservation. In the second chapter a review of the various preservation solutions in use is presented as well as the constituents of preservation solutions. The role of the organ flush is then presented, comparing warm and cold flush. The effect of viscosity and pressure is then examined followed by a review of hypothermic and normothermic preservation methods. The five main experimental chapters are then presented as a series of papers. The first of these aimed to assess the rate of organ cooling during back-table flush using different preservation solutions. In this paper, porcine kidneys were flushed with UW or Soltran solution, and the perfusion rate and cooling of the kidney was assessed. The second paper follows on comparing organ cooling using either a cold flush or a warm flush followed by a cold flush to compare flush rates and cooling times. The third paper assesses different flush techniques using a novel normothermic preservation solution, AQIX® RS-I, to assess the optimal flush conditions and functional outcomes. The fourth paper compares functional results of AQIX with the more commonly used cold flush solutions, Soltran and University of Wisconsin solution. The final experiment assesses the effectivness of complete normothermic preservation using AQIX® RS-I. An isolated organ perfusion system using cardiopulmonary bypass equipment was used for normothermic preservation and as a surrogate for transplantation. Porcine kidneys were used throughout all experiments as large animal models best reflect the human condition.

Platelets have been implicated in the pathogenesis and progression of atherosclerosis in patients with peripheral arterial disease. These patients have been shown to have increased platelet activation as assessed by flow cytometry. P-selectin expression and fibrinogen binding as well as increased platelet aggregation. Platelet activation is also believed to play an important role in the pathogenesis of arterial thrombosis and related acute myocardial infarction. Platelet activity is increased in patients with acute coronary syndromes and in those with ST-segment elevation MI. Biomarkers like C-reactive protein (CRP), Interluekin-6 (IL-6), N Terminal –pro-B type Natriuretic Peptide (NT-pro-BNP) have been shown to be risk assessment tools in non-cardiac vascular surgical patients. This research study was prospectively conducted to see if platelet activation markers, aggregation tests and biomarkers mentioned above had any relationship to post-operative myocardial ischaemic events detected by Troponin-I elevation with or without electrocardiogram/ Holter detected ischaemic changes. 136 patients due to undergo repair for abdominal aortic aneurysm or lower extremity revascularisation for severe limb ischaemia were recruited for the study.

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The aims of this study are to assess whether the introduction of a rigorous quality control method could produce a sustained reduction in the intraoperative stroke rate in this unit and whether it was feasible and practical to implement such a programme. The second part of this study will assess the incidence of sustained embolisation in the early post-operative period and investigate whether the antiplatelet agent Dextran 40 can help stop this embolisation, potentially preventing carotid artery thrombosis.;A prospective audit of all patients undergoing carotid endarterectomy was performed. The ability to monitor intraoperatively with TCD and perform completion angioscopy was assessed, as was the impact that these quality control techniques had on influencing the surgery. Patients were monitored postoperatively with TCD and any patient who developed sustained embolisation was commenced on an infusion of Dextran 40.;91% had continuous intraoperative TCD monitoring and 94% underwent successful completion angioscopy, a technical error was identified in 5% of angioscopic assessments. The intraoperative stroke rate was 0% during this study. Postoperative monitoring revealed that 5% of patients develop significant embolisation following CEA, Dextran 40 appeared to stop this embolisation. The overall 30-day stroke or death rate following CEA has fallen from 6% prior to 1992 to 2.2% in 1998.;It is possible to implement a quality control programme for CEA and this has been associated with a fall in the overall 30-day death and any stroke rate.

Critical to successful islet transplantation is the procurement of a high quality donor pancreas, maintenance of islet viability during pancreatic preservation and isolation of a high yield of viable and functioning islets. However, islet isolation exposes cells to considerable enzymatic and mechnical stressors resulting in the loss of tissue architecture, and such an environment can result in cell death by apoptosis and necrosis. To date it has not been possible to reliably predict the success of subsequent islet isolation by testing the donor pancreas, and many pancreata complete the time consuming and costly process only to result in a poor islet yield. It would be a significant clinical and financial advantage to be able to assess the suitability of the donor pancreas prior to islet isolation.;This thesis used a novel method of assessing donor pancreatic adenosine nucleotide concentrations throughout the isolation process and correlated these to conventional measures of islet yield, viability, function and pancreatic apoptosis. Pre-clinical rodent and porcine models were used to determine the effect of conventional and modified methods of pancreatic preservation using various preservation solutions. Finally an assessment of a small number of human donor pancreata was made using the new technique prior to clinical islet isolation.;The ADP:ATP ratio provided a means of predicting islet yield in both rodent and porcine models after pancreas preservation. Additionally, the ratio predicted islet purity and in vitro function of rodent islets. It provides a rapid means of assessing tissue viability during pancreas preservation and may provide the likelihood of subsequent successful islet isolation.

Delirium following surgery is common and is associated with negative outcomes. Across surgical populations pre-operative cognitive impairment is a consistent risk factor for post-operative delirium. This study tests the hypothesis that the quantification of brain vulnerability, using neuropsychological tests, plasma and cerebrospinal fluid (CSF) biomarkers, and Apolipoprotein E status, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery. An observational cohort study of patients over 65 years of age, admitted for elective primary hip or knee arthroplasty, under spinal anaesthetic, was undertaken with participants recruited between 23rd March 2012 and 21st October 2014. Of the 315 participants completing the study 40 (12.7%) developed delirium post-operatively. On univariate analyses several baseline characteristics, pre-operative performance on several neurocognitive tests, pre-operative plasma albumin concentration and CSF matrix metalloproteinase (MMP) 3 concentration were associated with post-oper:ative delirium. Only one pre-operative neuropsychological test - 3-item recall - and CSF MMP-3 concentration remained significant following multivariate analyses involving the entire cohort. The findings of this study support the hypothesis that quantification of brain vulnerability can predict the risk of delirium following elective arthroplasty surgery.