Complex Regional Pain Syndrome (CRPS) is an extremely debilitating condition, characterized by chronic pain with associated trophic changes. The 1st description of this condition dates back to 1864. The condition has been variously described over the years as “causalgia”, “Sudeck’s dystrophy” and “reflex sympathetic dystrophy”. In 1993 the International Association for the Study of Pain (IASP) introduced the term Complex Regional Pain Syndrome (CRPS) with diagnostic criteria that are currently used. CRPS was subdivided into type I and type II. CRPS type I is diagnosed when there is no obvious nerve injury, whereas CRPS type II refers to cases with nerve injury. It follows that the present diagnostic criteria depend solely on meticulous history and physical examination without any confirmation by specific gold standard tests. The pathophysiology of this pain syndrome is poorly understood; however there is growing evidence for an inflammatory or sympathetic cause. It is therefore not surprising that there is no uniform approach to its management. Therapy is often based on a multi-disciplinary team approach with use of non –pharmacological therapy (physiotherapy and occupational therapy), pharmacological therapy (analgesics, neuroleptics, bone metabolism drugs), and invasive therapy (stellate ganglion blocks and sympathectomy). This review acknowledges the humble beginnings of this condition, and provides an understanding for the evolution of its terminology. It objectively reviews the current IASP diagnostic criteria, challenging its efficacy and sensitivity. Despite its pathophysiology remaining an enigma, the latest pathophysiological advances are reviewed in the endeavour to better understand this condition and enhance treatment options. The role of surgical sympathectomy for this condition is reviewed, highlighting its importance and underappreciated success in the management of CRPS. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

Background: Downhill running involves eccentric contractions of the gluteal, quadriceps, hamstring and calf muscles and the lengthening of muscle fibres as they contract. Several studies have demonstrated that this type of prolonged eccentrically biased exercise induces tissue damage and subsequent enhancement of an inflammatory response. Traumeel® S (Heel GmbH, Baden-Baden, Germany) is a homeopathic-complex used to treat trauma and inflammatory processes that is sold as an over the counter remedy in pharmacies. Although the antiinflammatory and analgesic effects of Traumeel® S have been demonstrated in selected clinical trials as well as in in vitro experimental models, little is known of its scientific mechanisms of action. Aim: The aim of this study was to establish whether administration of Traumeel® S five days before and three days after a 90-minute downhill treadmill run at 75% V02 peak significantly changes systemic markers of the inflammatory response. These are to include blood-borne concentrations of Cortisol and examples of selected T-helperrcell cytokines, T-helper2-cell cytokines, chemokines and pro-inflammatory cytokines during the three days following the 90-minute downhill run. Method: This study was designed as a double-blinded, placebo-controlled clinical trial in which matched subjects were randomised to Traumeel (TRAU) and Placebo (PLAC) pairs and exposed to two 90-minute downhill running trials. Twenty subjects (12 men, 8 women) aged between 20 and 50 years, fully complied with all inclusion criteria set for the study. Following baseline laboratory and field testing, they were matched according to gender, body mass index (BMI), training age, training status, peak running performance and foot-strike patterns and randomized into TRAU and PLAC groups. One Traumeel® S tablet was ingested three times per day for five days prior to and three days following a 90-minute downhill run on a treadmill at a -6% gradient and at a speed eliciting 75% V02 peak on a level gradient. Blood samples were obtained immediately before the 90-minute trial (PRE), immediately after the trial (IPE) and 24 hours (24 PE), 48 hours (48 PE) and 72 hours (72 PE) following the trial. Each subject was also requested to complete a training record prior to the trial and keep a record of the daily symptoms of delayed onset muscle soreness (DOMS) both at rest (general pain) and while walking (daily living). Full blood counts, serum creatine kinase (CK) and Cortisol concentrations were determined using standard haematological laboratory procedures. A sandwich ELISA was used to determine plasma interleukin-6 (IL-6) concentrations. A commercial bead-array kit was used to conduct flow cytometric analysis of Interleukin-8 (IL-8), Interleukin-10 (IL-10), Tumour Necrosis Factor alpha (TNFa), and Interleukin-12p70 (IL-12p70) concentrations. Results: Paired student Mests indicate that the mean ± SEM of the two groups was not significantly different (p < 0.05) in terms of age, BMI, percentage body fat, training age, foot strike patterns, running performance, FVC, FEV1; baseline heart rate and blood pressure, RERmax, V02 peak, VEmax, or training status. Although the TRAU group completed the 90-minute downhill running trial at a significantly faster speed (13.3 ± 2.1 vs. 12.8 ±0.3 km.hr; p = 0.02) and covered a greater distance (20.1 ± 0.3 vs. 19.34 ± 0.4; p = 0.03), mean and maximum heart rate and RPE did not differ between trials in the TRAU and PLAC groups. The downhill running protocol resulted in significant increases in neutrophil counts and creatine kinase, Cortisol, IL-6, IL-8 and IL-10 concentrations in the circulation (n = 20; p < 0.001). When comparing the TRAU (n = 10) and PLAC (n = 10) groups, blood neutrophil counts, creatine kinase, Cortisol, and IL-6 concentrations over the 5 time points and PRE, IPE and 24 PE plasma TNF, IL-8, EL-10 and EL-12p70 concentrations did not differ significantly (p > 0.05). Blood creatine kinase was, however, significantly higher in the TRAU group at 24PE (p < 0.05). The post-trial DOMS scores reported by the TRAU group over the 3-day post-exercise recovery period were also significantly lower in the TRAU group at 24PE (p = 0.03). Conclusion: Despite a faster running speed and higher post trial CK concentration in the TRAU group following the 90-minute downhill run, statistically significant differences in circulating stress hormone, and cytokine concentrations (IL-6, IL-8, IL-10, TNFa and IL-12p70) between the TRAU and PLAC groups, were not identified. Delayed onset muscle soreness was also significantly lower in the TRAU group at 24 hours post trial (p = 0.03). While these findings would support attenuation of the post-exercise inflammatory response by Traumeel® S, further work is required to verify this possibility. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2008.

Thesis (M.S.)--University of Hawaii at Manoa, 2006. / Includes bibliographical references (leaves 108-110). / x, 110 leaves, bound ill. (some col.) 29 cm

Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references (leaves 40-51). / ix, 51 leaves, bound ill. (some col.) 29 cm

The objective of this thesis is to investigate the pathophysiology of the coronary slow phenomenon (CSFP). The experimental work of this thesis has taken a 'bedside to benchtop' approach with clinical observations made in the second chapter guiding the application of basic research techniques in subsequent chapters. Chapter 1 ; The CSFP is a disorder of the coronary microcirculation ; hence chapter 1 specifically reviews the current understanding of this vascular territory and concludes with a summary of the clinical disorders affecting it, concentrating on the CSFP. Chapter 2 ; investigated the angiographic response of the CSFP to a calcium channel blocking agent with antianginal efficacy in this disorder ( mibefradil ). Mibefradil administration was associated with an acute improvement of coronary flow indices which occurred despite background vasodilator therapy with conventional calcium channel antagonists. Chapter 3 ; investigated the in vitro response of human microvessels to mibefradil in comparison to conventional calcium channel blockers. Mibefradil was found to be a more potent agent both in terms of vasodilatation and the prevention of vasoconstriction. Both findings support the clinical observations and point to its selective action on the calcium T channel subtype as a potential mechanism. Chapter 4 ; examined the expression of T type calcium channels at the level of the microvasculature and compared T channel expression in CSFP patients and controls. T channels were found to be expressed at two or more orders of magnitude greater than the L channels. No difference in T channel expression between patients and controls was found. Chapter 5 ; examined the vasomotor reactivity of isolated subcutaneous arterial microvessels to various vasoactive substances between controls and CSFP patients. CSFP patients were found to have a selective hyper reactivity to endothelin. Chapter 6 ; examined plasma endothelin levels in CSFP patients and controls and the relationship between endothelin levels and angina frequency in the CSFP cohort. A small but statistically significant elevation of endothelin-1 was present in patients with the CSFP. A positive association between plasma endothelin fluctuation and angina frequency was also found in the CSFP cohort but not between absolute endothelin levels and angina symptoms. / Thesis (Ph.D.)-- The University of Adelaide, School of Medical Sciences, 2006.

This is an original study to quantify and grade defect healing in a large animal cranial bone substitute model. The study of various therapies to heal cranial defects requires an appropriate ?critical? animal model. An experimental animal model should be analogous and recognizable as an appropriate challenge to human physiology. In addition, the defect must fail to heal unless treated with the tissue engineering therapy under study. Sheep as a large animal model was chosen because of its ability to tolerate creation of large skull defects analogous to clinical scenario, and its biology of healing as a high order mammal would be closer human beings. There is no agreement on the critical size limits for cranial defects. Various sizes have been termed "critical" in publications utilizing sheep. These ranged from 20-22mm. This study will investigate whether a 20mm defect is adequate. Bilateral circular cranial defects of 10, 20 and 25mm diameters were created in 12 adult sheep. Based on guided tissue engineering principles, defect protection was utilized to prevent in-growth of fibroblasts and other connective tissue cells from the surroundings. As bone tissue regeneration strategies usually involve osteoconduction element, an animal model that considered the defect protection role of osteoconduction would be more appropriate. Repopulation and regeneration of the defect was maximized as an added challenge Bioresorbable polylactic acid co-polymer mesh (MacroPoreTM) and Titanium mesh (TiMeshTM) was used as defect protection. The cranial defects were harvested at 8 and 16 weeks. The end-point analysis included Faxitron X-ray images, DEXA (Dual Energy X-ray Absorptiometry), and histology. The defects were graded to assess their ability to eventually heal. 10mm defects fully healed at 16 weeks. There was new bone formation spanning the entire defect seen on histology. 25mm defects were spanned by thin fibrous tissue only. There was variability in the healing potential of 20mm defect. Based on presence of bone islands within the defect, half of the 20mm defects demonstrated ability to heal while the other half actually had new bone spanning the defects on histology. Critical size cranial defect in sheep for the study of bone graft substitute has to be larger than 25mm diameter. The model is then utilized to study the use of Pro Osteon and AGF compared with the gold standard of autologous bone graft.

Electrical stimulation of retinal neurons is known to elicit visual sensations. When applied to the retina in a spatial pattern, electrical stimulation may be capable of providing rudimentary patterned vision that may be of benefit to sufferers of degenerative retinal disorders. No such device has yet been devised to provide for chronic study of the psychophysical perceptions elicited from a prosthesis for retinal stimulation. In this study, steps towards achieving this goal have been successfully carried out. Foregoing research was reviewed such that appropriate stimulation parameters were incorporated in the design of a 100 stimulation channel, complimentary metal oxide semiconductor (CMOS) integrated circuit, small enough in size so as to be capable of being implanted within the ocular anatomy or surrounding orbit. The device, and its associated external hardware and software were designed, modeled, fabricated, and interfaced with stimulating electrodes in acute testing in a highorder mammal (Ovis aries) so as to assess the capabilities of the device to elicit cortical potentials as a direct result of stimulation of the neural retina. Testing was performed under conditions similar to those anticipated in chronic in-situ configurations wherein radio-frequency telemetry was used to deliver power and configuration parameters to the device thus avoiding the passage of wires through tissue in order to communicate to the implant circuit. The results of the testing indicate that the circuit is indeed capable of eliciting physiological responses in the animal and evidence is present that these responses could be elicited in patterned form. Further work undertaken includes the development of surgical methods for implantation, and application of the prosthesis circuit in functional electronic stimulation.

Bibliography: leaves 1-26. / xvi, [271] leaves : bill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Develops a sensitive rat model of benzodiazepine tolerance and withdrawal using objective and continuous measures (activity, electromyographic activity and body temperature) recorded by radiotelemetry / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 1998?

Bibliography: leaves 168-184. / 184 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The work in this study encompasses oxygen free radical related inflammation in the peripheral lung and in lung cells. Animal and human studies have been used. Methods include cell culture with function studies, protein chemistry, animal and human physiology, and cell and lung structure through histopathology, and various forms of electron microscopy. The work resulting from this thesis has formed an important basis for understanding acute and chronic lung injury. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 2000

Includes articles co-authored by the author during the preparation of this thesis. / Includes erratum on back leaf. / Includes bibliographical references (leaves 257-299). / xvii, 300 [27] leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines regional variations in trabecular bone remodelling and bone loss following oophorectomy in the distal femur of the rat. The studies reveal a complex interaction between weight bearing and ovarian hormone deficiency, and show that physiological signals exist which can negate all adverse effects of postmenopausal osteoporosis / Thesis (Ph.D.)--Adelaide University, Dept. of Physiology, 2001