Titanium and Its alloys have been used for many years as the material of choice for fabrication of dental, orthopaedic and maxillofacial implants, due to their excellent mechanical properties, biocompatibility, and the ability to osseointegrate with the surrounding bone. In order to improve the bioactivity and osseointegration of titanium implants, especially in compromised bone, surface modification of the implant surface and surface coatings have been introduced. There are different kinds of surface modification, such as, grinding, plasma spraying, sputter coatings, and alkaline treatment. More significantly, immobilization of drugs, such as, bisphosphonates, played an important role in enhancing the bone healing process. The main aim of the study is to develop and identify a facile surface modification method of immobilizing bisphosphonate molecules on commercially pure titanium and its alloy. 10mm discs of commercially pure titanium (CpTi) and titanium-aluminium-vanadium (Ti-6Al-4V) alloy were subjected to different surface treatments experiments; 1) the CpTi and Ti64 alloy surfaces were invested in phosphate bonded investment (Deguvest) and heated up to 900°C simulating superplastic forming process (SPF) creating an interaction layer on the surface upon which they were subjected to immersion in simulated body fluid (SBF) for 7 and 10 days, 2) the titanium surfaces were subjected to alkali treatment with 5M NaOH at 60°C for 24 hours, further more immersed in SBF solution for 7 and 10 days, 3) immobilization of sodium alendronate bisphosphonate on the pre treated titanium surfaces using microseeding method, and 4) tethering of Bioglass® and sodium alendronate bisphosphonate on the titanium surfaces using the electrohydrodynamic spraying method. The surface characterization of the treated surfaces was assessed using scanning electron microscopy (SEM/EDAX), Raman spectroscopy, surface roughness profilometer, and atomic force microscopy (AFM). In vitro cellular bioactivity and cytotoxicity were evaluated on the treated surfaces. This study established that both the interaction layer and its treatment further with simulated body fluids created a favourable interaction layer on the titanium surfaces, which induced the formation of apatite like layer on the surfaces when soaked in SBF solution. The interaction layer so formed was stable and not lost after physical methods of cleaning, thus can be considered to be a quick and inexpensive method of surface modification of titanium implants, during processing itself, which can enhance the bone healing and result in improved osseointegration. The surface modification of CpTi and Ti64 achieved with SPF and sodium hydroxide treatment and further treatment with SBF were further used to immobilize alendronate successfully, which yielded a simple method of incorporating bisphosphonates on implant surfaces, without causing any damage to the drug as no heat treatment or chemical crosslinking was required. Based on the cellular response to the investment treated titanium samples, sodium hydroxide treated samples followed by SBF treatment it can be concluded that these surfaces provide favourable conditions for cell growth, proliferation and differentiation when compared to the non-invested samples.

The aim of this study was to investigate the stability of positional identity markers and phenotypic differences in isolated osteoblasts from distinct anatomic regions. In addition, the ability of heterotypic co-cultures to reprogramme site-specific Hoxa gene expression also tested. Rat osteoblastic cells from femurs and calvariae were harvested as matched pairs of cultures from 4 male rats. Cells were expanded extensively in medium supplemented with FGF-2, and were shown to maintain their osteoblastic phenotype as characterised by alkaline phosphatase (ALP) staining, osteopontin (OPN), osteocalcin (OCN) expression and osteoblast-associated gene expression in long term culture. Gene expression of cells was determined by quantitative RT-PCR. Differences in Hoxa gene expression as markers of positional identity were maintained for up to at least 10 passages, with calvarial cells remaining Hoxa-ve throughout. The transcription factors Msx2 and Irx5 were consistently more highly expressed in calvarial cells, whereas Tbx3 expression was elevated in femoral cells. Expression of the osteoblast-associated genes Bglap and Sppl were elevated in femoral cells, and also associated with increased osteopontin secretion and bone nodule formation. Runx2 was elevated in calvarial cells. Cells were also pre-labelled with fluorescent vital staining and co-cultured for 7 days prior to separating by fluorescence activated cell sorter to investigate the possibility of re-programming of Hoxa negative cells by direct contact with Hoxa +ve cells. However no evidence was seen of modulation of positional identity genes and phenotypes in these heterotypic cultures. In conclusion, the results demonstrate persistence of expression of positional identity gene markers and phenotypic differences between femoral and calvarial osteoblasts for prolonged periods in culture. These data suggest that these differences in regionally defined osteoblasts are inherently programmed in the cells as a result of their embryological position. The results may have considerable implications when considering the transplantation of autologous cells in tissue engineering.

Traumatic brain injury (TBI) causes significant morbidity and mortality. Modern neurocritical care management utilises several monitoring techniques to identify or predict secondary insults but many of these techniques have significant limitations. The ideal cerebral monitor would be a non-invasive system able to provide realtime quantitative haemodynamic and metabolic information at multiple sites with high temporal and spatial resolution. Near infrared spectroscopy (NIRS) fulfils many of these requirements and has great potential as a cerebral monitoring tool. In addition to measurements of oxy- and deoxy-haemoglobin concentration, NIRS can monitor changes in mitochondrial redox state by measuring changes in oxidised cytochrome c oxidase (oxCCO) concentration. This is an attractive monitoring target as it is intimately involved in adenosine triphosphate synthesis and cellular homeostasis, yet few studies exist which investigate oxCCO concentration changes in either the normal or injured adult human brain. This thesis explores the use of NIRS, and in particular measurement of oxCCO concentration changes, for monitoring patients with TBI. Cerebral metabolism in both health and TBI is described and current monitoring tools and treatment strategies used in TBI are discussed. Studies investigating NIRS measurements in the brains of healthy volunteers during changes in arterial oxygen and carbon dioxide tension are described in order to determine the ability of NIRS to detect these physiological perturbations and to characterise the resulting metabolic changes. Spectroscopic data are analysed to investigate the methodology used to calculate oxCCO concentration changes. NIRS is used to monitor patients with TBI during normobaric hyperoxygenation and non-invasively measured NIRS variables are compared with those acquired using invasive cerebral monitoring devices. Correlations are shown between non-invasive measures of mitochondrial redox state and invasive measures of cellular redox state. NIRS can monitor changes in cerebral physiology after TBI and has the potential to guide neuroprotective strategies on the neurocritical care unit.

The aims of this research were to investigate the factors that limit in vitro storage of kidneys, establish how long kidneys could be preserved when storage conditions were made optimum, and determine whether measurements of the release of - the lysosomal enzyme N-Acetyl glucosaminidase, by kidneys during storage, could be used to predict the function of the kidneys after reimplantation. Methods are needed for storing human kidneys, after removal from cadaver donors, to allow sufficient time for transport of the kidneys, tissue typing of the donors, ' and pre-operative preparation of the recipients. At present, reliable 24 hour storage would provide adequate time for these -procedures to be performed. In future, as tissue typing techniques become more refined, and as more potential recipients develop antibodies as a result of previous failed transplants, it is likely that fewer kidneys will be able to be matched with recipients in the locality of the donor. , It will then be necessary to store kidneys reliably for longer periods if the best possible tissue. match is to be obtained. More reliable long term storage techniques would also allow mixed lymphocyte cultures (MLC) to be performed between donor and- recipient white cells; this may provide better evidence of the likelihood of graft rejection than serological determined incompatibility of HLA tissue types. At present the MLC test takes between 5 and 7 days. The techniques for storing a human kidney that are currently in use involve cold flushing the kidney with electrolyte solution, and then storage either in ice, or on a machine in which cooled oxygenated fluid is pumped continuously through the kidney's vascular system (hypothermic perfusion storage). The best results that have been published for ice storage of non warm injured human kidneys are, those of Squifflet (101) who reported 15 of 22 kidneys functioning immediately after storage for between 40 and ý 50 hours; the best results for hypothermic perfusion storage of -human kidneys are those of McCabe (78), who had 18 of 19 kidneys functioning immediately after storage for between 17 and 50 hours. These results are exceptional, and many -human kidneys - that are transplanted fail to function immediately after reimplantation, despite removing the kidneys from heart beating donors, and using storage times of less than 24 hours. Little is known about the nature of the injuries that limit long term kidney storage. It is well known that any period of warm injury prior to storage is harmful, but the progressive deterioration in the viability of non warm injured kidneys remains unexplained. If, the nature of these storage injuries could be determined, then not only could attempts be made to minimise the injury, but measurements made during storage might be used to predict the viability and function of kidneys after reimplantation. - One consequence of cellular injury is thought to be that the lysosomes rupture and release their contents. The lysosomal enzyme N-Acetyl glucosaminidase (NAG) is known to be present in high concentrations In kidney tubular cells, is stable after long periods, of storage, and can be easily assayed. Measurement of the release of this lysosomal enzyme, by non warm-injured kidneys during storage,, may therefore be of value in predicting the function of the kidneys after reimplantation. Experimentally, the dog kidney behaves, in a similar way to the human kidney when subjected to the same -storage, conditions. Use of an animal kidney auto-transplant model allows , the effects of the storage injury to be assessed without the additional complications of the immediate and delayed rejection phenomena that occur in human kidney transplantation. For the present study, uninjured dog kidneys were removed under controlled conditions and stored on a hypothermic perfusion apparatus, using a perfusate based on human albumin (Plasma Protein Fraction - PPF). After a period of storage, the kidneys were reimplanted as autografts, and at these operations contralateral nephrectomies were performed. During storage, the physical and chemical changes that occurred in the perfusate were measured, and serial estimations were made of the release by the kidneys of the lysosomal enzyme N-Acetyl glucosaminidase (NAG). After reimplantation, function of the kidneys was assessed by the clinical condition of the dogs, and by serial estimations of the dogs' serum creatinines. Post mortems were performed on all the dogs that died. Light, electron and immunofluorescent microscopy were performed on kidney biopsy specimens removed during perfusions, after reimplantation, and at post mortem.

The term "Entrapment" was first used by Russel Brain in 1947 to describe compression of a nerve in a closed compartment created in a fibrous or fibra-osseous tunnel through which the nerve should pass in its normal anatomical course. The nerve roots gain their exit to the exterior through conduits or tunnels and not through simple intervertebral foramina as was previously conceived. The attitude in tackling the lumbo-sciatic problem should be changed according to this concept and we should now manage this problem in terms of decompression of the affected nerve roots rather than in terms of simple disc surgery. This attitude has been made more feasible with the use ot contrast examination of the epidural canal - epidurography - in investigating these cases. The aim of this thesis is to discuss the anatomy, pathogentsis and pathology of lumbar nerve root entrapments and to present and discuss the clinical, epidurographic and operative findings in thirty patients treated at El-Zatoun Orthopaedic Hospital in Cairo for lumbo-sciatic problems.

The initial composition of acrylic bone cement along with the mixing and delivery technique can influence cement final properties and therefore clinical success in vivo. The aim of this research was to investigate the predominant factors that affect the efficacious mixing and delivery of acrylic bone cement, using a pre-filled mixing and delivery system. Using such a system would eliminate the operator dependant issues associated with current commercial systems, and allow control over final properties through altering the chemical composition of the initial constituents. As range of experimental.methods were used to analyse the resultant cement throughout the research. The properties of ISO 5833:2002 were of significant importance as this governs the clinical viability of the cement produced. Results highlighted that is was possible to alter not only the mixing method but also the levels of initial cement constituents, and produced cement that adhered to the requirements of ISO 5833:2002. A key finding was the impact of the initiation chemistry on the properties of the resultant cement, both as independent and interdependent factors. Investigating powder - liquid interactions during the mixing process was of high importance, emphasising the effect of both powder bed packing density and particle size on the ability to achieve a homogenous cement mix. A comparison of mixing systems indicated that removing operator dependency form the process enhanced the predictability of the fatigue performance, a vital characteristic in determining the long term survival of implants. Finally, cement properties versus shelf-life were investigated, highlighting spontaneous polymerisation occurs within the mixing system, during the storage period. The effect of this could led to complications during the surgical procedure, an adverse effect when considering the success of the joint replacement and quality of life for the patient.

OBJECTIVES: Primary end-point was to assess the cost-effectiveness of lumbar laminectomy versus X-stop insertion in patients with neurogenic claudication secondary to LSS. Secondary end-points were to compare quality of life, clinical outcomes, radiological parameters and complications within two groups. This is a pilot study to produce predictive models and allow sample size calculation. DESIGN: Multicentre randomised trial with two interventional arms, namely the lumbar laminectomy(LL) and X-stop(XS) groups. METHODS: Patients were recruited from two neurosurgical centres after fulfilling eligibility criteria and followed up for 1 year. Self-reported general quality of life and disease-specific questionnaires were used. The assessments were performed at discharge, 6 weeks, 6 and 12 months. Also, radiological parameters were analysed. RESULTS: In this pilot study 26 patients were identified of which 6 were excluded and 20 were randomised with 10 in lumbar laminectomy and 10 in X-stop(XS) group from June 2008 to January 2010. LL group incured lower costs than the XS group but showed no significant between-group differences in utility values (QALYs). We found that LL was perhaps more cost-effective than the XS but with uncertainty, suggesting the need for a larger trial. There were no significant differences between the two groups in quality of life, clinical outcomes or success rates but within group improvements were found. Importantly, 6 out of 10 patients (60%) from XS group crossed over to LL group. Sample size calculation with the original data showed the need for 25 patients in each arm to detect clinical significance in future clinical trial. CONCLUSION: Our results suggest that LL is possibly cheaper and more cost-effective than XS over a 1-year period, in National Health Service. No significant differences in quality of life and clinical outcomes between the two procedures were detected although this is only a pilot study with a small sample size.

Coronary artery disease and bypass surgery can have a major impact on many aspects of patients' lives. A substantial proportion of cardiac patients experience high levels of psychological morbidity and in many cases, this is not closely related to physical symptoms. From the current evidence it is not yet possible to reliably identify the factors that contribute to the development of patients' poor mental health. In this investigation, a detailed description of patients' social, psychological and medical history was gained both before and after surgery. Having had distressing experiences in the Intensive Care Unit was highly correlated with psychological morbidity six months after surgery. These findings were considered in relation to psychological theories of depression and anxiety in order to better understand the distress experienced by cardiac patients.

Obesity has reached epidemic proportion in the United States. Results of diet, exercise regimens, and/or medications are discouraging for most individuals; therefore, bariatric surgery is on the rise. Patients undergoing bariatric surgery are overwhelmingly female. There is a plethora of research regarding improvement of co-morbidities, but little focus has been placed on the impact of bariatric surgery on positive as well as negative psychosocial outcomes. The purposes of this study were to explore experiences of women who have undergone bariatric surgery and to gain an understanding of the decision to have surgery. No qualitative research was found regarding individuals' life experiences after bariatric surgery. This study used a qualitative research design, guided by a phenomenological approach, to investigate and describe the meaning of experiences of women before and after bariatric surgery. Initially, a focus group of six members of a bariatric support group was conducted to confirm data from individual interviews. Semi-structured in-depth interviews were then conducted on a sample of ten women who had undergone bariatric surgery and were two to four years postoperative. Eight main themes emerged from the data: (a) relationship with food, (b) interpersonal relationships, (c) relationship with self, (d) living with excess skin, (e) food intolerance, (f) treatment from society, (g) concern with aging, and (h) support systems. After further analysis, three subthemes then emerged from relationship with food: food and family, emotional response to food, and coping with temptations. Interpersonal relationships developed into two subthemes: limited activity with family and relationship with others. As analysis continued, three subthemes of concern with aging emerged: fear of not growing old, fear of the unknown, and fear of gaining weight. Themes that emerged from the women's experiences all revolved around the need to be better prepared for surgery and the need for continued support after surgery. Family was interconnected to most of the themes. In order to be successful, close family members should understand the requirements of lifelong medical monitoring and the necessary changes in diet and lifestyle. Results revealed limited psychological counseling as well as long-term nutritional counseling occurred. The majority did not attend support groups, although the need for support was expressed. Support groups conducted by health professionals benefit those who are considering surgery and those who have undergone bariatric surgery. Recommendations for health education include addition of bariatric surgery into curriculums. Knowledge of bariatric surgery would assist health educators in planning programs for this population.

Spinal cord injury (SCI) is a devastating condition affecting the quality of life of many otherwise healthy patients. To date, no cure or therapy is known to restore functional movements of the arm and hand, and despite considerable effort, stem cell based therapies have not been proven effective. As an alternative, nerves or muscles below the injury could be stimulated electrically. While there have been successful demonstrations of restoration of functional movement using muscle stimulation both in humans and non-human primates, intraspinal microstimulation (ISMS) could bear benefits over peripheral stimulation. An extensive body of research on spinal stimulation has been accumulated – however, almost exclusively in non-primate species. Importantly, the primate motor system has evolved to be quite different from the frog's or the cat's – two commonly studied species –, reflecting and enabling changes in how primates use their hands. Because of these functional and anatomical differences, it is fair to assume that also spinal cord stimulation will have different effects in primates. This question – what are the movements elicited by ISMS in the macaque – will be addressed in chapters 2 and 3. Chronic intraspinal electrode implants so far have been difficult to realise. In chapter 4 we describe a novel use of floating microelectrode arrays (FMAs) as chronic implants in the spinal cord. Compared to implanted microwires or other arrays, these FMAs have the benefit of a high electrode density combined with different lengths of electrodes. We were able to maintain these arrays in the cord for months and could elicit movements at low thresholds throughout. If we could build a neural prosthesis stimulating the spinal cord, how would it be controlled? Remarkable progress has been recently achieved in the field of brain-machine interfaces (BMIs), for example enabling patients to control robotic arms with neural signals recorded from chronically implanted electrodes. Chapter 5 of this thesis examines an approach that combines ISMS with cortical control in a macaque model for upper limb paralysis for the first time and shows that there is a behavioural improvement. We have devised an experiment in which a monkey trained to perform a grasp-and-pull task receives a temporary cortically induced paralysis of the hand reducing task performance. At the same time, cortical recordings from a different area allow us to control ISMS at sites evoking hand movements – thus partially restoring function. Finally, in appendix A we describe a system we developed in order to introduce automated positive reinforcement training (aPRT) both at the breeding facility and in our animal houses. This system potentially reduces time spent on training animals, adds enrichment to the monkeys' home environment, and allows for suitability screening of monkeys for behavioural neuroscience experiments.