Diese Arbeit stellt das neue Fesselballonsystem 'Balloon-bornE moduLar Utility for profilinG the lower Atmosphere' (BELUGA) vor, das für die Messung turbulenter Energie- und Strahlungsflüsse in der bewölkten arktischen atmosphärischen Grenzschicht entwickelt wurde. Mit dem Schwerpunkt auf Turbulenz werden der technische Aufbau und die drei Instrumentenpakete von BELUGA sowie Methoden zur Analyse von Turbulenzdaten beschrieben. BELUGA wurde während zweier Feldkampagnen in der Arktis eingesetzt, die auf dem arktischen Meereis im Juni 2017 und in Grönland im März/April 2018 stattfanden. Anhand zweier Fallstudien liefern die BELUGA-Messungen wertvolle Einblicke in die kleinskaligen turbulenten Prozesse und Strahlungsprozesse, die in der arktischen Grenzschicht wechselwirken. Eine erste Studie analysiert eine Inversion der spezifischen Luftfeuchte über einem beständigen Stratocumulus und die turbulente Kopplung zwischen diesen Regionen. Die Ergebnisse zeigen, dass ein turbulenter Austausch von Wärme und Feuchtigkeit zwischen der Feuchteinversion und der Wolke durch die stabile Inversionsschicht hindurch möglich ist, wenn sich die Feuchteinversion direkt über der Wolkendecke befindet. Die Bereitstellung von Feuchtigkeit durch turbulenten Transport trägt wahrscheinlich zur Langlebigkeit der arktischen Wolken bei. Die zweite Studie befasst sich mit einem Grenzschichtstrahlstrom, d.h. einem lokalen Windmaximum in niedriger Höhe, der in der spätwinterlichen stabilen arktischen Grenzschicht beobachtet wurde. Der Grenzschichtstrahlstrom zeigt eine charakteristische Vertikalstruktur von Turbulenzparametern wie lokalen Dissipationsraten, die direkt ober- und unterhalb des Windmaximums erhöht sind. Daraus folgt, dass das Vorhandensein eines Grenzschichtstrahlstromes die vertikale Durchmischung in der stabilen Grenzschicht unterstützt, was sich auf die vertikale Verteilung von advehierter Feuchtigkeit, Aerosolpartikeln und anderen Substanzen auswirken kann. Beide Fallstudien unterstreichen die Bedeutung der kleinskaligen Turbulenz für die Entwicklung der Grenzschicht in einer stabilen thermodynamischen Schichtung. Damit tragen die BELUGA-Messungen zu einem besseren Prozessverständnis in einer sich verstärkt erwärmenden Arktis mit vielfältigen Rückkopplungsprozessen bei. / This thesis introduces the new tethered balloon system Balloon-bornE moduLar Utility for profilinG the lower Atmosphere (BELUGA) that has been developed for collocated measurements of turbulent and radiative energy fluxes in the cloudy Arctic atmospheric boundary layer (ABL). With a focus on turbulence, the technical setup and the three instrument packages of BELUGA are presented together with turbulence data analysis methods. BELUGA was deployed during two field campaigns in the Arctic, which took place on Arctic sea ice in June 2017 and in Greenland in March/April 2018. By means of two case studies, the BELUGA measurements provide valuable insights into the small-scale turbulent and radiative processes interacting in the Arctic ABL. A first study analyzes a specific humidity inversion (SHI) above a persistent stratocumulus and the turbulent coupling between these regions. The results show that turbulent exchange of heat and moisture between the SHI and the cloud is possible through the stable inversion layer, when the SHI is located directly above the cloud top. Providing moisture via turbulent transport probably contributes to the persistence of Arctic clouds. The second study addresses a low-level jet (LLJ) observed in the late-winter stable Arctic ABL. The LLJ is associated with a characteristic vertical structure of turbulence parameters such as local dissipation rates, with enhanced intensity just above and below the jet core. It is concluded that the presence of a LLJ promotes vertical mixing in the stable ABL, which can impact the vertical distribution of advected moisture, aerosol particles, and other substances. Both case studies highlight the importance of small-scale turbulence for shaping the ABL under conditions of stable thermodynamic stratification. Thus, the BELUGA measurements contribute to an improved understanding of interacting atmospheric processes in Arctic amplification.

<p>Unexplained signals emanating from the pervasive Venusian clouds have intrigued scien- tists for more than half a century. Efforts to account for a myriad of perplexing measurements have motivated the development of new atmospheric missions to Venus. Fulfillment of science objectives in the inhospitable Venusian environment necessitates a range of mission archi- tectures, each of which poses significant design challenges which guide the development of new technologies. Missions of greater scope require increasingly intricate sample collection and measurement techniques, leading inevitably to the demand for long-duration science operations within the clouds. Sustained flight in the Venusian atmosphere may be afforded by high-altitude balloons. As such platforms have been studied extensively for terrestrial applications, it is prudent to consider which designs are most suitable for a given set of science goals. We present four balloon design options to accommodate Venus atmospheric science missions. We discuss system masses, envelope volumes, material characteristics, and mechanisms for altitude control as determined by the science objectives and cloud condi- tions. We consider three variations of a baseline mission architecture and corresponding gondola designs accommodating their distinct science instrument suites. The scientific value of long-duration in situ atmospheric sampling is surpassed only by the return of Venusian cloud material to Earth for investigation in a laboratory setting. Sample capture, orbit ac- quisition, and subsequent return to Earth may be accommodated by a high-altitude balloon, rocket, and rendezvous vehicle. Precise understanding of the balloon-rocket dynamics inside the clouds is required for launch attitude acquisition and may inform sample capture strat- egy. We present a generalized dynamical model for a balloon-gondola system. We model the system as a triple-spherical-floating-compound pendulum (TSFCP). Dynamical analyses of pendular motion frequently rely on the use of Eulerian angles as generalized coordinates, in- evitably resulting in the residence of trigonometric functions in the denominator. We present nonsingular equations of motion in terms of Euler parameters. We characterize a notional Venus sample return platform and simulate its motion in the Venusian atmosphere. We discuss the behavior of the system in response to wind gusts and initial perturbation. We consider limitations of the model as well as opportunities for its extension into future work.</p>

The UnoSat Platform is a software and 3D structure platform built with Arduino Uno boardsthat allows easier implementation of a satellite project in a 1-n unit CubeSat format. It isdesigned to improve and speed up development of balloon - nanosat projects of the M2 TSImaster. It provides a 3D-printable Lego based structure that can be extended by stackingmultiple pieces on top of each other. The structure parts allow to quickly increase thenumber of Arduinos and add shields on top of already integrated Arduinos. Because ofthis, the structure allows for easy prototyping, and printed pieces can be reused in futureprojects. The platform also provides a communication system that is very efficient andreduces the possibilities of programming mistakes when implementing communication. Itallows serializing and parsing data into and from a binary format, provides protection againsttransmission errors via cyclic redundancy checksum and allows dynamically sized messagepayloads. Additionally, it supports one way or both ways communication not only between agroundstation and an embedded device, but also between two embedded devices. The codeon the embedded device is generated specifically for a communication configuration, whichmakes it very efficient in terms of processing and memory usage on the embedded device.

Atrial fibrillation is a cardiac condition in which the heart rate is abnormally fast and/or irregular. While not yet proven to be fatal on its own, it severely increases the probability of developing further medical conditions including a five times higher risk of getting stroke. The prevalence has, over the past decades, increased significantly across the world and was in 2014 approximated at roughly 2% in the European population. Though, this number is expected to further increase in the coming years and decades. Therefore, in order to reduce suffering and save lives, it is vital that there is an efficient way of treating this condition. Current treatment methods include medicine, cardioversion, and tissue ablation. This thesis focuses on tissue ablation, more particularly cryoballoon ablation, which is a minimally invasive procedure in which a cryoballoon catheter is guided through a blood vessel (generally accessed through an incision made in the groin area) to the heart. When inside the atrial chambers the balloon can be inflated, put into contact with the faulty tissue and then be injected with liquid nitrous oxide which vaporizes and freezes said tissue isolating the currents causing the irregular heartbeat. This thesis aims to attach flexible electronics to the outside of the cryoballoon, which should then be able to inform the operator that adequate contact has been achieved before freezing, thereby increasing the probability of successful ablation. Three prototypes were created using polyurethane balloons, flexible circuit boards and a biocompatible, flexible cyanoacrylate adhesive. The flexible circuit boards were arranged in different patterns for each prototype to see which configuration would best suit the application. It was found that narrow strips (single trace) aligned axially and spaced evenly along the circumference best accomplished the goal. The traces did, however, not adhere as well to the balloon as was hoped which likely was due to user error during the gluing procedure but a further investigation may be desired to ensure that the materials and adhesive are compatible. / Förmaksflimmer är ett hjärtfel som gör att hjärtslagen blir ovanligt snabba och/eller oregelbundna. Trots att det inte bevisats vara direkt dödligt än, ökar det kraftigt risken för att utveckla ytterligare medicinska besvär, bland annat fem gånger större risk att drabbas av stroke. Utbredningen av förmaksflimmer har under de senaste decennierna ökat avsevärt över hela världen och under 2014 uppskattades det att ungefär 2 % av den europeiska befolkning var drabbade. Den här siffran förväntas dock fortsätta öka under de kommande åren och decennierna. Därför, för att i största mån lindra smärta samt förhindra dödsfall, är det mycket viktigt att det finns ett effektivt sätt att behandla tillståndet. I nuläget innefattas behandling av medicin, elektrokonvertering eller vävnadsablation. Det här examensarbetet fokuserar på ablation, närmare bestämt kryoballongsablation, vilket är ett minimalinvasivt ingrepp som innebär att en kryoballongskateter förs in genom en blodådra (ofta via ett snitt i ljumsken) in i hjärtat. Väl inne i förmakskammarna kan ballongen blåsas upp, läggas emot den felaktiga vävnaden och sedan fyllas med flytande kväveoxid som förångas och fryser vävnaden vilket isolerar strömmarna som ger upphov till den felaktiga hjärtrytmen. Målet med det här examensarbetet är att fästa flexibla kretskort på utsidan av dessa kryoballonger, vilka då ska kunna känna av fysisk kontakt med vävnaden och informera operatören om detta innan frysningen sker. Därmed bör sannolikheten för lyckad ablation öka. Tre prototyper tillverkades med polyuretanballonger, flexibla kretskort och ett biokompatibelt, flexibelt cyanoakrylatlim. Kretskorten arrangerades i olika mönster för respektive prototyper för att undersöka vilken konfiguration som skulle passa ändamålet bäst. Det visade sig att smala kretskort placerade längs med ballongen axiellt och jämnt utspridda längs med omkretsen gav bäst resultat. Däremot höll inte limmet så bra som förväntat vilket troligtvis handlar om användarfel vid limningen men en vidare utredning kan vara att önska för att säkerställa att limmet är kompatibelt med övriga material.

Orbital debris poses a serious threat to ongoing operations in space.  Recognising this threat, the European Commission has funded the three-year Technology for Self Removal (TeSeR) project with the goal of developing a standard scalable Post Mission Disposal (PMD) module to remove satellites from orbit following the completion of their mission.  As the project coordinator and key member of the TeSeR Project, Airbus Defence and Space Germany will invest significant resources in achieving this goal over the course of the project. This thesis details the initial analysis of potential PMD module designs conducted by the author during an internship within the AOCS/GNC department of Airbus Defence and Space Friedrichshafen between 1 April 2016 and 31 August 2016.  Three main concepts, drag sails, drag balloons and Electrodynamic Tethers (EDTs), were evaluated during this time with an emphasis on determining the ability of each design to permit passive attitude stabilisation of the satellite during PMD.  Following the required modification of a pre-existing MATLAB/Simulink model, several key findings were made for each device concept.  It was found that no drag sail designs investigated permitted passive aerodynamic attitude stabilisation at orbit heights above 550 km.  When deorbiting from 800 km, however, the lack of the desired and stable attitude was not found to have a significant increase on the deorbit time or the area‑time product. Drag balloon designs were predicted to be comparatively unstable and less mass efficient for deorbiting purposes, with area‑time products up to approximately 50 per cent higher than the equivalent mass drag sail designs.  In spite of this, unstable drag balloons were found to provide shorter deorbit times than stable balloons due to the contribution of the satellite body and solar array to the total frontal area of the satellite.  This indicated that attitude stabilisation is not required for satellites equipped with drag balloon devices. Modelling of bare EDTs suggested that tethers with lengths of 1000 metres or more would not permit passive attitude stabilisation at an orbit height of 800 km.  Simulation of a 500 metre EDT, however, indicated that passive attitude stabilisation can be achieved with EDT devices and proved that EDTs can generate significantly higher drag forces than aerodynamic devices while possessing a significantly lower device mass.  Following the analysis of these results, a recommendation was made for future work to be aimed at improving the EDT model used in this investigation.

Quinze dias após a lesão por cateter balão, observou-se que o efeito máximo da Ang II na artéria contralateral à lesão está aumentado em relação aos valores obtidos em artérias de animais intactos. Esse aumento do Emax da Ang II não é modificado na ausência do endotélio. A lesão por cateter balão não acarreta alterações morfológicas e morfométricas da artéria contralateral à lesão quando comparadas àquelas observadas na artéria de animais controle. A desenervação simpática com 6-hidrodopamina e a desnervação sensorial com capsaicina revertem o aumento do Emax da Ang II na artéria contralateral à lesão por cateter balão. As curvas concentração-efeito para o angiotensinogênio e para Ang I apresentam o mesmo perfil na artéria contralateral à lesão por cateter balão e na artéria de animais controle. Na presença do endotélio, o losartan (antagonista do receptor AT1) e PD 123,319 (antagonista do receptor AT2) antagonizaram de forma não-superável os efeitos contráteis da Ang II em artérias de animais controle e contralateral à lesão. Observou-se, ainda, que o efeito vasorelaxante de altas concentrações de Ang II é revertido para efeitos vasoconstrictores na presença dos antagonistas seletivos dos receptores AT1, Mas e B2, tanto em artérias de animais controle quanto em artérias contralaterais à lesão. Entretanto, o Emax da Ang II nessas condições é maior na artéria contralateral à lesão. Em artéria contralateral à lesão observou-se aumento na expressão dos receptores AT2 e Mas, enquanto receptores AT1 apresenta o mesmo perfil de expressão daquele observado em artéria de animais controle. A Ang (1-7) induz relaxamento em artérias com e sem endotélio. O parâmetro de Emax da Ang (1-7) está significativamente aumentado na artéria contralateral na presença e ausência de endotélio. O Emax da Ang II, em artérias controle com endotélio, na presença de inibidores da enzima NOS, está aumentada, enquanto que na artéria contralateral este parâmetro não sofre alteração. A produção dos metabólitos do óxido nítrico (nitrito e nitrato) está reduzida na artéria contralateral à lesão quando comparado ao observado em artérias de animais controle, bem como a expressão de todas as isoformas da NOS. A lesão por cateter balão promove aumento na formação de EROs na artéria contralateral à lesão, que desaparece na presença de tiron (seqüestrador de EROs). A lesão também induz aumento na expressão da enzima p22phox, subunidade do sistema NADPH oxidase. O Emax da Ang II em artéria contralateral à lesão na presença de Tiron é semelhante ao observado em artérias de animais controle na ausência do seqüestrador. Em conclusão, a lesão por cateter balão promove respostas neurocompensatórias e aumento do estresse oxidativo em artéria contralateral à lesão. Estas alterações podem influenciar a expressão do receptor AT2 e Mas, e também mecanismos intracelulares desencadeados pela ativação de receptores AT1 e Mas. / Fifteen days after balloon catheter injury Emax of Ang II was increased in the contralateral artery as compared to values obtained in arteries from intact animals. This increase in Ang II Emax was not modified in the absence of the endothelium. The morphological and morphometric characteristics in the contralateral artery were not altered as compared to control animals. The sympathetic desnervation and sensory desnervation abolished the increase Emax of Ang II in the contralateral artery. The concentration-effect curves to angiotensinogen and Ang I were similar in contralateral arteries and in control arteries. In the presence of endothelium, losartan (AT1 antagonist receptor) and PD 123,319 (AT2 antagonist receptor) showed noncompetitive antagonistic characteristics in control arteries and contralateral artery. It was also observed that vasorelaxant effect of high concentrations of Ang II was reversed to vasoconstrictors effects in the presence of selective antagonists of AT1 receptors, Mas receptors and B2 receptors in the control arteries and contraalteral arteries. However, Emax of Ang II in these conditions was greater in contralateral artery. Contralateral artery showed increased expression of AT2 and Mas receptors, while AT1 have the same expression when compared to control arteries. Ang (1-7) triggered concentration response curves in arteries with and without endothelium. However, was observed Emax Ang (1-7) values was significantly increased in the contralateral artery in presence or absence of endothelium. Emax of Ang II in control arteries with endothelium in the presence of NOS isoforms inhibitors was increased, whereas the contralateral artery this parameter was the same. Nitrite and nitrate production was reduced in the contralateral artery when compared to control artery. NOS isoforms expression were reduced in contralateral artery. Balloon catheter injury increased ROS formation in contralateral artery, which abolished in the presence of tiron (ROS scavenger). The injury also induced increased p22phox enzyme expression, subunit of the NADPH oxidase system. Ang II Emax in the contralateral artery in the presence of tiron was similar as obtained in control arteries without tiron. In conclusion, the balloon catheter injury promoted neurocompensatory responses and increased oxidative stress in the contralateral artery. These changes increased AT2 and Mas receptor expression and also intracellular mechanisms triggered by activation of AT1 receptors.

Quinze dias após a lesão por cateter balão, observou-se que o efeito máximo da Ang II na artéria contralateral à lesão está aumentado em relação aos valores obtidos em artérias de animais intactos. Esse aumento do Emax da Ang II não é modificado na ausência do endotélio. A lesão por cateter balão não acarreta alterações morfológicas e morfométricas da artéria contralateral à lesão quando comparadas àquelas observadas na artéria de animais controle. A desenervação simpática com 6-hidrodopamina e a desnervação sensorial com capsaicina revertem o aumento do Emax da Ang II na artéria contralateral à lesão por cateter balão. As curvas concentração-efeito para o angiotensinogênio e para Ang I apresentam o mesmo perfil na artéria contralateral à lesão por cateter balão e na artéria de animais controle. Na presença do endotélio, o losartan (antagonista do receptor AT1) e PD 123,319 (antagonista do receptor AT2) antagonizaram de forma não-superável os efeitos contráteis da Ang II em artérias de animais controle e contralateral à lesão. Observou-se, ainda, que o efeito vasorelaxante de altas concentrações de Ang II é revertido para efeitos vasoconstrictores na presença dos antagonistas seletivos dos receptores AT1, Mas e B2, tanto em artérias de animais controle quanto em artérias contralaterais à lesão. Entretanto, o Emax da Ang II nessas condições é maior na artéria contralateral à lesão. Em artéria contralateral à lesão observou-se aumento na expressão dos receptores AT2 e Mas, enquanto receptores AT1 apresenta o mesmo perfil de expressão daquele observado em artéria de animais controle. A Ang (1-7) induz relaxamento em artérias com e sem endotélio. O parâmetro de Emax da Ang (1-7) está significativamente aumentado na artéria contralateral na presença e ausência de endotélio. O Emax da Ang II, em artérias controle com endotélio, na presença de inibidores da enzima NOS, está aumentada, enquanto que na artéria contralateral este parâmetro não sofre alteração. A produção dos metabólitos do óxido nítrico (nitrito e nitrato) está reduzida na artéria contralateral à lesão quando comparado ao observado em artérias de animais controle, bem como a expressão de todas as isoformas da NOS. A lesão por cateter balão promove aumento na formação de EROs na artéria contralateral à lesão, que desaparece na presença de tiron (seqüestrador de EROs). A lesão também induz aumento na expressão da enzima p22phox, subunidade do sistema NADPH oxidase. O Emax da Ang II em artéria contralateral à lesão na presença de Tiron é semelhante ao observado em artérias de animais controle na ausência do seqüestrador. Em conclusão, a lesão por cateter balão promove respostas neurocompensatórias e aumento do estresse oxidativo em artéria contralateral à lesão. Estas alterações podem influenciar a expressão do receptor AT2 e Mas, e também mecanismos intracelulares desencadeados pela ativação de receptores AT1 e Mas. / Fifteen days after balloon catheter injury Emax of Ang II was increased in the contralateral artery as compared to values obtained in arteries from intact animals. This increase in Ang II Emax was not modified in the absence of the endothelium. The morphological and morphometric characteristics in the contralateral artery were not altered as compared to control animals. The sympathetic desnervation and sensory desnervation abolished the increase Emax of Ang II in the contralateral artery. The concentration-effect curves to angiotensinogen and Ang I were similar in contralateral arteries and in control arteries. In the presence of endothelium, losartan (AT1 antagonist receptor) and PD 123,319 (AT2 antagonist receptor) showed noncompetitive antagonistic characteristics in control arteries and contralateral artery. It was also observed that vasorelaxant effect of high concentrations of Ang II was reversed to vasoconstrictors effects in the presence of selective antagonists of AT1 receptors, Mas receptors and B2 receptors in the control arteries and contraalteral arteries. However, Emax of Ang II in these conditions was greater in contralateral artery. Contralateral artery showed increased expression of AT2 and Mas receptors, while AT1 have the same expression when compared to control arteries. Ang (1-7) triggered concentration response curves in arteries with and without endothelium. However, was observed Emax Ang (1-7) values was significantly increased in the contralateral artery in presence or absence of endothelium. Emax of Ang II in control arteries with endothelium in the presence of NOS isoforms inhibitors was increased, whereas the contralateral artery this parameter was the same. Nitrite and nitrate production was reduced in the contralateral artery when compared to control artery. NOS isoforms expression were reduced in contralateral artery. Balloon catheter injury increased ROS formation in contralateral artery, which abolished in the presence of tiron (ROS scavenger). The injury also induced increased p22phox enzyme expression, subunit of the NADPH oxidase system. Ang II Emax in the contralateral artery in the presence of tiron was similar as obtained in control arteries without tiron. In conclusion, the balloon catheter injury promoted neurocompensatory responses and increased oxidative stress in the contralateral artery. These changes increased AT2 and Mas receptor expression and also intracellular mechanisms triggered by activation of AT1 receptors.

Introdução: Pacientes com Polipose Adenomatosa Familiar (PAF) tem maior risco de desenvolvimento de carcinoma duodenal em comparação com a população em geral, sendo a classificação de Spigelman adotada como método de estadiamento da adenomatose duodenal em doentes com PAF. No entanto, a relação entre a gravidade da polipose duodenal e variáveis clínicas não é bem compreendida. Objetivos: 1) Avaliar, através do método endoscópico, a prevalência e a intensidade da adenomatose duodenojejunal em pacientes com PAF em nosso meio. 2) Verificar a associação de variáveis clínicas, com a gravidade fenotípica da adenomatose duodenal e ampular. Metodologia: Foram estudados prospectivamente, 62 pacientes com diagnóstico de PAF, atendidos no Ambulatório de Poliposes Intestinais do Departamento de Gastroenterologia do Hospital das Clínicas da Universidade de São Paulo. Os pacientes foram submetidos à duodenoscopia, classificados segundo Spigelman e a presença ou não de adenomas ampulares. Os pacientes foram distribuídos em dois grupos: Estadio de Spigelman de 0 a II, e Estadio III e IV. Estes grupos foram relacionados com variáveis clínicas, tais quais: sexo, idade, antecedentes familiares positivos de PAF, tipo de cirurgia do cólon, e tipo de polipose colônica. Naqueles pacientes classificados como Spigelman III e IV foi realizada enteroscopia assistida por balão via anterógrada para avaliação do jejuno. Resultados: Quarenta e nove pacientes foram classificados como estadios de Spigelman 0, I ou II, e 13 pacientes como estadios III ou IV. A análise da correlação destes grupos foi estatisticamente significativa com a variável história familiar (p = 0,03). Naquelas famílias que apresentaram vários parentes inclusos neste estudo, observou-se estadio de Spigelman similar entre os diferentes parentes de cada família. Sete pacientes apresentaram adenomas menores da papila duodenal. A associação da presença de adenoma de papila com a variável manifestações extraintestinais (p= 0,009) foi estatisticamente significante na análise multivariável. Enteroscopia assistida por balão foi realizada em 12 pacientes, dos quais 10 apresentaram adenomas tubulares com displasia de baixo grau no jejuno proximal. Conclusões: 1. A prevalência da adenomatose duodenal avançada e de adenomas ampulares é clinicamente significativa na PAF em nosso meio. 2. A prevalência de adenomas jejunais em pacientes com adenomatose duodenal avançada é alta, apesar de não serem lesões clinicamente significativas. No entanto, enteroscopia deve ser indicada de forma individualizada em casos de polipose duodenal avançada na avaliação da extensão do acometimento jejunal. 3. A intensidade da adenomatose duodenal pode ser previsível a partir da gravidade da adenomatose duodenal de algum parente de primeiro grau. 4. A presença de manifestações extracolônicas reforça a necessidade de avaliação da região da papila de Vater, desde que houve associação independente entre a presença de adenomas ampulares e as mesmas / Background: Patients with Familial Adenomatous Polyposis (FAP) have higher risk of duodenal cancer development compared with the general population. Spigelman classification has been adopted as the staging method of duodenal adenomatosis in patients with FAP. However, the relationship between the severity of duodenal polyposis and clinical variables is not well understood. Objectives: 1) To assess endoscopically, the prevalence and intensity of duodenojejunal adenomas in patients with FAP in our population. 2) To correlate clinical variables with the phenotypic severity of duodenal and ampullary adenomatosis. Methods: We prospectively studied 62 patients with FAP, attended at Intestinal polyposis Clinic of the Department of Gastroenterology, Clinics Hospital, University of São Paulo. Patients underwent duodenoscopy and were classified according to Spigelman and the presence or absence of ampullary adenomas. Patients were divided into two groups: Spigelman 0 to II and Stage III and IV. These groups were related to the clinical variables: gender, age, family history for FAP, type of colorectal surgery, and type of polyposis of the colon. Patients classified as Spigelman III and IV were submitted to balloon assisted enteroscopy for evaluation of the jejunum. Results: Forty-nine patients were staged as Spigelman 0, I or II, and 13 as stage III or IV. There was statistic significant correlation between these groups and family history (p = 0,03). Families that had several relatives included in this study showed that there was a similar Spigelman stage in different relatives of each family. Seven patients had minor ampullar adenomas. Association between ampullary adenomas and extraintestinal manifestations (p = 0.009) was statistically significant in multivariavel analysis. Balloon assisted enteroscopy was performed in 12 patients. Ten of those presented tubular adenomas with low grade dysplasia in the proximal jejunum. Conclusions: 1. The prevalence of advanced duodenal adenomatosis and ampullary adenomas is clinically significant in FAP patients of our population. 2. The prevalence of jejunal adenomas in patients with advanced duodenal adenomatosis is high, although lesions were not clinically significant. Indication for enteroscoDpy should be individualized in patients with advanced duodenal disease to evaluate jejunal disease. 3. The intensity of duodenal adenomatosis can be predicted upon the severity of duodenal polyposis of a first-degree relative. 4. The presence of extracolonic manifestations reinforces the importance for avaliation of the Vater Papilla since there was an independent association between ampullary adenomas and extracolonic manifestations

A lesão por balão cateterismo é um procedimento comumente utilizado para o estudo dos mecanismos de restenose. O estresse mecânico produzido pela passagem do balão promove alterações tanto na artéria lesada quanto na artéria contra-lateral. Observou-se um aumento da densidade de neurônios que contêm neuropeptídeos como a Substância P (SP) e o Peptídeo Relacionado com o Gene da Calcitonina (CGRP) na artéria contra-lateral à lesão, o que evidencia a ocorrência de um processo neurocompensatório. Observou-se ainda um aumento da reatividade desta artéria à fenilefrina (Phe) e à angiotensina II (Ang II) após 4 e 15 dias da lesão, respectivamente. O objetivo do presente trabalho foi estudar as conseqüências dos tratamentos com celecoxibe (inibidor seletivo da enzima COX-2), -tocoferol (Vitamina E, antioxidante natural) e losartan (antagonista dos receptores AT1), sobre a reatividade à Phe, Cloreto de Potássio (KCl), Acetilcolina (ACh), Ang II de artérias ipsilaterais e contra-laterais em relação a artérias controles. Em animais tratados com celecoxibe (10 mg/Kg - 2 vezes ao dia) ou -tocoferol (400 mg/Kg/dia) por 7 dias. Os resultados mostram que os dois tratamentos normalizam os valores de efeito máximo (Emax) da Phe nas artérias contra-laterais com endotélio aos níveis de artérias controle. Em animais tratados com celecoxibe, a artéria ipsilateral não respondeu à Phe, enquanto no tratamento com -tocoferol mostrou valores de Emax reduzidos em relação a animais controle. Os valores de Emax da ACh em artérias de animais controle e tratados com celecoxibe ou -tocoferol, são idênticos. Entretanto, ambos os tratamentos promoveram redução na potência da ACh em artérias controle quando comparadas com as de animais não tratados. A potência da ACh na artéria contra-lateral foi semelhante ao controle em todos os tratamentos. O Emax da Ang II estava aumentado na artéria contra-lateral à lesão. O tratamento com losartan (15 mg/Kg/dia) por 18 dias promoveu redução neste parâmetro na artéria contra-lateral aos níveis do controle. A potência da Ang II em artérias contra-laterais de animais tratados com losartan é igual ao da artéria de animais controle. Nos animais controles tratados com losartan a potência desse peptídeo foi menor do que controle e contra-lateral sem tratamento e contra-lateral tratada. Na artéria contra-lateral o Emax do KCL estava diminuído em relação ao controle e o tratamento com losartan não modificou este parâmetro. O Emax da ACh em artérias controle e contra-laterais não foi alterado pelo tratamento com losartan, entretanto houve aumento da potência deste agonista em artérias controles e contra-laterais em relação a artérias de animais controles. Os resultados obtidos no presente estudo indicam que a produção de espécies reativas de oxigênio, prostanóides vasocontritores e Ang II levam a alterações na reatividade aos agonistas estudados na artéria contra-lateral à lesão por cateter balão. / The injury by balloon catheter is a procedure commonly used to study the mechanisms of restenosis. The mechanical stress produced by the passage of the balloon promotes changes both in the injured artery in the contralateral artery. There was an increased density of neurons containing neuropeptides such as substance P (SP) and the Gene Related Peptide of Calcitonin (CGRP) in the contralateral artery to the lesion, which shows the occurrence of a process neurocompensatory. There was also an increase in the artery reactivity to phenylephrine (Phe) and angiotensin II (Ang II) after 4 and 15 days of injury, respectively. There was also an increase in the artery reactivity to Phe and Ang II after 4 and 15 days of injury, respectively. The objective of this work was to study the consequences of treatment with celecoxib (selective inhibitor of COX-2), -tocopherol (vitamin E, natural antioxidant) and losartan (AT1 receptor antagonist) on the reactivity to Phe, chloride Potassium (KCl), acetylcholine (ACh), Ang II in arteries ipsilateral and contralateral side for control arteries. In animals treated with celecoxib (10 mg / kg - 2 times daily) or -tocopherol (400 mg / kg / day) for 7 days. The results show that both treatments normalize the values of maximum effect (Emax) of Phe in the contralateral arteries with endothelium to the levels of control arteries. In animals treated with celecoxib, the ipsilateral artery did not respond to Phe, whereas the treatment with -tocopherol showed reduced values of Emax for the control animals. The values of Emax of ACh in arteries from control animals and treated with celecoxib or -tocopherol, are identical. However, both treatments promoted reduction in the potency of ACh in control arteries when compared with untreated animals. The potency of ACh in the contralateral artery was similar to control in all treatments. The Emax of Ang II was increased in the contra-lateral artery to the lesion. Treatment with losartan (15 mg / kg / day) for 18 days promoted reduction in this parameter in the contra-lateral artery levels of control. The potency of Ang II in contralateral arteries of animals treated with losartan is equal to the artery of control animals. In control animals treated with losartan the potency of this peptide was lower than control and contra-lateral untreated and control-treated side. Contralateral artery in the Emax of KCL was decreased in the control and treatment with losartan did not modify this parameter. The Emax of ACh in control arteries and contralateral side was not changed by treatment with losartan, however increased the power of this agonist in control arteries and contralateral side on arteries of control animals. The results of this study indicate that the production of reactive oxygen species and vasoconstrictors prostanoids Ang II lead to changes in reactivity to agonists studied in the contra-lateral to the artery by balloon catheter injury.

Magnetic Resonance Imaging (MRI) provides unique advantages such as superior soft tissue contrast, true multiplanar imaging, variable contrast mechanisms, measurement of temperature changes, perfusion and diffusion, and no ionizing radiation. Despite considerable research efforts in the field of interventional MRI, numerous challenges remain including restricted access to the patient, high acoustic noise and a shortage of MRI-safe devices. Novel methods and devices are presented in this thesis with the primary objective of enabling effective MRI-guided interventions, particularly abdominal needle and common catheter-based endovascular interventions. Firstly, a set of MRI-safe devices (guidewires, micro guidewires, catheters and micro catheters) were developed with passive or inductively coupling resonant markers for MRI visualisation. Secondly, a method was implemented for wireless tracking and dynamic guidance of instruments. Thirdly, a framework of technologies was developed for in-room display, wireless MRI remote control and multi-user communication along with a dedicated user interface and imaging protocol. These implementations were assessed in regards to MRI-safety, performance and usability and evaluated for MRI-guided liver biopsies, balloon angioplasty procedures and also for mechanical thrombolysis. Flow phantoms, Thiel soft-embalmed human cadavers with partially re-established perfusion and a porcine model were used for in vitro, ex vivo and in vivo validation, respectively. The results demonstrate that these interventions are experimentally feasible and practical when using the presented developments: automated device tracking and equipment designed for MRI-guided interventions streamlined procedural workflow. Specifically, it was shown that fast and accurate needle placements along complex trajectories were feasible using a wireless interactive display and control device with a dedicated user interface for interventions. Moreover, safe and efficacious balloon angioplasties of the iliac artery were practical using the described framework of technologies along with a dedicated MRI protocol. Finally, it was demonstrated that these developments could be adapted and applied to MRI-guided endovascular mechanical thrombolysis of the middle cerebral artery. The technologies, described in this thesis have been shown to overcome many of the present limitations and should therefore be useful for enabling MRI-guided interventions while not further constraining the operating physician in an already complex environment. Nevertheless, it is acknowledged that many crucial issues remain to be solved in the field of iMRI and in the context of the presented research. In particular further device optimisations, improvements of the tracking implementation along with further in vivo evaluations are required before moving towards clinical evaluation. This thesis sets the groundwork for moving ahead with the eventual clinical realisation of optimised MRI-guided interventions.