Radiographic hand osteoarthritis (OA) affects a large number of older people and can lead to significant pain and disability. Patterns of radiographic hand OA and associations with pain and function have not being studied in detail. A systematic search and review was undertaken to determine methods used to examine radiographic hand OA. The thumb interphalangeal joint was infrequently studied and inconsistently grouped with other hand joints. The Kellgren and Lawrence grading system was the most frequently used to assess and define hand OA within published communitybased epidemiological studies. Community-dwelling adults (z50 years) who had experienced hand pain or hand problems in the previous year were recruited to a cohort, the Clinical Assessment Study of the Hand (n=623). Presence of hand OA was assessed on radiographs using the Kellgren and Lawrence grading system. Patterns of radiographic OA in the hand joints were investigated and analysis identified that the finger joints grouped by rows whilst the four joints of the thumb grouped together as a ray. The location of radiographic OA in the hand and its contribution to hand pain and functional limitation were explored. Participants with combined radiographic finger and thumb OA had more pain and functional limitation than individuals with thumb or finger OA alone. Further study of the thumb found associations between thumb pain, thenar muscle wasting, presence of nodes, deformity or enlargement and the presence of radiographic thumb OA. Ei]The course of radiographic hand OA over time was examined. Almost half the individuals reported deterioration in their hand problem, and small increases in hand pain and functional limitation were seen at 18 months and 3 years. Poorer overall physical functioning was found in the combined finger and thumb OA sub-group at baseline. However, over a3 year period very little change was seen in overall physical functioning or general health

Systemic lupus erythematosus~(SLE} is the archetypal autoimmune disease, with a wide range of clinical manifestations. Among the clinical challenges of SLE one of the most compelling is the high incidence of atherosclerosis in young women that is not fully explained by traditional Framingham risk factors. The ability to identify early those individuals at greatest risk of future vascular events would enable appropriate therapeutic intervention and risk factor modification to be employed. This work investigated vascular reactivity from different arterial beds using flow mediated dilation of the brachial artery, frequency domain analysis of Pulsed Doppler velocity wav~forms and radial artery applanation tonometry in 60 patients with SLE(without excess of conventional cardiovascular risk factors or major organ involvement} and compared to a control group. There were significant differences in the measures of endothelial function and arterial compliance in the SLE patients and there was also evidence of an alteration in the haemodynamics of the microcirculation through interrogation of the arterial pressure and flow waveforms. Fish oils or omega-3-polyunsaturated fatty acids (PUFAs) have been shown to improve endothelial function in disease states associated with atherosclerosis, and previous work has highlighted their potential beneficial effect in reducing disease activity in SLE. In this work, a double-blind placebo-controlled clinical trial of supplementation with 3gram of omega-3 PUFAs for 24 weeks in SLE patients resulted in a significant improvement in endothelial function and measures of disease activity. Furthermore, using the platelet as a model for endothelial free radical production, there was also a significant reduction in the oxidative stress marker, 8-isoprostane, with fish oils.

Mitochondria are considered the powerhouse of the cell being the major site of ATP production but in addition to this function they also regulate ROS production and inhibition, calcium handling and apoptosis. Previous studies have reported a downregulation in the levels of superoxide dismutase 2 (SOD2), an inhibitor of mitochondrial superoxide (O2--), in osteoarthritic (OA) hip cartilage compared to that from healthy joints (neck of femur fracture; NOF). This finding provides the opportunity to characterise the functional effects of SOD2 downregulation in OA in the context of oxidative damage and mitochondrial dysfunction. SOD2 depletion increased the mitochondrial O2-- levels in human articular chondrocytes (HAC). Measurement of lipid peroxidation levels in OA and NOF cartilage showed that OA cartilage has higher levels of lipid peroxidation compared to NOF. SOD2 depletion in a chondrosarcoma cell-line, SW1353, also led to a significant increase in lipid peroxidation levels. Additionally, SOD2 depletion led to a significant increase in mtDNA strand breaks in SW1353 cells although there was no difference detected in OA compared to NOF mtDNA. However, large-scale mtDNA deletions were identified in OA cartilage and other OA joint tissues but the low levels of mutated mtDNA observed were not considered to be pathologically relevant. Mitochondrial respiratory function was also determined in OA and NOF isolated chondrocytes. OA chondrocytes showed less spare respiratory capacity (SRC), higher non-phosphorylating respiration and higher proton leak compared to NOF. SOD2-depleted HAC also showed a lower SRC and higher proton leak. Additionally, HAC demonstrated a very low mitochondrial/glycolysis ratio, suggesting that HAC are highly glycolytic cells. SOD2 depletion caused depolarization of the Δψm. NLRX1, a mitochondrially localised gene involved in innate immunity signalling was also identified to regulate basal levels of matrix metalloproteinase 13 (MMP-13) and double stranded RNA- induced ROS levels in chondrocytes. These findings suggest that SOD2 depletion in chondrocytes leads to oxidative damage and mitochondrial dysfunction caused by increasing ROS levels and can potentially lead towards alterations in cell signalling pathways, cellular dysfunction and cartilage degradation.

This thesis reports a study which explored children's understanding and experience of spina bifida. Semi-structured interviews were conducted with 8 children aged 8-11 years with spina bifida. A grounded theory approach was used to develop 'theories' from the data. Analysis of the data suggest that all participants were aware of 'being different' from their "normal" able-bodied siblings and peers and that many identified themselves in terms of having spina bifida; they spoke about being picked on, teased and about other types of bullying; and all of them disliked their physical appearance. Several ways of coping with spina bifid a were also talked about by the children. Knowledge about spina bifida tended to be functional and obtained from parents; most of the participants reported that little information about treatment was given by medical professionals which seemed to contribute to anxiety regarding treatment and hospitalization. The implications of the findings for clinical practice and further research are considered.

No description available.

Polymethylmethacrylate (PMMA) bone cement has been the most common choice for total hip replacement fixation for the last twenty five years. However, in recent years, it has fallen from favour with stem loosening and subsequent failure being attributed to fracture of the bone cement and bone necrosis. An alternative bone cement, polyethylmethacrylate (PEMA) is a more ductile material and is not as susceptible to brittle fracture. In addition, with a lower exotherm and monomer release rate the cement proves less damaging to the surrounding bone. Unfortunately, this material is inclined to creep, causing subsidence in the medullary canal. In an attempt to increase the creep resistance of the cement, hydroxyapatite particles can be added. The aim of this work was to undertake a thorough examination of the creep behaviour of a PEMA based bone cement, including the effects of curing regime, hydroxyapatite reinforcement, surrounding environment and ageing. Specimens were subjected to tensile creep tests at a number of temperatures, stresses and prior ageing times. Additionally, tests were performed to establish the effects on the creep properties of hydroxyapatite reinforcement. Ageing was found to increase the creep resistance with time, and therefore must play a vital role in the prediction of creep. This effect, as well as the effects of temperature and applied stress appeared relatively unchanged irrespective of testing environment. However, water based environments produced the lowest creep resistance in the PEMA cement and were therefore chosen as the worse case scenario. Hydroxyapatite reinforcement acted to increase the creep resistance, with creep compliance values for 25% reinforced samples being half that of unfilled cement at 1 million seconds. Predictions of the creep behaviour were made employing the effective time theory and time temperature superposition as well as those based on mathematical models. Both methods gave close matching predictions up to two decades beyond the testing times. At creep times up to three years the predictions show that if this material is to be used for joint replacements, hydroxyapatite reinforcement is not just beneficial but essential.

No description available.

No description available.

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No description available.