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Rheumatoid arthritis is a painful and debilitating disease which often afflicts the key joint of the hand, the metacarpophalangeal joint. In the worst cases the diseased joint has to be replaced with an artificial joint or prosthesis. The development of the Durham metacarpophalangeal prosthesis as it was taken from prototypes through to production samples, is described in this thesis. Testing of several Durham prostheses to over 70 million cycles has been carried out on a finger function simulator and consistent wear factors of the order of 0.4 x 10(^-) (^6)mm(^3)/Nm have been measured. These wear factors for the prosthesis were also significantly lower than any found previously. Production samples of the prosthesis have been manufactured together with appropriate surgical instrumentation. Tests of the prosthesis material, cross-linked polyethylene, rubbing against itself, have been undertaken on reciprocating pin on plate rigs and again show total wear factors of the order of 0.4 x lO(^-6)mm(^3)/Nm. Interestingly, it was found that pin wear was very much less than plate wear. The pin on plate tests were extended to include ultra-high molecular weight polyethylene (UHMWPE) rubbing against UHMWPE, as well as both polyethylenes against hard counterfaces and the results are reported. A new finger function simulator has been designed, manufactured and a validation test undertaken. Having written the necessary protocol, in conjunction with clinicians and the prosthesis manufacturer, ethical approval was obtained from the local research ethics committee and the Medical Devices Agency, to permit implantation of the prosthesis in human subjects. Lastly a hand strength measurement device for pre and post operation assessment of patients has been developed and manufactured.

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Title page, contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / "In early arthritis, it is important to make a diagnosis before structural damage has occurred, with early disease modifying therapy effective in improving long term outcomes. The first part of this thesis addresses the deficiency in our current knowledge of standardisation and reproducibility of ultrasound (US) findings. Chapter 2 describes a standardised protocol developed for assessing the metacarphphalangeal (MCP) joints and novel measurements of synovial inflammation. Chapter 3 compares early arthritis subjects to a control group, and showed significantly more US synovitis and abnormally increased measurements, with extensor tenosynovitis (ET) and power Doppler (PD_ positivity highly specific to the early arthritis group. Chapter 4 validates HRUS findings in a subset of subjects using MRI as the reference standard..Chapter 5 presents longitudinal data which suggests that clnical swelling and PD positivity at the MCP joints were the most sensitive to change as a reseult of disease-modifying therapy. Chapter 6 validates an US assessment tooldevelopedbadsed on “sentinel joints” whilst factors that may hemp to differentiate subjects with polyarthralgias from those with early RA are identified in chapter 7. The results of this study suggest that early RA needs to be redefined in the light of our US findings. The prognostic value of early US abnormalities will contlinue to be investigated." -- from Abstract. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1317258 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008

Title page, table of contents and introduction only. The complete thesis in print form is available from the University of Adelaide Library. / Apoptosis and inflammation have been considered to be linked mechanisms. Defective apoptosis may result in cell accumulation and prolonged half life of inflammatory cells in rheumatoid arthritis (RA). A similar phenomenon is seen in malignancy. Therefore, defects in apoptosis pathways that have been proposed to contribute to the pathogenesis of malignancy may also be seen in RA. It has been reported by many studies that treatments that induce apoptosis of malignant cells are advantageous for cancer treatment and this suggests that targeting apoptosis pathways may be important in the management of a variety of pathologies that involve abnormalities in cell proliferation. While apoptosis induction has been a common mechanism in the treatment of cancer, it has only recently been seriously considered to be effective in regulating proliferative cells in inflammation. This thesis provides important information regarding the TRAIL mediated pathway of apoptosis and possible factors that modulate the ability of this pathway to induce apoptosis in RA. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1286764 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2007

Title page, contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / "In early arthritis, it is important to make a diagnosis before structural damage has occurred, with early disease modifying therapy effective in improving long term outcomes. The first part of this thesis addresses the deficiency in our current knowledge of standardisation and reproducibility of ultrasound (US) findings. Chapter 2 describes a standardised protocol developed for assessing the metacarphphalangeal (MCP) joints and novel measurements of synovial inflammation. Chapter 3 compares early arthritis subjects to a control group, and showed significantly more US synovitis and abnormally increased measurements, with extensor tenosynovitis (ET) and power Doppler (PD_ positivity highly specific to the early arthritis group. Chapter 4 validates HRUS findings in a subset of subjects using MRI as the reference standard..Chapter 5 presents longitudinal data which suggests that clnical swelling and PD positivity at the MCP joints were the most sensitive to change as a reseult of disease-modifying therapy. Chapter 6 validates an US assessment tooldevelopedbadsed on “sentinel joints” whilst factors that may hemp to differentiate subjects with polyarthralgias from those with early RA are identified in chapter 7. The results of this study suggest that early RA needs to be redefined in the light of our US findings. The prognostic value of early US abnormalities will contlinue to be investigated." -- from Abstract. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1317258 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008