Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

M.A. / Spinal cord trauma resulting in paraplegia or quadriplegia is one of the most devastating injuries. A frequent complication of spinal cord injury is intractible pain. It compounds a host of personal and social consequences: disruption of personal roles, dysfunctional marital and family relationships, unemployment, financial hardship, depression, anxiety, lowered self-esteem and hopelessness. There is an abundance of research on pain in general, but a dearth of literature on chronic pain in the spinal cord injured population - especially in the South African context. This study examined the psychosocial impact of pain on spinal cord injured patients in a hospital setting. Specifically, it addressed six core research questions, concerned with the physiological components of pain, and the social, affective and rehabilitation consequences of pain for spinal cord injured patients. The effects of etiology and level of lesion, age, gender and culture on the general pain experience were investigated. The purpose of this study was to accurately describe the phenomenon of pain as experienced by spinal cord injured (SCI) patients. The evidence showed that pain was a serious problem for SCI patients. A variety of physical and social modifiers of the pain experience were identified, as were several important temporal features of pain. SCI patients reported high frequencies of social, affective (depression, low selfesteem, suicidal responses and partner relationship problems), and rehabilitation consequences. The etiology of spinal cord injury was found to be related to pain intensity, while the level of the lesion was not associated with pain intensity or frequency. Some effect was found for age, however, gender did not contribute to the variance of any of the dependent variables. The culture of SCI patients plays an important role in both pain perception and the psychosocial and rehabilitation consequences of chronic pain. The results suggest that pain in SCI patients, as in other pain populations, needs to be recognized as a complex, multidimensional phenomena. Successful treatment requires an understanding of the SCI patient's emotional and psychological, as well as his physical requirements. The role of pain assessment is fundamental to any pain management programme.

The prefrontal cortex (PFC) has long been thought to be the seat of social behaviours in mammals. Lesions of the orbitofrontal cortex (OFC), a subregion of the PFC, are known to cause social deficits in humans. Interestingly, social deficits are also seen in rats with OFC lesions. Rats that are deprived of peer play during development exhibit behaviour similar to OFC-ablated animals. Another subregion of the PFC, the medial prefrontal cortex (mPFC) is interconnected with the OFC. The mPFC and OFC have been shown to be reciprocally responsive to a variety of inuences, in terms of dendritic morphology. It was hypothesized that social experiences are necessary for the proper development of the OFC, and that, because of the interconnectivity, the mPFC would also be sensitive to social experience. The social condition in which juvenile rats were raised was manipulated, and the OFC and mPFC were shown to be differentially responsive to specific aspects of social experience. It was already known that OFC lesions produce specific social deficits, but the contribution of the mPFC to the production of social behaviour was unknown. To investigate the contribution of the mPFC to the performance of social behaviour, animals were given mPFC lesions, and their social play behaviour was quantified. mPFC-ablated animals had altered play patterns that were distinct from those seen in the OFC-ablated animals. It was concluded that the OFC and mPFC are differentially responsive to social stimuli during development, and that the OFC and mPFC make discrete contributions to the production of social behaviour. The results were interpreted in an evolutionary context. / x, 93 leaves : ill. ; 29 cm.

Hung, Sze Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 186-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

[Truncated abstract] There is limited intrinsic potential for repair in the adult human central nervous system (CNS). Dysfunction resulting from CNS injury is persistent and requires prolonged medical treatment and rehabilitation. The retina and optic nerve are CNSderived, and adult retinal ganglion cells (RGCs) and their axons are often used as a model in which to study the mechanisms associated with injury, neuroprotection and regeneration. In this study I investigated the effects of a variety of strategies on promoting RGC survival and axonal regeneration after optic nerve injury, including the use of reconstructed chimeric peripheral nerve (PN) grafts, gene therapy, and intraocular application of pharmacological agents and other factors . . . C3 transferase is an enzyme derived from Clostridium botulinum that inactivates Rho GTPase. Because SC myelin contains MAG and PN also contains CSPGs, I tested the effects of intraocular injection of a modified form of C3 (C3-11), provided by Dr Lisa McKerracher (CONFIDENTIAL data, under IP agreement with Bioaxone Therapeutic, Montreal) on RGC axonal regeneration into PN autografts. My results showed that there was significantly more RGC survival and axonal regeneration in PN autografts after repeated intraocular injection of C3. I also tested whether intraocular injections of CPT-cAMP and/or CNTF can act in concert with the C3 to further increase RGC survival and/or regeneration. Results showed that the effect of C3 and CPT-cAMP plus CNTF were synergistic and partially additive. The use of combination therapies therefore offers the best hope for robust and substantial regeneration. The overall results from my PhD project will help determine how best to reconstruct nerve pathways and use pharmacological interventions in the clinical treatment of CNS injury, hopefully leading to improved functional outcomes after neurotrauma.