Lithium (Li+) is the major drug presently prescribed in the treatment of manic depression. Its site of action within the central nervous system is unknown although it has been known for several years to have profound effects upon inositol (poly)phosphate metabolism. The basis of the work presented here is to investigate the effects of Li+ upon the accumulation of labelled and unlabelled inositol (poly)phosphates in muscarinic cholinergically stimulated rat cerebral cortical slices and cultured cell lines. Its effects on the accumulation of CMP-phosphatidic acid (CMP-PA), a precursor to (poly)phosphoinositide lipid resynthesis and upon the inhibition of inositol monophosphatase activity are also described. It has been shown that the presence of Li+ leads to reduced accumulation of, not only Ins(l,3,4,5)P4 but also of Ins(l,4,5)P3, the molecule responsible for the release of intracellular Ca2+. The labelled Ins(l,4,5)P3 and Ins(l,3,4)P3 which accumulate under these conditions were separated in the absence of mg++ using an enzymic preparation from rat cerebral homogenate. This technique allows an effective and accurate separation which circumventss the use of h.p.l.c. It has also been demonstrated that both [3H] InsP1 and [14C]CMP-PA increase with similar EC50 values in the presence of increasing Li+ concentrations and also with increasing time in the presence of Li+. Furthermore, work has indicated that the preincubation of rat cerebral cortical slices with myo-inositol can, at least partially, reverse the accumulation of labelled CMP-PA. However, if the myo-inositol is added subsequent to the Li+ block being established, incomplete reversal is only observed in the presence of very high concentrations of inositol. In addition, similar experiments were conducted to observe the effects of myo-inositol upon the Li+-induced reduced accumulation of both Ins(l,4,5)P3 and Ins(1,3,4,5)P4 as measured by radio-receptor assay. Whilst the presence of 10mM myo-inositol prolonged the lag phase routinely observed between 5 and 10 mins, it could not prevent the fall in accumulation from occurring. Scyllo-inositol, a naturally occurring isomer of myo-inositol, was found to be completely ineffective in reducing the accumulation of [14C]CMP-PA. In other experiments, the effects of Li+ upon the carbachol-stimulated inositol (poly)phosphate fractions were examined in CHO cells transfected with an M1 muscarinic receptor subtype and also in SH-SY5Y cells and the results compared to those obtained in rat cerebral cortical slices. Finally, an assessment of inhibition of the inositol monophosphatase activity was made in a variety of cell free systems. This inhibition was caused using either Li+ or polyclonal antibodies raised to purified inositol monophosphatase. In conclusion, the results obtained verify the profound effects which Li+ can have upon inositol (poly)phosphate metabolism and suggest that whilst the primary intracellular target of Li+ may indeed be the inositol monophosphatase it may also be causing other subtle alterations to the cell functioning. These possibilities and their implications are discussed.

Regarding the higher demand of the total joint replacement (TJR) and revision surgeries in recent years, an implant material should provide much longer lifetime without failure. Nickel titanium (NiTi) is the most popular shape memory alloy in the industry, especially in medical devices due to its unique mechanical properties such as pseudo-elasticity, damping capacity, shape memory and good biocompatibility. However, concerns of nickel ion release of this alloy still exist if it is implanted for a prolonged period of time. Nickel is well known for the possibility of causing allergic response and degeneration of muscle tissue as well as being carcinogenic for the human body beyond a certain threshold. Therefore, drastically improving the surface properties (e.g. wear resistance) of NiTi is a vital step for its adoption as orthopaedic implants. To overcome the above-mentioned risks, different surface treatment techniques have been proposed and investigated, such as Physical Vapour Deposition (PVD), Chemical Vapour Deposition (CVD), ion implantation, plasma spraying, etc. Yet all of these techniques have similar limitations such as high treatment temperature, poor metallurgical bonding between coated film and substrate, and lower flexibility and efficiency. As a result, laser gas nitriding would be an ideal treatment method as it could overcome these drawbacks. Moreover, the shape memory effect and pseudo-elasticity of NiTi from a reversible phase transformation between the martensitic phase and the austenitic phase are very sensitive to heat. Hence, NiTi implant is subjected to the following provisions of the thermo-mechanical treatment process, and this implant provides desired characteristics. It is important to suggest a surface treatment, which would not disturb the original build-in properties. As a result, the low-temperature methods for substrate have to be employed on the surface of NiTi. This present study aims to investigate the feasibility of applying diffusion laser gas nitriding technique to improve the wettability and wear resistance of NiTi as well as establish the optimization technique. The current report summaries the result of laser nitrided NiTi by continuous-wave (CW) fibre laser in nitrogen environment. The microstructure, surface morphology, wettability, wear resistance of the coating layer has been analysed using scanning electron microscopy (SEM), X-ray diffractometry (XRD), sessile drop technique, 3-D profile measurement and reciprocating wear test. The resulting surface layer is free of cracks, and the wetting behaviour is better than the bare NiTi. The wear resistance of the optimised nitride sample with different hatch patterns is also evaluated using reciprocating wear testing against ultra-high-molecular-weight polyethylene (UHMWPE) in Hanks’ solution. The results indicate that the wear rates of the nitride samples and the UHMWPE counter-part were both significantly reduced. It is concluded that the diffusion laser gas nitriding is a potential low-temperature treatment technique to improve the surface properties of NiTi. This technique can be applied to a femoral head or a bone fixation plates with relatively large surface area and movable components.

Abstract To facilitate the diagnosis of hypercholesterolemia, we wanted to create a simple and rapid method for diagnosing familial hypercholesterolemia in a homogenous population. The PCR method for the FH-Helsinki mutation detected 25 FH-Helsinki positive patients, two of whom had no clinical signs of FH, but had a positive family history for the disease. The method is exceptionally useful in Northern Finland, where 62% of the FH patients carry the FH-Helsinki mutation. The role of polymorphisms and mutations of the apo B particle as etiologic factors of hypercholesterolemia was studied in a population of moderately hypercholesterolemic individuals. The catabolism of the patients' own LDL was compared to that of a healthy and normocholesterolemic donor, and no major differences were observed. However, the presence of the XbaI cutting site was associated with elevated cholesterol values and a slightly lowered LDL catabolic rate. Patients homozygous for the EcoRI cutting site also had a slow LDL catabolic rate and slightly elevated cholesterol values. The MspI and Ins/del polymorphisms of the apo B particle were not associated with variations in LDL catabolism. The e 4 allele of apolipoprotein E was slightly more frequent in our hypercholesterolemic population than in the average population. The lipid values did not differ significantly between the apo E phenotypes in moderately hypercholesterolemic individuals, nor could we detect any differences in the catabolic rates of their LDL according to the apo E phenotype (individuals with the phenotype apo E 2/2 were excluded from the study). In our population of CAD patients, the frequency of the e 4 allele was lower than in CAD populations from Southern Finland (0.23 vs. 0.32), suggesting that apo E 4 is not so strongly associated with coronary disease in Northern Finland as in other populations. The E 4 phenotype was associated with slightly smaller LDL cholesterol reductions by colestipol and lovastatin treatment compared with patients with the phenotype 2/3. The lipid risk factors of male and female CAD patients were studied in a group of patients admitted to one ward of the Oulu University Hospital. We found the males to have the typical high LDL cholesterol and low HDL cholesterol lipid pattern, but women with two- or three-vessel CAD had high LDL and low HDL cholesterol associated with high VLDL lipids, and hypertension, diabetes or smoking. Pharmacological treatment of hypercholesterolemia was studied by comparing lovastatin to colestipol, and in a separate study where a new drug, enprostil was used. Enprostil, whose main effect is on the gastrointestinal tract, would be a useful alternative for long-term treatment of hypercholesterolemia. Unfortunately, however, gastrointestinal side-effects limit its long-term use. Colestipol reduced plasma LDL cholesterol and elevated plasma HDL cholesterol and triglycerides, but it, too, caused gastrointestinal side-effects. Lovastatin proved to be the most effective cholesterol-lowering drug with the least side-effects, and statins have now been established as the most widely used hypocholesterolemic drugs.

M.Tech. / Menopause refers to the natural cessation of the menstrual cycle at the end of the reproductive years, and is usually defined retrospectively after twelve consecutive months of amenorrhoea. Climacteric is the term used to describe the life period surrounding menopause. It begins with physiological changes that mark the transition between the reproductive and post-reproductive years (Lewis and Bernstein, 1996). The mean age of menopause is 51 years, with a normal range from 45 to 56 years (Chamberlain and Malvern, 1996). There are many symptoms associated with menopause, including hot flushes and night sweats, headaches, sleep difficulties, vaginal dryness and loss of libido, urinary problems, joint and muscle pains, depression, irritability, and poor memory and concentration. Long-term risks and effects include osteoporosis and coronary heart disease (MacGregor, 2000). The aim of this study was to determine the efficacy of the homoeopathic similimum in the treatment of climacteric symptoms. The research study was advertised in local newspapers, pharmacies, and on the Doornfontein campus of the University of Johannesburg in order to recruit volunteers for the study. All volunteers were required to complete a Suitability Criteria Questionnaire. Following this, ten participants were selected who met the inclusion criteria. The study involved four homoeopathic consultations for each participant over a period of three months. During the first consultation a consent form was completed, the procedures of the research were explained to the participant, a full case history was taken, and a physical examination was performed. According to each participant’s individualized physical, mental and emotional symptoms ascertained from the case history, the researcher determined a suitable similimum remedy. A similimum remedy can be defined as the single remedy that fits the symptom picture (Digby, 1997). The abbreviated Kupperman Menopause Index was completed by each participant at the beginning of the treatment, and then at four-weekly intervals for the duration of the twelve week trial. The results were then transferred to the participants’ main Kupperman Menopause Index and compared, thus determining the effect of the homoeopathic similimum in treating climacteric symptoms.

The first documented case of improved hearing following chiropractic adjustment was by D.D. Palmer in 1895 in which he restored Harvey Lillard’s hearing. Mr Lillard had been deaf for seventeen years. This brought about the birth of a new profession called chiropractic (Terrett 2002). It has been postulated that dysfunction or spinal joint motion restrictions of the cervical spine may lead to irritation of the sympathetic nervous system which may cause decreased blood flow to the auditory nerve via the labyrinthine artery (also known as the internal acoustic artery or internal auditory artery), which in turn may lead to a decrease in hearing acuity (Hawley 1964). The purpose of the dissertation was to determine whether cervical spine joint adjustment had an effect on the hearing acuity in individuals with some level of sensorineural hearing loss. Thirty symptomatic patients of either gender participated in this study. These patients were recruited by the use of advertisements placed in the Chiropractic Day Clinic, University of Johannesburg, Doornfontein Campus and by word of mouth. The inclusion criteria required the patients to present with some level of sensorineural hearing loss, be over the age of fifty years and have no contra-indications to chiropractic adjustments. Objective data was obtained by the Interacoustics Diagnostics Audiometer AD 229b, which determined the level of auditory acuity before and after chiropractic treatment was administered. Middle ear function and acoustic reflex was also tested with the GSI 38 Auto Tymp acoustic reflex machine. The objective results demonstrated that there was no statistically significant increase in auditory acuity following either the chiropractic treatment, or the detuned ultrasound treatment. In conclusion, it was shown that chiropractic adjustments in some patients presenting with sensorineural hearing loss, in the same subjects, exhibited a clinical improvement in hearing acuity however, not a statistically significant improvement following the treatment protocol discussed in the chapters that follow. These improvements suggested that the adjustment resulted in a decrease in sympathetic nervous system stimulation and an increase in blood flow through the labyrinthine artery, and therefore an increase in auditory acuity. These improvements were noted to a larger degree in individuals with a greater sensorineural hearing loss and not across the entire sample population. / Dr. M. Moodley Dr. S.M. Wilcox

Dr. J. Torline Dr. S. Sarawan Dr. H. Engelbrecht

OBJECTIVE: To determine and compare the electromyographic effect of cervical and lumbar spinal adjustments on the lumbar paraspinal muscles in subjects with chronic lower back pain. STUDY DESIGN: Thirty subjects with chronic lower back pain underwent 5 spinal manipulative treatments on alternative days over a 2 week period (excluding weekends) to test the electromyographic effect on the lumbar spinal muscles. SETTING: Technikon Witwatersrand Chiropractic Clinic, Johannesburg, South Africa SUBJECTS: Thirty subjects with chronic lower back pain participated in this study. Each of the subjects was assigned to one of three groups using age-matched sampling methods. Group 1 consisted of 10 subjects (mean age of 25 years) receiving lumbar spine and pelvis adjustments (L1 - L5, including Sacroiliac joints); Group 2 consisted of 10 subjects (mean age of 26 years) receiving cervical spine adjustments (Occiput - C7); and Group 3 consisted of 10 subjects (mean age of 26 years) receiving adjustments to the cervical spine, lumbar spine and pelvis. METHODS: Lumbar paraspinal muscle electrical activity was tested before and after the treatment one, three and five using surface electromyography (sEMG). One pair of bipolar electrodes was placed bilaterally over the paraspinal muscles at the level of L3. Subjects were asked to lie down in a prone position with their arms next to their sides. They were then instructed to perform a single voluntary lower back extension exercise by lifting their chests and shoulders as high as possible off the plinth. Each contraction lasted five seconds. The baseline and peak values from the surface electromyographic meter were recorded, analyzed and compared for reference. Information regarding the intensity and quality of the pain experienced by the subjects were also collected at the start of treatment one, three and five using approved research measurements, i.e. the Oswestry Questionnaire and the Visual Analogue Pain Scale. iv RESULTS: Comparison of the results indicated no statistically significant difference between the three groups and their responses to the treatments. Subjectively, all three groups showed trends of improvement, with group 2 showing the greatest percentage of improvement in pain. Objectively, group 2 also showed the greatest percentage of improvement in the resting rate of the paraspinal muscles, assuming that ideal sEMG resting rate is the lowest one possible. Comparing the results of the contraction ability of the paraspinal muscles, both prior to and after spinal manipulative treatment (SMT), group 1 demonstrated the greatest percentage in improvement followed by group 3. Group 3 also demonstrated the most balanced paraspinal muscles at the end of the study. CONCLUSION: In light of these findings it can be concluded that the treatment protocol as represented by group 2 showed the most favourable treatment efficacy in terms of subjective results and resting rate of the paraspinal muscles. The trends shown in this study should be used and tested in future similar research studies incorporating larger sample groups. / Ms. M. Jansen van Rensburg Dr. M. Buchholtz

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

M.Tech. (Homoeopathy) / Please refer to full text to view abstract

M.Tech. (Homoeopathy) / The aim of this study was to determine the effectiveness of Argentum nitricum 6CH and Lycopodium clavatum 6CH in the individualised treatment of patients suffering from Irritable bowel syndrome. These two homoeopathic remedies are well known for their effect on the gastrointestinal system, especially when the gastrointestinal symptoms are associated with emotional stress. 60 subjects participated in this single blind, placebo controlled study. Each subject underwent an initial evaluation in order to ascertain their symptoms prior to treatment. They were then given their appropriate remedy to be administered three times daily for one month. The subject's symptoms were monitored through questionnaires completed at two week intervals. The homoeopathic medication appeared to reduce the Irritable bowel syndrome symptoms, with the Lycopodium clavatum group achieving slightly better results than the Argentum nitricum group. It is, however, recommended that further similar studies using a larger sample group for a longer duration be conducted in order to verify these findings.