Thesis (M.Tech.: Chiropractic)- Dept of Chiropractic, Durban Institute of Technology, 2005. xiii, 129 leaves :|bill. (some col.) ;|c30 cm / Research indicates the sacroiliac joint (prevalence of sacroiliac syndrome ranges from 19.3% and 47.9% (Toussaint et al., 1999)) as being the primary source of low-back pain in 22.5% of patients with back pain (Bernard et al., 1987:2107-2130). Treatment options that are available for the treatment of low-back pain include allopathic (Hellman and Stone, 2000), and manual therapies such as hydrotherapy and traction (Cull and Will, 1995). It has been found that allopathic interventions have been less effective than spinal manipulative therapy, even with spinal manipulative therapy having various modes of application (e.g. side posture and drop piece manipulations) (Gatterman et al., 2001). Drop table thrusting techniques were found to be effective for patients with neuromuskuloskeletal problems such as facet syndrome (Haldeman et al., 1993), however, it is still not known which specific drop piece technique is the most appropriate for sacroiliac syndrome. Thus it is important to ascertain the clinical effectiveness of the technique as certain conditions prevent the patient from being positioned in the conventional side posture for treatment of sacroiliac syndrome (White, 2003; Pooke, 2003; Hyde, 2003; Pretorius, 2003; Haldeman, 2003; Cramer, 2003; Engelbrecht, 2003). Therefore this study aims at determining the efficacy of a maintained contact drop piece manipulation technique.

Dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban Institute of Technology, 2006. / Health care practitioners have known for some time that patients benefit from specific manual intervention effects, but also from the manner in which these are presented. The latter at times having as much impact on patient health as the former. Thus the purpose of this study was to determine the effect of the clinical ritual during instrument assisted adjusting whilst managing mechanical lower back pain. The study was a randomized prospective study comprising of sixty participants aged 18-59. These individuals were randomly allocated into two groups of thirty and then further stratified to control for gender. Both Groups were diagnosed according to the Activator Methods Chiropractic Technique (AMCT), however the tension was set at maximum for group A, whilst the device was set to the minimum tension for group B. Each patient received three treatments and one follow up visit over a two-week period. Subjective data was collected at the first, third and follow up visit. Subjective data was recorded using the Visual Analogue Scale, the Numerical Pain Rating Scale, the Roland Morris Questionnaire and the Short-form McGill Pain Questionnaire. Outcomes were analysed through with the SPSS statistical package at a 95% level of confidence. After analysis of the collected data it was found that there was no statistical difference between the groups, but there was a non-specific trend suggesting a better outcome in the full tension activator group (Group A). Thus, the research indicated that patients perceptions, the patient-practitioner relationship, and the assumption of an outcome of success as well as the power of placebo or non-specific effects play a large role in the managing of lower back pain in a chiropractic environment.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2010. / Two centuries ago it was possible to practice with only 100 remedies. Today with the constantly expanding materia medica, complexity itself tempts the homeopath to remain inside this range of remedies. It is due to the pioneering work of authors like Scholten (1993) and Sankaran (2005) that the vast materia medica of today can be summarized and understood through a method like group analysis which links naturally related substances via their common symptomatology. This not only offers new aspects to well known remedies, but highlights the smaller, not so well known remedies, resulting in a more comprehensive understanding of the materia medica. Relatively few homeopathic remedies derived from the Araneae order are extensively utilized for the homeopathic treatment of patients. Therefore the spider remedies represented in the literature of Mac Rep computer program® were subjected to the group analysis method in order to extend the overall knowledge of this particular group of homeopathic remedies. The spider remedies were first analyzed in terms of their quantitative representation in the repertory (amount of rubrics) and then a sample group was chosen. This selection was screened for common sensations using the above mentioned computer program. The significance of a common sensation was confirmed by cross-checking the materia medica of all16 homeopathic spider remedies listed in Mac Reference® computer software for its occurrence. The findings were interpreted within the backdrop of the established animal characteristics of homeopathic remedies (Sankaran, 2005:24-31). The primary sensations extracted and confirmed in the rest of the Araneae group were stinging, stitching, shooting, sensitive, sore, cold, faint, paralytic, twitching and full. Significant synonyms of the first order analysis were heaviness, spasm, cramp, numbness and weakness. Second order and third order analysis not only provided symptoms of the mind, but led to the proposed themes common in spider remedies. The majority of themes like hyperactivity, restlessness, increased sexuality, impulsive violence and aggression, the periodicity of complaints, heightened sensitivity to music and the love for dancing are comparable to Mangliavori’s (2004) clinical findings and to Sankaran’s (2005) proposed spider characteristics. A miasmatic differentiation of each member of the sample group was performed according to Sankaran’s extended miasmatic model (2005:7). Araneus diademus was found to belong to the sycotic- as well as malarial miasm, Latrodectus hasseltii to the syphilitic-, Loxoceles reclusa to the leprous- and Tarentula hispanica and Theridion curassavicum to the tubercular miasm. Pathological tendencies of the Araneae remedies were found to involve the nervous system, eyes, heart, muscular – skeletal system, sexual organs and the mind. Examples of diseases common in Araneae remedies were found to be: mental disorders like anxiety neurosis, ADHD, depression, mania, sexual disturbances, STD’s, neurological disorders, angina pectoris, myocardial infarction, spinal irritation, migraines, meningitis etc. The results of this research were found to support group analysis methodology as outlined by Sankaran (2005). However additional knowledge drawn from Sankaran’s 2008) most recent research into animal remedies and from the natural history of spiders was necessary to be able to interpret the results correctly and to illustrate an in-depth picture of the common characteristic features of the Araneae remedies.

Dissertation submitted in partial compliance with the requirements for the MTech: Chiropractic, Durban University of Technology, 2011. / Background: In terms of kicking speed the instep kicking technique is the most effective and commonly used method. Immobilization or restricted motion within a joint segment, results in adverse changes in the surrounding ligaments, tendons and muscular tissue. To improve joint mobility and thus improving flexibility, this study focused on spinal manipulation. Objectives: The main purpose of this study was to determine the immediate effectiveness of lumbar spine and sacroiliac manipulation on the range of motion (ROM) of the lumbar spine and sacroiliac joints as well as the kicking speed of the subjects. Methods: Forty asymptomatic soccer players, playing for the regional Premier League team or higher, were divided into four groups of 10 each. Group 1 received lumbar spine manipulation, Group 2 received sacroiliac (SI) joint manipulation, Group 3 received combined lumbar spine and SI joint manipulation and Group 4 received the sham laser intervention (placebo/control). Pre and post warm-up and post intervention lumbar and SI joint ROM were measured using a digital inclinometer. Kicking speed was measured post warm-up and post intervention with a Speed Trac™ Speed Sport Radar. The subjects’ perception of a change in kicking speed post intervention was also recorded. SPSS version 15.0 was used to analyse the data. Results: Pre and post outcome measurements were compared using a p value of < 0.05 to indicate statistical significance. Statistically significant ROM increases were noticed in left and right lumbar rotation motions post lumbar manipulative intervention. Lumbar extension, left and right lumbar rotation and SI joint extension ROM increased post combination of lumbar spine and SI joint manipulation. There VI was a significant increase in kicking speed post intervention for all three manipulative intervention groups. A significant correlation was seen between subjects’ perception of change in kicking speed post intervention and the objective results obtained. Conclusions: Lumbar spine and SI joint manipulation is an effective intervention for short-term increase in kicking speed.

Dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2012. / Introduction: This study aimed to apply the methodology of group analysis, as proposed by Sankaran, to an under-represented and poorly-understood biological class. The intention of the study was to extend the group understanding of the biological class, with a view to more notable utilization of the individual members of the class as therapeutic substances. The Salicaceae Family was to the knowledge of the researcher, under-utilized in homoeopathy and was expected to have a much larger scope of use than is current. Methodology: The family, Salicaceae, was classified taxonomically. Secondly, an extraction of all rubrics pertaining to the Salicaceae family was done using the Radar® repertory program. Those rubrics that contained at least two remedies from the Salicaceae Family were retained and the rest were eliminated. A search of Encyclopaedia Homoeopathica® and other resources was utilized to derive common sensations, reactions to sensation, and to classify the remedies miasmatically. Results: The primary sensation was a burning sensation, with heat or a sensation of being burnt, which was confined primarily to the respiratory, genitourinary and gastrointestinal system. The next sensation, which was on the physical level, was of a stinging sensation, which may be interpreted as either a tingling or a prickling sensation. This sensation was found to be mostly confined to the skin. Another sensation was a feeling of being alone, in isolation, detached from surroundings, or being forsaken. Passive reactions included numbness, inflammation, tearfulness, trembling and crying. Active reactions were restlessness, irritation and wanting to sneeze. Miasmatically the task was a challenge, as the researcher found materia medica to be lacking in certain remedies. However many of the remedies were found to be Acute, Sycotic, Malarial or Leprous. v Conclusion: The Salicaceae Family had an affinity for all orifices, with many pathological tendencies occurring throughout the gastrointestinal, genitourinary and respiratory system. The researcher felt that the Group analysis of remedies was a powerful tool that can assist in a homoeopathic prescription. It gave great insight to the Salicaceae Family, and exposed the researcher to the lesser known remedies.

Though Cognitive Remediation Therapy (CRT) for anorexia nervosa shows promising evidence, questions remain regarding specific mechanisms of change. This mixed methods study aimed to explore both longitudinal patient data (neuropsychological and self-report measures, before and after CRT) and therapist experiences of delivering CRT and their perceptions regarding what it offers. All patients had received treatment in a specialist inpatient unit. Complete data were available for both individual (n=56) and group (n=43) CRT; clinical audit data were also available. Semi-structured interviews of 11 therapists were analysed using Thematic Analysis. Statistically significant improvements were found in cognitive flexibility task performance for individual CRT (medium effect) and in self-reported cognitive flexibility for group CRT (medium effect). Three main themes were identified from the therapist interviews: “Anorexia and its treatment”, “CRT - its characteristics and delivery” and “CRT and its effectiveness”. The quantitative findings replicated some previous results and the therapist interviews provided insights regarding not only CRT’s delivery but adaptations made according to individual need and complexity. Both individual and group CRT appear to be feasible interventions for future trials but questions remain around CRT’s specific effects. Recommendations are made for future research studies on this complex intervention.

Anxiety disorder interventions usually require in vivo exposure without the use of safety behaviours. However, the literature has started to query whether safety behaviour use is harmful, and whether they might actually help to make therapy accessible for patients who usually refuse or drop-out of treatment. This study attempted to improve methodology and give greater consideration to the differing underlying theories. It was hypothesised that that role of safety behaviours would be in line with cognitive theory (Salkovskis, 1991) and the inhibitory learning model (Craske et al., 2008). Thirty-three participants with sub-clinical arachnophobia were recruited from student and community populations. N = 11 completed in vivo exposure without the use of safety behaviours (exposure), n = 11 with the use of safety behaviours (safety) and n = 11 were assigned to the no-exposure control group. Outcomes included two behavioural approach tests and two questionnaires. Results showed that the exposure group outperformed the safety group at post-exposure and follow-up. It is suggested that the role of safety behaviours is more likely to be unpinned by cognitive theory and the inhibitory learning model (than by emotional processing theory). However, these findings need to be replicated with clinical populations and more research is needed on what appropriate and relevant outcomes look like in anxiety interventions.

Candida biofilms have become an increasingly important clinical problem. The widespread use of antibiotics, frequent use of indwelling medical devices, and a trend towards increased patient immuno-suppression has resulted in a creation of opportunity for clinically important yeasts to form biofilms. Whilst there is growing evidence of the importance of Candida biofilms in clinical medicine, not all clinical isolates are able to form biofilms. There is therefore a fundamental gap in understanding exactly what drives biofilm formation and its clinical implications. These structures have become increasingly recognised as a significant clinical problem. One of the major reasons behind this is the impact that these have upon treatment, as antifungal therapy often fails and surgical intervention is required. This places a large financial burden on health care providers. Therefore, the discovery of alternative antifungal agents to be used in the treatment of fungal biofilms is in great demand for the management of these infections. A panel of Candida albicans bloodstream isolates were assessed for their biofilm forming ability by using the crystal violet assay and measuring cellular surface hydrophobicity. Scanning electron microscopy was used to visualise differences in the clinical biofilms. The impact of amphotericin B (AMB) treatment was determined next by broth microdilution method to assess differences in susceptibility profiles of the clinical isolates. The virulence of these clinical isolates was evaluated in vivo using a Galleria mellonella model and transcriptional analysis used to assess the expression of various genes associated with C. albicans biofilm formation within clinical isolates. Extracellular DNA (eDNA) in clinical biofilms was quantified using a microplate fluorescence assay and chitinase activity measured using a biochemical assay. Moreover, the potential of a novel antimicrobial agent Carbohydrate-derived fulvic acid (CHD-FA) was assessed against a panel of fungal and bacterial species. The mechanism of action of CHD-FA was determined using membrane assays include ATP release, and propidium iodide fluorescence, with various inhibitors used to determine whether CHD-FA activity is affected by known resistance mechanisms. Finally, the immunomodulatory properties of CHD-FA were investigated using ELISA and PCR arrays. The results from this study have shown C. albicans biofilm formation is differential within clinical isolates, where those with high biofilm formation (HBF) predominately consisted of hyphal cells, were more virulent in vivo and had decreased susceptibility to AMB, when compared to those with low biofilm formation (LBF). Furthermore, transcriptional analysis identified a number of genes that positively correlated with C. albicans biofilm formation. The novel agent carbohydrate-derived fulvic acid (CHD-FA) was shown to not only be highly active against C. albicans biofilms, but also against a range or orally relevant bacteria through non-specific membrane activity. Furthermore, CHD-FA was shown to down-regulate a number of pro-inflammatory mediators in an oral epithelial cell line. In conclusion, this study has characterised C. albicans clinical isolates based on their biological characteristics, where clear difference in virulence and antifungal treatment have been shown. It may be possible to develop a panel of genetic markers that could be used as a diagnostic tool for detecting biofilm formation in clinical isolates. CHD-FA is a microbiocidal compound that may serve as a potential novel antiseptic agent for the treatment of oral candidiasis and other candidal biofilm infections, whereby the immunomodulatory properties of CHD-FA could be exploited for controlling inflammation in a number of diseases.

Being one of the most rapidly advancing cancer imaging techniques in recent years, Positron Emission Tomography (PET) represents a standard of excellence with respect to sensitivity and resolution for the non-invasive in vivo molecular imaging of solid tumours via the detection of radiotracer molecules. Amongst these radiotracers, radiolabelled fluorinated nucleosides such as 3’-Deoxy-3’-[18F]-fluorothymidine (18F-FLT) has been widely recognized as a key, specific biomarker for tumour cellular proliferation. Current methods for the commercial production of [18F]FLT are characterized by low overall yields and time-consuming high-performance liquid chromatography (HPLC) purification. These disadvantages could be rectified by the development of a fast, efficient synthetic route to FLT that could enhance the productivity and reduce the reaction time of the fluoridation step necessary for the synthesis of short-lived radioisotope, 18F (t1/2=110 min) installed nucleoside. This project focussed mainly on the development of a new efficient chemical synthetic route to FLT. The synthesis and in vitro evaluation of a series of pro-nucleotide (ProTide) analogues of FLT as new potential therapeutic agents was also carried out. Various studies regarding FLT synthesis have been carried out on the cold (non-radioactive) 19F and radioactive 18F isomer by varying and optimizing conditions for the incorporation of different protecting groups and also different fluoridation reactions by nucleophilic displacement. Further optimization studies were made for the fluoridation step and the synthesis of [18F]FLTProTide analogues as new diagnostic PET imaging agents by variation of different chemical parameters on the phosphoramidate group was attempted. The synthesis of 19F- FLT based ProTides as new therapeutic agents were initiated by the introduction of the phosphoramidate group at the 5’-position of the furanosyl group of thymidine under basic conditions followed by fluoridation to generate the desired analogues. In addition to that, biological evaluation of the newly developed 19F-FLT ProTide analogues for anti-HIV 1 and anti-HIV 2 activities was undertaken on CEM cells. The results in those models indicated that the synthesized compounds were less potent than the parent nucleoside FLT. However in TK- (HIV-2) cells, the analogues retained biological activity in contrast to FLT. This suggested that the FLT ProTides bypassed the first phosphorylation step. However, the therapeutic in vitro evaluation for anti-tumour activity on L1210, CEM and HeLa cells showed no significant activity.

In this PhD project we show for the first time that novel dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with L-chirality represent promising antiviral candidates for use against pox and measles viruses. We suggest a mechanism of action based on a cellular target. Our lead compound (Cf2642, with side chain C9H18–O–C5H11) is active against vaccinia virus (a surrogate poxvirus for smallpox) and measles virus, with IC50 concentrations of 0.19 and 7.5 µM, respectively. This is a 60-fold enhancement over cidofovir (viral DNA polymerase inhibitor; IC50 of 11.5 µM against VACV). A structure activity relationship was established, which was similar for both viruses, indicating a common and specific mechanism of action. Cf2642 does not inhibit HSV-1/2, influenza, adeno or yellow fever viruses. The mechanism of action for the ddBCNAs has been investigated and, though not defined, has been narrowed down. Based on our observations of drug activity in cell lines derived from various sources, we have suggested a cellular target for the ddBCNAs, most likely cellular membrane compartments or the proteins located therein. Though inhibition of vaccinia is observed within two hours of infection, we have shown that the ddBCNAs are unlikely to be entry inhibitors. Acidification of the extracellular medium was observed but, whilst it may be linked to the mechanism of action, this is not the cause of the antiviral effects. With a possible cellular target, toxicity was carefully evaluated. We have not observed significant cytotoxicity in any of our cell models. Antivirals active against cellular targets are less subject to viral resistance, which may develop rapidly with virus-targeting drugs. This could be critical since, there are currently no effective measles antiviral drugs available on the market, and resistance to measles RNA polymerase inhibitors and the potential antipoxviral drug cidofovir has already been described.