A dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic at Technikon Natal, 2002. / Carpal Tunnel Syndrome is defined as a median nerve entrapment beneath the flexor retinaculum in the carpal canal such that it produces symptoms in the hand, wrist and upper extremity. A review of related literature suggests that statistics on the incidence of Carpal Tunnel Syndrome in South Africa are unavailable. In the U. s. A, Carpal Tunnel Syndrome occurs in 1% of the population and is the most frequently diagnosed peripheral neuropathy. Several studies investigating the use of conservative care in managing Carpal Tunnel Syndrome have been performed, but none have compared the effect of wrist joint manipulation and ultrasound in the management of Carpal Tunnel Syndrome, The purpose of this study was to investigate the effectiveness of wrist joint manipulation compared to ultrasound in the management of Carpal Tunnel Syndrome. This randomized controlled clinical trial consisted of a study population offorty patients. The patients were randomly allocated to two groups of twenty each. One group received wrist joint manipulation while the other received ultrasound application to the palmar-radial aspect of the wrist. Both groups received four treatments over a two week period. Subjective measures included the Numerical Rating Scale-I 0 1 Questionnaire and the Carpal Tunnel Pain and Disability Form and objective measures consisted of the grip strength reading and goniometer readings for wrist flexion and extension. Both the subjective and objective measures were taken before the first and third visit and at the fifth follow- up consultation which took place during the following week. Inter-group analysis was done using the Mann- Whitney U test. Friedman's T test was used for intra-group analysis. ct was set at the 0.05 level of significance. The results were illustrated by means of tables and bar- charts. The results indicated that for intragroup analysis, a statistically significant difference existed for both groups, warranting the use of a multiple comparison procedure (Dunn' s procedure) to determine at which stage the treatment made a significant difference. For all the measures except the wrist extension reading in the ultrasound group, most improvement occurred between the first and fifth consultations. For inter-group analysis, no significant difference for any of the measures, except the wrist extension readings, was present between the two groups indicating that both wrist joint manipulation and ultrasound were equally effective in treating Carpal Tunnel Syndrome. The improvement in wrist extension, in the wrist joint manipulation group was significantly better than that in the ultrasound group. Although this study was limited by its single researcher design and could not clarify which treatment protocol was more effective, it supports the existing body of evidence in favour of both wrist joint manipulation and therapeutic ultrasound application in the management of Carpal Tunnel Syndrome / M

M.A. (Counselling Psychology) / Please refer to full text to view abstract

Ph.D. (Botany) / The most well-known tonic plants in South Africa have been used traditionally for the treatment of a great variety of ailments but aspects of their ethnobotany and chemistry remain poorly studied. Possible relationships between their ethnobotany and pharmacology are mostly speculative. In this study, literature reviews of the ethnobotany of these plants were combined with phytochemical screening studies and bitterness taste testing results in order to establish constituent patterns which may contribute to a scientific rationale for the claimed tonic (stimulating) properties of these plants. The tonic concept and definitions of terms associated with it are often used incorrectly and ambiguously. An analysis of literature on the traditional healing systems across the globe was used to establish the historical and cultural aspects relevant to tonics. This analysis revealed that sickness/illness is usually considered to be a result of imbalance in many cultures, whether this imbalance is between the patient and the environment or due to a lack of homeostasis in the body. In several healing cultures substances or mixtures of substances are used to rectify these imbalances through proposed effects on several bodily systems concurrently. According to some cultures, as in Eastern and Indian traditional medicine, tonic plants are considered superior to other medicinal plants in that they impart health, strength and a general sense of well-being, as well as being prophylactic. This definition of a tonic plant is consequently broad, but excludes plants merely used as multipurpose medicines. Where these tonics exhibit a specific mode of action, further classification is required, i.e. as bitter, adaptogenic, alterative, adjuvant or stimulant tonics. The South African traditional tonic plants studied were Agathosma species (Rutaceae), Aloe species (Asphodelaceae), Arctopus species (Apiaceae), Artemisia afra (Asteraceae), Balanites maughamii (Balanitacae), Dicoma species (Asteraceae), Harpagophytum procumbens (Pedaliaceae), Hypoxis hemerocallidea (Hypoxidaceae), Muraltia heisteria (Polygalaceae), Sutherlandia species (Fabaceae), Vernonia oligocephala (Asteraceae), Warburgia salutaris (Canellaceae), Withania somnifera (Solanaceae) and Ziziphus mucronata (Rhamnaceae). A detailed compendium of medicinal applications was compiled following a thorough, in-depth scrutiny of the historical and medicinal ethnobotany of each of these species. Such ethnobotanical data is important in understanding the cultural aspects of healing in southern Africa, and provides valuable direction and focus with regards to the phytochemical and pharmacological research of these plants.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic in the Faculty of Health at Technikon Natal. / Myofasciitis IS a very common yet misunderstood problem. There are many treatments available yet there is no research to substantiate which of the many treatments available is the most effective (Travell and Simons 1983:6). The purpose of this study was to investigate the relative effectiveness of Cryotherapy versus moist heat in the treatment of myofasciitis of the shoulder girdle muscles. Patients for this comparative, randomized clinical trial were obtained by consecutive sampling. Any patient between eighteen and fifty-five presenting to the Chiropractic Clinic at Technikon Natal with neck pain, upper back pain or shoulder paIn was considered a potential candidate. Thirty patients underwent a screening process to assess their viability for the study. This screening procedure consisted of questions regarding the pattern of pain referral and of palpation of the relevant zones for muscle spasm, twitch responses, patient jump sign and/or referred palll. The thirty patients were randomly divided into two groups of fifteen. One group received cold and passive stretching and the other group received moist heat and passive stretching. Each patient was treated five times within a three week period. Thereafter a follow-up appointment was scheduled one month after the final treatment to assess the long term effects of the treatments . The subjective information was questionnaires: (1) the CMCC Neck Numerical Pain Rating Scale-l0l assessed us Ing three Disability Index, (2) the and (3) the Short Form McGill Pain Questionnaire. These three forms were used to subjectively assess vanaus aspects of the patient's pain. Patients were required to fill these forms out at the first and final appointment. / M

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic in the Faculty of Health at Technikon Natal / Myofasciitis IS a very common yet misunderstood problem. There are many treatments available yet there is no research to substantiate which of the many treatments available is the most effective (Travell and Simons 1983:6). The purpose of this study was to investigate the relative effectiveness of Cryotherapy versus moist heat in the treatment of myofasciitis of the shoulder girdle muscles. Patients for this comparative, randomized clinical trial were obtained by consecutive sampling. Any patient between eighteen and fifty-five presenting to the Chiropractic Clinic at Technikon Natal with neck pain, upper back pain or shoulder paIn was considered a potential candidate. Thirty patients underwent a screening process to assess their viability for the study. This screening procedure consisted of questions regarding the pattern of pain referral and of palpation of the relevant zones for muscle spasm, twitch responses, patient jump sign and/or referred palll. The thirty patients were randomly divided into two groups of fifteen. One group received cold and passive stretching and the other group received moist heat and passive stretching. Each patient was treated five times within a three week period. Thereafter a follow-up appointment was scheduled one month after the final treatment to assess the long term effects of the treatments . The subjective information was questionnaires: (1) the CMCC Neck Numerical Pain Rating Scale-l0l assessed us Ing three Disability Index, (2) the and (3) the Short Form McGill Pain Questionnaire. These three forms were used to subjectively assess vanaus aspects of the patient's pain. Patients were required to fill these forms out at the first and / M

Tumour initiation and progression occur due to oncogenic mutations that also contribute to therapeutic resistance in many human tumours. Mutations activating the "PI3K/AKT" signalling pathway and inactivating the "TP53" tumour suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. p53 mutant (p53mut) tumours not only fail to respond to DNA damaging therapy, but are also described to promote therapeutic resistance by dominant negative suppression of p53 dependent promoter activity. Our work identifies the crucial interaction between the PI3K/AKT pathway and p53 mutations that regulate treatment sensitivity in tumours. Using a combination of in vitro and in vivo techniques we demonstrate that AKT inhibition promotes reduced cellular levels of p53mut via a novel Nucleophosmin 1 (NPM) mediated regulation of the tumour suppressor p14ARF and promotes re-engagement of cell cycle arrest, senescence and increased sensitivity to ionising radiation in both in vivo and in vitro systems. We show that the PI3K/AKT pathway plays an important role in the regulation of p53mut and inhibitors of this pathway can re-sensitise treatment resistant tumours. This has helped us to simultaneously highlight the cohort of patients where the greatest efficacy may be achieved in clinical practise. We further show that the AKT mediated regulation of NPM that we describe in solid tumours is relevant in Acute Myeloid Leukaemia (AML) with mutated NPM, albeit showing physiologically different effects. This further highlights the necessity for rational treatment planning with the newer targeted agents that inhibit specific signalling pathways in AML patients.

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, Durban, South Africa, 2016. / There are now several thousand remedies available to a homoeopath and this number is continually increasing with the increase in homoeopathic research and provings. This growing wealth of data does, however, make choosing a homoeopathic remedy difficult and some homoeopaths argue that the essence of homoeopathic remedies are being lost in this excess of data. In an attempt to more accurately see a remedy’s ‘picture’ and gain deeper insight into remedies, Scholten (1993), Sankaran (2005a) and Mangialavori (2010) developed different methods which can now be collectively referred to as “group analysis”. The aim of group analysis is to find symptoms, sensations and pathological tendencies that are common to all remedies within a group. This study involved applying Sankaran’s group analysis approach to the psychoactive plant drug remedies with the rationale of filtering and organizing the mass of data we now have available on this group. This will enable both students and professionals of homoeopathy to develop a deeper understanding, and hence greater utilization, of the psychoactive plant drug remedies. The following five homoeopathic remedies were chosen for this study on the grounds that they have all been extensively proved through both homoeopathic provings and cured clinical cases and there is a vast amount of literature available on these remedies in materia medica and repertories: • Anhalonium lewinii (Cactaceae family) • Cannabis indica (Hamamalidae family) • Coffea cruda (Rubiaceae family) • Nux moschata (Magnolianae family) • Opium (Papaveraceae family) A computer repertory search was conducted using RadarOpus (Archibel, 2014) to extract all rubrics containing the selected remedies. Parameters were set to retain only rubrics that have less than 50 remedies and at least two of the selected psychoactive plant remedies in them. This was to ensure that only well-defined, characteristic remedies were looked at. The rubrics were visually analyzed, compared and contrasted to determine the common sensations within them and mental, general and particular symptoms were analyzed in terms of Sankaran’s model of Vital Sensation (2005a). The vital sensation of the psychoactive plant drug remedies was found to be that of horror, fear or fright. All the remedies belonging to this group experience the sensation of horror either through their perception of pain or through dreams, visions, hallucinations or anxiety. This sensation pervades all these remedies which are constantly trying to escape this sensation by either increasing or decreasing their activity and sensitivity. The active reaction to the sensation of horror is to increase activity. This is expressed through increased sensitivity; mental clarity; sensations of contraction, fullness, heaviness, heat or moisture; delirium, hallucinations and instability. The passive reaction to the sensation of horror is to decrease activity. This is expressed through insensitivity; lack of mental clarity; sensations of expansion, emptiness, lightness, cold or dryness; sleep, stupor and unconsciousness. The compensation, or coping mechanism that psychoactive plant drug remedies develop, is a transcendence of their condition: they transcend, or escape, their condition by no longer feeling or doing anything, by becoming numb and insensitive. The researcher suggests that although the remedies of the psychoactive plant drug group can be classified according to different miasms, the over-riding miasm of this group is the sycotic miasm with its fundamental sense of having a ‘fixed weakness’ within themselves. The researcher also proposes that the psychoactive plant remedies have an affinity for the central nervous system and for ailments caused by strong emotions such as joy, anger, excitement, fear or fright. These remedies tend to produce pathologies of the central nervous system and sleep including increased reflexes, involuntary motions, trembling, jerking; weakness, atrophy, slowness, paralysis; unconsciousness; catalepsy; Autism Spectrum Disorders; hypersensitivity; insensitivity or absence of sensitivity; pain; formication; mental confusion, poor comprehension, nonsensical speech; memory disorders; delirium, hallucinations, schizophrenia; mood disorders; behavioural disorders; anxiety; insomnia, narcolepsy and nightmares. The researcher found group analysis to be a powerful methodology that, if employed correctly, can aid homoeopaths to learn and understand remedies in their ‘totality’. / M

While a significant amount of research illustrates the positive effects of therapists’ use of mindfulness, few studies have addressed whether therapists’ mindfulness actually improves psychotherapy outcomes. Additionally, no existing research has examined whether therapists’ use of a mindfulness exercise immediately before meeting with a client could also have a positive impact on the following session. The purpose of this study was to test whether engaging in a centering exercise 5-10 minutes before a session could have a positive impact on therapy, in particular on the therapists’ ability to remain present in session. Results indicated that the trainee therapists did not report changes in mindfulness after the brief mindfulness training program. Results also indicated that completing the centering exercise before a session did not appear to impact client ratings of therapeutic presence and session outcomes. The results suggest that more intensive training in mindfulness may be necessary to impact psychotherapy outcomes.

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth factors. These paracrine factors affect other inflammatory cells, resident cells of the healing tissue, including fibroblasts and endothelial cells that are necessary for restoration of damaged tissue. The hypothesis of this investigation is that TUS enhances early healing, in part, through stimulation of macrophage release of paracrine factors involved in coordination of the cellular aspects of tissue healing and that specific levels of TUS are most stimulatory for macrophages. This study examined macrophage release of interleukin-1beta (IL-1Beta), vascular endothelial growth factor (VEGF), transforming growth factor-Beta 1 (TGF-B1) and fibroblast mitogens, in response to varied levels of TUS. Fibroblasts incubated up to 48-hours in media conditioned by TUS-stimulated macrophages were not induced to proliferate regardless of the parameters sets of TUS applied. TUS (1 MHz, 400mW/cm2 SATA, 20% duty cycle, 10-minute exposure) induced macrophage release of VEGF and IL-1Beta within 10-minutes post-TUS, without any additional release being stimulated at 1-hour post-insonation. No other combination of TUS parameters studied induced release of IL-1Beta and VEGF. TUS did not induce release of TGF-Beta 1 at either time point post-TUS. VEGF and IL-1Beta release occurred in conjunction with lactate dehydrogenase (LDH) release from treated macrophages, indicating non-specific cell membrane permeabilization was involved in the cellular response. For IL-1Beta, TUS-stimulated release was inhibited at lower exposure temperatures. Inhibition of TUS-induced release at lower temperatures indicates that a cellular metabolic process, most likely exocytosis, was also stimulated by TUS. Based on these results, it appears that TUS exposure at 1 MHz, 400mW/cm2 SATA, 20% duty cycle induces non-specific and cell-mediated release of secretory proteins. Thus, enhanced release of cytokines and growth factors from macrophages is a possible mechanism by which TUS enhances tissue healing.

It has been six decades since the discovery of lithium for the treatment of bipolar disorder. There is, as yet, no conclusive evidence as to how lithium produces this therapeutic effect, since it is known to interact with multiple cellular targets. One of the most credible targets is the enzyme, inositol monophosphatase (lMPase), which plays a crucial role in cell signalling. My aim was to find a novel IMPase inhibitor and evaluate it as a possible lithium-like mood stabiliser by using enzyme, cell and whole animal experiments. To achieve this, I created recombinant human and mouse IMPase enzymes and then used these for screening and crystallisation. I used two different approaches for the small-molecule screening: substrate-based virtual screening and drug repositioning using a library of compounds with clinically proven safety. I identified ebselen as a novel IMPase inhibitor suitable for drug repositioning. I determined thatebselen inhibited IMPase noncompetitively, likely through a covalent modification on a cysteine. In cell cultures, ebselen was found to inhibit not just IMPase but other steps that resulted in accumulation of higher inositol phosphates. When injected intraperitoneally into mice, ebselen crossed the blood- brain barrier and exhibited inhibition of IMPase ex vivo. Moreover, in mice, ebselen simulates some, but not all, of the behavioural effects of lithium. I have determined that ebselen inhibits IMPase and acts as a partial lithium mimetic. Given that ebselen is safe in man, it warrants clinical testing for the treatment of bipolar disorder.