Tropical ulcer is a very specific form of cutaneous ulceration. It occurs worldwide in most tropical and a number of subtropical areas. The disease occurs mainly in older children and young adults with children under the age of 5 and adults over 45 years rarely being affected. Ulcers occur most commonly on the lower leg but may occur on the upper limb. Although most ulcers normally heal slowly over many weeks or months, some ulcers may recur. Recognised complications include squamous cell carcinoma, gangrene and osteitis, although these are rare. A number of authors have reported on the disease and suggested diet, trauma and infection as aetiological factors for this condition. This survey was thus conducted to assess as many of these factors as possible. The study took place in 5 tropical areas, namely Zambia, Gambia, southern India, Fiji and Papua New Guinea. Consultations took place at hospitals, rural clinics, health centres and villages. Although many authors have suggested that the disease is related to malnutrition, few have objectively assessed the nutritional status of the patients and compared it with controls. Those studies which included objective assessments were limited to small areas and only investigated specific parameters. In order to investigate the immune response of the host to an anaerobic infection, the antibody levels to the organisms isolated from the ulcers were measured by an ELISA test. The local host response to an infection with a Fusobacterium species was assessed by the number of antibody secreting B-lymphocytes at the site of the ulcers. These parameters may play a role in the localisation of the ulcers and account for recurrent infections.

No description available.

The central nervous system is a potential site of action for the Fusarium mycotoxin Fumonisin B1 (FB1), and is exemplified in horses by the disease equine leukoencephalomalacia. Structurally resembling sphingoid bases, FB1 inhibits ceramide synthase, an enzyme involved in sphingolipid metabolism, leading to accumulation of free sphinganine (Sa) and sphingosine (So). This investigation focused on FB1, Sa, So and the Fusarium mycotoxins fusaric acid (FA), moniliformin (MaN), zearalenone (ZEA), deoxynivalenol (DON), and T-2 toxin (T2). Effects of the Fusarium mycotoxins and sphingoid bases on the N2a neuroblastoma cell line were assessed using the methylthiazol tetrazolium (MIT) and ApoGlow™ assays. The MIT assay revealed significant differences between the viability of N28 control cells and the cytotoxic effects of FB1 (p=0.001), So (p=1.1 x10-6 ), Sa (p=1.9x10-6 ), MON (p=0.002), DON (p=0.04) and ZEA (p=0.003) on N28 cells between 5-250µM. The cytotoxic effects of FA did not differ significantly from controls (p=0.1). The ApoGlow™ assay revealed that in N28 cells, FB1 at 8µg.ml-1, FA at 128µg.ml-1, and (FBI+FA) combined induced growth arrest at 2 and 4µg·ml-1. Assessment of the effects of FBI and FA on the Jurkat leukaemic suspension cell line revealed that FB1 induced apoptosis at 1.56,12.5 and 50µ.ml-1, growth arrest at 100, 200 and 800µg.ml-1 and proliferation at 400µg.mg-1. Fusaric acid induced proliferation at 1. 56µg.ml-1, apoptosis at 3.15µg.mrl, growth arrest at 100 and 200µg.mrl, and necrosis at 800µg.ml-1. Combined, (FB1+FA) induced apoptosis at 1.56, 3.15,12.5 and 800µg.ml-1. Flow cytometry and fluorescence microscopy revealed that mycotoxins, Sa and So induced varying levels of apoptosis and necrosis in N28 cells. Acridine orange and ethidium bromide staining facilitated discrimination between viable, apoptotic and necrotic cells. Transition of the mitochondrial transmembrane potential was measured using Rhodamine 123 with propidium iodide, and the dual emission potential sensitive stain JC-1. Changes in mitochondrial membrane potential and plasma membrane integrity were expressed as increases or decreases in fluorescence intensity. An increase in mycotoxin concentration from 50 to 200µM was usually paralleled by a decrease in J-aggregate formation, suggesting a decrease in the ?¦¥m. Staining with Rh 123/PI indicated at specific concentrations whether N28 cells were either late apoptotic or necrotic reflected by the levels of PI uptake. No dose dependant mechanism of cell death was established using either method, as fluctuations were evident. Immunolocalisation of T2, ZEA and FB1 within cellular organelles that exhibited ultrastructural pathology provided correlation between mycotoxin exposure and effects. Multinucleate giant cells and retraction of cellular processes were observed. At the electron microscope (EM) level, FB1 was immunolocalised within microsegregated and peripherally condensed nucleoli, the nucleoplasm, distorted mitochondria and dilated endoplasmic reticulum (ER). The capacity of cells to incorporate mycotoxins and effect cytological changes represents a major factor in the potential for initiation of malignant transformation. Exposure of N2a cells to FB1 for 72 hours increased intracellular free Sa and depleted complex sphingolipids. Using High Performance Liquid chromatography (HPLC), acid hydrolysis revealed reduction in Sa from a level of O.6±0.12µM in control cells, to 02±0.lµM in cells exposed to 50µM and lOOµM FB1. Base hydrolyses revealed increase in free Sa: So ratios from 0.52±0.2 in control cells, to 1.14±0.2 and 1.4±0.3 in cells exposed to 50 and l00µM FB1 respectively. The Sa: So ratio in the complete culture media (CCM) increased from 1. 7±0. 3 for control cells to 2.0±0.2 and 2.50±0.4 for cells exposed to 50 and lOOµM FB1 respectively. Correlation coefficients between Sa: So ratios to FB1 exposure in CCM (R=0.75) and within cells (R=0.85), imply that the free Sa: So ratio within cells appears to be a better biomarker for FB1-induced disruption of sphingolipid metabolism in vitro, than the Sa: So ratio in CCM. Optimisation of HPLC analytical procedures improved recovery of FB I from spiked human sera to 95.8% (n=15) and detection limits to -5ng.ml-1 at a signal to noise ratio of 5:1. Optimisation of methods for recovery of Sa and So from spiked sera, led to recoveries of 77.9% and 85.0%, for So and Sa respectively at levels of spiking with lOng per 500µl of serum. Matched sera Sa:So ratios and FB1 levels in brain cancer and non-cancer subjects in KwaZulu-Natal were determined using these optimised methods. Fumonisin B1 was detected in sera of non-cancer (76.7±62.2nM) and brain cancer subjects (l07.38±116nM). Mean serum Sa:So ratios of 21 non-cancer subjects was 1.7±0.7. There was no correlation (R=0.26) between these variables in non-cancer subjects. The mean serum FB1 level in brain cancer subjects was 107.4±116nM (range 10.5-298nM) (n=50) and the mean Sa:So ratio (n=50) was 1.9±1.7 (range 0.40-8.16). No correlation was found between these variables in the brain cancer subjects either (R = -0.23). Fumonisin B1 was irnmunolocalised in 49 of 76 brain tumour tissue samples analysed using immunohistochemistry (IHC). Thirty-eight of the 76 specimens had matched serum FBI levels and Sa: So ratios, and 23 of these were positive for FB1 presence. Although not significantly different (p=0.ll), the FBI sera levels in the cancer group with FBI within the tumour tissue had higher levels of FB1 in sera than the IHC FB1 negative group. Fumonisin B1 was localised within irregular profiles of nuclei, elongated and swollen mitochondria and ER. Immunolocalisation of FB1 within organelles in the brain showing ultrastructural cellular pathology suggests FBI may be implicated in the aetiology of human brain carcinogenesis. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2004.

A prospective cohort study of 412 professional rugby union players registered with the English Premiership clubs was conducted during the 2002-2003 season. Injuries were diagnosed and reported by the club medics and the training practices by the club strength and conditioners. A total of 1,090 club injuries (match: 818; training: 260; unidentifiable onset: 12) and 145 international injuries (match: 97; training: 48) were reported. The incidence and risk of club match injuries was 97 injuries and 1,480 days absence per 1,000 player-hours, and the incidence and risk of international match injuries was 218 injuries and 3,076 days absence per 1,000 player-hours. The highest incidence of match injuries occurred to the thigh, however, injuries to the knee were of highest risk. The incidence of club and international training injuries was 3.1 and 6.1 injuries per 1,000 player-hours, respectively. When intrinsic risk factors were assessed, the youngest players (<21 years old) had the highest incidence and a significantly higher risk of injury. Playing position appeared to be the most influential determinate of injury profile, rather than intrinsic anthropometric risk factors alone. The match injury with the second highest incidence and risk was hamstring muscle injuries and a number of risk factors and protective training factors were identified. Results presented from this study have provided the most comprehensive study of injury incidence, aetiology and risk factors in professional rugby union to date. The data provide objective evidence on which to base both preventative interventions to reduce the probability of sustaining an injury and therapeutic interventions to reduce the severity of an injury and thereby reduce the overall risk associated with injuries.

No description available.

No description available.

AIMS OF STUDY: 1. To analyse the patients . who have been treated at Groote Schuur Hospital over the last seven years for Pseudotumor Cerebri. 2. To document the clinical features of this group of patients. 3. To determine the visual prognosis of this group. 4. To assess the forms of treatment that have been used in this group. 5. To review the literature with regard to: a) a comparison of the results of other studies with the present one. b) the pathophysiology of the condition. c) treatment of the syndrome. d) the visual prognosis of the syndrome.

<p>This dissertation interrogates existing scholarly paradigms regarding aetiology in the Histories of Herodotus in order to open up new avenues to approach a complex and varied topic. Since aetiology has mostly been treated as the study of cause and effect in the Histories, this work expands the purview of aetiology to include Herodotus’ explanations of origins more generally. The overarching goal in examining the methodological principles of Herodotean aetiology is to show the extent to which they resonate across the Histories according to their initial development in the proem, especially in those places that seem to deviate from the work’s driving force (i.e. the Persian Wars). Though the focus is on correlating the principles espoused in the proem with their deployment in Herodotus’ ethnographies and other seemingly divergent portions of his work, the dissertation also demonstrates the influence of these principles on some of the more “historical” aspects of the Histories where the struggle between Greeks and barbarians is concerned. The upshot is to make a novel case not only for the programmatic significance of the proem, but also for the cohesion of Herodotean methodology from cover to cover, a perennial concern for scholars of Greek history and historiography.</p><p>Chapter One illustrates how the proem to the Histories (1.1.0-1.5.3) prefigures Herodotus’ engagement with aetiological discussions throughout the Histories. Chapter Two indicates how the reading of the proem laid out in Chapter One allows for Herodotus’ deployment of aetiology in the Egyptian logos (especially where the pharaoh Psammetichus’ investigation of the origins of Egyptian language, nature, and custom are concerned) to be viewed within the methodological continuum of the Histories at large. Chapter Three connects Herodotus’ programmatic interest in the origins of erga (i.e. “works” or “achievements” manifested as monuments and deeds of abstract and concrete sorts) with the patterns addressed in Chapters One and Two. Chapter Four examines aetiological narratives in the Scythian logos and argues through them that this logos is as integral to the Histories as the analogous Egyptian logos studied in Chapter Two. Chapter Five demonstrates how the aetiologies associated with the Greeks’ collaboration with the Persians (i.e. medism) in the lead-up to the battle of Thermopylae recapitulate programmatic patterns isolated in previous chapters and thereby extend the methodological continuum of the Histories beyond the “ethnographic” logoi to some of the most representative “historical” logoi of Herodotus’ work. Chapter Six concludes the dissertation and makes one final case for methodological cohesion by showing the inextricability of the end of the Histories from its beginning.</p> / Dissertation

Transient ischaemic attack (TIA) and ischaemic stroke is a heterogeneous disease with more than 150 known causes including different cardiac, arterial, hemodynamic and other systemic abnormalities. TIA and ischaemic stroke of different aetiology have been suggested to have different risk factor profiles, clinical manifestations and prognoses. Therefore categorization of patients into classes congruent with the aetiology is the key to both understanding and managing stroke. Such categorization requires assembling stroke features to create categories based on similarities and is known as aetiological classification. Accurate aetiological classification is indispensable in epidemiological and genetic studies and in clinical trials. However, all current stroke classification systems have limitations. Perhaps the most important limitation of all current stroke classification systems is that about one-third of TIA and ischaemic stroke are of undetermined aetiology despite standard diagnostic work-up, potentially undermining primary and secondary stroke prevention. Therefore, better understanding of stroke aetiology will help to improve the classification of TIA and ischaemic stroke hence ultimately improving the prevention strategy. The aim of my thesis has been to compare characteristics of currently used aetiological classification systems, to explore the underlying causes for TIA and ischaemic stroke of undetermined aetiology, and to study aetiological classification related aspects of TIA and ischaemic stroke, including risk factors, imaging characteristics, plasma biomarkers and prognoses. I have collected, collated and analysed data from the first ten years of the Oxford Vascular study (OXVASC), which is an ongoing prospective, population-based incidence study of vascular disease in all territories in Oxfordshire, UK. The study population comprises approximately 92,728 individuals registered with nine general practices and uses multiple overlapping “hot” and “cold” methods to identify all patients with acute vascular events. There are several clinically relevant findings in this thesis which address areas that could be improved for better aetiological classification of TIA and ischaemic stroke. First, I have validated the aetiological classification of TIA. Second, I have found that compared to the widely used TOAST aetiological classification system, the stringent requirements for adequate investigation in recently developed classification systems do not add subtype-specific information to reliably reduce the assignment to the undetermined subtype. Third, I have shown that neither occult atheroma nor traditional risk factors appear to account for undetermined TIA and ischaemic stroke. However, previous migraine may have a particular role in the aetiology of undetermined TIA and ischaemic stroke. Fourth, I have shown that compared to cases of non-small vessel disease, small vessel disease cases have higher long-term average systolic and diastolic blood pressure but less long-term blood pressure variability. Fifth, I have shown that in contrast to cases of small vessel disease, white matter changes on brain imaging are not independently associated with non-small vessel subtypes. Sixth, I have shown that applying haemostatic and inflammatory markers in stroke aetiological work-up would appear to have little potential to add very limited information regarding the specific underlying cause of different aetiological subtypes. Finally, I have highlighted the large clinical burden of TIA and ischaemic stroke of undetermined aetiology by showing that compared to cases of determined aetiology, undetermined TIA and ischaemic stroke appears to have non-benign short- and long-term prognoses.

Defects in fat metabolism are central to the aetiology and pathogenesis of obesity and type II diabetes. The liver plays a central role in these disease states via its regulation of glucose and fat metabolism. In addition, accumulation of fat within the liver has been associated with changes in key pathways of carbohydrate and fat metabolism. However a number of questions remain. It is hypothesised that fat accumulation within the liver is a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver is the result of changes in the gene expression of key enzymes and proteins involved with fat uptake, fat transport, fat oxidation, fat re-esterification or storage and export of fat from the liver and these changes are regulated by key lipid responsive transcription factors. To study these questions Psammomys obesus was utilised. This polygenic rodent model of obesity and type II diabetes develops obesity and diabetes in a similar pattern to susceptible human populations. In addition dietary and environmental changes to Psammomys obesus were employed to create different states of energy balance, which allowed the regulation of liver fat gene expression to be examined. These investigations include: 1) Measurement of fat accumulation and fatty acid binding proteins in lean, obese and diabetic Psammomys obesus. 2) Characterisation of hepatic lipid enzymes, transport protein and lipid responsive transcription factor gene expression in lean, obese and diabetic Paammomys obesus. 3) The effect of acute and chronic energy restriction on hepatic lipid metabolism in Psammomys obesus. 4) The effect of sucrose feeding on the development of obesity and type II diabetes in Psammomys obesus. 5) The effect of nicotine treatment in lean and obese Psammomys obesus, 6) The effect of high dose leptin administration on hepatic fat metabolism in Psammomys obesus. The results of these studies demonstrated that fat accumulation within the liver was not a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver was not the result of changes in the gene expression of key enzymes and proteins involved in hepatic fat metabolism. However changes in the mRNA level of the transcription factors PPAR∝ and SREBP-1C was associated with the development of diabetes and the gene expression of these two transcription factors was associated with changes in diabetic status.