Keloids are classically regarded as scars that `outgrow the boundary of the original injury'. Ambiguous data concerning certain characteristics of keloid fibroblasts (such as proliferation rates and collagen production), however, have served only to confuse researchersT. he lack of an in vivo model and of detailed clinical accounts are added problems. In this study, a murine granulomatous tissue resolution model was used to investigate the profile of a number of cytokines suspectedto be involved in the aetiology of keloids. The results obtained from these experiments were then extrapolated to clarify the observations made in keloids. The results of these extrapolated comparisons revealed elevated levels of interleukin (IL)-4, IL-10, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF)-ß in keloid samples and decreasedle vels of interferon (IFN)-y and IL-2. The murine model was also used to investigate the implications of the low levels of IFN-y known to be present in the serum of keloid patients and shown here to be present in clinical samples. The results were found to support the hypothesis that the addition of IFN-y reduces the fibrosis so typical of keloids by rectifying the abnormality of the absence of IFNy content. The same model was used to provide evidence that the inhibition of VEGF activity in resolving wounds may halt the development of keloid lesions. The immunohistochemical profiles of cellular proliferation, apoptosis, lymphokines and cytokines for resolution (and, to a certain extent, the model) were used to compare with the abnormally resolved wounds which were available as clinical samples. Immunohistochemistry was also employed to describe the cellular nature of the clinical tissue samples in detail and to facilitate the development of the following hypothesis for keloid formation and propagation: lymphocytes migrate to the site of an (alleged) endogenous antigen present in the skin. The nature of these lymphocytes is characteristic of a type 2 immune response, they produce IL-4 (and IL-10) which in turn inhibit(s) the production of IFN-y and IL-2. Aside from this immunological response, wound resolution is taking place: fibroblasts are producing PDGF, EGF and TGF-ß to aid matrix remodelling and collagen synthesis. The provisional matrix is being vascularised by the action of VEGF, to allow the replenishment of nutrients; regression of blood vessels occurs through the action of an apoptosis-dependent mechanism, as does the 'normalisation' of fibroblastic populations. The keloid scar continues to grow after the cessation of resolution because the immune response to the 'endogenous' antigen continues and the lymphocytes continue to migrate to the site of the wound and continue to stimulate fibroblast proliferation and collagen production through the release of IL-4.

This was a holistic study. Four themes were investigated to demonstrate the effectiveness of orthotic intervention for plantar ulceration affecting leprosy impaired subjects in India. 1. Efficacy Efficacy was demonstrated, primarily, through analysis of data pertaining to a controlled trial. Thirty-seven subjects, presenting with leprosy impairments including anaesthesia and plantar ulceration, were fitted with orthoses and allocated to an experimental group. Thirty-four similar subjects, were not offered orthoses and were allocated to a control group. After 8 months 52% of the ulcers presented by Experimental group and 12% of the ulcers presented by the Control group had healed. The rationale supporting the prescription of orthoses was investigated using the EMED system. It was demonstrated that intervention with orthoses resulted in significantly lower sub pedal peak pressures than intervention with leprosy sandals. 2. Implementation and Sustain ability Ulcer assessment data from March 1994 to January 1995 were used to compare the effects of orthoses supplied by the investigator with orthoses supplied by an Indian technician. The service, evaluated on the strength of these findings, was considered to have been successfully implemented. The analysis of data, collected from January 1995 to December 1995, was used to explain why the service was not sustained at an acceptable level. 3. Acceptability Interview data were analysed to describe the attitudes of the subjects to the intervention (n = 46). Indications from the analysis were that neither ulcer status (healed or unresolved) nor group allocation (Experimental or Control) affected attitudes towards the intervention. A general indication was that the intervention was favourably endorsed. 4. Appropriateness Using the Delphi technique (n = 10), a consensus on indicators of "appropriate" impairment control measures was sought. Differences of opinion were not resolved, but group priorities were ranked and a polled response was recorded. The results of the study were similar to the criteria suggested by the Delphi contributors.

English men's community rugby boasts the largest adult rugby playing population in the world. While regular participation in rugby has been linked to clinical health benefits there is an inherent risk of injury associated with rugby participation due to its collision based nature. This programme of research was conducted to identify means to reduce the injury risk in the context of men's community rugby. In Chapter 3, the Functional Movement Screen is used to assess the movement competency of men's community rugby players. Injury match exposure data was recorded for each player, and analysed to determine associations between players' movement competency and injury outcomes. Players that displayed both of pain and asymmetry on screening were associated with an incidence of overall injury at 22.0 injuries/1000 player match-hours. Players that scored 16 or more had an incidence of overall injury at 12.4 injuries/1000 player match-hours. Chapter 4 details the multi-stage process used to develop the injury prevention exercise programme specific to men's community rugby. Chapter 5 investigated barriers and facilitators to programme implementation in a sample of men's community rugby clubs. Results informed the refinement of the intervention exercise programme and detailed means to maximise successful delivery of the programme to clubs. Chapter 6 was a cluster randomised controlled trial of the final injury prevention exercise programme. Clear beneficial effects following implementation included a 40% reduction in targeted lower-limb injury and a 60% reduction in concussion compared to the control group. The injury burden for intervention clubs with higher compliance was reduced 50% compared to intervention clubs with lower compliance. Functional Movement Screening™ may identify men's community rugby players at higher risk of match injury. A targeted movement control exercise programme can provide efficacious means to reduce injury that is practicable within the men's community rugby environment.

Introduction Non-union (NU) is a fracture that will not unite. With over one million fractures per annum in the UK long bone non-union has serious social and economical implications. There is little epidemiological data available specifically looking at this NU patient cohort. Studies that are bone specific quote rates of non-union as a proportion of their study group but there is no data quantifying the incidence of NU in the population or per fracture. Studies have highlighted risk factors associated with atrophic non-union including age, diabetes, non-steroidals, and cigarette smoking. There is scientific interest regarding how best to classify non-unions and the role of biological agents in treating them. Aims • To quantify the incidence of non-union in a large population and calculate the risk of non-union per fracture according to age, sex and anatomical distribution. • To assess the causes contributing to non-union and outcomes of treatment in a non-union cohort and validate a new non-union scoring system. • To test the treatment potential of a novel molecule (monobutyrin) and a growth factor in a small animal model of non-union. Method • Using the ICD-10 data from the Scottish population as collected by NHS Scotland the incidence of non-union and fractures were calculated. • A cohort of 100 non-union patients were studied for risk factors associated with their non-union, treatment outcome and to assess a new NU classification system. • A rat model of tibial non-union was used to assess the potential of monobutyrin and BMP-2 in treating non-union in an animal model. Results • Fracture non-union is very rarely found in children (1 in 500 fractures) and occurs in up to 1 in 50 adult fractures. Non-union of a fracture has a significantly higher risk in young adults than the elderly by about 3 fold. Osteoporosis may not be a risk for non-union. The tibia and clavicle are the sites with the greatest potential for fracture non-union. • Non-union is multifactorial in two out of three patients. Biomechanical stability, patient host factors and infection must all be considered in every patient. Occult or unexpected recurrent infection is present in up to 10% of patients. When all factors are considered in treatment the outcome is 95% successful with 88% requiring 2 or less procedures to heal the non-union and only a minority requiring adjuvant graft or biological agents. The proposed new classification system is complex and did not clearly identify those patients who would require adjuvant treatment (eg bone grafting or BMP) or those likely to have unsuccessful non-union treatment. • Monobutyrin and BMP-2 when tested on the small animal non-union model did not improve the success rate of union. Conclusions Non-union affects approximately 1000 people per year in Scotland, this figure is not as high as 5-10% of all fractures. It is associated with fractures in young adults and of the clavicle and tibia, treatment can have a very high success rate without the need for adjuvant biological polytherapy when all contributing factors are considered and managed appropriately. A new non-union classification needs to incorporate the multifactorial aspects of non-union without being too complex to use in everyday clinical situations.

The aim of this study was to investigate the effects of various polysaccharides and their breakdown products on the proliferation and migration of cells involved in wound healing, both in vitro and in vivo, with the ultimate aim of developing a commercially viable collagen dressing containing an active polysaccharide fragment which would stimulate the wound healing response to such a degree that good quality and significantly faster healing would take place. Hyaluronic acid (HA), chondroitin sulphate (CS), heparin, Oxidised Regenerated Cellulose (ORC) and pectin were tested in this study. Some HA fragments and CS fragments significantly stimulated (p<O.05) the proliferation of Bovine Aortic Endothelial (BAEC) cells, although other HA or CS fragments were without effect. All HA and CS fragments tested also had no effect on the migration of L929 cells in the Boyden Chamber assay. Pectin stimulated the proliferation and migration of L929 cells, whereas, ORC 1 and heparin both suppressed proliferation (25% - 45% inhibition) of these cells but stimulated their migration. When injected subcutaneously into Polyvinyl alcohol sponges in the rat wound model at concentrations of 10 and 50J.1g/ml, heparin brought about an increased presence of granulation tissue in the wound after 10 days and 7 days respectively. These results indicate that structurally similar polysaccharides can have profoundly different effects on cell proliferation and migration, and thus have potential therapeutic use in guiding cell movement in wound healing.

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No description available.

The thesis comprises literature reviews which present arguments novel to the field and two discrete but related studies, which in combination make a contribution to the classification, assessment of risk and prevention of pressure sores. The first study, a randomised controlled trial involving 446 patients undergoing vascular, general and gynaecology surgery, the use of a dry visco-elastic polymer pad intra-operatively reduced the probability of pressure sore development by half. Pressure sore incidence was 11 % (22/205) for patients allocated to the dry polymer pad and 20% (43/211) for patients allocated to the standard operating table mattress. Both studies explored key prognostic factors using multi-variate methods. Analysis of data derived from the randomised controlled trial found four factors to be independently associated with post-operative pressure sore development including intra-operative hypotensive episodes, Day I Braden mobility scale and intraoperative mean core temperature. The second study, a prospective cohort study involving 101 patients identified non-blanching erythema, pre-operative albumin, weight loss preceding admission and intra-operative minimum diastolic blood pressure. Results are consistent with findings from the literature review which identified key factors in the prediction of pressure sore development (reduced mobility, nutrition, perfusion, age and skin condition). The second study also explored the clinical significance of erythema in defining and classifying the term 'pressure sore'. Using laser Doppler imaging it was determined that blanching and non-blanching erythema are characterised by high blood flow of differing intensity. Discriminant analysis identified three general patterns in skin blood flow, which enabled scan classification with good agreement between clinical and predicted classifications. The results confirm data derived from the prospective observations of skin suggesting that non-blanching erythema is not indicative of irreversible ischaemic damage and resolves in approximately two thirds of cases. The point at which non-blanching erythema becomes irreversible remains unknown

No description available.

Hip fracture is one of the most common, serious injuries in old people in England, and with a growing older population it is increasingly important to understand the impact of hip fracture from the patient perspective in order to develop relevant and appropriate healthcare services. The aim of this study was to explore the lived experience of hip fracture in older people in England to inform service development. A scoping review of the literature highlighted the lack of current evidence for hip fracture experience in England, with a particular dearth of evidence concerning the lived experience of hip fracture following discharge from hospital. However, the reviewed highlighted some international evidence around the lived experience of hip fracture while in hospital, and during initial rehabilitation. A meta-synthesis of the data was therefore conducted providing a more interpretive approach to analysing this data, and establishing a better understanding of the current literature on hip fracture patient experiences. The gaps in the evidence reported in the current evidence base provided a rationale for a qualitative study. Hip fracture patients were interviewed at their place of residence 12 to 16 weeks after surgery. Interpretative phenomenological analysis methodology was used for 24 interviews, and patient and public involvement was integral to the study. The study reported the impact on self, and the role of biographical disruption in triggering feelings of incompetency and frustration, particularly in those who had been relatively active prior to hip fracture. Participants perceived that others labelled them as ‘old’ and ‘disabled’ as they became less mobile and more dependent on those around them. Macro health care policies limited individualised care practices, and a greater emphasis is needed on discharge planning and continuity of care after discharge home. The study also reported the need for improved information provision and verbal communication throughout the care trajectory, and a key worker to co-ordinate their care to provide realistic expectations, reassurance and support throughout the recovery period is recommended. A model of continuity of care is presented to provide insight for the development of patient centred health care for this population.