Search

Palliative care has become an important public health issue in recent years and has been declared a universal human right. A wealth of literature can be found describing its effectiveness and numerous benefits, yet significant disparities exist in worldwide palliative care development between, and within, countries. To date, previous studies indicate that it has steadily improved in the more economically developed countries, although its utilisation remained uneven in western societies between the blacks compared with the white people. In low- and middle-income countries, palliative care has continued to be less available, underutilised and not integrated in many of the healthcare systems, especially in the African countries such as Nigeria. This qualitative study using an ethnographical approach to understand the cultural, socio-political, environmental, and organisational dynamics which influenced the provision of palliative care, and the patients' and relatives' behaviour towards its utilisation in a Nigerian hospital. Data was collected using participant observation, ethnographic interview and review of documentary sources, involving 43 participants, comprising healthcare professionals, members of the hospital management, patients and their families. The findings show a dominant discourse of culturally-based perceptions rooted in belief systems and inadequate knowledge of palliative care associated with insufficient education and training which manifested in several ways, such as conceptualisation of palliative care as a 'dead end'. The service-users predominantly used their belief systems in decision-making, whereas dichotomy existed amongst the professionals about using either ethno-religious knowledge or biomedical knowledge to inform practice. These culturally-based perceptions were found to be contributory to, and a result of, a political and organisational culture that did not value palliation. Thus, the insensitivity of the bureaucrats was displayed in numerous ways, such as lack of funding for palliative care. Consequently, the environment for care represented space rather than a place that could promote the wellbeing of the service-users, which thereby contributed to various organisational cultures, such as weak interdepartmental collaboration and work-stoppage, with negative impacts for the service-users. The findings also suggest that the customary code of behaviour used by the service users was conditioned mainly by complex interactions of economic conditions, social relationships and lack of a governmental social support system. The professionals, therefore, used their personal resources as well as provided physical cash to the patients to cushion the effect of government inadequacies and to improve their wellbeing. These findings indicate the need for a cultural shift towards a mind-set that values palliative care in Nigeria in order to enhance its development. This study adds to the knowledge of this field and provides clinicians around the world with further understanding of meaning making in illness from the perspective of the Nigerian culture, which may be applicable to other people of African ancestry and could be used to boost cultural competence in palliative care.

Listeria monocytogenes is a food-borne pathogen and the causative agent of listeriosis, a severe infection resulting in septicaemia, meningitis and still birth. Infection typically arises through the consumption of contaminated foodstuffs. L. monocytogenes is a hardy organism which can survive several food control measures. Psychotrophic and facultatively anaerobic properties permit growth under refrigeration conditions and within modified atmosphere packaging. Through transcriptional and translational changes L. monocytogenes is able to mount adaptive responses against stressors. Such responses typically cross protect against subsequent stresses, including effectors of the human immune system. The aim of this study was to assess the ability of L. monocytogenes to adaptively respond to stressors, and to assess the phenotypic and molecular responses that such exposures have on resistance and virulence potential. Using adaptation and repeated exposure assays L. monocytogenes cells were assessed for their ability to develop resistance and to adaptively respond to stressors. Using qRT-PCR and insertional mutagenesis the roles of several candidate genes in stress response were assessed. Using a simulated gastro-intestinal transit model the effects of refrigeration and oxygen limitation on virulence potential were investigated, while microarray analysis allowed elucidation of the molecular mechanisms accounting for altered resistance properties and virulence potential. Stationary phase L. monocytogenes cells were not found to adapt to sub lethal exposure to citric acid, TSP, NaCIO and H2O2. Susceptibility to stressors was increased or unchanged following sub-lethal pre-exposure. Sub-lethal exposure to NaCIO increased expression of Imo0669 (oxidoreductase) by 4.6-fold, while a 2-fold increase in gadA was observed during TSP exposure. These responses permit survival under NaCIO and TSP stress, and may have implications in subsequent stress exposure and/or virulence potential. Inactivation of ctsR, hfq, lisR and lisK by site-directed mutagenesis gave rise to mutant cells with increased sensitivity to H2O2. Citric acid resistance was impaired by ctsR and hfq disruption. Pre-conditioning under oxygen limiting conditions significantly increased acid tolerance in L. monocytogenes FSL R2-499. When assessing the effects of pre-conditioning on gastro-intestinal transit L. monocytogenes FSL R2-499 displayed growth phase, pre-conditioning and pH dependant resistance profiles. Cells grown under oxygen limiting conditions typically demonstrated increased resistance towards simulated gastric juice (pH 2.5), however, only stationary phase cells were able to survive bile salt exposure. L. monocytogenes cells grown under oxygen limiting conditions displayed increased acid tolerance but decreased H2O2 resistance. Transcriptional analysis revealed significant up-regulation of the acid response gene, gadA, under oxygen limiting conditions, while catalase was significantly down-regulated. The findings of this study provide important information for food manufacturers who can use this data to "intelligently apply" food control measures, or hurdles, to improve food safety.

Staphylococcus aureus and Enterococcus sp. infections occur in hospital and, increasingly, in community settings, with the potential of having different susceptibility to antimicrobial agents. The purpose of this study was to investigate the effect of antimicrobial agents against community acquired S.aureus and investigate antibiotic characteristics, biofilm formation and gene expression following exposure to an antimicrobial agent. The susceptibility of S. aureus isolates and a vancomycin resistant Enterococcus faecium isolate to antibiotics, essential oils and disinfectants were investigated under planktonic conditions using standardised antimicrobial susceptibility tests and the Quantitative suspension and surface tests (EN 1276 and EN 13697) for the disinfectants. Biofilm formation, inhibition and eradication was investigated using the crystal violet (CV) assay while the viability of treated biofilms were investigated using the 2, 3-bis [2-methyloxy-4-nitro-5- sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay and CFU/ml assay. Multiplex PCR was used to determine the presence of PVL, icaA and IcaD genes as well as SCCmec typing while RT-PCR used to investigate changes in gene expression in five target genes following treatment of PVL CA MSSA and CA MRSA MW2 biofilms with grapefruit EO. The S. aureus isolates all formed biofilms and had similar molecular characteristics however one isolate (CA MRSA SR) was multidrug resistant and PVL negative. The VRE isolate was negative for biofilm formation. In suspension, household bleach and NaDCC caused > 5 log reduction in viable counts and on stainless steel surfaces, there was < 3.5 log reduction. Against biofilms, Household bleach at 5000ppm caused 100% biofilm eradication within 10 minutes while NaDCC eradicated <50% of the biofilm within one hour at 10,000ppm. The eco-friendly product did not demonstrate any antimicrobial activity against planktonic cells or biofilms. Antimicrobial activity of six essential oils (EO) (lime, lemon, lemongrass, geranium, grapefruit, bergamot), and two components (limonene and citral) was investigated for the S. aureus isolates. Following exposure to lemongrass EO extensive disruption to S. aureus biofilms was shown under scanning electron microscopy. The most notable changes in gene expression following exposure to grapefruit EO were the /caD, luxS and sodA genes when the PVL CA MSSA biofilms was compared to the prototype community acquired strain, CA MRSA MW2. The S. aureus isolates were susceptible to the essential oils with the exception of limonene and lemon EO. Lemongrass EO inhibited biofilm formation, metabolic activity and viability. No anti-biofilm activity was observed for Grapefruit EO against S. aureus except for one isolate (PVL positive CA MSSA), where an increase in metabolic activity was observed following treatment. Lemongrass EO was effective as an antibacterial and antibiofilm agent and could be a potential alternative to chemical based antimicrobial agents in both healthcare and non-healthcare environments.

This thesis collates, records and reviews pioneering studies performed by the author on the formulation, use, advantages, and applications of acrylic plastic embedding media for the histological examination of tissue using light microscopy, with particular emphasis on histochemical and molecular techniques. Nine key papers by the author are reviewed. The first relates to a number of modifications of an established method for the histological examination and investigation of metabolic bone diseases. As a result it was reported that the procedure had resulted in significant time saving without detrimentally affecting quality, and has been used for investigating approximately 10,000 cases of metabolic bone diseases for diagnosis. In a further separate development, the enzymes lactase and sucrase were first reported in plastic-embedded jejunum. Subsequently it was shown that these two important disaccharidases for assessing malabsorption were sensitive to specific processing agents and could easily be lost, resulting in false negative staining. However, by using a specific processing schedule and times, the author was able to demonstrate how best tissue could be processed to retain these and other enzymes in various plastic embedding media. A number of procedures were initiated for the application of IHC on plastic- embedded tissue that included the development of a modified plastic with new preparatory techniques, and changes in immunocytochemical staining protocols to enable IHC to be routinely performed. Previously, this had been regarded as technically not possible. Later in a series of papers published, procedures were described where the use and evaluation of enzyme, and/or antigen retrieval techniques using microwave heating and/or pressure cooking were assessed. Numerous antigens were successfully demonstrated, and subsequently specific diagnostic applications on various tissues were reported, including extensive routine use on approximately 35,000 cases to date of bone marrow trephines. In a further development, the application of ISH techniques for the detection of mRNA in chick tissue for the demonstration of transcription Sox genes 11 and 21 was reported, which subsequently was combined with IHC for bromodeoxyuridine or neurofilament protein for simultaneous double staining on the same section.