Foram estudados 115 pacientes, de ambos os sexos, com idade igual ou superior a 15 anos, residentes na cidade de Manus ou na sua zona rural, portadores de derrame pleural de qualquer etiologia, exceto a traumática, no período de 01/07/84 a 01/07/86. Foram estudados os aspectos etiológicos, clínicos e sócio-econômico dos pacientes, através da aplicação de um questionário padrão, bem como a realização de exames complementares, necessários para a detrminação dea etiologia do derrame pleural. Os dados coletados foram analisados , quando quantitativos, pelo teste "f' de Student, e quando qualitativos pelo teste do "Qui-quadrado", com a utilização da correção de Yates para pequenas amostras; adotando-se o nível de 5% para o alfa. No estudo da correlação utilizou-se o teste de Pearson, com igual nível de significância. O estudo demonstrou que o derrame pleural foi mais frequente no sexo masculino, em brancos, de famílias mais numerosas, de menor poder aquisitivo e de menor cobertura previdenciária que o restante da população manauara. A tuberculose foi a causa, confirmada, de maior frequência, mais comum no sexo masculino e acomentendo a faixa etária mais jovem. / We studied 115 patient, of both sexes, with the same or superior age to 15 years, rinesidents in the city of Manaus or in its rural zone, carriers of pleural effusion of any origin except the traumatic, in the period from 01/07/84 to 01/07/86. They were studied the etiologics aspects , clinicai and socioeconomic of the patients, through the application of a standard questionnaire, as well as the accomplishment of complementai exams, necessary for the determination of the origin of the pleural effusion The collected data were analyzed, when quantitative, for the test "t" of Student, and when qualitative for the test of the "Qui-square", with the use of the correction of Yates for small samples; being adopted the levei of 5% for the alpha. In the study of the correlation the test of Pearson was used, with the same significance levei. The study demonstrated that the pleural effusion was more frequent in the masculine sex, in whites, of more numerous families, of smaller purchasing power and of smaller covering social security than the remaining of the population manauara. The tuberculosis went to cause, confirmed, of larger frequency, more common in the masculine sex and reaching the youngest age group.

Resumo não disponível.

Foram estudados 115 pacientes, de ambos os sexos, com idade igual ou superior a 15 anos, residentes na cidade de Manus ou na sua zona rural, portadores de derrame pleural de qualquer etiologia, exceto a traumática, no período de 01/07/84 a 01/07/86. Foram estudados os aspectos etiológicos, clínicos e sócio-econômico dos pacientes, através da aplicação de um questionário padrão, bem como a realização de exames complementares, necessários para a detrminação dea etiologia do derrame pleural. Os dados coletados foram analisados , quando quantitativos, pelo teste "f' de Student, e quando qualitativos pelo teste do "Qui-quadrado", com a utilização da correção de Yates para pequenas amostras; adotando-se o nível de 5% para o alfa. No estudo da correlação utilizou-se o teste de Pearson, com igual nível de significância. O estudo demonstrou que o derrame pleural foi mais frequente no sexo masculino, em brancos, de famílias mais numerosas, de menor poder aquisitivo e de menor cobertura previdenciária que o restante da população manauara. A tuberculose foi a causa, confirmada, de maior frequência, mais comum no sexo masculino e acomentendo a faixa etária mais jovem. / We studied 115 patient, of both sexes, with the same or superior age to 15 years, rinesidents in the city of Manaus or in its rural zone, carriers of pleural effusion of any origin except the traumatic, in the period from 01/07/84 to 01/07/86. They were studied the etiologics aspects , clinicai and socioeconomic of the patients, through the application of a standard questionnaire, as well as the accomplishment of complementai exams, necessary for the determination of the origin of the pleural effusion The collected data were analyzed, when quantitative, for the test "t" of Student, and when qualitative for the test of the "Qui-square", with the use of the correction of Yates for small samples; being adopted the levei of 5% for the alpha. In the study of the correlation the test of Pearson was used, with the same significance levei. The study demonstrated that the pleural effusion was more frequent in the masculine sex, in whites, of more numerous families, of smaller purchasing power and of smaller covering social security than the remaining of the population manauara. The tuberculosis went to cause, confirmed, of larger frequency, more common in the masculine sex and reaching the youngest age group.

Objectives: To develop a clinical prediction rule (CPR) for the diagnosis of pleural tuberculosis (PT) in patients with pleural exudates in Peru. Methods: Clinical and laboratory information was collected from patients with exudative pleural effusion attending two reference hospitals in Lima, Peru. Predictive findings associated with PT in a multiple logistic regression model were used to develop the CPR. A definite diagnosis of PT was based on a composite reference standard including bacteriological and/or histological analysis of pleural fluid and pleural biopsy specimens. Results: A total of 238 patients were included in the analysis, of whom 176 had PT. Age, sex, previous contact with a TB patient, presence of lymphadenopathy, and pleural adenosine deaminase (ADA) levels were found to be independently associated with PT. These predictive findings were used to construct a CPR, for which the area under the receiver operating characteristics curve (AUC) was 0.92. The single best cut-off point was a score of ≥60 points, which had a sensitivity of 88%, specificity of 92%, a positive likelihood ratio of 10.9, and a negative likelihood ratio of 0.13. Conclusions: The CPR is accurate for the diagnosis of PT and could be useful for treatment initiation while avoiding pleural biopsy. A prospective evaluation is needed before its implementation in different settings.

Thoracic injuries caused by blunt trauma are commonly encountered emergencies in veterinary medicine. However, no literature exists comparing radiography to computed tomography (CT) in blunt thoracic trauma caused by motor vehicle accidents in canine patients. The aim of this prospective case series was to estimate the sensitivity (Se) and specificity (Sp) of thoracic radiography relative to CT for detecting lung contusions, pneumothorax, pleural effusion and rib fractures. The study further aimed to establish a severity scoring system for radiography and CT and to compare the findings between the two modalities. The hypothesis was that radiography would be less sensitive than CT at detecting these injuries and that radiography would underestimate the severity of lung contusions compared to CT. Fifty-nine patients met the inclusion criteria. Radiography underestimated the presence of lung contusions (Se = 69%, 95% Confidence interval (CI)) and overestimated the severity of the contusions relative to CT. There was also high interobserver variability in evaluating lung contusion severity (coefficient of variation = 91%). Both the three-view thoracic and horizontal beam radiography had poor sensitivities for the detection of pneumothorax (Se = 19% and 63% respectively) and pleural effusions (Se = 43% and 71% respectively). Similarly, the sensitivity (56%) of three-view thoracic radiographs for the detection of rib fractures was poor relative to CT. To conclude, three-view thoracic radiography had low sensitivity for pathology related to blunt thoracic trauma caused by motor vehicle accidents and CT could be considered as an additional diagnostic imaging modality in these patients. / Dissertation (MMedVet (Diagnostic Imaging))--University of Pretoria, 2019. / Companion Animal Clinical Studies / MMedVet (Diagnostic Imaging) / Unrestricted

No description available.

全文データ差替え待ち / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20268号 / 医博第4227号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 武藤 学, 教授 原田 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DAM

Yes / Malignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. Although miR-31 re-expression increased chemoresistance, paradoxically, a higher relative intracellular accumulation of platinum was detected. This was coupled to a significantly decreased intranuclear concentration of platinum. Linked with a downregulation of OCT1, a bipotential transcriptional regulator with multiple miR-31 target binding sites, we subsequently identified an indirect miR-31-mediated upregulation of ABCB9, a transporter associated with drug accumulation in lysosomes, and increased uptake of platinum to lysosomes. However, when overexpressed directly, ABCB9 promoted cellular chemosensitivity, suggesting that miR-31 promotes chemoresistance largely via an ABCB9-independent mechanism. Overall, our data suggest that miR-31 loss from MPM tumors promotes chemosensitivity and may be prognostically beneficial in the context of therapeutic sensitivity.

Le mésothéliome pleural malin (MPM) est un cancer au pronostic sombre, en lien avec des traitements décevants. Quand la chirurgie fait partie d’un traitement multimodal, il est essentiel de l’associer avec un traitement adjuvant local pour tuer les cellules tumorales résiduelles. Récemment, la thérapie photodynamique (PDT) intrapleurale intra-opératoire, après exérèse tumorale chirurgicale, est apparue comme un traitement prometteur. Son succès repose sur l’illumination la plus complète et homogène de la cavité pleurale, contrôlée par une dosimétrie de lumière. Celle utilisée aujourd’hui en pratique clinique aux Etats-Unis repose sur la dosimétrie ponctuelle de sept capteurs intrathoraciques, mais ne permet pas d’avoir un reflet de la lumière délivrée sur l’ensemble des surfaces pleurales. Mon projet de recherche se décline sur un axe clinique et un axe expérimental : 1) mettre en place un essai de clinique de phase II au CHRU de Lille, associant la PDT intrapleurale au traitement multimodal du MPM, 2) développer une méthode de dosimétrie de lumière peropératoire innovante par la caractérisation du dispositif lumineux et l’utilisation de l’imagerie.L’essai clinique a démarré en Février 2016, en utilisant la dosimétrie de référence avec les sept capteurs en suivant le protocole américain. Une baguette lumineuse innovante a été conçue au laboratoire, ainsi que le système de dosimétrie. Quatre patients ont bénéficié d’une pleurectomie/décortication suivie d’une PDT intrapleurale (avec le photosensibilisateur Photofrin®) et d’une chimiothérapie adjuvante, sans toxicité majeure. Concernant le projet expérimental, un profil d’illumination de la baguette lumineuse a été défini en combinant les mesures de puissance ponctuelles (Watt) et celles de pixel à partir d’une photographie digitale. Un coefficient d’atténuation effectif a été calculé : µeff = 0,705 cm-1. A l’aide d’un système de repérage spatial électromagnétique (TrackStar®), la position de la baguette lumineuse est connue à l’intérieur de la cavité pleurale en temps réel, et ses coordonnées spatiales sont projetées sur le TDM thoracique en 3D. Après avoir intégré le profil d’illumination de la baguette au système de repérage, un logiciel dédié permet la représentation spatiale sur imagerie de la dose cumulée de lumière délivrée. Ce travail a été réalisé et validé sur un fantôme de cavité thoracique intra opératoire, puis notre méthode de dosimétrie a été comparée à celle de référence.Les perspectives sont de pouvoir tester la faisabilité cette nouvelle méthode de dosimétrie chez l’homme et de développer des dispositifs lumineux innovants pour une meilleure standardisation de la PDT pour le MPM. / Malignant pleural mesothelioma (MPM) is a cancer with a poor prognosis due to deceiving treatments. When surgery is part of a multimodal treatment for MPM, it is crucial to combine it with a local adjuvant treatment to kill residual tumour cells. Recently, intrapleural photodynamic therapy (PDT) after surgical resection has appeared to be a promising treatment for MPM. Its success relies essentially on the most complete and homogeneous illumination of the pleural cavity, monitored by light dosimetry. The dosimetry method used today in the United States, with intrathoracic probes collecting the light at 7 strategic locations, does not give information about the light delivered on the whole pleural surface. This research project has a clinical and experimental axis: 1) to set up a phase II clinical trial in Lille University Hospital, combining intrapleural PDT to surgery within a multimodal treatment, 2) to develop an innovative peroperative light dosimetry method by the characterization of a light device and use of imaging.Clinical trial has started in February 2016, with the seven probes dosimetry method of reference, following the American protocol. An innovative light wand was conceived within the laboratory, as well as the dosimetry sytem. Four patients have undergone pleurectomy/decortications, intrapleural PDT (with photosensitizer Photofrin®) and adjuvant chemotherapy, without major toxicity. Regarding the experimental project, an illumination profile of the light wand was defined using two complementary methods: power measurements (Watt) and pixel intensity from digital photography. An effective attenuation coefficient was calculated: µeff = 0.705 cm-1. With an electromagnetic spatial tracking system (TrackStar®), we localized in real time the position of the light wand within the pleural cavity and projected its spatial coordinates to the 3D CT scan images. After having inserted the illumination profile of the light wand to the tracking system, a dedicated software allowed the spatial representation on CT images of the cumulated light dose. This work has been completed on an intraoperative thoracic cavity phantom. Our dosimetry method was validated on this phantom and compared to the one of reference.The perspectives are to test the feasibility of this new dosimetry method in humans, and to develop alternative light devices for a better standardization of the intrapleural PDT technique for MPM.

Le mésothéliome pleural malin (MPM) est une tumeur rare et agressive qui se développe au niveau de la plèvre.L'Adrénomedulline (AM) est un peptide de 52 acides aminés. Il intervient dans plusieurs processus physiologiques et physiopathologiques. Il est surexprimé dans plusieurs tumeurs où il joue un rôle important dans la croissance tumorale.Dans un premier temps nous avons montré que l'AM et ses récepteurs sont exprimés dans des biopsies de patients atteints de MPM suggérant son implication dans la croissance tumorale du MPM. In vitro l'incubation de lignées de MPM: H2452 et MSTO_211H avec des anticorps αAM ou αAMR inhibent la prolifération, l'invasion et la migration cellulaires. In vivo, le traitement avec un anticorps αAM ou l'antagoniste AM22-52, inhibe la croissance tumorale des xénogreffes de MSTO_211H par rapport au groupe contrôle. L'analyse histologique montre une augmentation significative de l'apoptose et une diminution importante de la vascularisation chez les tumeurs traitées par rapport aux tumeurs contrôles. Ces résultats démontrent le rôle important joué par l'AM dans la croissance tumorale du MPM et fait du système de l'AM une cible thérapeutique potentielle.Dans un deuxième temps, Nous avons émis l'hypothèse de la transactivation de l'EGFR par l'AM. Notre hypothèse s'est concrétisée dans la mesure où L'inhibition de l'EGFR par un inhibiteur spécifique l'AG1478 abolie l'activation de ERK par l'AM,La phosphorylation de l'EGFR par l'AM,La neutralisation de l'EGFR avec son propre anticorps inhibe la phosphorylation par l'AM suggérant une activation ligand dépendante. Ces résultats nous permettent de mieux comprendre le mécanisme d'action de l'AM. / Malignant pleural mesothelioma (MPM) grows aggressively in the thoracic cavity without curative possibilities, underlining the need for new therapeutic targets. Adrenomedullin (AM), a multifunctional peptide, is highly expressed in several tumors and plays an important role in angiogenesis and tumor. In the first part of our work, QRT-PCR showed an increase of AM mRNA levels in MPM when compared to normal pleura tissue. Immunohistochemically, AM and its receptors were localized in the carcinomatous epithelial compartment of MPM. The MPM cell lines H2452 and MSTO_211H expressed AM with a significant increase under hypoxia. The proliferation, migration and invasion of MPM cells are decreased by anti-AM and anti-AM receptors antibodies (αAM and αAMR) supporting that MPM cells can be regulated by AM. In vivo, αAM and AM22-52 antagonist therapies of MSTO_211H xenografts blocked angiogenesis and stimulated apoptosis, resulting in tumor regression. Histologic examination of treated tumors showed evidences of disruption of tumor vasculature. These findings highlight the implication of the AM pathway in the MPM growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis.In the second part of this work, we reported that the EGFR becomes rapidly tyrosine-phosphorylated upon stimulation of lung cancer cells lines with AM, suggesting that there is an intracellular mechanism for transactivation. Specific inhibition of EGFR function by the AG1478 or EGFR blocking antibody suppressed MAPK activation. These results suggest strongly a ligand-dependent mechanism of EGFR transactivation by AM.