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1
Strickland, Thomas. "Experimental spaces: megastructures, medicine and McMaster." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110431.
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This thesis is an architectural study that focuses on an anxious and exciting period for medicine and architecture between 1960 and 1975. This time was an important moment of adjustment and adaptation for medicine, architecture and community. Collateral to the establishment of national health insurance (Medicare, 1966), architects and hospital planners sought to use the space of the hospital to foster this new relationship with their constituency. This happened in multiple and surprising ways, from the introduction of public spaces in hospitals, to a medical exhibit at Expo 67 that was as much an amusement ride as it was a didactic space, to a significant reorganization of the socio-spatial hierarchy of the hospital - all of which foreshadowed the influential atrium hospital of the 1980s and its shopping mall-like setting. The primary focus of this thesis is a building that Reyner Banham touted as the "ultimate medical megastructure" (1976), the McMaster Health Sciences Centre (1972) designed by the Toronto firm of Craig, Zeidler and Strong Architects. At the core of this study is the belief that hospital architecture is influenced by medical ambitions, but also architectural discourse and social dynamics. Based on this understanding, the analysis examines how the social ambitions of the Megastructuralist polemic interacted with the powerful urge to assimilate biological research activities with the clinical setting. Archival resources, interviews and a broad range of architectural precedents are presented and analyzed to understand the medical and architectural trends that contributed to McMaster Health Sciences Centre's innovative and influential design. In this thesis, megastructuralist experimental, utopian projects and, importantly, the broader debate over the future of the postwar city is brought to bear on biomedical ambitions and the architecture of the hospital.D'un point de vue architectural, cette thèse s'intéresse à la relation qui émerge entre médecine, architecture et communauté dans les années 1960 à 1975 : période charnière d'ajustement et d'adaptation. Parallèlement à la création des organismes nationaux d'assurance maladie (Medicare, 1966), les architectes et les planificateurs des hôpitaux ont cherché à utiliser l'espace même de l'hôpital pour favoriser de nouvelles relations auprès de la collectivité. Cette approche est apparue de multiples manières et, parfois même, de façon surprenante ; pensons à l'introduction des espaces publics dans les hôpitaux, à une exposition sur la médecine présentée à Expo'67 qui s'apparentait autant à une attraction publique qu'à un espace didactique, ou encore à l'importante réorganisation de la hiérarchie socio-spatiale des hôpitaux. Tous ces éléments préfiguraient l'influence et la prégnance de l'atrium, et de ses espaces commerciaux, dans les hôpitaux des années 1980. La thèse examinera plus précisément le Centre des sciences de la santé de l'Université McMaster (MHSC) de Hamilton, conçu par la firme d'architectes Craig, Zeidler & Strong, que Reyner Banham décrit comme l'ultime mégastructure médicale (1976). Sur les bases du discours architectural, de la dynamique sociale et, surtout, d'une profonde conviction que la production de l'architecture hospitalière est influencée par certaines visées médicales, cette analyse portera sur la façon dont les ambitions sociales de la polémique mégastructuraliste interagissent avec l'assimilation des activités de recherche biologique au sein des installations cliniques. Diverses ressources, telles que des archives, des entrevues et un large éventail de précédents, seront décrites, utilisées et analysées afin de cerner les tendances médicales et architecturales qui ont contribué à la conception, innovante et influente, du Centre des sciences de la santé de l'Université McMaster. Le mégastructuralisme expérimental, les projets utopiques ainsi que le débat plus large sur l'avenir de la ville d'après-guerre permettront à la thèse de porter un regard nouveau sur les ambitions biomédicales et architecturales dans les hôpitaux.
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Olofsson, Pia. "Experimental studies on Damage Control Surgery and Intraabdominal Hypertension." Doctoral thesis, Linköpings universitet, Kirurgi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-17796.
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Damage control surgery (DCS) offers an alternative to the traditional surgical management of complex or multiple injuries in critically injured patients. If a patient survives the initial phase of DCS, complications may occur, one of these being intraabdominal hypertension (IAH) and it´s potential development into the abdominal compartment syndrome. The indications for DCS have been widened and DCS principles can be applied in situations where time and resources are essential factors. The DCS principles of rapidly controlling intestinal spillage have not been evaluated. The aim of the studies in Papers I and II was to evaluate the principles of spillage control of intestinal contents according to the DCS concept and more specifically the effects of early rapid control of multiple bowel perforations on cardiovascular and pulmonary function compared with conventional small bowel resections in an animal model with abdominal trauma. In Paper I the animal model using anaesthetised pigs included a gunshot wound to the abdomen which caused multiple small bowel injuries. Haemorrhagic shock was combined with the gunshot wound in Paper II. The results presented in Paper I showed a significant reduction in rise in systemic vascular resistance and pulmonary vascular resistance, and a trend towards higher cardiac output and lower oxygen consumption in the bowel ligation group. In Paper II the results show a longer persistence of lactic acidaemia in the bowel ligation group. The aim of the study in Paper III was to assess visceral (intestinal, gastric and renal) microcirculation parallel with central haemodynamics and respiratory function during stepwise increases in intraabdominal pressure. In Paper IV we studied mucosal barrier function and morphology in the small bowel and colon of the pigs which were subjected to IAH. The IAP in anaesthetised pigs was increased stepwise using CO2 inflation, by 10 mm Hg at 10-minute intervals up to 50 mm Hg, and followed by exsufflation (Paper III). The microcirculation was selectively studied using a 4-channel laser Doppler flowmeter (Periflex 5000, Perimed, Sweden). The mucosal tissues were mounted in modified Ussing chambers for assessment of barrier function (E.coli K12 uptake and 51Cr-EDTA permeability) (Paper IV). The results showed that the microcirculation of the small bowel mucosa and colon mucosa was significantly less affected compared to the seromuscular layers. The microcirculation of gastric mucosa, renal cortex and the seromuscular layer of small bowel and colon were significantly reduced with each increase. Cardiac output (CO) decreased significantly at IAP levels above 10 mm Hg and the respiratory function data showed an increasing airway pressure and a concomitant reduction in thoracic compliance. Transmucosal passage of E. coli was increased three-fold in the small bowel after ACS with a significant correlation to the degree of mucosal microcirculatory reperfusion after exsufflation. 51Cr-EDTA permeability was unaffected. Bacterial passage in the colon was unchanged, whereas 51Cr-EDTA permeability after ACS increased by up to 181% of baseline and was correlated to significant histopathological changes in the mucosa. In Paper I we have demonstrated that early rapid control of multiple bowel perforations in a model with moderate shock resulted in less impairment of SVR and PVR than conventional resection and anastomosis. The use of DCS principles, however, had no beneficial effect on cardiovascular function when haemorrhagic shock was combined with abdominal missile trauma (Paper II), on the contrary bowel ligation was followed by more prolonged lactic acidosis than conventional repair. The studies in Paper III and IV indicate that the microcirculation of intestinal mucosa and especially small bowel mucosa seem better preserved in response to intraabdominal hypertension caused by CO2 insufflation than other intraabdominal microvascular beds. The short term ACS in this model caused morphological changes in the intestinal mucosa, and mucosal barrier dysfunction. The response pattern concerning barrier function changes after CO2 insufflation differs between small bowel and colonic mucosa. The small bowel mucosa showed increased bacterial passage, and the colonic mucosa an increase in paracellular permeability and secretory response.
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Amandusson, Åsa. "Estrogen Receptor Expression in Relation to Pain Modulation and Transmission: Experimental Studies in Rats." Doctoral thesis, Linköpings universitet, Cellbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-17978.
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Estrogens have a remarkably wide range of actions in the mammalian brain. They not only play a pivotal role in reproductive behavior and sexual differentiation, but also contribute to e.g. thermoregulation, feeding, memory, neuronal survival and the perception of somatosensory stimuli. A multitude of studies on both animals and human subjects has demonstrated potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and therefore need to be evaluated specifically in relation to the localization and intrinsic characteristics of the neurons engaged. The overall aim of this thesis is to gain specific knowledge of the possible cellular mechanisms by which estrogens may influence the transmission of nociceptive stimuli at the level of the spinal cord. The estrogen receptors, by which estrogens regulate non-genomic as well as genomic mechanisms, are crucial to estrogen signaling in general and essential to the estrogen-induced effects in the brain. In Paper I, we use immunohistochemistry to label neurons containing estrogen receptor-! (ERα) in the medullary and spinal dorsal horn of female rats. Large numbers of ER!-expressing neurons were found in lamina I and lamina II, i.e. in the areas involved in the processing of primary afferent nociceptive information. This distribution in part overlaps that of enkephalin, a potent pain-inhibiting endogenous opioid. The effects of gonadal hormones on pain modulation may, to a great extent, be blocked by the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the prosecution of hormonal pain regulation. By combining immunohistochemical labeling of ERα with in situ hybridization of preproenkephalin mRNA (Paper II), we demonstrate that the majority of enkephalinergic neurons in the superficial laminae of the spinal and medullary dorsal horn express ER!. This co-localization and the fact that the preproenkephalin gene contains a sequence that binds ERs, suggest that estrogens may potentially regulate enkephalin expression in these cells. This is further supported by the findings in Paper III in which we show that a single subcutaneous injection of estradiol induces a significant increase (on average 68%) in preproenkephalin mRNA content in the spinal cord after 4 hours. The expression of the enkephalin gene in the spinal cord is thus sensitive to fluctuating estradiol levels. In Paper IV, a noxious injection of formalin is used to induce activation of a neuronal population involved in nociceptive transmission from the face. By using a dual-labeling immunohistochemistry protocol, we were able to identify ER!-expressing cells within this neuronal population suggesting that nociceptive-responsive neurons in the medullary dorsal horn express ER!. In all, our findings provide morphological as well as biochemical evidence in support for an estrogen-dependent modulation of nociceptive processing at the level of the dorsal horn.
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Samuelsson, Anders. "Effects of burns and vasoactive drugs on human skin : Clinical and Experimental studies using microdialysis." Doctoral thesis, Linköpings universitet, Anestesiologi med intensivvård, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59519.
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Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function. Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling. Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis. We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries. In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (Emax) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model. We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.
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Blakytny, Robert. "Experimental cataract and its prevention." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333181.
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Hillman, Nicola Jane. "Hypertension and experimental diabetic retinopathy." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241987.
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Hübbert, Laila. "Between the Probe and the Pump : An experimental study on cardiac performance analysis based on Echocardiography, tissue and laser Doppler." Doctoral thesis, Linköpings universitet, Kardiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-61518.
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Echocardiography is an ultrasound-based bedside, non-invasive and easily available cardiac diagnostic technique visualising the heart’s morphology and function. Quantification of cardiac wall motion can be measured with the tissue Doppler Imaging (TDI) modality which provides in humans a high diagnostic capacity to differentiate healthy from diseased myocardium with reduced function. Heart failure, as a consequence of, for example, myocardial or ischaemic heart disease, demands both bedside and intraoperative diagnostic procedures for myocardial functional and perfusion assessment. In the late stages of heart failure cardiac left ventricular assist devices (LVAD) may be the treatment of choice. Such new technologies are commonly evaluated in large animals before application in humans is accepted. With the aim of evaluating TDI´s applicability and feasibility in a large animal model 21 calves (aged 3 months and weight around 70 kg), were studied with colour TDI (Paper I). Analysis was performed either during coronary artery occlusion when the laser Doppler perfusion imaging technique (LDMP) was refined (Paper II), or after implantation of the LVAD, Heart Mate II® (Papers III, IV). All animals were haemodynamically monitored (pressures, flows, heart rate) and ECG was continuously recorded. Transthoracic and epicardial echocardiography (TTE) were performed before and after sternotomy and intraoperatively during experimental progressive heart failure. Heart chamber dimensions, native stroke volume, systolic and diastolic regional basal myocardial peak velocities (cm/s; systolic S´, early diastolic E´, and atrial A´, strain (%), strain rate (s-1) and displacement (mm) were determined. Second harmonic imaging (SHI) was applied in order to better visualise air bubbles (Paper IV). In Paper I compiled baseline values were established before and after sternotomy for central haemodynamic and echocardiographic parameters, including the TDI myocardial motion variables velocity, strain rate, strain and displacement. Blood pressure and heart rate changed significantly after sternotomy, but the TDI derived data did not change significantly. In Paper II we report that movement artifacts of the laser Doppler myocardial perfusion measurements can be reduced, both when myocardium is normally perfused and during coronary occlusion, by using the TDI velocity registrations showing wall motion to be minimal. The optimum interval depends on the application but late systole as well as late diastole is preferred. After LVAD implantation in Paper III the flow characteristics and myocardial motion during variations in afterload TDI show that myocardial velocities decrease concomitantly with myocardial depression and are significantly correlated to native stroke volume, heart rate, systemic arterial resistance and cardiac output, but not with left ventricular size, fractional shortening or pump speed. Echocardiography together with TDI thereby offers additional means for monitoring and quantifying residual myocardial function during LVAD treatment. SHI is superior in the early detection of single air-bubbles in the ascending aorta prior to significant air embolism during manipulation of the LVAD pump speed, as shown in Paper IV. A prompt decrease in size of the left atrium during speed adjustment may be a warning that massive air embolism is imminent whereas the commonly used left atrial pressure not provide the same warning.The title of article II is in the list of publications "Correlation between laser Doppler perfusion monitoring and myocardial tissue Doppler echocardiography in the beating heart" and in the published article the title is "Myocardial tissue motion influence on laser Doppler perfusion monitoring using tissue Doppler imaging".
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Leclair, Robert J. "X-ray scatter imaging in medicine, model and experimental validation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/NQ57615.pdf.
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Leclair, Robert J. (Robert Joseph) Carleton University Dissertation Physics. "X-ray scatter imaging in medicine; model and experimental validation." Ottawa, 2000.
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Galloway, D. J. "Dietary manipulation of experimental colorectal cancer." Thesis, University of Glasgow, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374513.
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Pekiner, Can. "Molecular remodelling in experimental diabetic neuropathy." Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317219.
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Ma, Jennifer. "Role of inhibitors of apoptosis proteins (IAPs) and Smac/DIABLO in regulating activated T-lymphocyte survival." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95585.
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Activation of primary lymphocytes leads to the initiation of the apoptotic program • although cells do not undergo apoptosis. The aim of this study was to investigate the key regulatory proteins controlling caspase activation during T-Iymphocyte activation. We analyzed the apoptotic pathways in highly purified T-Iymphocytes. Our data revealed that following activation of T lymphocytes with a-CD3 and a-CD28 in the presence of IL-2, initial processing of caspase-3 took place into an inactive p20 fragment and the key substrates essential in mediating the apoptotic machinery were not cleaved. This initial processing of caspase-3 was concomitantly accompanied by the up-regulation of lAP family members, namely XIAP, c-IAPl, c-IAP2 and survivin. We further demonstrated by co-immunoprecipitation assays that the inhibition of apoptosis in activated T cells could be attributed to XIAP binding to the cleaved forms of caspase-3. This led us to investigate whether the translocation of SmaclDIABLO from mitochondria to cytosol regulates XIAP repression of further caspase-3 processing during T-Iymphocyte activation. We observed that there was no release of Smac/DIABLO from the mitochondria, which appears to be the second signal required for apoptosis induction in activated T lymphocytes since a-Fas cross-linking or UV-irradiation allows for Smac/DIABLO translocation from the mitochondria into the cytosol. Indeed, SmaclDIABLO translocation accompanied caspase-3 activation and substrate cleavage as well as the formation of Smac/DIABLO-XIAP hetero-complex. These findings clearly suggest the existence of multi-regulatory steps implicating Smac/DIABLO-XIAP interaction in regulating caspase-3 activity during T-Iymphocyte activation, preventing undesirable induction of cell death.L’activation de lymphocytes pnmaIres induit l’initiation du programme apoptotique. Parcontre, les cellules ne meurent pas par apoptose. L’objectif de cette étude était de déterminer les protéines clées régulatrices qui contrôlent l’activation des caspases lors de l’activation des lymphocytes T. Pour ce faire, la signalisation impliquée dans l’apoptose a été analysée au niveau de lymphocytes T hautement purifiés. Les résultats obtenus révèlent que, suivant l’activation de lymphocytes T par anti-CD3 et anti-CD28 en présence d’IL-2, un clivage initial de caspase-3 générant le fragment inactif p20 a lieu et les substrats clés, essentiels à la signalisation apoptotique, n’ont pas été clivés. Ce clivage précurseur de caspase-3 était accompagné par une augmentation de l’expression des protéines de la famille des IAPs, dont XIAP, c-IAPl, c-IAP2 et survivine. Des expériences de co-immunoprécipitation démontrent que l’inhibition de l’apoptose au niveau des cellules T activées pourrait être attribuée à la liaison de XIAP aux formes clivées de caspase-3. Suite à ces observations nous avons voulu déterminer si la translocation de Smac/DIABLO des mitochondries au cytosol régule l’activité répressive de XIAP sur les clivages subséquents de caspase-3, au cours de l’activation des lymphocytes T. Les résultats démontrent que Smac/DIABLO n’est pas relâchée de la mitochondrie, ce qui apparaît comme étant le deuxième signal requis pour l’induction de l’apoptose dans les lymphocytes T activés puisque l’interaction de Fas avec un anticorps anti-Fas ou une irradiation aux UV permet la translocation de Smac/DIABLO des mitochondries au cytosol. En effet, la translocation de Smac/DIABLO accompagne l’activation de caspase-3 ainsi que le clivage des substrats et la formation d’un complexe hétérodimère Smac/DIABLO-XIAP. Ces données révèlent donc d’une façon évidente l’existence d’un processu
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Ker, Mary Virginia. "Using texture to predict diagnosis and disease from nuclear medicine lung perfusion scans: A comparison of nuclear medicine physicians to the slope of the power spectrum." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185562.
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The lung has been satisfactorily modelled as a fractal, and change in lung structure due to disease is assumed to change the fractal dimensionality of the lung. It is hypothesized that those changes in fractal dimension affect perceptually relevant elements (perceived texture) of the lung, and therefore the fractal dimension may prove to be a predictor of diagnosis. If the fractal dimensionality reflects structure in ways more accurately reflecting changes in lung structure than can be achieved by nuclear medicine physicians, then it may also prove useful as a diagnostic tool. Fractal dimension is linearly related to the slope of the power spectrum (SPS) as plotted on log-log paper, and the SPS was used as the metric reflecting the fractal dimension. Seventy-two cases were selected that were either normal, had congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or pulmonary embolism (PE). Five of the cases had both CHF and COPD. The lung scans from these cases were digitized, with appropriate corrections for linearization, edge artifacts, target nonuniformities and film gamma. Fast Fourier Transforms provided the power spectrum from which the SPS was calculated. Four nuclear medicine physicians read the original lung scans and rated their certainty about the presence of two texture elements, the extensiveness of disease involvement, and presence of the three diseases used (CHF, COPD, and PE). The results found the SPS to be significantly related to both texture ratings and diagnostic certainty, but inferior as a predictor of disease to either texture rating or diagnostic certainty. This study reveals the SPS to be a promising but incomplete candidate for machine-algorithm generated diagnosis.
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MacPhee, I. A. M. "The cellular basis of experimental allergic encephalomyelitis." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235040.
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Stewart, Adrian John. "Clinical and experimental studies of ventricular fibrillation." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334535.
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Corcoran, John David Ross. "Surfactant replacement therapy : experimental and clinical studies." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387871.
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Lewis, Harry Lewis. "Experimental and clinical studies in acute pancreatitis." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387895.
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Diamond, Thomas. "Experimental aspects of endotoxaemia in obstructive jaundice." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334469.
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Jakes, Ian C. "An experimental investigation of obsessive compulsive disorder." Thesis, King's College London (University of London), 1992. https://kclpure.kcl.ac.uk/portal/en/theses/an-experimental-investigation-of-obsessive-compulsive-disorder(eaf9023a-2ed0-4e7f-b7dc-1fde9c5dee50).html.
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The thesis is divided into four parts. In Part A, what are termed the "standard diagnostic criteria" for Obsessive-Compulsive Disorder" (OCD) are reviewed, and argued to be implausible. The beginnings of an alternative approach to the definition of the disorder are presented. Empirical investigations of the characteristics of obsessive-compulsive experience among OCD sufferers are also reported. The results of these investigations both confirm the critique of the "standard diagnostic criteria", and are consistent with previous phenomenological investigations of OCD patients. Judgment is suspended as to the full importance of these diagnostic and phenomenological considerations to the understanding of OCD. In Part B, a number of theoretical approaches to OCD are discussed, including behavioural/learning accounts, "Pavlovian" personality theories, Janet's account, a "cybernetic" approach, an account from a psychodynamic perspective, and the "cognitive-structural" theory. It is argued that none of these approaches is able fully to explain the phenomena associated with OCD. In Part C, the "cognitive-structural" theory of OCD is tested empirically. Three investigations are reported, none of which provide strong support for this theory. In Part D, an attempt is made to pick out, from the approaches considered earlier, any ideas which may offer some hope of progress in the understanding and/or treatment of OCD. The suggestion which is examined to this end, made by several of the accounts considered above, is that the unassertive behaviour of some OCD patients may be an important precipitant of their symptoms. Evidence relevant to this claim, and its implications for treatment, are reviewed. It is suggested that this approach may offer some insights and useful suggestions for some cases of OCD. Some suggestions are offered as to further work which might be conducted along these lines. 4
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PORCU, ELENA PIERA. "Development of novel platforms for diagnosis and therapy in experimental medicine." Doctoral thesis, Università degli studi di Pavia, 2017. http://hdl.handle.net/11571/1215981.
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Qasim, Faieza Jabeen. "Study of an animal model of experimental vasculitis." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361670.
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Dolan, Seamus Joseph. "Endotoxin and proinflammatory cytokines in experimental acute pancreatitis." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263319.
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Boyd, Alison Catherine. "Clinical and experimental studies on glycated human insulin." Thesis, University of Ulster, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390153.
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Pryce, Gareth. "Cannabinoids for the control of experimental multiple sclerosis." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/673.
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There have been numerous studies reporting that cannabinoids, both exogenous and endogenous, have a potential beneficial function during incidences of neurological damage. Using gene knockout mice and cannabinoid-selective agents, this study demonstrates the diverse actions of cannabinoids with a particular focus on experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The results presented here report on the action of stimulators of cannabinoid receptors in the nervous system (CNS) on; immune function, as a mechanism of suppressing autoimmune attack of the central nervous system, as agents to suppress neurodegenerative events leading to disease progression and as agents that can control signs of disease that occur as the consequences of autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the psychoactive component in cannabis and the CB1 cannabinoid receptor appears to be central to many of the therapeutic actions of cannabis but also to the side-effect potential of cannabinoid drugs. This study reports on methods to avoid psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists whilst exploiting the therapeutic potential of the cannabinoid system in order to control spasticity. This was achieved by targeting mechanisms of endocannabinoid degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore, this study also reports the development of novel cannabinoid compounds that are excluded from the brain and inhibit spasticity and also demonstrates the mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This study provides further evidence for the efficacy of cannabinoid compounds during an ongoing CNS disease and also their efficacy for treating the consequences of CNS autoimmune disease, which hopefully, will give additional impetus for further clinical investigations of cannabinoid agents in not only multiple sclerosis but also other neurodegenerative diseases of the CNS.
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Frith, Daniel. "Clinical & experimental characterisation of acute traumatic coagulopathy." Thesis, Queen Mary, University of London, 2011. http://qmro.qmul.ac.uk/xmlui/handle/123456789/2419.
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Acute traumatic coagulopathy (ATC) is a recently identified entity describing an early impairment of haemostasis after injury. Retrospective observational studies have associated it with a significant increase in patient morbidity and mortality. It does not appear to be caused by conventional mediators of haemorrhagic coagulopathy, such as iatrogenic haemodilution or hypothermia. Rather, it has been postulated that it is endogenous systemic anticoagulation modulated by activation of the protein C pathway in response to shock and tissue injury. The aims of this thesis were to characterise the aetiology and clinical significance of ATC and test the hypothesis that activated protein C plays a functional role in the pathophysiology of this condition. A retrospective analysis of patients admitted to 5 major international trauma centres was performed. Admission prothrombin times were correlated with aetiological variables and clinical outcomes. A structured literature review was subsequently conducted to identify the strengths and weaknesses of existing animal models of traumatic coagulopathy. Novel rodent (rat and mouse) models of ATC were then developed to elucidate how it develops. Clinical data on 3646 trauma patients identified a significant and dose-dependent increase in mortality and transfusion requirements with admission prothrombin time ratio > 1.2. The incidence of ATC co-associated with both the degree of tissue injury and the depth of haemorrhagic shock. Literature review identified a general failure of animal models to accurately simulate the clinical trajectory of injury. Specifically, only one (mouse) model of ATC was identified. Novel rodent models of ATC were developed that demonstrated endogenous coagulopathy in response to 60 minutes of haemorrhagic shock, with or without significant tissue injury. This was mediated predominantly by autogenous haemodilution and activated protein C anticoagulation. Acute traumatic coagulopathy is an endogenous impairment of haemostasis that develops in response to severe haemorrhagic shock. Manipulation of the protein C pathway may represent a novel therapeutic strategy for reducing blood loss and improving outcomes after injury.
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Chamberlain, Lisa M. "Pathogenesis and immunity in experimental infection with Neisseria gonorrhoeae." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320009.
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Gardiner, Keith Reginald. "Systemic endotoxaemia in inflammatory bowel disease and experimental colitis." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333776.
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Yates, John. "Haemodynamic effects of vasoactive drugs in experimental portal hypertension." Thesis, Liverpool John Moores University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337787.
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Docherty, James G. "Local recurrence of colorectal cancer : clinical and experimental studies." Thesis, University of Aberdeen, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363685.
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Clinical and experimental studies which investigate factors affecting local recurrence of colorectal cancer are detailed. Three hundred and six patients underwent potentially curative surgery and had their anastomosis randomised to either sutures or staples. There was a 7.5% difference in overall recurrence rates in favour of the stapled patients (Log Rank X2=2.88, 1 df, p=0.09) and there was a similar difference in cancer specific mortality (Log Rank X2=2.41, 1 df, p=0.12). Anastomotic technique was an independent predictor of both tumour recurrence and cancer specific mortality. The effect that anastomotic integrity had on long term outcome was investigated using 177 patients. Tumour recurred in 44.7% of patients with an anastomotic leak and 30.2% of patients with an intact anastomosis (Long Rank X2=8.62, 1 df, p=0.002). Local recurrence occurred in 36.8% and 15.1% respectively. Cancer specific mortality was also significantly better for patients with an intact anastomosis (Log Rank X2=8.19. 1 df, p=0.004). The rates of clinical anastomotic leakage and peri-operative deaths between the surgeons participating in the study varied. Overall recurrence rates varied significantly between the surgeons, however there was a more marked difference in local recurrence rates (Log Rank X2=19.4, 6 df, p=0.004). There was no difference in cancer specific mortality between the surgeons. Experimental studies investigated ways of killing viable exfoliated tumour cells. In vitro, all tumouricidal agents caused 100% tumour cell death. In vivo, only povidone, iodine and sodium hypochlorite reduced the incidence of tumour growth. Tumouricidal agents were inactivated by the presence of whole blood in vitro. Intraperitoneal aqueous mitomycin C (MMC) and MMC adsorbed on activated carbon (MMC-CH) were investigated. The LD10 of MMC-CH was four fold greater and the dose corrected AUC was 17 times greater. Both preparations abolished tumour growth in vivo, but both had variable toxicity and markedly impaired anastomotic healing.
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Ramsay, Jonathan R. "Experimental studies on prediction of response to cancer treatment." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388333.
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Zuiderent-Jerak, Teun. "Standardization healthcare practices; experimental interventions in medicine and science and technology studies." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10605.
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Bäckman, Ulrika. "Treatment of Experimental Neuroblastoma with Angiogenic Inhibitors." Doctoral thesis, Uppsala University, Department of Medical Cell Biology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3536.
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Neuroblastoma is a childhood cancer that originates from neuroblasts in the peripheral nervous system. Neuroblastoma show considerable heterogeneity with respect to location, responsiveness to treatment and prognosis. Since current therapy involves drugs with risk of serious side effects in the growing child, there is a clinical need for more effective and less toxic treatment strategies.
Angiogenesis, the formation of new blood vessels, is critical for tumor progression. Specific inhibition of tumor-induced angiogenesis should restrict growth of most solid tumors and thereby provide a new treatment strategy. The aim of this study was to investigate the effects of angiogenic inhibition in experimental neuroblastoma in mice.
We found that experimental neuroblastomas expressed the perhaps most potent angiogenic growth factor, VEGF-A, and that plasma VEGF-A levels correlated with tumor size. SU5416, a novel antagonist of VEGFR-1 and 2, reduced angiogenesis and tumor growth in our model. We also investigated the properties of SU11657, a new, orally available, synthetic small molecule multi-targeted tyrosine kinase inhibitor. SU11657, at a well-tolerated dose, was more potent than SU5416 in reducing tumor growth rate and angiogenesis, even in MYCN-amplified tumors. Chemotherapeutics can also inhibit angiogenesis, when administrated daily in a non-toxic dose. CHS 828, a new chemotherapeutic, given orally, alone induced complete neuroblastoma regression in 44 % of the animals. Furthermore, the bisphosphonate zoledronic acid, developed to reduce bone resorption, showed anti-tumor activity in our model. Zoledronic acid was more potent than the angiogenic inhibitor TNP-470. Thus bisphosphonates may have other beneficial properties in patients with cancer apart from preventing bone resorption.
In conclusion, SU5416, SU11657, CHS 828, and zoledronic acid represent new drugs with potent anti-tumor effects. Angiogenic inhibition as single therapy or in combination with chemotherapeutics may be beneficial in the treatment of rapidly growing and highly vascularized solid tumors of childhood such as neuroblastoma.
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Nandra, Kiran Kaur. "Novel therapeutic approaches for experimental trauma-haemorrhage." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8470.
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Haemorrhagic shock (HS) is commonly associated with trauma. Severe haemorrhage causes hypoperfusion of tissues resulting in a global ischaemic state, and resuscitation is performed to restore circulating volume. However, the return of oxygen to ischaemic tissues causes the induction of a systemic inflammatory response, which contributes to cell death leading to organ failure. In trauma patients, failure of more than four organs is linked to certain mortality, highlighting the need for interventions that may reduce or prevent the deterioration in organ function. The aim of this thesis was to investigate the effect of therapeutic approaches on the organ injury and dysfunction induced by HS. Briefly, male Wistar rats were subjected to haemorrhage by withdrawal of blood to reduce the mean arterial pressure to 35 ± 5 mmHg for 90 min. Followed by resuscitation with 20 ml/kg Ringer’s lactate for 10 min and 50% of the shed blood for 50 min. Organ function was determined 4 h after the onset of resuscitation. This model was used to investigate the effect of three different interventions on the organ injury and dysfunction induced. In the first study, administration of bone marrow-derived mononuclear cells (BMMNCs) upon resuscitation resulted in (1) significant attenuation of the organ injury and dysfunction associated with HS, and (2) restoration of the activation of the Akt pro-survival pathway. It is possible that these beneficial effects are mediated by paracrine mediators secreted by BMMNCs, which modulate this pathway, however injection of large numbers of cells is not practical in the acute setting of trauma. Therefore, in the next study erythropoietin (EPO) was used as a daily pre-treatment for three days prior to the induction of haemorrhage, as EPO is a known stimulus of endothelial progenitor cell (EPC) mobilisation. EPO pre-treatment resulted in (1) significant attenuation of the organ injury and dysfunction associated with HS, (2) mobilisation of EPCs (CD34+/flk-1+), and (3) activation of the Akt pro-survival pathway with enhanced activation of eNOS. However, when used clinically EPO is associated with an increased risk of thrombotic events, therefore in the final study a non-erythropoietic analogue of EPO was investigated. Treatment with pyroglutamate helix B surface peptide (pHBSP) resulted in (1) significant attenuation of the organ injury and dysfunction associated with HS, and (2) activation of the Akt pro-survival pathway with enhanced activation of both eNOS and STAT3. Additionally, late pHBSP treatment, up to 60 min after the onset of resuscitation, exerted the highest degree of protection. The findings of this thesis support the view that modulation of the Akt pro-survival pathway is a potential therapeutic target in the treatment of the ischaemia-reperfusion injury associated with severe haemorrhage and resuscitation.
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Bertti, Rodolfo Otávio Tomaz 1974. "Modelo experimental de obstrução ureteral em coelhos." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310675.
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Orientadores: Marcelo Lopes de Lima, Carlos Arturo Levi D¿AnconaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A estenose da junção pieloureteral (JUP) é uma das anomalias congênitas mais frequentes. Clinicamente, pode se manifestar por infecção do trato urinário, por dor e pela perda da função renal. Portanto, o estudo desta doença é importante para se determinar a melhor forma tratamento. O objetivo deste trabalho foi criar um modelo experimental de estenose ureteral. Dez coelhas da raça New Zealand foram estudadas, com idade de três meses e peso aproximado de 3,5kg. Através de laparotomia e abordagem do retroperitôneo, um segmento do ureter esquerdo foi introduzido no músculo psoas ipsilateral de forma padronizada. O lado direto funcionou como controle. Um mês após a cirurgia, os animais foram submetidos a estudo renal cintilográfico com o ácido dietilenotriaminopentacético marcado com 99mTc (DTPA-99mTc). Em seguida, os animais foram submetidos à eutanásia e as peças (rins e ureteres) retiradas para análise histológica. O estudo cintilográfico demonstrou que sete unidades renais esquerdas apresentaram padrão de obstrução ureteral. A porcentagem de excreção após a administração de furosemida variou de 1 +/- 74% para DTPA-99mTc, apresentando uma diferença estatisticamente significante (p<0,05). No estudo anatomopatológico, concluiu-se que os rins e ureteres mantinham hidronefroses leves em dois e moderadas em sete animais, caracterizando diagnóstico de obstrução em nove coelhas (90%). Houve, também, discreto processo inflamatório e ausência de fibrose no segmento ureteral introduzido no músculo psoas. A técnica experimental de obstrução ureteral criou um modelo de hidronefrose em coelhos
Abstract: The stenosis of the ureteropelvic junction (UPJ) is one of the most frequent congenital anomalies and are clinically important to be treated not only for the quality of life that gets worse, pain and urinary tract infection, but also the loss of the kidney function (1,2,3). So, the study of UPJ model will be used for future treatment. The aim of this study was to create an experimental model of ureteral obstruction in rabbits. The sample of this project was composed by a number of ten female rabbits from New Zealand, three months old, weighing about 3.5kg. An intra-peritoneal medium laparatomy was made, pushing the abdominal organs in order to have a large access to the retroperitoneal. The studies consist of creating an experimental ureteral obstruction model through the introduction of its segment inside the psoas ipsilateral muscle in a standard way. The right side was used as the control. After one month, the rabbits were underwent the intravenous injection of 99mTc-DTPA. After the diuretic renogram analysis was realized, the animal was sacrificed end the removed parts, kidneys and ureters were submited histological analysis. The study showed that seven left kidneys presented obstruction. The excretion after furosemide injection was 1 ± 74% for 99mTc-DTPA, with a statistically significant difference between both renal (p<0.05). In the anatomopathological study, two animals were classified as light and seven as moderate obstruction, characterizing diagnosis of obstruction in nine rabbits (90%). The lack of an inflammatory process and fibrosis in the circumvolution location was observed. The experimental technique of ureteral obstruction created a model of hydronephrosis in rabbits
Mestrado
Cirurgia
Mestre em Cirurgia
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Torres, Fabrício Carvalho. "Panículo adiposo interescapular de coelho da espécie Oryctolagus cuniculus como fonte de células-tronco." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-31082009-162219/.
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Nos últimos anos, as células-tronco, devido a sua capacidade de originar diversos tecidos corporais e pelo poder de auto-renovação, impulsionaram os estudos de engenharia tecidual, sobretudo em medicina regenerativa. Nesse aspecto, o tecido adiposo vem se mostrando como fonte ideal para obtenção de tais células, devido à facilidade de captação, à baixa morbidade associada ao procedimento e ao elevado rendimento celular. Com o objetivo de estabelecer um modelo experimental versátil e que satisfizesse várias áreas de interesse, propôs-se o coelho Oryctolagus cuniculus como fonte de tecido adiposo. Esse animal apresenta bolsa adiposa interescapular com peso médio de 17,2g, o que corresponde a cerca de 6,6 g/Kg em machos adultos (peso corporal médio de 2590g). A coleta do material foi por meio de lipoaspiração a seco, com cânula de 3,5mm; levou-se em média, 11 minutos para o procedimento, obtendo-se aproximadamente 10 ml de gordura. Após o processamento pela técnica enzimática, em cada mililitro de gordura encontrou-se em média 1x105 células-tronco. O estudo constatou ainda que, por meio da criopreservação em nitrogênio líquido, as células mantinham suas características citométricas após períodos de congelamento que variaram de uma semana a 13 meses. As células apresentaram características de sua indiferenciação, como a expressão dos marcadores de superfície: CD90, 80,6%; HLA-DR, 2,8% e caspase 3, 10,5%. A análise do ciclo celular com 100% de confluência mostrou que 70,8% das células encontravamse quiescentes; 22,1% apoptóticas. As células com alta capacidade replicativa, que corresponde à fase S do ciclo celular, 1,4% e 0,9% encontravam-se em replicação, mostrando que as células-tronco do tecido adiposo, em cultura, não apresentam uma proliferação descontrolada, tendendo a se estabilizar, principalmente quando atingem confluência máxima em monocamada. Todas essas vantagens fazem com que o modelo proposto possa ser facilmente reprodutível, contribuindo para o estudo das células-tronco do tecido adiposo.In the latest years, the study on tissue engineering, mainly in the area of regenerative medicine, has advanced because the medical community is highly interested in stem cells. This is due to both the potential of these cells to originate any body tissue and their power of self-renewal. Adipose tissue has been used as an ideal source of such cells, due to the simplicity of their collection, high cellular yield, and low morbidity associated with the procedure. In order to establish a versatile experimental model, which could meet the needs of researchers from various areas, the rabbit Oryctolagus cuniculus was proposed as a source of adipose tissue. This animal has an adipose pad in the interscapular region with an average weight of 17.2g, which corresponds to about 6.6g of fat material per kilogram of an adult male animal (mean body weight = 2.6kg). The material was collected by means of a liposuction procedure. Using a 3.5- mm diameter tube, a volume of nearly 10ml of fat material was obtained in a mean time of 11min. After processing the fat tissue by enzymatic technique, about 1x105 stem cells were found per milliliter of fat material. Using cryopreservation of the cells by freezing them in liquid nitrogen, it was observed that the cytometric characteristics were maintained after a period of time ranging from 1 week to 13 months. The cells presented evident characteristics of undifferentiation, such as expression of the surface markers CD90, HLA-DR, and Caspase-3 (80.6, 2.8, and 10.5 %, respectively). Analysis of the cellular cycle with 100% confluence allowed us to show that 70.8% of the cells were quiescent, 22.1% were apoptotic, 1.4% had high replication capacity (phase S of the cellular cycle) and 0.9% were already in replication (phase G2/M), indicating that stem cells from adipose tissue did not show uncontrolled proliferation, tending to stabilize, mainly when they reach maximal confluence in monolayer. These advantages make this model easily reproducible, facilitating the study of adipose tissue stem cells.
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Bavetta, Sebastiano. "New methodologies for the treatment of experimental spinal cord injury." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312840.
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Harney, B. A. "Investigations of a subunit vaccine in experimental herpes simplex keratitis." Thesis, University of Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375020.
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Lemming, Dag. "Experimental Aspects on Chronic Whiplash-Associated Pain." Doctoral thesis, Linköpings universitet, Rehabiliteringsmedicin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-10693.
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Introduction: Chronic pain after whiplash trauma (chronic WAD) to the neck is still a common clinical problem in terms of pain management, rehabilitation and insurance claims. In contrast to the increased knowledge concerning mechanisms of chronic pain in general, no clinical guidelines exist concerning assessment, pain control and rehabilitation of patients with chronic WAD. Aim: The general aim of this thesis was to use experimental techniques to better understand the complex mechanisms underlying chronic pain after whiplash trauma. The specific aims of papers I and II were mainly to use analgesic drugs with different target mechanisms alone or in combinations to assess their effects on pain intensity (VAS). Experimental pain techniques were used in all studies to assess deep tissue sensitivity (electrical, mechanical and chemical stimuli). Paper IV aimed at assessing deep tissue sensitivity to mechanical and chemical stimulation. The aim in paper III was to investigate if biochemical changes in interstitial muscle tissue (trapezius muscle) could be detected in WAD patients. Materials and Methods: The thesis is based on three different groups of patients with chronic WAD. In paper III and IV two different groups of healthy controls also participated. All patients were initially assessed in the pain and rehabilitation centre. In paper I (30 patients) and II (20 patients) two different techniques of drug challenges were used. In paper I: morphine, ketamine and lidocaine were used as single drugs. In paper II: remifentanil, ketamine and placebo were used in combinations and together with experimental pain assessments. Microdialysis technique was used in paper III (22 patients from study IV and 20 controls). In paper IV (25 patients and 10 controls) a new quantitative method, computerized cuff pressure algometry, was used in combination with intramuscular saline. In all papers, experimental pain techniques for deep tissue assessment (except cutaneous electrical stimulation in paper I) were used in different combinations: intramuscular hypertonic saline infusion, intramuscular electrical stimulation and pressure algometry. Results and Conclusion: There are multiple mechanisms behind chronic whiplash-associated pain, opioid sensitive neurons, NMDA-receptors and even sodium channels might play a part. A significant share of the patients were pharmacological non-responders to analgesic drugs targeting the main afferent mechanisms involved in pain transmission, this implies activation of different pain processing mechanisms (i.e. enhanced facilitation or changes in the cortical and subcortical neuromatrix). Experimental pain assessments and drug challenges together indicate a state of central hyperexcitability. Ongoing peripheral nociception (paper III), central sensitization and dysregulation of pain from higher levels in the nervous system may interact. These findings are likely to be present early after a trauma, however it is not possible to say whether they are trauma-induced or actually represents pre-morbid variations. Clinical trials with early assessments of the somatosensory system (i.e., using experimental pain) and re-evaluations, early intervention (i.e. rehabilitation) and intensified pain management could give further knowledge.
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Aarvold, Alexander. "Bone tissue engineering : experimental strategies and clinical application." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/362817/.
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Skeletal stem cell based therapies offer tremendous potential for regeneration of a patient's bone. With the demo graphics of an ageing population, the demand for skeletal reconstruction to replace lost or damaged bone is expanding dramatically. Novel bone tissue engineering techniques offer the opportunity to push the boundaries of bone regeneration, yet few strategies have been translated to clinical practice. This thesis aims to explore novel bone regeneration strategies in vitro and in vivo, and details the clinical application of those techniques. The effects of skeletal stem cells, growth factors and material properties on osteogenesis of bone tissue engineering constructs were explored: • Skeletal stem cells and human fibronectin were shown to augment the biomechanical characteristics of impacted allograft. • Alteration of porosity in a synthetic ceramic scaffold had an effect on osteogenesis. • Innovative technology for enriching the skeletal stem cell fraction from aspirated bone marrow was successfully trialled on bone marrow from an elderly COhOli of . patients, reaching a therapeutic cellular concentration. • A pathological role for osteogenic cells was demonstrated in unicameral bone cysts, with up-regulation of RANI
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Neilly, Paul John David. "Inflammatory mediators and amino acid therapy in experimental inflammatory bowel disease." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361291.
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Cope, Richard Adrian. "An experimental investigation into the early treatment of life threatening hyperkalaemia." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307574.
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Morris, Margaret Mary. "Immune-mediated mechanisms of demyelination in experimental models of multiple sclerosis." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299695.
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Lin, Wey-Ran. "Tracing cell lineages in health and disease : experimental and human studies." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/556.
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This study aimed to investigate stem cell biology in the normal and diseased pancreas and liver employing robust methods for tracking stem cells and their progeny in both pre-clinical and human scenario. Bone marrow (BM) plasticity had been demonstrated in diseased organ remodelling. By detection of the Y chromosome in female mice receiving a sexmismatch BM transplantation, BM-derived cells were present in murine pancreas with cerulein-induced pancreatitis. BM-derived myofibroblasts functionally contributed to around 8% of the total population of myofibroblasts, the cells with a key fibrogenic role. Fibrocytes are circulating pro-fibrogenic cells; a decrease of BM-derived fibrocytes in blood and detection of these cells in areas of collagen deposition indicated they migrated to inflamed pancreas and played a role in extracellular matrix formation. IL-10 is an anti-inflammatory cytokine mainly secreted by BM; a lack of IL-10 increased the fibrosis, the inflammation and the numbers of BM-derived myofibroblasts suggesting a potential role of IL-10 in chronic pancreatitis. Mitochondrial DNA (mtDNA) mutations permit lineage tracing within human tissues. Cells having identical mtDNA mutations within a cytochrome c oxidase (CCO)- deficient area must be related having originated from a common founder cell, presumably a stem cell. I have demonstrated that regenerative nodules in cirrhotic liver are invariably clonal populations, and that these nodules often originate from progenitor cells from the abutting ductular reactions. An attempt to build a phylogenetic tree based on the accumulation of mutations in normal liver reinforced the belief that hepatic stem cells are located within the portal tract area and that their cell progeny migrate centrifugally from the portal tract region. The same techniques were applied to the pancreas, but many areas of CCO deficiency could be ascribed to autolysis, while the 3 discovery of identical mtDNA base changes within and outwith CCO-deficient patches suggested these were genetic polymorphisms, previously unreported.
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Neumann, Peter. "Airway pressure release ventilation : a systematic experimental approach /." Uppsala, Sweden : Uppsala University : Distributed by Uppsala University Library, 2000. http://w3.ub.uu.se/diss/eng/abstract.cfm?ISBN=91-554-4723-6.
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Rafiei, Abdollah. "Studies on the immunodiagnosis of cystic echinococcosis in experimental and human infections." Thesis, University of Salford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360448.
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Roberts, Richard Edwards. "Protein kinase C, protein phosporylation, and nerve regeneration in experimental diabetic neuropathy." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295836.
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Gilbert, Angela Doreen. "Inherited variation of host response to experimental periodontal disease in the mouse." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/18905.
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Spencer, Robert F. "The effect of head injury on fracture healing : clinical and experimental studies." Thesis, University of Edinburgh, 1990. http://hdl.handle.net/1842/19310.
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Winter, Andrew John. "Hearing loss in experimental bacterial meningitis." Thesis, University of Birmingham, 1997. http://etheses.bham.ac.uk//id/eprint/32/.
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Experimental meningitis was induced in pigmented guinea pigs by subarachnoid inoculation of \(1 \times 10^9\) Escherichia coli K-12 or \(3 \times 10^7\) CFU Streptococcus pneumoniae serotype 2 D39 (NCTC 7466) or PLN-A, \(\Delta\)NA1 or \(\Delta\)HY1, defined isogenic derivatives of D39 deficient in pneumolysin, neuraminidase or hyaluronidase respectively. All animals developed a meningeal inflammatory response and a labyrinthitis. Hearing loss in pneumococcal meningitis was measured by recording the evoked auditory nerve compound action potential from the round window membrane. Animals infected with PLN-A sustained significantly less hearing loss than those infected with wild-type D39 (12 dB vs. 50 dB 12 h post inoculation; P<0.0001), Neuraminidase deficiency did not alter the course of the meningeal inflammatory response nor affect hearing loss. The \(\Delta\)HY1 mutant survived poorly in the cerebrospinal fluid and blood but still caused hearing loss. Both pneumococcal and E. coli meningitis induced specific ultrastructural lesions in the organ of Corti as judged by high-resolution scanning and transmission electron microscopy, and these lesions were most severe with pneumolysin-sufficient pneumococcal infection. Microperfusion of \(5\times10^6\) CFU S.pneumoniae D39 directly into the scala tympani of guinea pigs also resulted in electrophysiological and ultrastructural damage to the organ of Corti that could be diminished by pretreatment with antibiotics. The data confirm the cochlea as the site of meningogenic deafness. They suggest that pneumolysin expression is chiefly responsible for meningogenic deafness and that if pneumococci invade the inner ear during bacterial meningitis, cochlear deafhess will rapidly ensue.
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Jayanth, Aiden Matthew. "Experimental studies on the microbiota associated with urinary tract infections." Thesis, University of Essex, 2017. http://repository.essex.ac.uk/20191/.
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Urinary tract infections (UTIs) are one of the most common healthcare associated infections (HCAIs) accounting for 17.2% of the total HCAI’s in England. Some of the underlying issues associated with UTIs include recurrent infections, catheter associated UTIs and antibiotic resistance. These issues are responsible for prolonged hospital admissions, increased costs and significant morbidity. Another possible issue relates to the ubiquitous protozoa, Acanthamoeba. Although it is known to cause infections in humans, the amoeba has been isolated from apparently healthy people. Furthermore, Acanthamoeba is known to have an endosymbiotic relationship with bacteria. Therefore, it is reasonable to hypothesise that Acanthamoeba may possibly play an important role in UTIs. Clinical isolates of E. coli, K. pneumoniae and P. mirabilis were used in the current study. All uropathogens exhibited the ability to form biofilms in a nutrient dependent manner and complete the biofilm cycle within 24h. They also displayed the ability to form intracellular bacterial communities in urothelial cells and induce significant cytotoxicity. Moreover, they were able to associate, invade and survive within Acanthamoeba castellanii (T4). Furthermore, 200 urine samples from patients suspected of UTIs were collected from Colchester University Hospital NHS Trust and analysed for the presence of Acanthamoeba. Nineteen samples were positive for Acanthamoeba spp. (unclassified) and two samples for A. castellanii supporting our hypothesis that the amoeba possibly plays a role in UTIs. This is the first study in the UK to have confirmed the presence of Acanthamoeba in urine. This study also investigated the antimicrobial efficacy of cetylpyridinium chloride (CPC). CPC coated latex catheters were able to prevent biofilm formation at very low concentrations. This finding provides promising evidence for the potential application of CPC impregnated catheters in preventing CAUTIs. In conclusion, the findings from this study can be used to develop targeted interventions aimed at the underlying issues associated with UTIs.