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Toracoscopia vídeo-assistida para crianças com derrame parapneumônico complicado : quando indicar?Knebel, Rogério January 2012 (has links)
Objetivo: Avaliar a efetividade e o momento ideal da realização da toracoscopia vídeoassistida (TVA) para o tratamento de crianças com derrame pleural parapneumônico complicado (DPPC), bem como determinar se a drenagem torácica realizada como procedimento inicial pode influenciar os resultados da TVA. Métodos: Estudo retrospectivo de 79 crianças (idade média de 35 meses) submetidas à TVA, entre janeiro de 2000 e dezembro de 2011. Os pacientes foram tratados com o mesmo algoritmo de tratamento e os procedimentos cirúrgicos foram realizados ou supervisionados pelo mesmo cirurgião. As crianças foram divididas em dois grupos de acordo com o intervalo de quatro dias entre o diagnóstico do DPPC e a cirurgia. Resultados: Pacientes operados até o 4º dia após o diagnóstico do DPPC apresentaram menor tempo de internação (p=0,008), de uso de antibióticos (p=0,023) e de uso de dreno torácico (p=0,019), além de serem submetidos a menor número de procedimentos cirúrgicos (p<0,001). A drenagem pleural prévia retardou a realização da TVA em três dias, com consequente aumento no tempo de internação (p=0,050), no tempo de permanência do dreno torácico (p<0,001) e no tempo cirúrgico da TVA (p<0,001). TVA foi eficaz em 73 crianças (92,4%). Nem o intervalo entre o diagnóstico e a cirurgia, nem a drenagem pleural prévia, influenciaram a taxa de insucesso da TVA. Conclusões: TVA é um procedimento altamente efetivo em crianças com DPPC. TVA realizada até quatro dias após o diagnóstico do DPPC está associada à redução nos tempos de internação, de permanência do dreno torácico e do uso de antibióticos, além de diminuição no número de intervenções invasivas. / thoracoscopic surgery (VATS) in the treatment of children with complicated parapneumonic pleural effusion (CPPE) and to determine whether the use of initial chest tube drainage (CTD) may influence VATS outcome. Methods: We retrospectively reviewed medical records of 79 children (mean age, 35 months) undergoing VATS from January 2000 to December 2011. The same treatment algorithm was used in the management of all patients, and all surgical procedures were performed or supervised by the same surgeon. The children were divided into two groups according to a 4-day interval between CPPE diagnosis and surgery. Results: Patients undergoing VATS within 4 days of CPPE diagnosis had a shorter hospital stay (p=0.008), fewer number of antibiotics administered (p=0.023), and decreased time with a chest tube (p=0.019), in addition to undergoing fewer number of surgical procedures (p<0.001). Initial CTD resulted in a delay of 3 days in performing VATS, leading to longer hospital stay (p=0.050), increased time with a chest tube (p<0.001), and longer VATS operating time (p<0.001). VATS was effective in 73 children (92.4%). The interval from diagnosis to surgery and initial CTD had no influence on VATS failure rate. Conclusions: VATS is a highly effective procedure for treating children with CPPE. VATS performed within 4 days of CPPE diagnosis is associated with shorter hospital stay, decreased time with a chest tube, fewer antibiotics administered, and fewer invasive interventions.
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Toracoscopia vídeo-assistida para crianças com derrame parapneumônico complicado : quando indicar?Knebel, Rogério January 2012 (has links)
Objetivo: Avaliar a efetividade e o momento ideal da realização da toracoscopia vídeoassistida (TVA) para o tratamento de crianças com derrame pleural parapneumônico complicado (DPPC), bem como determinar se a drenagem torácica realizada como procedimento inicial pode influenciar os resultados da TVA. Métodos: Estudo retrospectivo de 79 crianças (idade média de 35 meses) submetidas à TVA, entre janeiro de 2000 e dezembro de 2011. Os pacientes foram tratados com o mesmo algoritmo de tratamento e os procedimentos cirúrgicos foram realizados ou supervisionados pelo mesmo cirurgião. As crianças foram divididas em dois grupos de acordo com o intervalo de quatro dias entre o diagnóstico do DPPC e a cirurgia. Resultados: Pacientes operados até o 4º dia após o diagnóstico do DPPC apresentaram menor tempo de internação (p=0,008), de uso de antibióticos (p=0,023) e de uso de dreno torácico (p=0,019), além de serem submetidos a menor número de procedimentos cirúrgicos (p<0,001). A drenagem pleural prévia retardou a realização da TVA em três dias, com consequente aumento no tempo de internação (p=0,050), no tempo de permanência do dreno torácico (p<0,001) e no tempo cirúrgico da TVA (p<0,001). TVA foi eficaz em 73 crianças (92,4%). Nem o intervalo entre o diagnóstico e a cirurgia, nem a drenagem pleural prévia, influenciaram a taxa de insucesso da TVA. Conclusões: TVA é um procedimento altamente efetivo em crianças com DPPC. TVA realizada até quatro dias após o diagnóstico do DPPC está associada à redução nos tempos de internação, de permanência do dreno torácico e do uso de antibióticos, além de diminuição no número de intervenções invasivas. / thoracoscopic surgery (VATS) in the treatment of children with complicated parapneumonic pleural effusion (CPPE) and to determine whether the use of initial chest tube drainage (CTD) may influence VATS outcome. Methods: We retrospectively reviewed medical records of 79 children (mean age, 35 months) undergoing VATS from January 2000 to December 2011. The same treatment algorithm was used in the management of all patients, and all surgical procedures were performed or supervised by the same surgeon. The children were divided into two groups according to a 4-day interval between CPPE diagnosis and surgery. Results: Patients undergoing VATS within 4 days of CPPE diagnosis had a shorter hospital stay (p=0.008), fewer number of antibiotics administered (p=0.023), and decreased time with a chest tube (p=0.019), in addition to undergoing fewer number of surgical procedures (p<0.001). Initial CTD resulted in a delay of 3 days in performing VATS, leading to longer hospital stay (p=0.050), increased time with a chest tube (p<0.001), and longer VATS operating time (p<0.001). VATS was effective in 73 children (92.4%). The interval from diagnosis to surgery and initial CTD had no influence on VATS failure rate. Conclusions: VATS is a highly effective procedure for treating children with CPPE. VATS performed within 4 days of CPPE diagnosis is associated with shorter hospital stay, decreased time with a chest tube, fewer antibiotics administered, and fewer invasive interventions.
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Habilidade de atenção auditiva em crianças de sete anos com fissura labiopalatina: estudo comparativo / Auditory attention ability in 7 years old cleft palate and lip children: comparative studyIsabel Cristina Cavalcanti Lemos 02 March 2007 (has links)
A fissura labiopalatina é um indicador de risco para alterações de orelha média e estas podem prejudicar o desenvolvimento de habilidades auditivas como, por exemplo, a atenção, que é essencial para o aprendizado de novas habilidades, inclusive da comunicação oral e escrita. O estudo do processo atencional na população com fissura labiopalatina é algo recente e pouco explorado na literatura específica consultada, assim, este trabalho poderá contribuir com novos subsídios na área, uma vez que teve como objetivos: a) verificar o desempenho de crianças com essa anomalia craniofacial em dois testes, o THAAS e o teste dicótico de dígitos (etapa de escuta direcionada, que avaliaram processos de atenção auditiva); b) comparar o resultado com um grupo sem fissura labiopalatina e; c) verificar a associação entre os dois testes aplicados. Fizeram parte do estudo 55 crianças, de ambos os gêneros, na faixa etária de 7 anos a 7 anos e 11 meses, que foram distribuídas em dois grupos: a) grupo controle, formado por crianças sem fissura labiopalatina; b) grupo experimental, formado por crianças com fissura labiopalatina. Para ambos os grupos, o processo de avaliação constituiu-se em: aplicação de um questionário; bateria de testes auditivos convencionais; aplicação do teste da habilidade de atenção auditiva (THAAS) (FENIMAN, 2004) e do teste dicótico de dígitos etapa de escuta direcionada (SANTOS; PEREIRA, 1997). Foi possível observar que o desempenho do grupo com fissura labiopalatina foi inferior ao do grupo controle em todos os tipos de resposta do THAAS e diferença estatisticamente significativa ocorreu para o decréscimo da vigilâ (p=0,014). No teste dicótico de dígitos - etapa de escuta direcionada, o grupo com fissura labiopalatina apresentou porcentagens de acerto inferiores ao grupo controle, tanto para a orelha direita quanto para a orelha esquerda. A análise estatística mostrou interação estatisticamente significante entre grupo e gênero (p=0,026). Ao comparar o THAAS com o teste dicótico de dígitos, foi possível observar que existe associação entre os testes, mas, essa associação mostrou-se muito baixa (R²=0,27). As crianças com fissura labiopalatina apresentaram desempenho no THAAS inferior àquelas sem esta anomalia craniofacial, apenas para o decréscimo da vigilância. No teste dicótico de dígitos - etapa de escuta direcionada, somente as crianças do gênero feminino com fissura labiopalatina obtiveram índices de acerto inferiores às do grupo controle. Uma baixa associação foi verificada entre o THAAS e o teste dicótico de dígitos - etapa de escuta direcionada, permitindo supor que habilidades diferentes são responsáveis pelo desempenho nos dois testes. / Cleft lip and palate indicates risk to alterations in the middle ear. These risks may impair the development of some hearing abilities, such as attention, which is essential to learn new abilities, including oral and written communication. Studies on attention process with the population with cleft lip and palate are recent and not widely found in literature. Therefore, this study can contribute to the area. The aims of this study were to examine children with this craniofacial anomaly through two tests: The SAAAT and the Dichotic Digit test - directed hearing stage which evaluated the hearing attention processes; to compare the results with a group without cleft lip and palate; to verify the association between the two tests. 55 children, both genders, aged 7 to 7 years and 11 months old were divided in two groups to be submitted to the study. Experimental group consisted of children with cleft lip and palate and Control group consisted of children without it. Both groups were assessed through a questionnaire, conventional hearing tests battery, the Sustained Auditory Attention Ability test (SAAAT) (Feniman, 2004), and the Dichotic Digit test - directed hearing stage (Santos; Pereira, 1997). Experimental group showed lower performance than the control group in all kinds of answers of the SAAAT and, significant difference regarding decrease in vigilance (p=0,014). In the Dichotic Digit test the experimental group showed lower percentages of right answers than the control group, not only for the right ear but also for the left ear. Statistic analysis showed significant interaction between group and gender (p=0,026). When compared, the SAAAT and the Dichotic digit test had low association (R²=0,27). Experimental Group presented lower performance in the SAAAT only at the vigilance decrease. At the Dichotic Digit test female children with cleft lip and palate presented lower scores of right answers than the Control group. The SAAAT and The Dichotic Digit test - directed hearing stage - were not closely associated. Thus, it is possible to assume that different abilities are responsible for the performance in both tests.
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Modélisation aérodynamique et thermique des plaques multiperforées en LES / Aerodynamic and thermal modeling of effusion cooling systems in Large Eddy SimulationBizzari, Romain 05 November 2018 (has links)
Dans les chambres de combustion aéronautiques, le refroidissement par micro-percage est la technique privilégiée pour protéger les parois contre les gaz chauds. L’air frais provenant du contournement traverse des milliers de perforations inclinées et for- ment des micro-jets. Ces derniers coalescent en un film qui protège les parois du tube a flamme. Avec les moyens informatiques actuels, effectuer une simulation aux grandes échelles d’un moteur réel est impossible. En effet, le nombre de micro-trous est beaucoup trop important pour permettre une résolution détaillée de chacun. Des modèles numériques sont donc nécessaires. Le modèle homogène, développé en 2008, permet de simuler des plaques multiperforees avec des maillages dont la résolution est supérieure a celle du trou. Il ne permet cependant pas de représenter la pénétration ni le mélange des jets avec les gaz chauds. Pour remédier a cela, une approche hétérogène, appelée modèle a trou épaissi, a été développée au cours de cette thèse. La précision étant toujours relative au maillage, une méthode de maillage adaptatif augmentant automatiquement la résolution dans les zones clés a été propose afin d’obtenir de meilleurs résultats pour un faible surcoût. Predire la température des parois du tube a flamme est l’objectif final des ingénieurs. A cet effet, une méthodologie appelée Adiab2colo, permettant d’évaluer la température de paroi a partir d’un calcul adiabatique non résolu, a également été développée. Ces trois techniques sont maintenant couramment utilisées par Safran Helicopter Engine pour la conception des moteurs de demain. / Numerical simulation is progressively taking importance in the design of an aero- nautical engine. However, concerning the particular case of cooling devices, the high number of sub-millimetric cooling holes is an obstacle for computational sim- ulations. A classical approach goes through the modelling of the effusion cooling by homogenisation. It allows to simulate a full combustor but failsin representing the jet penetration and mixing. A new approach named thickened-hole model was developed during this thesis to overcome this issue. A work on improving the mesh resolution onkey areas thanks to an automatic adaptive method is also presented, leading to a clear breakthrough. In parallel, as the flame tube temperature is a cornerstone for the combustor durability,a low-cost approach is proposed to predict it. To meet the time-constraints of design, it is based on thermal modelling instead of a direct thermal resolution.
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Cardiac amyloidosis secondary to waldenström macroglobulinemia / Amiloidosis cardiaca secundaria a macroglobulinemia de waldenströmLachira-Yparraguirre, Lizbeth, Al-kassab-Córdova, Ali, Quispe-Silvestre, Edgar, Enriquez-Vera, Daniel 01 January 2020 (has links)
Introduction: Waldenström's macroglobulinemia is a hematological neoplasm belonging to the group of monoclonal gammopathies, which includes systemic symptoms and those related to an increase in M paraprotein. Objective: To describe a case of cardiac amyloidosis associated with macroglobulinemia. Clinical case: Male patient who was admitted for asthenia, dysphonia, and who, during his evolution, developed progressive dyspnea, heart failure and pleural effusion. Additionally, echocardiography showed myocardial granular pattern, while pleural biopsy was positive for Congo red staining. Subsequently, he received treatment with bortezomib, dexamethasone and rituximab, with favorable evolution. Conclusions: In this disease, early diagnosis is an important advantage for survival. Therefore, its management is palliative of cardiac manifestations. The present case shows a diagnostic challenge, in which the less frequent etiologies of heart failure must be taken into account. / Revisión por pares
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Early post-transplant echocardiographic screening identifies serious pathology in children and young adultsDandoy, Christopher E. 18 June 2014 (has links)
No description available.
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ARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycleWood, J.J., Boyne, James R., Paulus, C., Jackson, B.R., Nevels, M.M., Whitehouse, A., Hughes, D.J. 10 August 2016 (has links)
Yes / KSHV is the causative agent of commonly fatal malignancies of immuno-compromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic lifecycle – viral latency and the productive lytic cycle, and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein, replication and transcription activator (RTA), is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts on cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied SILAC-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B, ARID3B) whose expression was enhanced by RTA and that relocalised to replication compartments upon lytic reactivation. We also show that siRNA knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation.
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Experimental characterisation of the coolant film generated by various gas turbine combustor liner geometriesChua, Khim Heng January 2005 (has links)
In modern, low emission, gas turbine combustion systems the amount of air available for cooling of the flame tube liner is limited. This has led to the development of more complex cooling systems such as cooling tiles i.e. a double skin system, as opposed to the use of more conventional cooling slots i.e. a single skin system. An isothennal experimental facility has been constructed which can incorporate 10 times full size single and double skin (cooling tile) test specimens. The specimens can be tested with or without effusion cooling and measurements have been made to characterise the flow through each cooling system along with the velocity field and cooling effectiveness distributions that subsequently develop along the length of each test section. The velocity field of the coolant film has been defined using pneumatic probes, hot-wire anemometry and PIV instrumentation, whilst gas tracing technique is used to indicate (i) the adiabatic film cooling effectiveness and (ii) mixing of the coolant film with the mainstream flow. Tests have been undertaken both with a datum low turbulence mainstream flow passing over the test section, along with various configurations in which large magnitudes and scales of turbulence were present in the mainstream flow. These high turbulence test cases simulate some of the flow conditions found within a gas turbine combustor. Results are presented relating to a variety of operating conditions for both types of cooling system. The nominal operating condition for the double skin system was at a coolant to mainstream blowing ratio of approximately 1.0. At this condition, mixing of the mainstream and coolant film was relatively small with low mainstream turbulence. However, at high mainstream turbulence levels there was rapid penetration of the mainstream flow into the coolant film. This break up of the coolant film leads to a significant reduction in the cooling effectiveness. In addition to the time-averaged characteristics, the time dependent behaviour of the .:coolantfilm was. also investigated. In particular, unsteadiness associated with large scale structures in the mainstream flow was observed within the coolant film and adjacent to the tile surface. Relative to a double skin system the single skin geometry requires a higher coolant flow rate that, along with other geometrical changes, results in typically higher coolant to mainstream velocity ratios. At low mainstream turbulence levels this difference in velocity between the coolant and mainstream promotes the generation of turbulence and mixing between the streams so leading to some reduction in cooling effectiveness. However, this higher momentum coolant fluid is more resistant to high mainstream turbulence levels and scales so that the coolant film break up is not as significant under these conditions as that observed for the double skin system. For all the configurations tested the use of effusion cooling helped restore the coolant film along the rear of the test section. For the same total coolant flow, the minimum value of cooling effectiveness observed along the test section was increased relative to the no effusion case. In addition the effectiveness of the effusion patch depends on the amount of coolant injected and the axial location of the patch. The overall experimental data suggested the importance of the initial cooling film conditions together with better understanding of the possible mechanisms that results in the rapid cooling film break-up, such as high turbulence mainstream flow and scales, and this will lead to a more effective cooling system design. This experimental data is also thought to be ideal for the validation of numerical predictions.
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Beiträge zur Untersuchung des Strahlaustrittsverhaltens aus EffusionskühlbohrungenSchlott, André 07 April 2017 (has links) (PDF)
Die Kühlung thermisch hoch belasteter Bauteile wird häufig mit Kühlverfahren realisiert, die auf dem Prinzip des Massetransports durch die Bauteilwand beruhen. Neben der Film- und Transpirationskühlung gehört die Effusionskühlung zu diesen Verfahren und basiert auf einer Reihe oder einem Raster von Bohrungen. Dieser Ansatz ermöglicht sowohl den Abtransport von Wärme aus dem Bauteil als auch die Ausbildung eines schützenden Kühlmittelfilms auf der Bauteiloberfläche.
Viele Autoren beschäftigten sich in ihren Arbeiten mit den Auswirkungen der Filmkühlung auf den Wärmeübergang an der Bauteilwand und definierten einen Filmkühlwirkungsgrad, der die Effektivität der Kühlung widerspiegelt. Auch die Freistrahlen aus Effusionskühlbohrungen wurden mit diesen Mitteln untersucht und eine Vielzahl unterschiedlicher Einflussgrößen auf den Filmkühlwirkungsgrad identifiziert. Dazu gehören insbesondere geometrische Bedingungen, wie z.B. der Bohrungswinkel, das Verhältnis von Länge zu Durchmesser der Bohrung und die Austrittsgeometrie der Bohrungen. In späteren Beiträgen analysierten verschiedene Autoren die Einflüsse der Turbulenz sowie der Stoffwerte von Kühlmittel und Hauptströmung. Dabei kamen meist Luft und seltener Kohlendioxid oder Stickstoff als Kühlmittel zum Einsatz.
In den letzten Jahren wurde das Verhalten des Kühlmittelstrahls vor allem numerisch untersucht. Dabei beschränkte sich das Berechnungsgebiet oftmals auf das direkte Umfeld der Effusionskühlbohrung und die Identifikation und Beschreibung auftretender Wirbelstrukturen. Der Bereich weiter stromab der Bohrung blieb oft unberücksichtigt. Die vorliegende Arbeit verfolgt den Ansatz, den Kühlmittelstrahl in der Hauptströmung zu beobachten. Das wird durch die Verwendung von Helium und Argon als Kühlmittel möglich, denn diese Gase können in der Luftströmung detektiert werden. Durch eine in zwei Richtungen bewegliche Kombisonde wird Gas aus der Grenzschicht abgesaugt und die Konzentration des Kühlmittels bestimmt. Die so an diskreten Punkten stromab der Effusionskühlbohrung erhaltenen Konzentrations- und Geschwindigkeitsprofile ermöglichen die Verfolgung des Kühlmittelstrahls und dessen Wechselwirkungen mit der Hauptströmung.
Für eine vergleichende Analyse der gemessenen Profile entstand ein empirisches Verfahren zur Systematisierung der gesamten Messdaten. Die Definition einer mittleren Kühlmittelkonzentration innerhalb einer zweckmäßig festgelegten Höhe über der Wand und eines normierten Einblasparameters, der das Verhältnis der molaren Massen von Kühlmittel und Hauptströmung berücksichtigt, sind der Kern des empirischen Verfahrens. Für Vergleiche mit der Literatur erfolgte die Berechnung eines Filmkühlwirkungsgrads auf Basis der Massebilanz in der Grenzschicht und der mittleren Kühlmittelkonzentration. Während der Datenauswertung zeigte sich, dass der Bohrungswinkel einen geringen Einfluss auf die mittlere Kühlmittelkonzentration hat und so ein Bohrungswinkel von 30° ein guter Kompromiss zwischen Herstellungsaufwand und Kühlwirkung ist. Kühlmedien mit geringer molarer Masse und hoher spezifischer Wärmekapazität sollten bevorzugt werden, da deren Kühlwirkung hoch, der Einfluss auf die Grenzschicht aber gering ist. / The cooling of thermally heavily loaded components is commonly performed by injecting a mass flow through the component’s wall into the hot flow, which is called Film cooling. The main goal is to form a coolant film to reduce the hot side heat transfer and to absorb thermal energy in order to protect the component’s wall. There are different techniques available called film cooling, transpiration cooling and effusion cooling. By applying transpiration cooling, the cooling fluid is injected through a porous material into the hot gas flow. Unfortunately, these porous materials do not have the physical strength required to work within gas turbines. If the injection is done with a row or a pattern of holes so the cooling film is renewed at certain positions, the cooling technique is called effusion cooling. Film cooling means the injection of fluid through a slot without renewing the film.
Many authors analyze the effect of the film or effusion cooling on the wall temperature, the heat transfer coefficient or the cooling effectiveness. Many influencing factors were identified, such as the length to diameter relation, the hole’s alignment, fluid properties as well as turbulence and vortices. Recent works use numerical simulations to investigate the turbulent flow and vortex development in the near field of the injection hole. Due to the complexity of the simulation, the effects far downstream area were not covered by these simulations.
This work investigates the behavior of the cooling jet within the boundary layer above the wall. Therefore a foreign gas (Helium, Argon) was injected as coolant into a cross flow and a pitot probe was used to get gas samples out of the boundary layer and the coolant gas fraction was measured. The measured concentration was empirically systematized by comparative data analysis. Therefore, a mean concentration within a certain height above the wall was calculated. Also a normed blowing rate was used to include the molar masses of coolant and cross flow. With this mean concentration a cooling effectiveness is calculated based on a balance model and compared to the results in the literature.
As a result of the data evaluation, the hole’s angle was found to have a minor influence on the mean coolant concentration. An angle of about 30° is a good compromise between production effort and cooling efficiency. Also coolant fluids with a low molar mass and high specific heat capacity should be preferred because of their low impact on the boundary layer.
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Influência do anticorpo anti-VEGF bevacizumab na inflamação pleural e na pleurodese experimental induzida por talco ou nitrato de prata / Influence of anti-VEGF bevacizumab in pleural inflammation and experimental pleurodesis induced by talc or silver nitrateRibeiro, Sabrina Corrêa da Costa 01 August 2011 (has links)
Introdução: A pleurodese química é rotineiramente utilizada para o controle de derrames pleurais recidivantes. O fator de crescimento do endotélio vascular (VEGF) é uma citocina produzida em resposta à inflamação pleural induzida por esclerosantes e possui papel essencial na angiogênese e na fibrose pleural. O anticorpo monoclonal bevacizumab bloqueia a ação do VEGF, sendo utilizado no tratamento de algumas neoplasias malignas com o objetivo de inibir a angiogênese e a progressão tumoral. Os efeitos do bevacizumab sobre o processo inflamatório pleural e sobre a pleurodese induzida por talco e nitrato de prata ainda não foram totalmente descritos. Objetivo: Caracterizar a influência do anticorpo monoclonal anti-VEGF, bevacizumab, nas fases precoce e tardia da pleurodese induzida pelo talco ou nitrato de prata. Métodos: Foram estudados 152 coelhos que receberam injeção intrapleural de talco (n=76) ou nitrato de prata (n=76). Metade dos animais em cada grupo recebeu injeção intravenosa de bevacizumab 30 minutos antes do agente esclerosante. Após a injeção intrapleural de talco ou nitrato de prata, 5 animais em cada grupo foram sacrificados em 1, 2, 3, 4, 7, 14 e 28 dias. Um subgrupo de 12 animais recebeu azul de Evans 1 hora antes do sacrifício realizado no terceiro dia, para análise de permeabilidade pleural. Em todos os animais, o líquido pleural obtido foi quantificado, sendo realizadas análises bioquímica, citológica e imunológica. A cavidade pleural foi avaliada macroscopicamente através de escore para quantificação de aderências. Microscopicamente, a pleura visceral foi analisada por escore para o grau de inflamação e fibrose; a densidade vascular foi avaliada por imunohistoquímica (anti fator VIII) e o espessamento pleural e a quantidade de colágeno (fibras colágenas coradas pelo método de picrosirius) mensurados através de um sistema de análise de imagem. Análise Estatística: Os resultados estão expressos em média e erro padrão (SEM). Comparações entre os grupos foram feitas utilizando-se o teste t não-pareado ou Mann-Whitney, sendo considerado significativo um valor de p inferior a 0,05. Resultados: Nos animais que receberam injeção de bevacizumab observamos redução significativa do volume de líquido pleural e da permeabilidade vascular, assim como dos níveis pleurais de VEGF e de IL-8, porém sem diferença na celularidade, nos níveis de DHL, proteínas e TGF1. O grau de aderências pleurais também foi significativamente reduzido em todos os coelhos pré-tratados com bevacizumab, porém sem evidente diferença no escore de inflamação pleural independente do esclerosante utilizado. Observou-se ainda, nos animais que receberam anti-VEGF, diminuição da densidade vascular tanto no grupo talco como no nitrato de prata. Houve redução significativa de espessamento e fibrose pleural e da quantidade de colágeno apenas nos animais que receberam nitrato de prata e tratamento prévio com bevacizumab. Conclusão: Este estudo experimental demonstrou que a administração de bevacizumab intravenoso interfere na fase aguda do processo inflamatório pleural induzido pelo talco ou nitrato de prata, provavelmente através de redução da permeabilidade vascular. Evidenciou-se também que este fármaco inibe a formação de aderências pleurais, reduz a densidade vascular, a produção de colágeno e o espessamento pleural, potencialmente interferindo na efetividade da pleurodese induzida por talco ou nitrato de prata. Estes resultados alertam para uma possível redução de efetividade da pleurodese em pacientes em uso de anticorpos anti-VEGF / Introduction: Chemical pleurodesis is widely used to control recurrent malignant pleural effusion. Vascular endothelial growth factor (VEGF) is produced in response to mesothelial injury by sclerosing intrapleural injection and it is a potent angiogenesis inducer. The monoclonal anti-VEGF bevacizumab inhibits VEGF and has been used in the treatment of cancer to reduce angiogenesis and tumour progression. The effects of VEGF blockage on pleural inflammation and pleurodesis induced by talc and silver nitrate were not completely known. Objective: To describe the effects of monoclonal anti-VEGF bevacizumab in the early and late phase of pleurodesis induced by talc or silver nitrate. Methods: One-hundred and fifty-two rabbits were submitted to intrapleural injection of talc (n = 76) or silver nitrate (n = 76). Half of the animals in each group received intravenous bevacizumab, 30 minutes before the sclerosing agent. In each of the four groups, five animals were sacrificed 1, 2, 3, 4, 7, 14 and 28 days after the intrapleural injection. . A subgroup of twelve animals received intravenous Evans blue one hour prior to sacrifice, to estimate the vascular permeability. The pleural fluid volume was quantified and sent for biochemical, cytological and immunological analysis. Macroscopic pleural adhesions were evaluated using a semiquantitative score. The visceral pleura was submitted to microscopic examination to quantify, by score, inflammation and fibrosis. Anti-factor VII immunostaining was used to evaluate vascular density. Pleural thickness and collagen quantification (sirius red stain was used to identify collagen fibers) were evaluated by an image analysis system. Statistical analysis: Results are expressed as mean and standard error measurement (SEM). Differences between two groups were analyzed using t- test and Mann-Whitney rank sum test and considered statistically significant when p-value was <0.05. Results: Animals pretreated with anti-VEGF antibody developed lower volumes of pleural fluid and presented a significant reduction in pleural permeability, VEGF and IL-8 levels in both groups (talc and silver nitrate). There was no difference in total number of cells, TGF1, LDH and total protein in the pleural fluid. Macroscopic adhesions scores were lower and angiogenesis was reduced after pretreatment with bevacizumab in both groups. No significant difference was found in inflammation scores between the two groups. Pleural fibrosis, thickening and collagen were reduced in animals submitted to pleurodesis only in the group silver nitrate pretreated with bevacizumab. Conclusion: This experimental study shows that the administration of anti-VEGF antibody interferes in the acute phase of acute inflammation induced by silver nitrate and talc by reducing vascular permeability. It also reduces macroscopic adhesions, pleural thickening and interferes with pleural fibrosis, decreasing angiogenesis and collagen production. These findings suggest a potential for pleurodesis failure in patients treated with bevacizumab for cancer
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