published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Spinal cord injury (SCI) is a debilitating condition accompanied by motor and sensory deficits and a reduced quality of life. Current treatment options are limited and are associated with variable efficacy and a risk of adverse effects. The pathophysiology of SCI is initiated by a primary mechanical insult to the spinal cord, followed by a complex series of deleterious events known as secondary injury. Secondary injury processes include free radical formation, glutamate excitotoxicity, inflammation and cell death. Apoptotic cell death in particular plays a key role in the secondary injury processes and exacerbates tissue degradation and loss of function. The role of Fas-mediated apoptosis in SCI pathophysiology is poorly defined in the literature to date. Correlative evidence suggests that this form of cell death is delayed and occurs in white matter adjacent to sites of primary damage. The cellular and temporal mechanisms of Fas-mediated apoptosis following experimental SCI were evaluated using a clinically relevant clip compression SCI model in the rat. Furthermore, therapeutic manipulation of Fas activation using a soluble form of the Fas receptor (sFasR) was carried out to establish the efficacy and clinical relevance of targeting this aspect of secondary injury. This work shows that Fas-mediated apoptosis is an important contributor to secondary SCI pathology. Oligodendrocytes are targeted by this form of cell death in a delayed fashion post-injury, providing an opportunity for therapeutic intervention. Intrathecal administration of sFasR following SCI reduced post-traumatic apoptosis, improved cell survival, enhanced tissue preservation and resulted in an improved motor recovery. Administration of sFasR was effectively delayed by up to 24 hours post-injury, however a shorter delay of 8 hours post-injury was most efficacious. A surprising result emerged from this work. Delayed intrathecal administration of IgG following SCI showed significant efficacy in both cellular and tissue level outcomes, as well as at the functional level. Fas-mediated apoptosis is an important aspect of secondary SCI pathophysiology and is an attractive therapeutic target. The beneficial outcomes of manipulating Fas activation using sFasR provide further evidence for this. Future work will refine this treatment strategy, bringing it into the SCI patient population.

Pain is a remarkably complex and a multifaceted process, involving the interaction between physiological and psychological factors in unique ways. Among many other factors, the size of the affected surface area contributes to the pain experience, altering one’s pain perception. Spatial summation is the term used to describe this phenomenon, and is characterized by an increase in pain perception, or a decrease in pain threshold, when the affected surface area is increased. This project investigated the neuronal processes underlying spatial summation of heat sensations in healthy female volunteers, by means of functional magnetic resonance imaging (fMRI) of the central nervous system. The first study of this project involved increasing the surface area of skin stimulated by manipulating the number of thermal probes delivering thermal stimulation, which was delivered just below participants’ measured pain threshold. Surface area was increased on one hand and across two hands to determine the extent of spatial summation, and furthermore, to determine the effect on neural activity in the spinal cord and brainstem. The second study of this project involved increasing the surface area of skin stimulated by a noxious heat stimulus and its effect on pain perception and corresponding neural activity in the spinal cord, brainstem, and brain. Results from this project suggest that the central mechanisms contributing to the spatial summation of heat sensations involve many of many of the brainstem and brain regions involved in processing the emotional, motivational, and cognitive aspects of pain. Therefore, increasing the surface area of stimulation may alter pain perception by influencing the affective dimension of the sensation, rather than the sensory/discriminatory component. The combination of such structures may interact in a unique way to protect the body from potential, or further damage, by increasing the perception of pain through emotional, motivational and cognitive mechanisms. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-07-15 19:01:37.694

Dissertation submitted in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, Durban Institute of Technology, 2006. / Chronic Idiopathic Constipation (CIC) is a common patient complaint (Browning 1999) and as such is defined as : “Constipation” being the infrequent or difficult evacuation of faeces, “idiopathic”, denoting the condition occurs in the absence of any known cause and “chronic”, implying a problem that has persisted for a long time (Anderson 1989). It has been suggested that the bony subluxation or motion segment dysfunction in the spine, could produce these symptoms (e.g. altered visceral function) in the segmentally related visceral structures (Korr 1976, Nansel and Slazak 1995, Budgell 2000). In support of this three case reports in the literature suggest that spinal manipulative therapy to effect removal of these bony subluxations or motion segment dysfunctions, may relieve chronic idiopathic constipation (Hewitt 1993, Marko 1994, Redly 2000). However all three cases involved a single patient case analysis, where patients received spinal manipulation and a vast improvement in bowel function within three weeks of the initiation of the intervention was noted. Only one case report measured global wellbeing outcomes and was able to document a steady increase in the patient’s sense of wellbeing (Redly 2000). As a result of the above evidence in the literature, the researcher was led to the following hypotheses regarding spinal manipulation and chronic idiopathic constipation: • That spinal manipulation would affect a decrease in the subject’s abdominal pain intensity and level of constipation and an increase in the subject’s sense of wellbeing and spinal range of motion. • That placebo would affect an increase in the subject’s abdominal pain intensity and level of constipation and a decrease in the subject’s sense of wellbeing and spinal range of motion. • That spinal manipulation would be more effective than placebo in bringing about a decrease in the subject’s abdominal pain intensity and level of constipation and an increase in the subject’s sense of wellbeing and spinal range of motion. / M

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban Institute of Technology, Durban, 2006. / Core strengthening has become a major trend in the rehabilitation of patients suffering with lower back pain. Clinical trials have shown that core strengthening is beneficial for patients with low back pain. According to the literature, core strengthening consists of activating the trunk musculature in order to stabilize hypermobile symptomatic joints and thus lessen mechanical stress to the spine. Spinal manipulative therapy has also proved itself to be beneficial, particularly in the case of post-natal low back pain sufferers, as manipulation may correct hypomobility associated with spinal subluxations. Literature suggests that spinal manipulative correction of spinal subluxations in combination with core stability exercises, that stablise symptomatic hypermobile joints, may have more advantages than using these interventions singularly in the treatment of post-natal low back pain. However, the combination of a core stability muscle training program with spinal manipulative therapy has yet to be investigated. In order to choose the most appropriate therapy for managing this condition, it is essential for research to be carried out to identify the most effective treatment, which would allow for better overall management of low back pain during the post-natal period. Therefore this study was designed to establish the effectiveness of a combined protocol of spinal manipulation and core stability exercises in the treatment of post-natal mechanical low back pain and to establish whether this protocol should be utilized routinely in the management of this condition. / M

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban University of Technology, Durban, 2008. / Objectives: To compare trunk flexion and lateral flexion range of motion (ROM) pre-post intervention. To compare the bowling speed of Action Cricket fast bowlers pre-post intervention. To determine the correlation between change in bowling speed immediately post-intervention to change in trunk flexion and lateral flexion ROM immediately post-intervention. To determine the association between change in bowling speed immediately postintervention and the subjects' perception of change in bowling speed. Methods: Forty asymptomatic Action Cricket fast bowlers were divided into four groups of ten each. Group 1 received lumbar spine manipulation, Group 2 received thoracic spine manipulation, Group 3 received combined thoracic and lumbar spine manipulation and Group 4 received the sham laser intervention (placebo). Pre- and post-intervention trunk flexion and lateral flexion ROM and bowling speed were measured using a digital inclinometer and a SpeedTrac\x99 Speed Sport Radar. The subjects' perception of a change in bowling speed post-intervention was also recorded. SPSS version 15.0 was used to analyse the data. Twotailed tests were used in all cases. Results: Trunk flexion and lateral flexion increased significantly (p < 0.05) post-spinal manipulation. There was a significant increase in bowling speed post-thoracic (p = 0.042) and postcombined manipulation (p < 0.000). A significant yet weak positive correlation (p = 0.003; r = 0.451) was seen in change in bowling speed and change in thoracic flexion and lateral flexion. There was no significant difference in the percentage subjective change by intervention group (p = 0.217). Conclusions: Spinal manipulation is a valid intervention for short-term increase in bowling speed. / M

Class of 2012 Abstract / Specific Aims: The goal of this project was to evaluate the use of a preparation of the brainstem and spinal cord of neonatal rats that has been widely used for observing and quantifying central nervous activity, as well as the response to pharmacological manipulation. To achieve this, we specifically aimed to remove the intact brainstem and spinal cord of newborn rats, and develop a preparation that would maintain physiological function and allow for recording of electrical activity. Methods: Multiple dissections were performed on neonatal rats. Conditions during the dissections were controlled to maintain physiological function. Once removed, the intact brainstem and spinal cord was placed in a preparation that allowed for manipulation and access to nerve rootlets. Finally, glass suction electrodes were used to record electrical activity directly from the nerve rootlets. Once recorded, the data were stored on a hard drive for further analysis. Main Results: We were successful in isolating the intact brainstem and spinal cord in neonatal rats while maintaining physiological conditions and nervous activity. The preparation allowed for easy access to nerve roots as well as customization for different experiments. We were also successful in recording nerve activity in the preparation and collection of data for use in future experiments Conclusions: We conclude that the brainstem spinal cord preparation described in this study is a valuable tool that allows for recording and analysis of nerve activity, and specifically for measurement of respiratory motor output. This is a preparation that can be used in a variety of experiments that attempt to observe or quantify the activity of central nerve cells and allows for pharmacological interventions that could be applied in various experiments.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban Institute of Technology, Durban, 2006. / Core strengthening has become a major trend in the rehabilitation of patients suffering with lower back pain. Clinical trials have shown that core strengthening is beneficial for patients with low back pain. According to the literature, core strengthening consists of activating the trunk musculature in order to stabilize hypermobile symptomatic joints and thus lessen mechanical stress to the spine. Spinal manipulative therapy has also proved itself to be beneficial, particularly in the case of post-natal low back pain sufferers, as manipulation may correct hypomobility associated with spinal subluxations. Literature suggests that spinal manipulative correction of spinal subluxations in combination with core stability exercises, that stablise symptomatic hypermobile joints, may have more advantages than using these interventions singularly in the treatment of post-natal low back pain. However, the combination of a core stability muscle training program with spinal manipulative therapy has yet to be investigated. In order to choose the most appropriate therapy for managing this condition, it is essential for research to be carried out to identify the most effective treatment, which would allow for better overall management of low back pain during the post-natal period. Therefore this study was designed to establish the effectiveness of a combined protocol of spinal manipulation and core stability exercises in the treatment of postnatal and mechanical low back pain and to establish whether this protocol should be utilized routinely in the management of this condition. / M

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Surgical correction of Adolescent Idiopathic Scoliosis (AIS) carries a substantial risk of complication. The literature supports improved perioperative outcomes through the two surgeon strategy in other complex orthopedic procedures. Does the presence of 2 versus 1 attending surgeons affect the perioperative morbidity of posterior spinal fusion (PSF) in patients with AIS curves greater than 70°? We reviewed the database from a large regional children’s hospital of all patients with AIS curves greater than 70° who underwent PSF from 2009‐2014 and divided the cohort into single versus 2‐surgeon groups (28 vs. 19 cases, respectively). We analyzed cases for length of surgery, estimated blood loss, and length of stay. The groups were identical when comparing age, gender, spinal levels fused, and average ASA score. However, the average Cobb angle in the single surgeon group was significantly less than in the 2 surgeon group at 78.4 vs 84.0 degrees, respectively (p=0.049). Mean operative time for single versus 2 surgeons was 238 (SD 48) vs 212 (SD 46) minutes (p=0.078). Mean percent estimated blood loss was 26% (SD 14.1) for single surgeon vs 31% (SD 14.9) for 2 surgeons (p=0.236), and mean estimated blood loss for single surgeon vs 2 surgeons was 830ml (SD 361) vs 1045ml (SD 346) (p=0.052). Mean length of stay was significantly decreased in the 2 surgeon group at 5.16 days (SD 1.7) versus the single surgeon group at 6.82 days (SD 6.82) (p=0.002). The use of 2 surgeons in AIS deformity correction at an experienced regional children’s hospital did not improve clinical outcomes. The average length of stay was reduced in the two‐surgeon group, but there was no significant impact on blood loss or operative time. However, this study does not rule out the potential for positive impact with a two‐surgeon strategy, and given previous supportive data in the literature, this approach should further evaluated to determine its effect on improving perioperative outcomes.