Includes bibliography (leaves 191-219). Examines the levels of insulin-like growth factor and the presence of IGF binding proteins in human wound fluid. Tests the potency of IGF-1 and 2 analogues in in vitro models of fibroblast activity and their effect on healing in normal and diabetic rodent wounds. Shows that IGF-1, IGF-2 and their binding proteins are present in fluid from a partial thickness cutaneous wound; that the binding proteins negatively modulate the activity of insulin-like growth factors in vitro, but that the IGFs do not necessarily show enhanced activity in vivo at the wound site if binding protein affinity is decreased. Discusses possible roles of these binding proteins in wound repair.

Nitric oxide is a small free radical generated by family of enzymes, the nitric oxide synthases. In a series of experiments performed over the last 15 years we showed that nitric oxide is induced by all three isoforms of nitric oxide synthase during tendon healing and that it plays a crucial beneficial role in restoring tendon function. In normal tendon we found very little nitric oxide synthase activity while in injured rat and human tendons nitric oxide synthase activity was expressed in healing fibroblasts in a temporal fashion. In healing rat Achilles tendon fibroblasts the first isoform to be expressed was endothelial nitric oxide synthase (eNOS), followed by inducible nitric oxide synthase (iNOS), and then brain or neuronal nitric oxide synthase (bNOS). Systemic inhibition of nitric oxide synthase activity decreased the cross sectional area and mechanical properties of the healing rodent Achilles tendons. Addition of nitric oxide via NO-flurbiprofen or NO-paracetamol enhanced rat Achilles tendon healing. Addition of nitric oxide to cultured human tendon cells via chemical means and via adenoviral transfection enhanced collagen synthesis, suggesting that one mechanism for the beneficial of nitric oxide on tendon healing might be via matrix synthesis. The final part of the work involved three randomized, double-blind clinical trials which evaluated the efficacy of nitric oxide donation via a patch in the management of the tendinopathy. In all three clinical trials there was a significant positive beneficial effect of nitric oxide donation to the clinical symptoms and function of patients with Achilles tendinopathy, tennis elbow and Achilles tendonitis.

Aim The purpose of the study was to formally identify trauma care delivery problems at the study institution, implement a solution in the form of trauma case management (TCM), and measure the effect of TCM on staff satisfaction, clinical coding accuracy and patient outcomes, using practice-specific outcome variables such as in-hospital complication rates, length of stay, resource use and allied health service intervention rates. This research also aimed to make a unique contribution to the international trauma literature by addressing the lack of any evidence specifically measuring the impact of trauma case management intervention. Methods St George Hospital is a 600 bed urban Teaching Hospital of the University of NSW. It is a designated Trauma Centre, seeing around 200 severely injured patients and around 2500 injury admissions per year. A series of focus groups and a staff satisfaction survey identified perceived problems associated with trauma care, and a trauma case management program was implemented. A preliminary study was conducted with positive results and funding was obtained to provide TCM seven days a week to all trauma patient admissions. A larger clinical trial was conducted and data from 754 patients were collected over fourteen months after TCM was introduced at the study hospital. These data were compared with 777 matched patients from the previous 14 months as a control group. An audit was conducted on trauma patient clinical coding using the daily progress record kept by the trauma case manager. The data were analysed with SPSS. The statistical tests used were Mann-Whitney U, chi-squared (2) logistic regression and generalised linear models. Results Focus groups and the staff satisfaction survey identified communication and coordination as the main problems associated with trauma care delivery. Following the initial implementation of the program, staff support for TCM was overwhelming. TCM greatly improved the rate of and time to Allied Health intervention (p&lt0.0001). Results demonstrated a decrease in the occurrence of deep vein thrombosis (p&lt0.038), coagulopathy (p=0.041) and respiratory failure. A reduced hospital length of stay (LOS), particularly in the paediatric (p&lt0.05) and 45 - 64 years age group was noted. There were 6621 fewer pathology tests performed (p&lt0.0001) and the total number of bed days was 483 days less than predicted from the control group. Many hospital clinical coding errors and omissions were highlighted by the TCM record comparison. The use of TCM records resulted in Twenty eight percent of recoded records having their Australian national diagnostic related group (AN-DRG) changed, which resulted in the identification over $39,000 in unidentified funding. Conclusion TCM improves staff satisfaction, communication and clinical coding accuracy. The introduction of TCM improved the efficiency and effectiveness of trauma patient care in our institution. This initiative demonstrates that TCM results in improvements to quality of care, trauma patient morbidity, financial performance and resource use. This research makes an important and original contribution to the international trauma literature by providing the results of a clinical trial formally measuring the impact of trauma nursing case management intervention.

Doctor of Philosophy / The general aim of this current work was to examine spinal cord injury (SCI), and in particular to examine the pathology of injury as it relates to changes in sensory transmission. Due to the limited possibilities for experimentation in humans, a range of animal models of SCI have been developed and are reviewed here. The weight drop SCI model is the most similar to the clinical presentation of SCI in humans and has been widely used in the rat. It was selected for the series of experiments reported in this thesis. Many of the functional deficits produced by SCI result from a cascade of biochemical events set into motion by the injury. Included amongst these is the activation of the enzyme nitric oxide synthase which produces the gaseous neuromodulator, nitric oxide (NO). NO is amongst the most widely distributed and widely utilised molecule in virtually all living organisms, and it is an important signalling molecule in the nervous system. One of the major functions performed by NO appears to relate to sensory transmission, and thus alterations in sensory transmission observed as a result of SCI may involve alterations to NO synthesis. One of the principal aims of this thesis was to examine the effect of SCI on the NO producing cells of the spinal cord and to consider what any changes in NO synthesis may suggest in regards to sensation. NO producing cells were examined using NADPH diaphorase (NADPH-d) histochemistry. As the symptoms of SCI such as motor loss and changes in sensory processing are functional changes, it was also useful to examine changes in neuronal function as a result of SCI. Widespread neuronal function was examined via immunohistochemical detection of the gene product of the immediate early gene, c-fos. It is not known how extensive the biochemical changes resulting from SCI may be, thus another of the aims of the present thesis was to examine the effects of SCI on NO synthesis not only at the level of injury, but also distant to the injury. Findings of the present thesis indicated that traumatic SCI resulted in a decrease in the number of NADPH-d positive cells from the superficial dorsal horn (SDH) of the spinal cord, while the number of these cells are increased in the ventral horn. These changes were restricted to spinal segments adjacent to the injury. Fos expression was also altered by injury and was found to decrease. The most profound changes were found to occur in lamina III, although the other laminae also demonstrated similar changes. Changes in fos expression however were notably more widespread than those for NADPH-d and were not restricted to the level of the injury, occurring at all levels of the spinal cord examined. It was interpreted that alterations in NO synthesis appear to be modulated by the local injury-induced environment while fos expression may be altered by widespread changes to the global level of activity within the central nervous system. Having observed that the number of NADPH-d positive cells of the SDH is reduced following injury, it was of interest to determine whether these cells were in fact killed, or whether they were still present but with reduced NADPH-d activity. Cell counts suggested that the NADPH-d positive cells, which were likely to represent a population of inhibitory interneurons, were not killed following injury, but rather are disrupted such that their normal biochemistry is altered. Since these cells were likely to be inhibitory and were located in laminae involved in sensory transmission, the question arose how disruption of these cells may relate to the neuropathic pain observed to develop following SCI. Thus both NADPH-d and fos expression were again examined, but this time in conjunction with the sensory function of the rats. Sensory thresholds to pain-like behaviour were determined prior to and after injury using Von Frey filaments. Rats that demonstrated a decrease in sensory threshold of at least two Von Frey filament gradations (>70%) were classed as allodynic, while those with a less than a 70% decrease in threshold were classed as non-allodynic. A subpopulation of each of the groups of rats (uninjured, non-allodynic and allodynic) underwent a somatic stimulation paradigm. It was found that stimulation resulted in an increase in the number of NO producing cells but only in the allodynic group of animals. Since this group of animals by definition would perceive this stimulation as noxious, it is likely that the noxious nature of the stimulation resulted in the increased number of NO producing cells observed. This effect occurred only in segments adjacent to the injury. When fos expression was examined in the uninjured animals it was noted that somatic stimulation resulted in a decrease in fos expression, almost exclusively in lamina III. Following injury, there was no change in fos expression in lamina III observed. Instead the only change observed was an increase in fos expression in the deep dorsal horn (DDH, lamina IV and V). This occurred most profoundly in the allodynic group. These results suggested that SCI may lead to misprocessing of sensory signals such that non-noxious somatic stimuli are processed in the DDH rather than lamina III following SCI. It is proposed here that this change in laminae processing may be responsible for the perception of pain towards a non-noxious stimulus, and that the reported injury-induced loss of NO producing inhibitory interneurons in the SDH may be responsible for this alteration in sensory processing following SCI. Sensation is also processed by a number of supraspinal structures and a number of these have been implicated in the development of neuropathic pain states. The effects of SCI on neuronal activity as well as NO synthesis were examined in the periaqueductal grey region of the mid brain (PAG). SCI was shown to result in reduced neuronal activity in the PAG. This reduction in activity did not follow the somatotopy of the lateral column of the PAG (lPAG). It was suggested the reduced activity may not be solely caused by reduced spinal input as a result of SCI. Reduced neuronal activity in the PAG may indicate reduced PAG function, which includes descending modulation of spinal sensory transmission. Injury was not found to alter NADPH-d expression in the PAG. The effect of traumatic lumbar SCI on the parietal (sensorimotor) cortex of the rat was also examined, as loss of inputs following SCI have been shown to result in a profound reorganisation of the cortex. Results indicated that SCI results in a virtual cessation of neuronal activity in areas 1 and 2 of the parietal cortex, likely as a result of lost afferent drive. Theories of cortical plasticity suggest that while the primary inputs via the lumbar spinal cord may be lost following SCI, other less dominants input will remain and become more dominant. It has been proposed previously that cortical reorganisation involves a rapid reorganisation of the entire sensory system. It was interpreted that a similar process may explain the system-wide reduction in neuronal activity observed in the present series of studies.

Includes bibliography (leaves 191-219). / Copy 2 lacks some pages. / x, 219 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the levels of insulin-like growth factor and the presence of IGF binding proteins in human wound fluid. Tests the potency of IGF-1 and 2 analogues in in vitro models of fibroblast activity and their effect on healing in normal and diabetic rodent wounds. Shows that IGF-1, IGF-2 and their binding proteins are present in fluid from a partial thickness cutaneous wound; that the binding proteins negatively modulate the activity of insulin-like growth factors in vitro, but that the IGFs do not necessarily show enhanced activity in vivo at the wound site if binding protein affinity is decreased. Discusses possible roles of these binding proteins in wound repair. / Thesis (M.D.)--Dept. of Surgery, University of Adelaide, 2001?

Thesis (M.S.) -- Mississippi State University. Department of Agricultural and Biological Engineering. / Title from title screen. Includes bibliographical references.

Tibial stress fractures are common in runners. However, it is unclear what factors are associated with tibial stress fractures. This study aimed to investigate 1) magnitudes of bone contact forces occurring while running 2) whether or not repeated application of running loads is sufficient to explain tibial stress fractures and 3) whether or not muscle fatigue alters the potential of tibial stress fractures. Tibial stress fractures were predicted through an estimation of the minimum number of cycles to failure (Nfail) using an integrated experimental and mathematical modeling approach. Short running trials within a speed range of 3.5-4 m/s of ten male runners were evaluated with a coupled force plate and 3 dimensional motion analysis system. The collected data were used to estimate joint reaction forces (JRF) and joint moments. Using these JRF and muscle forces predicted from optimization, 2-D bone contact forces at the distal end of the tibia were determined. Next, tibial stresses were estimated by applying these bone contact forces to a tibial model, which were then used to predict the Nfail. All procedures were repeated after plantarflexors fatigued from prolonged running. This study found that peaks of compressive and posterior shear forces occurred during mid stance, and these peaks equaled 8.91 ± 1.14 BW and -0.53 ± 0.16 BW, respectively. These bone contact forces led to a backward bending of the tibia during most of the stance phase and resulted in the maximum stresses of - 43.4 ± 10.3 MPa on the posterior face of the tibia. These maximum stresses predicted the group mean of Nfail as being 5.28*10⁶ cycles. However, 2.5% to 56% of population of runners have a chance of getting tibial stress fractures within 1 million cycles of a repeated foot impact. Within the context of muscle force and stress estimation procedures used in this study, Nfail appeared to increase after fatigue, not decrease as we hypothesized. / Graduation date: 2005

The purpose of this study was to compare the levels of bone mineral density (BMD) of the whole body (WB) and proximal femurs of physically active men with spinal cord injuries (SCI) to nonactive men with spinal cord injuries. Also, the lean muscle mass (LMM) of active men with SCI was compared to the LMM of nonactive men with SCI. In addition, BMD values of the radii of physically active men with SCI were compared to that of able bodied men of the same age. The subjects N. 46 were between the age of 20-55 (��=37.83 �� 6.63 years), and were at least 2 years post spinal cord injury. Subjects with SCI were matched on similar level of lesion of the spinal cord, age, height, weight, and years post injury for the purpose of analyzing data. There were 14 active men with paraplegia and 14 nonactive men with paraplegia, 9 active men with quadriplegia and 9 nonactive men with quadriplegia. All BMD data was obtained utilizing a Hologic QDR 1000W dual energy x-ray absorptiometer. A two-factor (level by group) analysis of variance revealed no significant difference for all sites (Whole body, Total hip, radii, LMM) comparing the active and nonactive men with SCI. T-scores and z-scores generated from the Ho logic QDR 1000/W were analyzed using two-factor ANOVA (level by group). The active men with paraplegia had significantly higher BMD levels for all sites when compared to the other groups. These values may be explained by the number of incomplete injuries in the experimental group. Subjects in the physically active group did not clearly show a statistically significant difference on any of the dependent measures. However, values for the dependent measures were higher for the physically active group compared to the values of the nonactive group. / Graduation date: 1995

Graduation date: 2006 / We hypothesized that calpain activity is elevated in response to muscle damage. To test this hypothesis, we examined the degradation of α-fodrin into its 150 and 145 kDa fragments following either 20 eccentric or isometric contractions. In addition, experiments were performed in the presence or absence of E-64-d, a calpain inhibitor. Both EDL and SOL muscles displayed significant differences (p<0.003 and p<0.002 respectively) between the raw and normalized 150 and 145 kDa α-fodrin fragments of the DMSO + E-64-d compared to the other bath treatments. Based on our model of exercise-induced muscle damage, we expected to see greater levels of 150 and 145 kDa α-fodrin fragments in those muscles that performed the eccentric protocol. However, there was no evidence that eccentric muscle damage increased the levels of 150 and 145 kDa α-fodrin fragments over the levels observed in the isometric trials. These findings suggest that the magnitude of damage was insufficient to activate calpains.

Augmented Soft Tissue Mobilization, a massage therapy which uses a solid instrument rather than human fingers to treat musculoskeletal injuries, has been successful in treating tendinitis. Davidson et al. studied the functional and morphological affects of ASTM on collagenase induced Achilles tendinitis in Sprague-Dawley rats. Morphological observations showed a significant increase in the number and activation of fibroblasts in the ASTM treated Groups. The authors suggested that the physical force of ASTM may promote tendon healing via increased fibroblast recruitment. An important, but unexplained, question is how ASTM would affect the fibroblasts of native, noncollagenase injured, tendons. Studies have shown that mechanical forces can alter cellular functions. The purpose of this study was to examine the morphological changes in native Sprague-Dawley rat Achilles tendons after ASTM therapy using different application pressures.Three animal Groups were randomly established: A) control Group with no ASTM; B) light ASTM with 1 Newton of pressure; and C) heavy ASTM with 3 Newtons of pressure. Upon completion of the therapy, the Achilles tendons of each Group were examined with light and electron microscopy techniques to assess fibroblast number, tendon morphology, and the presence of type I and type III collagen. Fibroblast counts from each Group were compared using a two-way ANOVA, multiple regression, and curvilinear regression analysis. Morphological differences were shown between the three Groups, especially between the non force Group and the two force Groups. The ASTM Group treated with one Newton demonstrated the greatest mean fibroblast count (165.1+/-55.8&160.7+/-49.8). Electron microscopy revealed the presence of activated fibroblasts in the tendons of the two force Groups, ASTM Groups. Polarizing microscopy showed a dramatic increase in the amount of Type III collagen in the two force Groups compared to the non force Group.Ball State UniversityMuncie, IN 47306