Resumo: Estresse oxidativo e inflamação são importantes mecanismos na fisiopatologia da pré-eclâmpsia e das doenças dos prematuros, entretanto, não está estabelecido se o prognóstico de prematuros de mães hipertensas é decorrente de efeito direto da doença materna ou devido à prematuridade. Determinar as concentrações de marcadores de estresse oxidativo e de inflamação em vias aéreas de prematuros de mães hipertensas e normotensas nos primeiros 3 dias de vida, investigar a influência do tipo de assistência respiratória e a relação dos biomarcadores com o prognóstico respiratório neonatal. Estudo prospectivo com prematuros < 34 semanas, nascidos no serviço e submetidos ao CPAP nasal ou ventilação mecânica no 1o dia de vida, estratificados em 2 grupos: mães hipertensas e mães normotensas. Critério de exclusão: diabete melito, corioamnioite, malformação, infecção congênita, óbito < 24 horas. No aspirado de vias aéreas, do 1o e 3o dias de vida foram dosados malondialdeído (MDA), óxido nítrico (NO) e interleucina 8 (IL-8). Além dos biomarcadores foram avaliadas variáveis gestacionais, do parto e da evolução neonatal. Desfecho: alta sem displasia broncopulmonar (DBP) ou DBP/morte. Realizada análise estatística uni e multivariada. Foram estudados 73 prematuros com idade gestacional média de 29 semanas, sendo 32 de mães hipertensas e 41 de normotensas. Nos 2 momentos de avaliação as concentrações de MDA, NO e IL-8 não diferiram entre os prematuros de mães hipertensas e normotensas. Ao comparar os prematuros em ventilação mecânica versus CPAP nasal não houve diferença nos valores de MDA e NO, mas a IL-8 foi maior no 1o dia de ventilação mecânica. Os prematuros que evoluíram com DBP/óbito tiveram maiores níveis de IL-8 nos primeiros 3 dias de vida. A idade gestacional e o uso de ventilação mecânica foram fatores de risco para DBP/óbito ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and neonatal diseases, however, it is unclear whether the outcome of preterm infants of hypertensive mothers is due to a direct effect of maternal disease or to short gestation. To determine the levels of oxidative stress markers and inflammation in the airways of preterm infants of hypertensive mothers and normotensive ones in the first three days of life; to evaluate the influence of the respiratory support and the relationship between the biomarkers and neonatal respiratory outcome. A prospective study of inborn preterm infants <34 weeks gestation, requiring nasal CPAP or mechanical ventilation in the first day of life, stratified into two groups: hypertensive mothers and normotensive ones. Exclusion criteria: diabetes mellitus, chorioamnionitis, congenital malformation or infection, death <24 hours. Determination of malondialdehyde (MDA), nitric oxide (NO) and interleukin 8 (IL-8) levels were carried out in airway aspirate samples at the first and third days of life. Gestational, delivery and neonatal data were evaluated. Outcome: discharge without bronchopulmonary dysplasia (BPD) or BPD/ death. Data were analyzed by univariate and multivariate statistical analysis. We studied 73 preterm infants, mean gestational age of 29 weeks, 32 infants were born to hypertensive mothers and 41 born to normotensive mothers. There were no differences in the MDA, NO and IL-8 levels between the two groups, in day 1 and day 3. By comparing neonates on mechanical ventilation versus nasal CPAP the concentrations of MDA and NO didn't differ, but the IL-8 was higher in the first day of mechanical ventilation. Preterm infants with BPD / death had higher levels of IL-8 in the first 3 days of life. Gestational age and mechanical ventilation were risk factors for BPD / death ... (Complete abstract click electronic access below) / Orientador: Lígia Maria Suppo de Souza Rugolo / Coorientador: Cilmery Suemi Kurokawa / Banca: Paulo Roberto Pachi / Banca: João Cesar Lyra / Mestre

Displasia ectodérmica hipoidrótica é uma doença genética rara, clinicamente caracterizada por alterações envolvendo os dentes, pele e suas estruturas anexas. Manifestações orais comuns incluem anadontia ou oligodontia, dentes conóides e xerostomia. Poucos relatos associam displasia ectodérmica e redução do fluxo salivar. O objetivo desse estudo é analisar possíveis alterações nas glândulas salivares de dez portadores de displasia ectodérmica que fazem acompanhamento no Departamento de Dermatologia Pediátrica da Universidade de São Paulo. Ultrassonografia foi realizada em dez casos em infantes portadores de displasia ectodérmica hipoidrótica nas suas glândulas salivares parótida e submandibular. Três apresentaram alterações na glândula parótida e/ou submandibular. Aplasia ou hipoplasia das glândulas salivares maiores é associada a casos de displasia ectodérmica e sugere-se acompanhamento rotineiro das glândulas salivares maiores usando ultrassonografia para prevenção de alterações decorrentes da hiposalivação na cavidade oral. / Background- Hypohidrotic ectodermal dysplasia is a rare genetic disease, clinically characterized by defects involving skin and their adnexal structures, as well as oral structures such as teeth, and occasionally salivary glands. These latter manifestations include anodontia or hypodontia, conical teeth and xerostomia. Objective- To analyze possible alterations in major salivary glands of ten patients with ectodermal dysplasia, using image exam. Methods- Ultrasonography was performed in ten pediatric cases of hypohidrotic ectodermal dysplasia to investigate the status of parotid and submandibular salivary gland. Results- Three patients presented aplasia/hypoplasia of at least one gland examined. The other 7 patients did not present any alterations in parotid and submandibular glands. Limitations- Although ultrasonography exam is adequate to investigate the presence and status of major salivary glands, other important glands such as sublingual and minor mucous salivary glands are not well-visualized using this technique. Conclusions- Aplasia or hypoplasia of the major salivary gland is strongly related to ectodermal dysplasia and we suggest routine evaluation of the major salivary gland using ultrasound to monitor and manage the possible impact of xerostomia in oral health.

Um dos objetivos da pesquisa científica, atualmente, é encontrar biomarcadores que possam auxiliar na definição da probabilidade de progressão das lesões orais displásicas, e ainda sejam capazes de identificar os principais agentes moleculares envolvidos na carcinogênese de um determinado tipo de tumor. Assim, o objetivo deste estudo foi investigar a expressão de &#x3B2;-catenina, ciclina D1 e Ki-67 em 15 espécimes de epitélio oral normal, 45 queilites actínicas displásicas e em 30 carcinomas espinocelulares de lábio. Essa amostra foi constituída por pacientes tratados na Faculdade de Medicina de Botucatu (Brasil) e no Hospital Clínico San Cecílio de Granada (Espanha). O grau de displasia epitelial e de diferenciação tumoral foi classificado com base nos critérios definidos pela Organização Mundial da Saúde. A avaliação dos biomarcadores foi realizada por meio da técnica imunohistoquímica, dividindo a espessura do epitélio em quatro compartimentos (basal, suprabasal, terço médio e terço superior) para o grupo controle e para as queilites actínicas e em três compartimentos (basal, suprabasal e região interna) para o grupo dos carcinomas espinocelulares de lábio. Para a comparação da média de expressão de cada marcador, nas diferentes localizações do epitélio foi utilizado o teste estatístico de Kruskal-Wallis. Para a correlação da expressão dos três marcadores entre os grupos foi utilizada a correlação de Spearman, com nível de significância de 5%. Os resultados demonstraram uma perda discreta da expressão membranosa de &#x3B2;-catenina na camada basal das queilites actínicas com displasia epitelial intensa (Cis) e nos carcinomas espinocelulares de lábio, assim como uma expressão citoplasmática e nuclear, discreta e diretamente proporcional à desorganização epitelial nas camadas basal e suprabasal das queilites actínicas e carcinomas espinocelulares de lábio. Notou-se também um aumento da expressão de ciclina D1 e Ki-67 na camada basal à medida que aumentava a desorganização epitelial. Houve uma associação estatisticamente significativa da expressão de ciclina D1 e Ki-67 na camada suprabasal do grupo controle (p=0,030) e das queilites actínicas (p=0,001) e ainda na região interna dos carcinomas espinocelulares de lábio (p=0,000). Não houve correlação significativa entre as expressões nucleares de ß-catenina e de ciclina D1. Nossos resultados reforçam que a &#x3B2;-catenina, a ciclina D1 e o Ki-67, podem ser utilizados como biomarcadores preditivos para o câncer de lábio. Além disso, sugerem que a &#x3B2;-catenina e a ciclina D1 participam da carcinogênese labial, em eventos independentes da via de sinalização/Wnt. / One of the goals of scientific research today is to find predictive biomarkers that can help define the probability of progression of dysplastic oral lesions, and are still able to identify key molecular agents involved in the carcinogenesis of a particular type of tumor. The objective of this study was to investigate &#x3B2;-catenin, cyclin D1 and Ki-67 expression in 15 specimens of normal oral epithelium, 45 dysplastic actinic cheilitis and 30 squamous cell carcinoma of the lip. This sample consisted of patients treated at the Botucatu Medicine School (Brazil) and the Clinical Hospital San Cecilio of Granada (Spain). The degree of epithelial dysplasia and tumor differentiation was classified based on the criteria defined by the World Health Organization. The evaluation of biomarkers was performed by immunohistochemical technique, dividing the thickness of the epithelium into four compartments (basal, suprabasal, middle third and upper third) for the control group and actinic cheilitis and three compartments (basal, suprabasal and inner region) to the group of squamous cell carcinoma of the lip. For comparing the average expression of each marker in different locations of the epithelium we used the statistical test of Kruskal-Wallis. For the correlation of the three markers expression between the groups was used Spearman, with 5% significance level. The results showed a slight loss of membranous expression of &#x3B2;-catenin in the basal layer of actinic cheilitis with severe epithelial dysplasia (Cis) and squamous cell carcinoma of the lip, and a cytoplasmic and nuclear expression, slight and directly proportional to the epithelial disorganization in layers basal and suprabasal of actinic cheilitis and squamous cell carcinoma of the lip. It was also noted an increase in expression of cyclin D1 and Ki-67 in the basal layer as increased epithelial disorganization. There was a statistically significant association of cyclin expression D1 and Ki-67 in the suprabasal layer of the control group (p=0.030) and actinic cheilitis (p=0.001) and also in the inner region of squamous cell carcinoma of the lip (p=0.000). There was no significant correlation between the nuclear expression of ß-catenin and cyclin D1. Our results emphasize that &#x3B2;-catenin, cyclin D1 and Ki-67 can be used as predictive biomarkers for lip cancer. Moreover, they suggest that &#x3B2;-catenin and cyclin D1 acts on the lip carcinogenesis, in independent events signaling pathway/Wnt.

INTRODUÇÃO: A lesão pulmonar da nova displasia broncopulmonar se caracteriza por uma diminuição da septação alveolar e do desenvolvimento vascular, ocorre um bloqueio no desenvolvimento pulmonar e consequentemente uma diminuição da alveolarização. A lesão pulmonar ocorre devido à associação de diversos fatores, incluindo a prematuridade, defesas antioxidantes inadequadas, e a ativação da resposta inflamatória. A exposição prolongada ao oxigênio também resulta em anormalidades na formação e na morfologia dos alvéolos, com redução tanto do volume pulmonar como da área de superfície interna alveolar. O objetivo do presente estudo foi comparar dois modelos de indução de lesão pulmonar através da exposição à hiperoxia prolongada em coelhos. MÉTODOS: Coelhas grávidas da raça New-Zealand-White foram sedadas para realização do parto cesáreo no 28º dia de gestação (termo = 31dias), coelhos prematuros foram expostos ao ar ambiente ou FiO295%. Outro grupo nasceu no 29º dia de gestação e foi exposto ao ar ambiente ou a uma FiO2=80%. Os animais foram mantidos em incubadora com controle de temperatura e alimentação e uma fórmula especial de leite similar ao leite de coelha por 11 dias. Desta forma, foram constituídos quatro grupos de estudo: Ar ambiente com 28 dias de gestação (Ar 28); exposição ao oxigênio (FiO2 95%) com 28 dias de gestação (O2 28); ar ambiente com 29 dias de gestação (Ar 29); exposição ao oxigênio (FiO2 = 80%) com 29 dias de gestação (O2 29). Após o sacrifício os pulmões foram fixados com 30 cmH2O de pressão transtraqueal. As lâminas do tecido pulmonar foram submetidas às seguintes colorações: hematoxilina e eosina para análise morfométrica; Weigert, resorcina-orceína modificado para a análise das fibras elásticas e Picrosirius para análise do colágeno. Foi realizada a contagem do Intercepto Linear Médio (Lm), determinada a Área de Superfície Interna (ISA), o número de alvéolos por campo microscópico, o espessamento septal e a proporção de fibras elásticas e colágenas. Análise Estatística: As variáveis contínuas foram analisadas por ANOVA One Way e a análise da sobrevida foi realizada através de uma curva de Kaplan-Meyer. O nível de significância adotado foi de 0.05. RESULTADOS: A sobrevida nos grupos de 29 dias foi melhor quando comparados com o grupo 28 dias. A hiperoxia bloqueou o desenvolvimento normal do pulmão, demonstrado por um aumento no Lm, uma diminuição significativa na ISA, uma diminuição no número de alvéolos, um aumento na espessura do septo interalveolar e também um aumento na proporção de fibras elásticas e uma diminuição na proporção de fibras colágenas nos dois grupos de animais expostos ao oxigênio em relação aos grupos que permaneceram em ar ambiente. CONCLUSÕES: Em coelhos prematuros o uso de uma concentração de oxigênio menor e um dia a mais de gestação reduziu a taxa de mortalidade mantendo os achados histopatológicos compatíveis aos da displasia broncopulmonar em humanos / INTRODUCTION: The lung injury of the \"new\" bronchopulmonary dysplasia is characterized by a decrease in alveolar septation and vascular development, resulting in a pulmonary arrest and a decrease in alveolarization. Lung damage occurs due to the association of many factors, including prematurity, inadequate antioxidant defenses and activation of the inflammatory response. Prolonged exposure to oxygen also results in abnormalities in the formation and morphology of the alveoli, with reduced lung volume and alveolar internal surface area. The aim of this study was to compare two models of lung injury induced by prolonged exposure to hyperoxia in rabbits. METHODS: New Zealand-White pregnant rabbits were sedated to perform a cesarean section on day 28 of gestation (term = 31days), premature rabbits were exposed to room air or FiO295%. Another group of animals was born at day 29 of gestation and was exposed to room air or FiO2=80%. The animals were kept in an incubator with temperature control and fed with a special milk formula similar to rabbit milk for 11 days. Four study groups were formed: Room air and 28 days of gestation (Air 28); exposure to oxygen (FiO295%) and 28 days of gestation (O2 28); room air and 29 days of gestation (Air 29 ); exposure to oxygen (FiO2=80%) and 29 days of gestation (O2 29). For microscopic evaluation, after sacrifice the lungs were fixed in situ at a constant inflation pressure of 30 cm H20. Lung slices were processed for hematoxylin-eosin staining - for morphometric analysis, Weigert\'s resorcin-orcein modified for the analysis of elastic fibers and Picrosirius - for analysis of collagen. The mean linear intercept (Lm), the internal surface area (ISA), the number of alveoli, the septal thickness and the proportion of elastic and collagen fibers were quantified. Statistical analysis was by One Way ANOVA for continuous variables, survival analysis was performed using a Kaplan-Meyer plot. The level of significance was 0.05. RESULTS: Survival in both 29 days groups was better when compared with 28 days groups. Hyperoxia impaired the normal development of the lung, demonstrated by an increase in Lm, a significant decrease in ISA, a decrease in the alveoli number, an increase in the septal thickness and an increase in the proportion of fibers elastic and a decrease in the proportion of collagen fibers in oxygen exposed animals. CONCLUSIONS: In premature rabbits using a lower concentration of oxygen and one more day of gestation reduced the mortality rate maintaining the histopathological findings similar to bronchopulmonary dysplasia in humans

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-05-21T12:08:38Z No. of bitstreams: 1 Renan Brabosa.pdf: 1060823 bytes, checksum: fc955ead19a6d7919dd5e205508e4971 (MD5) / Made available in DSpace on 2018-05-21T12:08:38Z (GMT). No. of bitstreams: 1 Renan Brabosa.pdf: 1060823 bytes, checksum: fc955ead19a6d7919dd5e205508e4971 (MD5) Previous issue date: 2017-11-07 / Developmental dysplasia of the hip (DDH) is one of the main causes in early degeneration of the hip joint, which causes pain, gait alteration, funcional and labor incapacity in the young adult, often leading to total arthhroplasty of hip. It is know that with early diagnosis, in the first months of life, a succes rate of about ninety percent is achieved with the use of the Pavlik suspender. The study estimated the prevalence of DDH in newborns(NB) from Pelotas city. For the accomplishment of the study was carried out the revision of the medical records of DDH carriers in the period from January 2014 to December 2016 and the data of Information System on Live Births (SINASC), of the same period was used. We observed 33 patients with DDH, 2.3 cases per 1000 live births, the following characteristics were evaluated: gender, color, maternal age, birth order, gestational age, fetal position, family history, affected side, birthweight and associated malformations. The variables: gender, color, maternal age, gestational age, birthweight and fetal presentation were analyzed in relation to SINASC, and gender (female) and pelvic presentation had a significant association with DDH. It is recommended that ultrasound should be perfomed in all NB who presented one or more of the following characteristics: positive Ortolani, family history and pelvic presentation. / A displasia do desenvolvimento do quadril (DDQ) é uma das principais causas de degeneração precoce da articulação coxo femoral, o que ocasiona dor, alteração da marcha, incapacidade funcional e laboral no adulto jovem, levando, muitas vezes, à realização de artroplastia total de quadril. Sabe-se que, com o diagnóstico precoce, nos primeiros meses de vida, consegue-se um índice de sucesso de cerca de noventa por cento com o uso do suspensório de Pavlik. O estudo estimou a prevalência de DDQ nos recém-nascidos (RN) da cidade de Pelotas. Para realização do estudo foi feita revisão dos prontuários de RN portadores de DDQ no período de janeiro de 2014 a dezembro de 2016 e utilizou os dados do Sistema de Informações Sobre Nascidos Vivos, do mesmo período. Observou-se 33 portadores de DDQ, 2,3 casos por 1000 nascidos vivos. Foram avaliadas as seguintes características: sexo, cor, idade materna, ordem de nascimento, idade gestacional, posição fetal, história familiar, lado acometido, peso ao nascer e malformações associadas. As variáveis: sexo, cor, idade materna, idade gestacional, peso do RN e tipo de apresentação fetal foram analisadas em relação ao SINASC, sendo que sexo (feminino) e apresentação pélvica apresentaram associação significativa com DDQ. Vinte e uma crianças necessitaram tratamento imediato dos quadris. Recomenda-se a realização do ultrassom em todos os RN que apresentem uma ou mais das seguintes características: Ortolani positivo, história familiar e apresentação pélvica.

As displasias corticais focais constituem um grupo de malformações do desenvolvimento cortical cerebral. São consideradas a causa mais comum de epilepsia refratária na população pediátrica. A hemimegalencefalia faz parte deste grupo de malformação do desenvolvimento cortical e clinicamente devastadora em crianças, caracterizada pelo crescimento distorcido e anormal de um hemisfério cerebral. O mTOR (Mammalian Target of Rapamycin) é uma proteína quinase, que normalmente funciona como um regulador central de importantes funções fisiológicas, incluindo o crescimento e proliferação celular, metabolismo, autofagia, e sobrevivência e morte celular. O objetivo deste estudo foi identificar o defeito genético específico da hemimegalencefalia analisando os genes das vias de sinalização do mTOR. Foram selecionados 10 pacientes diagnosticados com hemimegalencefalia com faixa etária entre 0 á 18 anos de idade. Os pacientes submetidos ao procedimento cirúrgico foram designados para a coleta do material biológico (sangue e tecido encefálico) para análise genômica. Foram encontradas variantes somáticas de três genes relacionados a via mTOR com alto índice de patogenicidade, sendo elas; mutações missense na MTOR, HME 6584 (c.7255G> A, p.Glu2419Lys), HME 4146 (c.7498A> T, p.L7105f) mutações missense do gene PIK3CA, HME 4149 E542K (c.1624G> A), HME 4143 (c.1258T> C, p.C420R). A hipótese mediante esses resultados é que a mutação somática de genes que estão presentes na via mTOR podem ser uma das causas genéticas da HME. Essas observações sugeriram que a HME representa um espectro de distúrbios do neurodesenvolvimento resultando de distintas progenitoras que são determinados pelo tempo em que a mutação ocorreu durante o desenvolvimento cerebral. Pode-se esperar que uma mutação que ocorre precocemente durante o desenvolvimento afete um grande número de células e resulte em uma malformação maior, ao passo que a mesma mutação ocorrendo mais tarde no desenvolvimento poderia causar uma menor malformação. No futuro, numerosas mutações somáticas em genes conhecidos ou novos serão, sem dúvida, reveladas em amostras de cérebros ressecados e assim, possíveis correlações entre genótipos e fenótipos podem emergir, permitindo que o diagnóstico clínico genético ajude a prever o desfecho do paciente / Focal cortical dysplasias constitute a group of malformations of cerebral cortical development. They are considered the most common cause of refractory epilepsy in the pediatric population. Hemimegalencephaly is part of this group of malformation of cortical development and clinically devastating in children, characterized by the distorted and abnormal growth of a cerebral hemisphere. MTOR (Mammalian Target of Rapamycin) is a protein kinase, which normally functions as a central regulator of important physiological functions, including cell growth and proliferation, metabolism, autophagy, and cell death and survival. The aim of this study was to identify the specific genetic defect of hemimegalencephaly by analyzing the genes of the mTOR signaling pathways. Ten patients diagnosed with hemimegalencephaly with ages ranging from 0 to 18 years of age were selected. Patients submitted to the surgical procedure were assigned to the collection of biological material (blood and brain tissue) for genomic analysis. Somatic variants of three genes related to the mTOR pathway with high pathogenicity index were found; missense mutations in the MTOR, HME 6584 (c.7255G> A, p.Glu2419Lys), HME 4146 (c.7498A> T, p.Leu7105Phe) missense mutations of the PIK3CA gene, HME 4149 (c.1624G> A Glu542Lys), HME 4143 (c.1258 -> C, p.Cys420Arg). The hypothesis by these results is that the somatic mutation of genes that are present in the mTOR pathway may be one of the genetic causes of HME. These observations have suggested that HME represent a spectrum of neurodevelopmental disorders resulting from distinct progenitors that are determined by the time the mutation occurred during brain development. A mutation that occurs early in development may be expected to affect a large number of cells and result in a larger malformation, whereas the same mutation occurring later in development could cause a minor malformation. In the future, numerous somatic mutations in known or new genes will undoubtedly be revealed in samples of resected brains and thus, possible correlations between genotypes and phenotypes may emerge, allowing genetic clinical diagnosis to help predict the outcome of the patient

A displasia do cotovelo é considerada uma disfunção ou má formação da articulação umerorradioulnar com causas multifatoriais, é a causa mais comum de claudicação de membros torácicos em cães jovens e acomete principalmente cães de raças grandes e gigantes. As alterações da displasia do cotovelo incluem não união do processo ancôneo, fragmentação do processo coronóide medial, osteocondrose da tróclea umeral, incongruência articular e doença articular degenerativa. Esse estudo teve como objetivo apresentar de forma detalhada dados morfológicos e morfométricos da articulação umerorradioulnar de cães de raça definida avaliados por meio de exames clínicos, radiográficos e tomográficos. A amostra de cães dessa pesquisa constituiu-se de 44 cotovelos de cães com idades variadas. Realizou-se a comparação do desempenho de diferentes projeções radiográficas individualmente e sua análise comparativa com o exame tomográfico, mensuração da incongruência radioulnar ao exame tomográfico e posterior comparação à análise qualitativa ao exame radiográfico, cálculo do ângulo da incisura ulnar e sua comparação entre exames radiográfico e tomográfico e verificação da concordância entre avaliadores para as diferentes mensurações realizadas nos exames radiográfico e tomográfico. Para análise dessas informações, o coeficiente kappa, correlação interclasse e testes Fischer e McNemar foram realizados. Constatou-se que o desempenho individual de cada projeção radiográfica teve pobre concordância com o exame tomográfico sugerindo-se a realização de mais de duas projeções radiográficas; não houve concordância entre os três observadores para as mensurações do ângulo da incisura ulnar ao exame radiográfico e tomográfico. Porém houve boa/moderada concordância para mensuração da incongruência radioulnar no plano sagital entre os observadores. Concluiu-se que nenhuma das cinco incidências radiográficas foi superior à outras para análise radiográfica, uma vez que cada projeção apresentou melhor identificação de um compartimento do cotovelo; medidas ao exame tomográfico para incongruência radioulnar não apresentam reprodutibilidade no corte dorsal, no corte sagital apresentaram boa e moderada concordância entre os observadores e que a mensuração do ângulo da incisura ulnar não apresentou repetibilidade ao exame radiográfico e reprodutibilidade ao exame tomográfico. / Elbow dysplasia is considered a dysfunction or malformation of the elbow joint with multifactorial causes and is the most common cause of thoracic limb lameness in young dogs and mainly affecting large and giant breeds. Elbow dysplasia disease include ununited anconeal process, fragmented medial coronoid process, osteochondrosis of humeral trochlea, articular incongruity and degenerative joint disease. The aim of this study was to present detailed morphologic and morphometric aspects of the elbow joint in Labrador retriever and Australian shepherd dog in clinical and correlate with radiographic and tomographic (CT) exam. Interobserver variation for articular incongruity measurements by CT, comparative analysis in the radiographic exam, angle in ulnar notch and its comparative analysis between radiographic and tomographic agreement examination in 44 elbow of dogs with different ages were evaluated. The statistics analyses included the kappa coefficient and interclass correlation and Fischers test and McNemars test. It was evidenced that individual performance of each radiographic incidence had poor agreement with the tomographic exam, suggesting that the accomplishment of more than two radiograph views are needed. There was no agreement between the three evaluators in the ulnar notch angle at radiographic and tomographic exams. However, there was good/moderate agreement for articular incongruity measurement in the sagittal plane between evaluators. It was possible to conclude that none of the five radiographic incidences was better than the others for radiographic analysis because each incidence had a better identification of a particular elbow compartment; measurements at the tomographic exam to evaluate radioulnar incongruity had no reproductiveness in the dorsal plane, but in sagittal plan had a good/moderate agreement between observers and the angle in ulnar notch presented no repeatability at radiographic exam and no reproductiveness at tomographic exam.

Acetabular dysplasia, a deformity characterized by the presence of a shallow acetabulum inadequately covering the femoral head, alters force transfer through a joint, causing early-onset hip pain and degeneration. Dysplasia is often treated surgically with a periacetabular osteotomy (PAO), which permits multiplanar acetabular reorientation to stabilize the joint and alleviate pain. PAO alters joint mechanics, including contact stress, which can be assessed via computational methods. This work sought to enhance a discrete element analysis (DEA) model for assessment of the dysplastic hip. The primary focus was on understanding how the gait parameters used to load a DEA model affect the computed contact stress. Several additional studies focused on understanding specific anatomic and demographic factors contributing to the contact stress evaluation were also performed. Implementation of a dysplastic gait pattern to load the DEA models resulted in more cases with improved contact stress and clinical measures after PAO, which concurred with clinical findings. Patient demographics and acetabular and femoral geometry all affected the computed contact stress distributions, emphasizing the importance of proper cohort categorization prior to interpretation of DEA-calculated contact stress. These results indicate that accurate modeling of the particular deformity in this cohort likely requires evaluation of both functional and anatomic differences. These studies improve the ability to realistically model and characterize dysplastic hip contact mechanics. DEA is a valuable tool for assessing contact stress in dysplastic joints, which has the potential to improve patient outcomes by guiding clinicians in non-operative treatment, pre-operative PAO planning, and evaluating intraoperative success.

Abstract Introduction: Current evidence suggests that the lungs of infants with the debilitating disorder, bronchopulmonary dysplasia (BPD), react to the challenges of extra-uterine adaptation with inappropriately aggressive inflammation. The reasons for this are not entirely clear and this study hypothesizes that a deficiency of interleukin (IL)-10, a potent anti-inflammatory mediator, leads to the functional and architectural changes characteristic of BPD. Aim: To characterize the behaviour of IL-10 and neutrophil apoptosis in the tracheal fluids (TF) of infants at risk of developing BPD. Method: TF from intubated infants of varying gestations at the Royal Hospital for Women, Randwick was spun and ILs 8, 10 and 16 were measured in the supernatant. The residual pellets of white cells were used to determine differential white cell counts and neutrophil apoptosis. Results: None of the 20 TF specimens from the extremely premature infants with BPD (n=11) had detectable IL-10, compared to 14/20(70%) of the specimens from preterm infants without BPD (n=20) and to 5/19 (26%) of the specimens from term infants (n=19). BPD infants also had a significantly lower number of apoptotic neutrophils during the 1st week of life. Premature infants with TF IL-10 &gt5pg/ml did not develop BPD. Levels of IL-8, a neutrophil chemotaxin, and white cell counts, while not differing significantly between the groups, increased considerably towards the end of the first week of life in the BPD group. IL-16, a chemotaxin for inflammatory CD4+ cells, was also detected in more BPD than non-BPD specimens (BPD: 16/46 (35%) v 1/30 (0.3%) non-BPD preterm and 2/7 (28%) term TF specimens). Conclusions: Extremely premature infants prone to BPD have decreased pulmonary anti-inflammatory activity as demonstrated by decreased IL-10 and apoptotic neutrophils in tracheal fluids. The lack of a counter-regulatory response to the inflammatory processes that are an inevitable consequence of extra-uterine adaptation may therefore place the extremely premature newborn infant at a considerable risk of developing BPD.

Ulcerative colitis is a chronic inflammatory disease that mainly affects the colon and rectum. Onset of disease is most common between the ages of 15-35 years. There is an observed increased risk of colorectal cancer associated with the disease. The risk is often described to be 2% after 10 years, 8% after 20 years and 18% after 30 years disease. Since 1977, all known patients with ulcerative colitis in the catchment area of Örnsköldsvik Hospital have been invited to attend a colonoscopic surveillance programme. At endpoint of the studies included in this thesis there were 214 patients that had attended the surveillance programme. The aims of these studies have been to evaluate the efficiency of the surveillance programme, analyse the impact of findings of DNA aneuploidy, and determine the outcome for patients that underwent limited resections instead of complete proctocolectomy. Further, we have studied the long-term outcome for patients who had an early onset of disease and analysed the expression of cytokeratin 7 and 20 in respect to findings of dysplasia, DNA aneuploidy and colorectal cancer. At the end of the studies the prevalence for ulcerative colitis was 261/100 000 and the incidence rate was 7.6/100 000/year. During the period 1977-2005, four patients died of ulcerative colitis. Nine colorectal cancers were diagnosed in eight patients, one of whom died of the cancer. Fifty-two patients had findings of dysplasia and five of these patients developed colorectal cancer. In the subgroup of patients studied (N= 147) for DNA aneuploidy, 20 were found to have specimens with DNA aneuploidy on at least one occasion. The sensitivity of aneuploidy for development of dysplasia (LGD or higher) was found to be 0.50 and the specificity 0.94. The investigation of the outcome for the patients that underwent limited resections of the colon or rectum showed that none of the patients under surveillance died of colorectal cancer or metachronous cancer in their remaining colon or rectum. A separate study concerning early onset of ulcerative colitis revealed no particular increased risk of colorectal cancer in this cohort but a fairly high incidence of primary sclerosing cholangitis was seen. In the analyses of cytokeratins it was found that 7 out of 10 patients with low-grade dysplasia and 3 of 6 with high-grade dysplasia were positive for CK7. Our results indicate a possible relationship between the expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. The studies on which this thesis is based, were performed on a relatively small number of patients, however the time of observation was long and, most importantly, the patients were from a well defined catchment area. We conclude that the surveillance programme has been efficient in minimising the risk of lethal colorectal cancer. Analysing DNA ploidy helps to target the patients that need more attention but the method cannot stand alone. Our study on cytokeratins points to a relationship between dysplasia and CK7 but the results are preliminary and further studies needs to be done. We have shown that it is safe to do a limited colorectal resection in respect to lethal colorectal cancer. Early onset of ulcerative colitis as a risk factor for colorectal cancer was not found in the group we have studied, which could be due to effective surveillance and/or medication. A fairly high operation rate in this group may also have contributed. The most important variable in the beneficial outcome regarding lethal colorectal cancer in these studies is, in our opinion, the outstanding compliance of the patients to the colonoscopic surveillance programme.