ETD Collection
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Item The association between substance abuse, psychosis and activity participation in adults: a retrospective record review(2017) Nepaul, QulintaBackground: Co‐morbid substance abuse and psychotic disorders result in decreased activity participation. However, the association between substance abuse and activity participation in psychotic disorders has not been explored. In this study, the activity participation on admission and discharge were compared between Substance Induced Psychosis (SIP) and Schizophrenia without substance abuse. Methodology: A quantitative, descriptive, retrospective case study design with correlations was used. A database with demographic information and activity participation assessments of mental health care users (MHCUs) was used. Descriptive quantitative analysis, correlations and effect sizes was used to analyse the data. Results: The largest age groups for the SIP group were the 20 to 29 and 30 to 39‐year‐old cases. Activity participation scores for both groups showed impaired functioning on the creative ability level of Self‐presentation, with changes after intervention from patient‐directed to the transitional phase for the SIP group and therapist‐directed to patient‐directed phase for the Schizophrenia group. In terms of cognitive functioning, the Schizophrenia group improved by one phase, for Process skills, matching the SIP group on discharge. Conclusion: Activity participation is impaired in SIP but also in Schizophrenia without substance abuse. Concerning demographic data showed the prevalence of substance abuse in young adults and the disruptions of employment. Effect sizes showed clinically small changes but noteworthy improvements, as MHCUs move closer to independence.Item Bioactive nano-liposhells matricized within a polymectic scaffold for prolonged sidt-specific neurotherapy of schizophrenia(2012) Govender, ThiresenAn impediment in the long-term treatment and positive therapeutic outcome of psychoses is patient non-compliance to treatment regimens. The cognitive impairment associated with psychoses together with the inability to manage the intolerable side-effects of antipsychotic drug, inevitably predisposes the psychotic patient to non-compliance. Furthermore, the highly restricting Blood-Brain Barrier (BBB) has proved to be a significant limitation for the systemic delivery of antipsychotic drugs to the brain. The benefits of site-specific drug delivery combined with nanobiotechnology serves to enhance drug therapy by evading the BBB, increasing the bioavailability of the drug, enabling effective drug penetration into the brain, avoiding the need to administer potentially toxic doses of antipsychotic drugs and reducing systemic toxicity. In addition, controlled drug release over a prolonged period will ensure improved patient compliance and reduced rates of relapse. Therefore, the aim of this study was to develop of a drug-loaded Nano-enabled Polymeric Membranous Device (NPMD) for intraparenchymal implantation into the sub-arachnoid space in the region of the frontal lobe of the brain that circumvents the limitations of current antipsychotic modes of treatment. Chlorpromazine hydrochloride (CPZ)-loaded, polycaprolactone (PCL)-based nanoparticles were synthesized by a novel melt-dispersion technique.CPZ was selected as a model drug owing to the fact that it is a highly hydrophilic, cost-effective antipsychotic drug and its use has declined due to its significantly low bioavailability. The employment of a Face-Centered Central Composite Design resulted in an optimized formulation with a desirable size (140.30±3.39nm), stability in terms of its zeta potential (-26.40±2.11mV) and CPZ entrapment (8170.23±173.39µg) (~16%). Drug release was biphasic with an initial burst release followed by controlled release over 30 days. Furthermore, no thermo-degradation of the drug and constituent polymers were observed with the novel melt-dispersion technique. Novel implantable polyamide-ethylcellulose (PA 6,10-EC) composite membranes were prepared by a modified wet-phase inversion reaction employing a dialysis apparatus. Composites were optimized by experimental design, which resulted in highly resilient devices with an unhydrated and hydrated matrix resilience of 74.24±0.88 and 84.35±1.22% respectively. Furthermore, minimal erosion was observed over a period of 30 days (3.64±0.08%). The optimized CPZ-loaded, PCL-based nanoparticle formulation was combined with the optimized PA 6,10-EC composite membrane formulation to form the intracranial implantable NPMD to be further evaluated in vivo. A further preliminary study investigated the synthesis of encapsulated or adsorbed essential fatty acids in the form of cod-liver oil (CLO) (Gadus Morrhua) within the CPZ-loaded, PCL nanoparticles to form dual-acting nano-liposhells that combine the benefits of conventional with complementary medicine. The rationale for incorporating CLO was due to its high levels of omega-3 fatty acids, Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA), which have been proven to be neuroprotective with proven benefits in conditions such as schizophrenia. Transmission electron microscopy (TEM) revealed that the nano-liposhells were small and denser when compared to nanoparticles devoid of CLO (16.50±6.79nm in size). A highest absolute zeta potential of -30.25±0.06mV confirmed the stability of the nano-liposhells and a highest CLO and CPZ entrapment of 98.26±0.13% and 6690.55±207.30µgrespectively was determined. Ex vivo cytotoxicity studies using mammalian Pheochromocytoma (PC12) neuronal cells were carried out on the NPMD and the CLO and CPZloaded nano-liposhells as well as both their componential elements. A lactate dehydrogenase (LDH) release assay was undertaken and proved that the NPMD and its componential elements were biocompatible and displayed no significant cytotoxicity (p>0.05). The nano-liposhells and the CLO itself did display significant (p<0.05) cytotoxicity and reduced cell viability by 23.27±2.40% and 45.68±6.12% respectively and was attributed to free radical formation by auto-oxidation. An in vivo pilot study explored the surgical intraparenchymal implantation of the NPMD into the brain of the New Zealand White Rabbit model. The study was performed over 30 days and Cerebrospinal Fluid (CSF) as well as blood plasma samples were withdrawn at predetermined intervals to evaluate the release of CPZ from the NPMD using Ultra Performance Liquid Chromatography. Results were compared to a group of rabbits given commercially available CPZ in the form of intramuscular (I.M.) Fresenius Chlorpromazine hydrochloride® 25mg/mL. Results revealed higher levels of CPZ in the CSF (2.08-2.92ng/mL) from the NPMD when compared to the I.M. dose (0.85-2.32ng/mL). Furthermore, miniscule quantities of CPZ from the NPMD were detected in the blood (≤0.95ng/mL) The CPZ release from the NPMD was far superior to the commercially available form of the drug. Implantation at the site of action allowed for a drastic increase in the CPZ bioavailability. Furthermore, the drug was released in a pseudo-steady state with CSF levels being maintained between 2.00-3.00ng/mL with no fluctuations observed. Ultrasonic imaging was utilized to view the NPMD post-implantation. Rabbits displayed no evidence of motor dysfunction or general brain damage post-implantation for the duration of the study. Histomorphological analysis revealed that the NPMD was biocompatible as no evidences of bleeding, ischemia or major chronic inflammation was observed. Light microscopy was used to characterize the bioerosion of the NPMD midway through as well as at the end of the study and revealed minimal erosion at the termination of the study (14.87%).Item A retrospective review of lifetime prevalence of traditional healer consultation by an outpatient of Xhosa schizophrenia sufferers(2015) Sutherland, TAIM: To describe the demographic and clinical characteristics of a group of patients of Xhosa ethnicity diagnosed with schizophrenia. To also determine the prevalence of their consultations with a traditional healer as well as the factors associated with an increased likelihood of such consultations. METHOD: The study was a review of a database originally compiled as part of an ongoing genetic study. Patients on the database were all of Xhosa ethnicity, with a diagnosis of schizophrenia and had all been recruited from community clinics and psychiatric hospitals in the Cape Town Metropole region. RESULTS: Data was extracted and analysed for 92 patients, who met the criteria for inclusion in this study. The majority of the patients were male (77.2%), single (88%) and unemployed (96%). The mean duration of illness was 20.5 years and the mean number of hospital admissions for their mental illness was 2.4. Close to half (43.5%) of the patients reported being non-compliant on their medication. Ten percent admitted to making one or more suicide attempts in their lifetime. Nicotine was the most commonly used substance (69.6%) followed by alcohol (55.4%), cannabis (37%) and methamphetamines (9.8%). Thirty eight percent of the patients reported having a traditional healer in their family. Twenty two percent had consulted with a traditional healer. In the bivariate analysis the following factors were significantly associated with consulting a traditional healer: having two or less psychiatric admissions (p=0.014); compliance on medication (p=0,012); and having a traditional healer in the family iii (p=0.005). When controlling for age, sex and marital status only having a traditional healer in the family was significantly associated with consulting traditional healer (p=0.011). CONCLUSIONS: This study found that a high proportion of the participants had consulted a traditional healer. This was significantly associated with having a traditional healer as a family member. It is recommended that programmes, to improve the mutual understanding and co-operation between Western practitioners and traditional healers and consequently mental health outcomes, need to be developed and implemented.Item The specificity of platelet glutamate receptor sensitivity as a putative marker for schizophrenia(2014-03-07) Belsham, Brendan CliveHypoglutamatergic function is implicated in the pathogenesis of schizophrenia, and supersensitivity of platelet N-methyl-D-aspartate (NMDA) receptors has been reported in schizophrenia. The aim of this study was to examine the platelet glutamate receptor sensitivity in patients with schizophrenia as well as other psychotic conditions, and matched controls, in order to assess if this is a specific marker of schizophrenia or occurs in other psychotic conditions. Glutamate receptor sensitivity was assessed using the intracellular calcium response to glutamate measured with spectrofluorometry. The percentage responses to glutamate stimulation of the schizophrenic subjects and those with depression with psychotic features were significantly greater than control subjects (p<0.005). The mania with psychotic features group was not significantly different to controls. This data suggests that platelet glutamate receptors may be supersensitive in schizophrenia and depression with psychotic features. The platelet may be a possible peripheral marker of glutamate function in schizophrenia and depression with psychotic features.