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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
211

Analýza fotbalového klubu FC Bayern Mnichov / Analysis of the football Club FC Bayern Mnichov

Valta, Viktor January 2015 (has links)
Objectives: The main objective of this thesis is to analyse football club FC Bayern Munich. This thesis analyse organizational structure, finances, infrastructure of the club, its market position and marketing. The other objective is to create prognosis of future finance development of the club. Methods: Document analysis, interviews and SWOT analysis are the main methods used in this thesis. Results: FC Bayern Munich is very well organized club. It belongs amongst the best teams in the world by the sport results. It is one of a little, that has profit every year and has no depts. As the prognosis say, Bayern will be one of the best teams in the world in the future and will set course in football development. Key words: Football, analysis, FC Bayern Munich, prognosis
212

NHL a krize / NHL and crisis

Menčíková, Tereza January 2015 (has links)
Title: NHL and crisis Objectives: The goal of this diploma thesis is to analyze crisis of the National Hockey League and to make the economic forecast of the league and chosen clubs. Other goals are to introduce the league, its game system and the way of leading. Then to make an analysis of each crisis which the NHL went through during its history and to identify their causes. Methods: A qualitative and quantitative research, concretely descriptive analysis and the linear regression, which was made by the Microsoft Excel programme and its function TREND, were used in this thesis. Descriptive analysis was used for introduction of the National Hockey League and for definition of the main terms about the topic. The Microsoft function TREND was used for the forecast of the NHL and NHL team's economic situation. Results: Result of this diploma thesis is a summary of the most important terms and facts about the National Hockey League. Also a summary of the NHL crisis and an identification of their reasons. The main reason is that the team owners have completely different interests than the players, which can result to the lockout. The lockouts harm the richest teams and help the poorer ones, sometimes it can even solve them from bankruptcy. The biggest problem has been the high level of player's salary....
213

Biomarkery prognózy a účinnosti terapie ovariálního karcinomu / Biomarkers of prognosis and therapy efficacy in ovarian carcinoma

Cerovská, Ela January 2016 (has links)
Ovarian carcinoma is a serious illness with the highest mortality rate among all female cancers. No suitable methods for early diagnosis, precise determination of prognosis or prediction of therapy efficacy are currently available, which leads to diagnosis in advanced stages of disease and therapy efficacy limitation. Consequently, the development of chemoresistance to conventional drugs and frequent relapse of the disease pose a fundamental complication too. The main goal of the current study was identification of new putative prognostic and therapeutic biomarkers, whose introduction into clinical practice could help to improve the dismal outcome of ovarian carcinoma patients. The present master thesis provides results of expression analysis of genes whose products take part in the transport, metabolism and mechanism of action of platinum based drugs and taxanes, and also the regulation of cell cycle and signaling. Transcript levels of these genes have been assessed in series of tumor and control ovarian tissue samples and the difference between both tissue types was evaluated. Gene expression level in tumors was then compared with patient's clinical data and candidate genes, ABCA2 and PRC1, were selected from the obtained results for more detailed analysis. The protein level of candidate genes...
214

Le mélanome acro-lentigineux : étude rétrospective épidémiologique, clinique et anatomopathologique, et recherche de facteurs pronostiques d’un sous-type rare de mélanome / Acral Lentiginous Melanoma : a retrospective, epidemiological, clinical and histological study of a rare subtype of melanoma, with identification of prognostic factors

Phan, Alice 04 May 2011 (has links)
Le mélanome acro-lentigineux (ALM) est le 4ème sous-type histologique de mélanome et représente moins de 10% des mélanomes. Beaucoup de controverses entourent ce sous-type rare, comme un plus mauvais pronostic. L’objectif de notre travail était de mieux caractériser l’ALM sur le plan épidémiologique, clinique, histologique, et évolutif et d’identifier d’éventuels facteurs pronostiques. Entre 1996 et 2004, 126 cas d’ALMs (6% des mélanomes) ont été répertoriés et suivis dans le service de dermatologie de l’Hôpital de l’Hôtel-Dieu, Lyon. Toutes les lames histologiques ont été récupérées et systématiquement relues. Les analyses statistiques ont été réalisées par comparaison de sous-groupes, calculs et comparaison des courbes de survie par la méthode de Kaplan-Meier et le test de Log-Rank, et recherche de facteurs pronostiques indépendants en utilisant le modèle de régression logistique de Cox. La survie médiane sans récidive et spécifique étaient respectivement de 10,1 et 13,5 ans. Le taux de survie à 5 ans était de 76%. Dans la première partie de notre travail, nous avons étudié toutes les caractéristiques épidémiologiques et cliniques de l’ALM, afin de mieux comprendre l’histoire clinique. Les hommes avaient un plus mauvais pronostic ainsi que les formes achromiques. La seconde partie est une étude détaillée des particularités anatomo-pathologiques des ces tumeurs, avec une évaluation de leur signification pronostique. L’analyse multivariée des facteurs pronostiques a permis de souligner l’impact de l’index mitotique et de la présence de microsatellites en histologie. Enfin, la troisième partie de notre travail avait pour but de préciser les critères dermoscopiques d’aide au diagnostic de l’ALM, dont le retard diagnostique est fréquent. A partir d’une des plus grandes séries de cas d’ALM, notre travail souligne le caractère distinct de ce sous-type de mélanome, dont le mauvais pronostic est vraisemblablement lié à un stade avancé au diagnostic, la dermoscopie constituant une aide précieuse pour un diagnostic plus précoce. / Acral Lentiginous Melanoma (ALM) is the fourth main histological subtype of melanoma and accounts for less than 10% of all melanomas. Many controversies surround this rare subtype, as a poorer prognosis. The aim of our study was to investigate the distinctive epidemiological, clinical and histological characteristics and outcome of ALM, and to evaluate their prognostic values in order to identify independent prognostic factors. Between 1996 and 2004, 126 patients with ALMs (6% of all melanomas) were retrieved and followed up at the Department of Dermatology, Hôtel-Dieu University Hospital, Lyon, France. All histological material were systematically reexamined. Statistical analysis was performed by comparing the baseline characteristics of subgroups with appropriate tests. ALM-specific and disease-free survivals were estimated using the Kaplan-Meier method and compared using the Log-Rank test. A Cox proportional hazards model was used to identify independent prognostic factors. The median disease-free and ALM-specific survivals were 10.1 and 13.5 years, respectively. The 5-year survival rate was 76%. In the first part of this study, we reviewed patient demographics, the initial presentation of the lesion, and clinical outcome. Male gender and amelanosis were significantly associated with a poorer prognosis. The second part is a detailed analysis of histopathological features, with evaluation of their prognostic value. The presence of microsatellites and a high mitotic rate appeared to be of particular importance in predicting the outcome of ALM. Then, the third part emphasized all dermoscopic features of ALM, in order to improve recognition of suspicious cases and to permit an earlier diagnosis. This large register-based review of ALM shows that ALM is an unusual subtype of melanoma that exhibits distinctive epidemiological, clinical and pathological features. The classical poorer prognosis is mainly due to a more advanced stage at the time of diagnosis. Dermoscopy could be helpful to improve the diagnostic accuracy in such locations.
215

Vývoj cen za první místa ve vybraných sportech / Evolution of Prize Money for the first places in selected sports

Rybářová, Adéla January 2015 (has links)
Title: Evolution of Prize Money for the 1st places in selected sports Objectives: The main aim of this Master Thesis is to analyse evolution of prize money for winners in selected competitions and disciplines of golf, tennis, athletics and figure skating and prognosis of their evolution until 2020. Another goal is to compare the results of this prognosis and try to determine what influences the evolution. Methods: Methods used for prognosis of the future evolution are prognostic functions FORECAST and LOGLINTREND. Quality of prognosis is based on the Theil Index of Inequality. Trendline is also used to determine future evolution of the data. The correct trendline is chosen based on its reliability value. Results: Result of this theses is the discovery that prize money in history was progressively growing especially in traditional tournaments in tennis and golf. In younger series of competitions in figure skating and athletics prize money remained constant within the years. Prognosis suggests further increase in prize money in Grand Slam and Major tournaments and stagnation in Diamond League and ISU Grand Prix. Keywords: prize money, prognosis, professional sport, golf, tennis, athletics, figure skating
216

Histoire naturelle de la maladie rénale : Analyse des facteurs physiopathologiques et évaluation pronostique de l’insuffisance rénale terminale et de ses complications / Natural history of chronic kidney disease : Analysis of pathophysiological and prognostic factors of renal failure and its complications

Duranton, Flore 17 December 2013 (has links)
L'insuffisance rénale chronique (IRC) et son stade terminal sont associés à diverses complications, parmi lesquelles de nombreuses modifications du milieu intérieur : urémie, anémie, hyperparathyroïdie, rétention urémique… Les taux d'urée plasmatique ont longtemps été utilisés comme critère diagnostique de l'IRC, malgré l'absence de caractéristiques essentielles à un tel marqueur. Ces caractéristiques ont été discutées au regard de l'utilisation historique des déterminations d'urée. La caractérisation des altérations plasmatiques des patients en IRC est essentielle à la compréhension de la maladie et de leur lien avec la morbi-mortalité. Nous avons alors étendu notre champ d'intérêt à l'ensemble des solutés de rétention urémique, et sommes parvenus à identifier 56 nouveaux solutés à partir des études cliniques récemment publiées. L'évaluation diagnostique s'est poursuivie par l'étude des concentrations plasmatiques et urinaires en acides aminés et de leur association avec le stade d'IRC et ses complications, permettant alors la génération d'hypothèses sur l'origine métabolique de ces altérations. D'autre part, la mise en place d'une méta-analyse à montré une réduction du risque de décès chez les patients traités par dérivés de la vitamine D. La correction des comorbidités (hypovitaminose, perturbations du métabolisme phosphocalcique) et d'autres effets néphroprotecteurs expliqueraient ces bénéfices. Enfin, l'évaluation du protéome urinaire et du score CKD273 qui en résulte s'est avérée très intéressante pour l'identification des patients à risque de progresser, ce qui est un enjeu de santé publique. Ces travaux d'analyse bibliographique et de recherche clinique s'intègrent dans une volonté d'amélioration de la caractérisation de l'IRC et de l'évaluation de sa progression dans le but de prévenir ses complications. Ils sont le socle d'un projet plus large d'observation et d'analyse des caractéristiques des patients en IRC et de leur évolution. / Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with various complications, many of which occur within the internal environment: uremia, anemia, hyperparathyroidism, uremic retention… Plasma urea concentrations have long been used as a diagnostic criterion of CKD, despite the absence of some key characteristics. We discussed these features with regards to the historical uses of urea determinations. It is essential to characterize the plasma changes which occur in CKD to understand the disease and the relationship with comorbidities. We expanded our focus to all of uremic retention solutes, and identified 56 new solutes from recently published clinical studies. The study of plasma and urinary concentrations of amino acids and their association with CKD stage and complications further extended the study of CKD diagnosis, and allowed to generate hypotheses on the metabolic origin of these alterations. On the other hand, by meta-analysis, we showed a reduced risk of death in patients treated with vitamin D derivatives. Correcting comorbidities (hypovitaminosis, disturbances of bone and mineral metabolism) and other renoprotective effects may explain these benefits. Finally, the determination of the urinary proteome and the resulting CKD273 score was proved to be very useful for identifying patients at risk of progression, which is a public health issue. This work based on clinical research and literature analyses is part of an effort to improve the characterization of CKD and the evaluation of progression in order to avoid complications. It is the basis for a wider observational project: analyzing the characteristics of CKD patients and their changes over time.
217

Pneumonia no acidente vascular cerebral: frequência, preditores e desfechos associados / Pneumonia in stroke: frequency, predictors and associated outcomes

Miranda, Rúbia Poliana Crisóstomo 11 June 2018 (has links)
Introdução: Pneumonia é uma das complicações mais frequentes após Acidente Vascular Cerebral (AVC), com incidência variando de 2,3% a 47,3%. Nesse estudo, nosso objetivo foi identificar a frequência e os fatores associados com pneumonia após AVC e avaliar o impacto da pneumonia quanto ao óbito intra-hospitalar e quanto aos desfechos dependência funcional e óbito em três meses após o AVC. Métodos: Participaram do estudo pacientes que preencheram os critérios de inclusão (Idade maior que 18 anos de ambos os sexos e diagnóstico médico de AVC isquêmico ou hemorrágico agudo, confirmado por exames de neuroimagem) e nenhum dos critérios de exclusão (Ataque Isquêmico Transitório, Hemorragia Subaracnóidea, Trombose Venosa Cerebral, outros quadros clínicos em que não foi confirmado diagnóstico de AVC, ictus antigo, AVC hemorrágico de causa secundária por malformação arteriovenosa, aneurisma cerebral, neoplasia craniana, distúrbios da coagulação, entre outros; não concordância em participar do estudo ou não assinatura do Termo de Consentimento Livre e Esclarecido). Estes pacientes foram admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP) e incluídos no Registro de Acidente Vascular Encefálico (REAVER) no período de abril de 2015 a setembro de 2016. Os dados demográficos e clínicos foram coletados de forma prospectiva pelos coordenadores de pesquisa do REAVER. Quando possível, os pacientes foram submetidos à avaliação clínica da deglutição por três fonoaudiólogas. Os prontuários de todos os pacientes foram revisados por um infectologista para confirmar o diagnóstico de pneumonia. Resultados: Foram estudados 478 pacientes com AVC agudo. Considerando a amostra total do estudo, encontramos uma frequência relativa de 24% de pneumonia, 11,5% de óbito intra-hospitalar e 36,8% de dependência funcional ou óbito após três meses do AVC. Dos pacientes com pneumonia, 32,2% foram a óbito intra-hospitalar e 84,3% apresentaram dependência funcional ou óbito após três meses do ictus.Na análise multivariada por regressão logística para preditores de pneumonia após AVC, a gravidade do AVC (p=0,001), AVC hemorrágico (p=0,012) e disfagia (p=0,001) foram preditores independentes para pneumonia. Conclusão: Nosso estudo confirma que a pneumonia é uma complicação frequente após o AVC, sendo associada com gravidade do AVC, AVC hemorrágico e disfagia. Os pacientes com pneumonia apresentaram alta frequência de óbito intra-hospitalar e alta dependência funcional ou óbito após três meses do AVC. / Introduction: Pneumonia is one of the most frequent complications after stroke, with an incidence varying from 2.3% to 47.3%. In this study, our goal was to identify the frequency and factors associated with post-stroke pneumonia and to assess the impact of pneumonia on in-hospital death, functional dependence outcomes and death at three months after stroke. Methods: Were included in the study, patients who met the criteria for participation (over 18 years old for both sexes and medical diagnosis of acute hemorrhagic or ischemic stroke, confirmed by neuroimaging exams) and none of the exclusion criteria (Transient Ischemic Attack, Subarachnoid Hemorrhage, Cerebral Venous Thrombosis, clinical conditions in which a diagnosis of stroke was not confirmed, not acute stroke, hemorrhagic stroke due to arteriovenous malformation, brain aneurysm, brain tumor, coagulation disorders, other diagnosis; non-agreement to participate in the study or non-signing of the Informed Consent Form). These patients were admitted to the University Hospital Emergency Unit of the Medical School of Ribeirão Preto (HCFMRP-USP) and included in the Registry of Stroke (REAVER) from April 2015 to September 2016. Demographic and clinical data were collected prospectively by the REAVER research coordinators. The patients underwent clinical evaluation of swallowing by three speech therapists whenever possible. The medical records of all patients were reviewed by an infectious disease specialist to confirm the diagnosis of pneumonia. Results: A total of 478 patients with acute stroke were included. Considering the total sample of the study, we found a relative frequency of 24% of pneumonia, 11.5% of in-hospital death and 36.8% of functional dependence or death after three months of stroke. Regarding the patients with pneumonia, 32.2% died in the hospital and 84.3% had functional dependence or death after three months of stroke. In the multivariate logistic regression analysis for predictors of poststroke pneumonia, the severity of stroke (p = 0.001), hemorrhagic stroke (p = 0.012), and dysphagia (p = 0.001) were independent predictors for pneumonia. Conclusion: Our study confirms that pneumonia is a common complication afterstroke and is associated with severity of stroke, hemorrhagic stroke and dysphagia. Patients with pneumonia had a higher frequency of in-hospital death and greater functional dependence or death after three months of stroke.
218

Apports de l’imagerie médullaire et par USPIO au pronostic de la sclérose en plaques rémittente débutante / Prognostic value of spinal cord MRI and USPIO in early relapsing remitting multiple sclerosis

Kerbrat, Anne 24 October 2018 (has links)
La Sclérose en Plaques (SEP) est la plus fréquente des maladies neurologiques acquises conduisant à un handicap chez l’adulte jeune. Le repérage précoce des patients susceptibles d’évoluer vers un handicap est un enjeu majeur afin de proposer un traitement adapté. Dans ce domaine, l’imagerie par résonnance magnétique (IRM) a complètement modifié la prise en charge des patients. Dans cette thèse, deux pistes sont explorées en vue d’améliorer le caractère pronostique de l’imagerie réalisée en début de maladie. Une première partie est consacrée aux apports potentiels de l’imagerie médullaire. Une deuxième partie s’intéresse à l’imagerie spécifique de l’inflammation par USPIO. La première partie de cette thèse correspond à un projet longitudinal et multicentrique intitulé EMISEP. Il vise à mesurer l’atteinte tissulaire médullaire en IRM conventionnelle et quantitative chez les patients atteints de SEP rémittente débutante, puis à étudier son lien avec le handicap ambulatoire à 5 ans. Aucune donnée n’était disponible concernant la variabilité en multicentrique des métriques issues de l’IRM médullaire quantitative. Notre première étude est donc consacrée à l’évaluation de la variabilité de la mesure du ratio de transfert d’aimantation (MTR) médullaire chez les sujets sains. Nous avons montré que la variabilité globale de la mesure du MTR médullaire était modérée avec un coefficient de variation de l’ordre de 3 %. Dans une deuxième étude, nous avons analysé les mesures de MTR initiales chez les patients SEP rémittents, comparativement à une population contrôle, afin de détecter une atteinte médullaire précoce. Nous avons mis en évidence une diminution significative des valeurs de MTR chez les patients comparés aux contrôles, mesurable dans la moelle épinière d’apparence normale et plus marquée proche de son centre et de sa périphérie. Puis nous avons réalisé une troisième étude centrée sur les voies motrices, particulièrement fonctionnelles. Nous avons quantifié spécifiquement l’atteinte du tractus cortico-spinal encéphalique et médullaire en IRM et évalué ses conséquences fonctionnelles cliniquement et en électrophysiologie. Nous avons montré que cette atteinte est fréquente, d’étendue très variable selon les patients, et qu’elle prédomine sur le segment médullaire des voies motrices. La sévérité de l’atteinte focale mesurée en imagerie en début de la maladie est déjà corrélée à ses conséquences cliniques et électrophysiologiques. Enfin, l’étude longitudinale, permettant d’évaluer le caractère pronostique de l’atteinte médullaire focale et diffuse précoce est en cours. La deuxième partie de cette thèse correspond à une autre étude longitudinale intitulée USPIO-CIS. Ses objectifs étaient d’étudier les prises de contraste USPIO comparativement au gadolinium dans une population de patients ayant un syndrome cliniquement isolé et d’évaluer leur rôle pronostique à moyen terme (3 ans). Nous avons montré que les prises de contraste USPIO sont rarement visualisées comparativement aux prises de contraste après injection de gadolinium dans cette population, mais sont associées à une déstructuration tissulaire initiale majeure, qui diminue progressivement au cours de la première année. Elle reste cependant plus marquée dans les lésions initialement USPIO positives comparées aux lésions seulement positives pour le gadolinium à 3 ans. En conclusion, nos travaux ont montré que l’atteinte médullaire est précoce chez les patients ayant une SEP rémittente, de sévérité variable selon les patients et intéresse notamment des zones très fonctionnelles comme les voies motrices. Son rôle pronostique, prometteur, est en cours d’évaluation. L’imagerie spécifique de l’inflammation par USPIO permet quant à elle d’expliquer les différents degrés de sévérité des lésions focales à moyen terme, mais les risques liés à son utilisation chez l’homme compromettent son potentiel comme outil pronostique en routine clinique. / Multiple Sclerosis (MS) is the most frequent acquired neurological disease leading to disability in young adults. In clinical practice, the identification of patients at risk of disability is a major issue, in order to adapt the treatment. Thus, prognostic factors are needed from the diagnosis and the very first years of the disease. In this area, MRI potentially has a crucial role. Two main avenue will be investigated in this work. The first part will be dedicated to spinal cord quantitative MRI and the second part to inflammation imaging using ultra-small paramagnetic iron oxides (USPIO). The first part of this work is a longitudinal, multicenter project called EMISEP. Its objectives are to quantify the structural damage of the spinal cord in early relapsing remitting MS patients, and to describe the link between spinal cord damage and walking disability at 5 years. In a first study, we assess the multicenter variability of magnetization transfer ratio (MTR) measurements in the spinal cord of healthy controls, before investigating this metric in MS patient. We demonstrate that the overall variability of the MTR measurements is low, with a coefficient of variation of 2.9%. The between-session variability represents the major part of the overall variability, compared to between-scanner variability. These results pave the way for multicenter analyses in MS patients. In a second study, we analyze MTR measurement in the spinal cord of early relapsing-remitting MS compared to controls. The MTR values are significantly lower in patients than controls, even after excluding lesions. We observe a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4) and at the spinal cord periphery and barycentre. A third study focuses on the motor tracts. We specifically evaluate the cortico-spinal tracts damage in it brain and spinal cord portion and the functional consequences from the electrophysiological and the clinical point of view. The focal damage on CSTs is very frequent in our cohort of early RRMS patients. The spinal cord portion of the CSTs is the most affected by lesions, with a substantial variability between patients. We already find significant associations between the lesion volume fraction in the CSTs and clinical and electrophysiological motor tracts related abnormalities. Finally, longitudinal studies are ongoing to evaluate the prognostic value of initial spinal cord and cortico-spinal tract damage on subsequent ambulatory disability 5 years later. The second part of this work is another longitudinal study called USPIO-CIS. Its objectives are to describe the USPIO enhancement compared to gadolinium enhancement in a population of clinically isolated syndrome patients and to study their 3-years prognostic value. We demonstrate that USPIO enhancements are rare compared to gadolinium enhancement, and transient. USPIO positive lesions are associated with greater damage than gadolinium positive only lesions at baseline and throughout the 3-year follow up. In conclusion, our work demonstrates that spinal cord involvement is measurable using quantitative MRI in early relapsing remitting MS, even in a multicenter context. This early spinal cord damage is highly variable among patients, and is present in very functional tracts such as the cortico-spinal tracts. The prognostic value of this early damage is promising and will be evaluated in ongoing longitudinal studies. Inflammation imaging using USPIO is promising to explain the various degree of MS lesion severity. However, the risks associated with USPIO compromise it used as a prognostic tool in clinical routine.
219

Comparação das técnicas de PCR em tempo real e PCR para o estudo dos genes MYCN, DDX1 e NAG em pacientes portadores de neuroblastoma / Comparison between real time PCR and PCR for the determination of MYCN, DDX1 and NAG amplification in patients with neuroblastoma

Souza, Ana Carolina Mamana Fernandes de 02 May 2007 (has links)
O neuroblastoma é o tumor sólido extra-cranial mais comum e mortal da infância, sendo o tempo de sobrevida nos casos mais agressivos ainda muito curto. Uma das esperanças nesses casos é que os estudos moleculares possam fornecer informações sobre os genes ou as vias moleculares que governam a patogênese dos neuroblastomas. Pois, há poucos genes como o MYCN, que foi descrito por estar diretamente ligado ao neuroblastoma. A amplificação deste oncogene ocorre em pouco mais de 25% dos neuroblastomas e é considerada como o mais importante marcador de prognóstico nestes tumores, sendo fortemente relacionada aos estádios avançados da doença e falha no tratamento. Outros genes do amplicon do MYCN, incluindo o DDX1 \"DEAD box polypeptide 1 gene\" e o NAG \"neuroblastoma-amplified gene\", estão sendo observados por se apresentarem co-amplificados com o MYCN. Entretanto, a importância deste fenômeno no prognóstico ainda é desconhecida. Os objetivos deste trabalho foram determinar qual o melhor método para estudar a amplificação dos genes MYCN, DDX1 e NAG, além de esclarecer a importância da coamplificação dos genes DDX1 e NAG no prognóstico. Procedimento: O número de cópias dos genes MYCN, DDX1 e NAG foi determinado por PCR em Tempo Real e PCR convencional em 100 neuroblastomas primários. Os dados da PCR em Tempo Real foram analisados por quantificação absoluta e relativa. Os resultados da PCR convencional foram analisados por eletroforese em gel de agarose, medindo a intensidade das bandas formadas no gel no sistema Kodak. A relevância da amplificação gênica como marcador de prognóstico foi avaliada em 74 pacientes, dos quais nós obtivemos o acompanhamento clínico. Resultados: Nos 74 casos estudados, ambos os métodos demonstraram que a amplificação do MYCN estava associada com os estádios mais avançados da doença. A análise das curvas de sobrevida livre de progressão confirmou que pacientes com ausência de amplificação do MYCN apresentavam maior tempo de sobrevida. Nós também analisamos a amplificação do DDX1 nas mesmas amostras incluindo aquelas com ausência de amplificação de MYCN. Não foi encontrada nenhuma relação entre a co-amplificação com idade ao diagnóstico ou tempo de sobrevida. Conclusões: Os métodos aplicados para calcular o número de cópias dos genes na PCR em Tempo Real mostraram-se equivalentes. A PCR em Tempo Real apresentou maior acurácia nos resultados quando comparada à PCR convencional. A análise da sobrevida não demonstrou relação entre a amplificação dos genes DDX1 e/ou NAG com piora no prognóstico. / Neuroblastoma is the most common and deadly extra-cranial solid childhood tumor. Survival rates for aggressive neuroblastomas are still disappointingly low. One of the hopes is that molecular studies will provide insights into the genes and molecular pathways that govern neuroblastoma pathogenesis. However, at present only a few genes as MYCN have been directly linked to neuroblastoma. MYCN oncogene amplification, occurring in up to 25% of neuroblastomas, has been considered the most important prognostic factor, strongly correlating to advanced stage disease and treatment failure. Another genes in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and neuroblastoma-amplified gene (NAG gene), have been found to be frequently co-amplified with MYCN in NB. But the prognostic significance of the coamplification remains unclear. The aims of this study were to evaluate which is the best method to study the gene amplification of those three genes MYCN, DDX1 and NAG, as well as clarify the prognostic significance of the co-amplification or DDX1 and NAG with MYCN. Procedure: The gene copy numbers of MYCN, DDX1, and NAG were determined by the real-time quantitative polymerase chain reaction and conventional polymerase chain reaction in 100 primary NBs. Real-Time data were analyzed by absolute and relative quantification. For conventional PCR, samples were electrophoresed on a 2% agarose gel and the intensity of each band evaluated by Kodak image software. To evaluate of the prognostic significance of the gene amplification we had only 74 cases in witch we could analyze the follow-up. Results: In all 74 cases, both methods demonstrated that MYCN amplification was associated mainly with advanced cancer stages, and the analysis of overall survival confirmed that patients without MYCN amplification had a cumulative survival significantly higher than patients with oncogene amplification. We also studied DDX1 and NAG amplification for all NB samples even that without MYCN amplification. No relationship between any gene co-amplification status and disease stage, age at diagnosis, or overall survival was found. Conclusions: The two methods used to calculate gene copy number for Real Time PCR assay shown to be equivalent. Real Time PCR assay shown to be more accurate to study gene amplification than conventional PCR assay. Survival analysis pointed out that DDX1 and/or NAG amplification has no additional adverse effect on prognosis.
220

Estudo da sobrevida e de fatores prognósticos em cães com cardiomiopatia dilatada idiopática / Survival study and assessment of prognostic factors in dogs with idiopathic dilated cardiomyopathy

Yamaki, Fernanda Lie 30 August 2007 (has links)
Cardiomiopatia dilatada (CMD) é uma das doenças cardiovasculares adquiridas mais comuns em cães afetando principalmente cães de raças grandes e gigantes, além do Cocker Spaniel Inglês e Americano. A anormalidade primária é a diminuição da contratilidade miocárdica, com dilatação secundária das câmaras cardíacas, que pode evoluir para insuficiência cardíaca, apresentar arritmias (atrial e/ou ventricular) e resultar em óbito em qualquer estágio da doença (sendo a morte súbita relativamente comum). Poucos estudos em cães, sendo a maioria retrospectiva, têm o objetivo de determinar fatores prognósticos, e predizer o prognóstico em qualquer paciente continua a ser um desafio. Portanto, no presente trabalho objetivou-se estudar a sobrevida de cães com CMD, assim como observar possíveis fatores determinantes de sobrevida. Para tal, foram avaliados 50 cães com CMD por meio de exame físico, radiográfico de tórax, eletrocardiográfico (eletrocardiograma de repouso e monitorização Holter) e ecocardiográfico. Os animais foram acompanhados por pelo menos 150 dias ou até o óbito. Avaliou-se a influência da idade, raça, sexo, fração de encurtamento do ventrículo esquerdo (FE), da classe funcional da insuficiência cardíaca, da presença de ascite, efusão pleural, edema pulmonar, insuficiência cardíaca bilateral, fibrilação atrial (FA) ou de arritmias ventriculares na sobrevida. A sobrevida dos cães com CMD variou de cinco dias a 1021 dias, com tempo médio de 347 dias, e tempo mediano de sobrevida foi de 223 dias; a probabilidade de sobreviver por seis meses foi de 51%, por um ano foi de 37% e por dois anos foi de 13%. Os cães da raça Cocker Spaniel Inglês apresentaram maior sobrevida em relação aos cães da raça Doberman e aos cães de outras raças. A presença de FA (p<0,03) e de arritmias ventriculares (tanto de ectopias ventriculares no eletrocardiograma de repouso (p<0,02) como de taquicardia ventricular não sustentada (p<0,0001) na monitorização Holter) foram associadas a menor sobrevida, enquanto que a idade, FE, sexo, classe funcional da insuficiência cardíaca, presença de ascite, efusão pleural, edema pulmonar ou insuficiência cardíaca bilateral não estiveram associados a aumento da mortalidade. A sobrevida foi variável, mas o prognóstico em geral foi ruim. O melhor preditor diagnóstico foi a presença de taquicardia ventricular não sustentada na monitorização Holter. / Dilated cardiomyopathy (DCM) is one of the most common acquired cardiovascular disease of dogs, affecting mainly large and giant breeds, as well as English and American Cocker Spaniels. The primary abnormality is decrease in myocardial contractility with secondary cardiac chambers dilatation. The clinical presentation may include development of heart failure, arrhythmias (atrial and/or ventricular), and death in any phase of the disease (with sudden death relatively frequent). Few studies have been described in dogs with the purpose of determining prognostic indicators for DCM, and predicting prognosis in any given single patient continues to be a challenge. The aim of this study was to evaluate survival time, and if possible, to find factors influencing prognosis in dogs with dilated cardiomyopathy. Fifty dogs with DCM have been included in the study. The patients were prospectively evaluated by physical examination, ten-lead electrocardiography, thoracic radiography, 24-hour Holter monitoring, and echocardiography. The animals were followed-up for at least 150 days or until death. Studied variables were left ventricle shortening fraction, age, sex, breed, presence of ascite, subcutaneous edema, pulmonary edema, pleural effusion, biventricular heart failure, as well as, presence of atrial fibrillation and ventricular arrhythmias, including non-sustained ventricular tachycardia on Holter monitoring. The mean and median survival time were, respectively, 347 days and 223 days (range 5 to 1021 days). Probability of survival at six months was 51%, at 1 year was 37%, and at 2 year was 13%. The survival time was significantly longer in English Cocker Spaniel, versus Doberman Pinschers, or versus other breeds. Atrial fibrillation (p<0,03) and ventricular arrhthmias (ventricular ectopy on ten-lead electrocardiography (p<0,02) and non-sustained ventricular tachycardia (p<0,0001) on Holter monitoring) were associated with increased mortality. While age at the time of presentation, shortening fraction, gender, presence of ascites, pleural effusion, or pulmonary edema were not associated with increased mortality. Survival time was variable, but the prognosis was usually poor. The best prognostic indicator was the presence of non-sustained ventricular tachycardia in Holter monitoring.

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