Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Searching to trace the clinical profile, epidemiologist, evolution and laboratorial of the internments of patients with Sickle Cell Disease (SCD); to identify factors that can be related with the sprouting and evolution of Acute Chest Syndrome (ACS), as well as; to evaluate if the average saturation of oxygen through the oximetry of pulse is diagnosis or prognostic of ACS; a study of coorte with 168 carrying patients was carried through of SCD. During all the year of 2006, 168 patients with SCD had been studied, had predominance of the males (51.8%) and of the age band between 5 and 15 years (53.3%), 81 (48.2%) patient ones had suffered at least a hospital internment, 34 (41.9%) had diagnosis of ACS in at least an internment and 47 (58.1%) had other causes internment as intense painful and anemia crisis. When we compare the ambulatorial accompaniment of the patients who had interned with of that they had not interned in 2006, perceive that the splenomegaly presence was more common between the patients whom they had interned (27.3%), with significance statistics (p = 0, 0006). The average saturation of oxygen through the oximetry of pulse also was significantly different (p = 0, 0092) between the two groups, a time that the patients who had suffered internment had gotten one better performance (95.6%) against 94,1 % of the patients who had not interned in 2006. When analyzing the variable hemoglobin and white cell count, we do not find differences significant. In relation to the patients with ACS, the fever complaint was more prevalent (70.6%), whereas the pain complaint more was related by the patients with other causes of internment (93.3%). With regard to the age band, it enters the older than 15 years, we notice minors indices (6.1%) of internment for ACS (p= 0, 04). It did not have significant difference with regard to the hemoglobin and the saturation of oxygen through the oximetry of pulse when compared the out results with the ones of the hospital admission. The total white globule counting was significantly superior in the occasion of the internment (p=0,001). One concludes that the average saturation of oxygen by pulse oximetry was not capable to identify the patients who would come to be interned with ACS. / Buscando traçar o perfil clínico, epidemiológico, evolutivo e laboratorial das internações de pacientes com Anemia Falciforme (AF); identificar fatores que possam estar relacionados com surgimento e evolução de Síndrome Torácica Aguda (STA), bem como; avaliar se a saturação média de oxigênio através da oximetria de pulso é diagnóstica ou prognóstica em relação a STA; foi realizado um estudo de coorte com 168 pacientes portadores de AF. Houve predomínio do gênero masculino (51,8%) e da faixa etária entre 5 e 15 anos (53,3%), 81(48,2%) pacientes sofreram pelo menos uma internação hospitalar, 34 (41,9%) tiveram diagnóstico de STA em pelo menos uma internação e 47 (58,1%) tiveram outras causas internação como crise dolorosa e anemia intensa. Quando comparamos o acompanhamento ambulatorial dos pacientes que internaram com o dos que não internaram em 2006, percebemos que a presença de esplenomegalia foi mais comum entre os pacientes que internaram (27,3%), com significância estatística (p = 0,0006). A saturação média de oxigênio através da oximetria de pulso também foi significativamente diferente (p = 0,0092) entre os dois grupos, uma vez que os pacientes que sofreram internação obtiveram um melhor desempenho (95,6%) contra 94,1% dos pacientes que não internaram em 2006. Ao analisarmos as variáveis hemoglobina e leucometria, não encontramos diferença estatisticamente significativa. Em relação aos pacientes com STA, a queixa de febre foi mais prevalente (70,6%), enquanto que a queixa de dor foi mais referida pelos pacientes com outras causas de internação (93,3%). Com relação à faixa etária, entre os maiores de 15 anos, notamos menores índices (6,1%) de internação por STA (p= 0,04). Não houve diferença estatisticamente significante com relação à hemoglobina e a saturação de oxigênio através da oximetria de pulso quando comparados os resultados ambulatoriais com os da admissão hospitalar. A contagem total de glóbulos brancos foi significativamente superior na ocasião da internação (p=0,001). Conclui-se que a saturação transcutânea média de oxigênio não foi capaz de identificar os pacientes que viriam a ser internados com STA.

No description available.

The objective of this study was to evaluate the relationship between tissue oxygen saturation (StO2) and oxygen delivery index (DO2I). Oxygen delivery index is product of two factors arterial oxygen content (CaO2) and cardiac index (CI). In this study the relationship between DO2I and StO2 was evaluated by manipulating both of these factors independently. In phase one of the study, CaO2 was altered by manipulating the fractional inspired oxygen (FiO2) concentration. Anesthetized dogs were evaluated at both high (0.40 and 0.95) and low (0.15 and 0.10) FiO2 sequences. In phase two of the study, CI was altered by manipulating the volemic state. Anesthetized dogs were evaluated at hypovolemic, normovolemic and hypervolemic states. In each phase dogs were instrumented for thermodilution cardiac index (CI) and sartorius muscle StO2. Data collected included hemoglobin concentration, heart rate (HR), MAP, CI, StO2. Arterial oxygen content and DO2I were calculated at each time point. Data analysis included Pearson's correlation and mixed model ANOVA (p < 0.05). In both phases one (r = 0.97; p = 0.0013) and two (r = 0.97; p = 0.005) there was a strong correlation between StO2 and DO2I. Under the conditions of this study, there was a strong correlation between StO2 and DO2I, suggesting that StO2 may be used to estimate the adequacy of oxygen delivery in dogs. / Master of Science

INTRODUÇÃO: Hipoxemia é frequente em pacientes com fibrose cística (FC), portanto testamos a hipótese que a gravidade da doença na fibrose cística, está correlacionada a maior risco de apneia obstrutiva do sono (AOS). MÉTODOS: 34 pacientes realizaram avaliação clínico-funcional, polissonografia tipo III, espirometria, e dosagem de interleucina1-β (IL-1β). RESULTADOS: A média do índice de apneia hipopneia (IAH) foi de 4,8±2,6, saturação de oxigênio em ar ambiente 95,9±1,9% e escala de sonolência de Epworth (ESE) 7,6±3,8. Dezenove eram eutróficos, seis apresentavam risco nutricional e nove apresentavam desnutrição. No modelo multivariado para prever IAH, permaneceram significativas: estado nutricional (β= -0,386; p=0,014), saturação de oxigênio na vigília (β= -0,453; p=0,005) e ESE (β=0,429; p=0,006). CONCLUSÃO: Os maiores determinantes de apneia do sono foram o estado nutricional, saturação na vigília e sonolência. O modelo explica 51% da variância do IAH representando chance de definir clinicamente o risco de apresentar apneia do sono. / BACKGROUND: Hypoxemia is a frequent finding in cystic fibrosis patients; therefore we tested the hypothesis that disease severity in cystic fibrosis (CF) is correlated with increased obstructive sleep apnea (OSA) risk. METHODS: Thirty-four patients underwent clinical and functional evaluation, type III polysomnography, spirometry, and measurement of interleukin 1-β (IL-1β). RESULTS: The mean values for apnea hypopnea index (AHI), room-air oxygen saturation, and the Epworth sleepiness scale (ESS) were 4.8±2.6, 95.9±1.9%, 7.6±3.8, respectively. Nineteen patients had normal weight, six had nutritional risk, and nine had malnutrition. In the multivariate model to predict AHI, the following variables remained significant: nutritional status (β= -0.386, p=0.014), oxygen saturation during wakefulness (β= -0.453, p=0.005), and ESS (β=0.429; p = 0.006). CONCLUSION: The major determinants of sleep apnea were: nutritional status, oxygen saturation during wakefulness, and sleepiness. The model explains 51% of variance in AHI, representing the chance to clinically define the risk for sleep apnea.

INTRODUÇÃO: Hipoxemia é frequente em pacientes com fibrose cística (FC), portanto testamos a hipótese que a gravidade da doença na fibrose cística, está correlacionada a maior risco de apneia obstrutiva do sono (AOS). MÉTODOS: 34 pacientes realizaram avaliação clínico-funcional, polissonografia tipo III, espirometria, e dosagem de interleucina1-β (IL-1β). RESULTADOS: A média do índice de apneia hipopneia (IAH) foi de 4,8±2,6, saturação de oxigênio em ar ambiente 95,9±1,9% e escala de sonolência de Epworth (ESE) 7,6±3,8. Dezenove eram eutróficos, seis apresentavam risco nutricional e nove apresentavam desnutrição. No modelo multivariado para prever IAH, permaneceram significativas: estado nutricional (β= -0,386; p=0,014), saturação de oxigênio na vigília (β= -0,453; p=0,005) e ESE (β=0,429; p=0,006). CONCLUSÃO: Os maiores determinantes de apneia do sono foram o estado nutricional, saturação na vigília e sonolência. O modelo explica 51% da variância do IAH representando chance de definir clinicamente o risco de apresentar apneia do sono. / BACKGROUND: Hypoxemia is a frequent finding in cystic fibrosis patients; therefore we tested the hypothesis that disease severity in cystic fibrosis (CF) is correlated with increased obstructive sleep apnea (OSA) risk. METHODS: Thirty-four patients underwent clinical and functional evaluation, type III polysomnography, spirometry, and measurement of interleukin 1-β (IL-1β). RESULTS: The mean values for apnea hypopnea index (AHI), room-air oxygen saturation, and the Epworth sleepiness scale (ESS) were 4.8±2.6, 95.9±1.9%, 7.6±3.8, respectively. Nineteen patients had normal weight, six had nutritional risk, and nine had malnutrition. In the multivariate model to predict AHI, the following variables remained significant: nutritional status (β= -0.386, p=0.014), oxygen saturation during wakefulness (β= -0.453, p=0.005), and ESS (β=0.429; p = 0.006). CONCLUSION: The major determinants of sleep apnea were: nutritional status, oxygen saturation during wakefulness, and sleepiness. The model explains 51% of variance in AHI, representing the chance to clinically define the risk for sleep apnea.

INTRODUÇÃO: Hipoxemia é frequente em pacientes com fibrose cística (FC), portanto testamos a hipótese que a gravidade da doença na fibrose cística, está correlacionada a maior risco de apneia obstrutiva do sono (AOS). MÉTODOS: 34 pacientes realizaram avaliação clínico-funcional, polissonografia tipo III, espirometria, e dosagem de interleucina1-β (IL-1β). RESULTADOS: A média do índice de apneia hipopneia (IAH) foi de 4,8±2,6, saturação de oxigênio em ar ambiente 95,9±1,9% e escala de sonolência de Epworth (ESE) 7,6±3,8. Dezenove eram eutróficos, seis apresentavam risco nutricional e nove apresentavam desnutrição. No modelo multivariado para prever IAH, permaneceram significativas: estado nutricional (β= -0,386; p=0,014), saturação de oxigênio na vigília (β= -0,453; p=0,005) e ESE (β=0,429; p=0,006). CONCLUSÃO: Os maiores determinantes de apneia do sono foram o estado nutricional, saturação na vigília e sonolência. O modelo explica 51% da variância do IAH representando chance de definir clinicamente o risco de apresentar apneia do sono. / BACKGROUND: Hypoxemia is a frequent finding in cystic fibrosis patients; therefore we tested the hypothesis that disease severity in cystic fibrosis (CF) is correlated with increased obstructive sleep apnea (OSA) risk. METHODS: Thirty-four patients underwent clinical and functional evaluation, type III polysomnography, spirometry, and measurement of interleukin 1-β (IL-1β). RESULTS: The mean values for apnea hypopnea index (AHI), room-air oxygen saturation, and the Epworth sleepiness scale (ESS) were 4.8±2.6, 95.9±1.9%, 7.6±3.8, respectively. Nineteen patients had normal weight, six had nutritional risk, and nine had malnutrition. In the multivariate model to predict AHI, the following variables remained significant: nutritional status (β= -0.386, p=0.014), oxygen saturation during wakefulness (β= -0.453, p=0.005), and ESS (β=0.429; p = 0.006). CONCLUSION: The major determinants of sleep apnea were: nutritional status, oxygen saturation during wakefulness, and sleepiness. The model explains 51% of variance in AHI, representing the chance to clinically define the risk for sleep apnea.

The diagnostic accuracy attained with the use of transbronchial fine needle aspiration biopsy, aspiration of bronchial secretion, bronchial washing, brush biopsy and forceps biopsy via a flexible fiberoptic bronchoscope was compared in patients with carcinoma of the lung. In endoscopic visible tumours the sensitivity of forceps biopsy was higher than that of the other methods. When forceps biopsy was combined with bronchial washing the overall diagnostic accuracy was significantly higher than that of any of the single methods, while no appreciable increase was obtained by adding additional methods. Selective brush biopsy from every segment bronchus has been established as a method in the search for occult bronchial carcinoma. The extent of respiratory mucosal damage and wound healing after brush biopsy was therefore studied in rabbits. Large differences in the extension and depth of the damage was observed. The basement membrane was often penetrated. Regeneration started during the first day after brush biopsy and a normal ciliated epithelium was restored within three weeks. To determine if the bronchoscope itself damaged the respiratory epithelium, bronchial mucosa was studied in the pig after examination with a flexible fiberoptic bronchoscope. The columnar epithelial cells were torn off in areas where the bronchoscope had rubbed against the airway wall but the basement membrane was not damaged. Since the function of the respiratory epithelium is to remove inhaled particles from the airways, mucociliary clearance was studied in man after fiberoptic bronchoscopy. The study suggests that the tracheobronchial clearance system has a large reserve for mechanical trauma. Mucociliary clearance can however be decreased after fiberoptic bronchoscopy in some patients. An increasing number of patients with impaired cardiopulmonary function are today subjected to examination with flexible fiberoptic broncoscopy. The haemodynamic effects of fiberoptic bronchoscopy performed under topical anaesthesia were therefore studied in patients with restrictive lung disease. The procedure induced marked haemodynamic changes during passage of the larynx and during suctioning. A slight fall in arterial oxygen tension was observed during bronchial suctioning and in the post-bronchoscopic period. Three of ten patients developed ST-T-segment changes during bronchial suctioning. / <p>S. 1-48: sammanfattning, s. 49-126: 5 uppsatser</p> / digitalisering@umu.se

La rectocolite hémorragique (RCH) est une maladie inflammatoire chronique de l'intestin responsable d'un handicap et d'une altération de la qualité de vie pouvant exposer les patients à des complications sévères en dépit des thérapeutiques actuelles. L'objectif de cette thèse était d'analyser les voies possibles d'amélioration de la prise en charge thérapeutique des patients à partir de données expérimentales et cliniques. Au niveau expérimentale nous nous sommes intéressés au mécanisme impliqué dans la régulation de l'expression de PPARγ, récepteur nucléaires aux propriétés anti-inflammatoires, primitivement diminuée au cours de la RCH et cible des 5-aminosalicylés. Il a été montré que son expression était d'une part sous le contrôle de la stéroidogenèse intraépithéliale, elle-même sous contrôlée par LRH-1 et d'autre part que l'hypoxie épithéliale diminuait son expression via une sur-expression de miR-27a. Par ailleurs, les effets de l'hypoxie sur l'expression de PPARγ étaient inversés en présence de sildénafil. Sur le versant clinique, l'analyse d'une nouvelle stratégie thérapeutique ciblant la cicatrisation muqueuse, c'est à dire l'abrogation de l'inflammation colique macroscopique était efficace et possible dans la pratique clinique. Cet objectif semble aujourd’hui fondamental pour diminué la morbi-mortalité induite par cette maladie. Enfin nous avons observé l'efficacité des anti-TNF dans le cas spécifique de la rectite réfractaire et l'importance de son utilisation prolongée pour éviter les rechutes de la maladie et l’obtention d’une rémission prolongée. / Ulcerative colitis (UC) is a chronic disabling and relapsing inflammatory disease of the colonic mucosa that for more than half of patients results in chronic intermittent or continuous symptoms of increased stool frequency, fecal urgency and rectal bleeding The aim of the present work was to assess experimental ways and new therapeutic strategies with current treatments to improve long-term outcomes of UC. We focused experimental work on the peroxisome proliferator-activated receptor γ (PPARγ), a key factor of gut homeostasis and a target of mesalamine. The mechanism of primary impaired expression of PPARγ in colonic epithelial cells (CEC) during UC remains unknown. We demonstrated the control of PPARγ expression by intracellular CEC production of cortisol and the lack of cortisol production during UC that may participate towards the decreased expression of PPARγ. Furthermore hypoxia, a driver of mucosal inflammation during UC, markedly decreased PPARγ expression through the over-expression of miR-27a that was reversible by the use of sildenafil. From a clinic point of view, we assessed the efficacy and feasibility of a treat to target strategy which implies treatment optimization to achieve mucosal healing a key factor of long-term outcomes. Finally we addressed the long-term outcomes of patients treated with infliximab including the case of refractory proctitis.

In der vorliegenden Arbeit wurden die Sedativa und Sedativa-induzierte Komplikationen bei gastroenterologischen endoskopischen Untersuchungen an der Universitätsmedizin Göttingen in den Jahren 2008-2009 retrospektiv untersucht. Es wurden 2456 endoskopi-sche Untersuchungen eingeschlossen, davon 983 Ösophagogastroduodenoskopien (ÖGD), 978 Ileokoloskopien und 495 retrograde endoskopische Cholangiopankreaticographien (ERCP). Als Datenquellen dienten die Sedierungsprotokolle und die Befundberichte. Zur Sedierung wurden standardmäßig Midazolam und Propofol verwendet, teilweise wur-de ergänzend Piritramid appliziert. Die mittleren Propofoldosierungen betrugen bei ÖGDs 58,5 mg, bei Koloskopien 78,1 mg und bei ERCPs 157,0 mg. Höhere Propofoldo-sierungen waren signifikant mit jüngerem Patientenalter, ambulanten Untersuchungen und therapeutischen Endoskopien assoziiert. Die Sicherheit der Sedierung wurde anhand der Sauerstoffsättigung und der Herzfrequenz untersucht. Insgesamt kam es in 2,8% der Untersuchungen zu einer Hypoxie (Sauerstoffsättigungsabfall unter 90%). Patienten, die eine Hypoxie erlitten, waren jeweils signifikant älter. In 7,5% der Untersuchungen veränderte sich die Herzfrequenz um mehr als 20% vom Ausgangswert. Großteils kam es zu einem Anstieg der Herzfrequenz. Bradykardien waren selten (2,4% aller endoskopischen Untersuchungen). Innerhalb der ÖGDs bestand ein signifikanter Zusammenhang zwischen dem Anstieg der Herzfrequenz und einer höheren Propofoldosis. Außerdem stieg die Herzfrequenz bei therapeutischen ÖGDs signifikant häufiger an. Zusammengefasst konnte bei gastroenterologischen endoskopischen Untersuchungen mit einem Kombinationsregime aus Midazolam und Propofol mit niedrigen Dosierungen und wenigen Komplikationen sediert werden.

Pulse oximeters are low-cost, easy to use, and effective at detecting hypoxemia (low blood oxygen levels), a common complication of bronchiolitis, asthma, and pneumonia, the leading infectious cause of death in children worldwide. However, pulse oximeters are often unavailable in lowincome settings, and if available, often underused, yet little research investigates why. In this thesis, I examine pulse oximeter implementation in low-income settings, focusing on Kenyan hospitals as a case study, and using a mixed-methods approach. I conducted a systematic literature review, examining how pulse oximeter use with children at admission to hospital impacts health outcomes; I then conducted quantitative analyses of 28,000 children admitted to seven Kenyan hospitals to determine with which children pulse oximeters are used, and pulse oximetry's impact on treatment provision; these analyses informed the qualitative research component, for which I conducted interviews with 30 healthcare workers (HCWs) and staff in 14 Kenyan hospitals and employed theoretical frameworks to determine how HCWs decide whether to use pulse oximeters, and the barriers to pulse oximetry. I found that pulse oximeter use varies substantially between and within Kenyan hospitals over time. After adjusting for case-mix and signs of illness severity, HCWs were most likely to use pulse oximeters with children with a very high respiratory rate, indrawing and/or who were not alert; children who obtained a pulse oximeter reading were more likely to be prescribed oxygen than if a pulse oximeter was not used; and children with a reading below 90% were more likely to be prescribed oxygen than those with higher readings, suggesting that HCW decision-making is influenced by international and national guidelines. However, HCWs sometimes cannot use pulse oximeters when they intend to, because of insufficient pulse oximeter availability, largely due to inefficient and confusing procurement processes and repair delays. Furthermore, HCWs sometimes use pulse oximeters incorrectly or misinterpret their results, because of insufficient training. Pulse oximeter promotion programme planners can use the recommendations I provide to effectively target barriers to pulse oximeter uptake in low-income settings. Increased pulse oximetry implementation could enable early detection of hypoxemia, improving accurate diagnosis, and supporting prompt, effective treatment, which could help reduce mortality in children needing oxygen, in line with Sustainable Development Goal 3.