Introdução: A dissecção endoscópica submucosa (ESD) de neoplasias superficiais extensas de esôfago pode evoluir com altas taxas de estenose pós operatória, resultando em uma importante piora na qualidade de vida. Diversas terapias estão disponíveis para prevenir essa complicação. Entretanto, até o momento, nenhuma revisão sistemática e metanálise foram realizadas para avaliar esses resultados. Métodos: Uma revisão sistemática e metanálise foram realizadas utilizando as bases de dados eletrônicas Medline, Embase, Cochrane, LILACS, Scopus e CINAHL. Ensaios clínicos e estudos observacionais foram pesquisados de março de 2014 a fevereiro de 2015. Os termos pesquisados foram: endoscopy, ESD, esophageal stenosis, e esophageal stricture. Três estudos retrospectivos e quatro prospectivos (três randomizados) foram selecionados. Um total de 249 pacientes com diagnóstico de neoplasia superficial de esôfago, submetidos a ESD de pelo menos dois terços da circunferência do órgão foram incluídos. Foram selecionados estudos comparando diversas técnicas para prevenir a estenose de esôfago após extensa ESD. Resultados: Foram realizadas diferentes metanálises com ensaios clínicos randomizados (RCT), ensaios clínicos não randomizados (non- RCT) e uma análise global. Nos RCT (três estudos, n=85), a terapia preventiva diminuiu o risco de estenose (diferença de risco = - 0,36, IC 95% - 0,55 a - 0,18, p = 0,0001). Dois estudos (um randomizado e um não randomizado, n = 55) demonstraram que a terapia preventiva diminui o número médio de dilatações (diferença média = - 8,57, IC 95% - 13,88 a - 3,25, p < 0,002). Não houve diferenças significativas em três RCT em relação à taxa de complicações entre pacientes submetidos à terapia preventiva e aqueles não submetidos (diferença de risco = 0,002, IC 95% -0,09 a 0,14, p = 0,68). Conclusão: O uso da terapia preventiva após extensa ESD no esôfago, reduz o risco de estenose e o número de dilatações endoscópicas para resolução da estenose, sem aumentar o número de complicações / Background: Endoscopic submucosal dissection (ESD) of extensive superficial cancers of the esophagus may progress with high rates of postoperative stenosis, resulting in significant decrease in quality of life. Several therapies are performed to prevent this complication. However, they have not yet been compared in a systematic review. Methods: A systematic review of the literature and meta-analysis were performed using the Medline, Embase, Cochrane, LILACS, Scopus, and CINAHL databases. Clinical trials and observational studies were searched from March 2014 to February 2015. Search terms included: endoscopy, endoscopic submucosal dissection, esophageal stenosis, and esophageal stricture. Three retrospective and four prospective (3 randomized) cohort studies were selected. They involved 249 patients with superficial esophageal neoplasia who underwent ESD of at least two-thirds of the circumference. We grouped trials comparing different techniques to prevent esophageal stenosis post-ESD. Results: Were realized different meta-analyses on randomized clinical trials (RCT), non-RCT, and global analysis. In RCT (3 studies, n=85), preventive therapies decreased the risk of stenosis (risk difference = -0.36, 95% CI= -0.55 to -0.18, p = 0.0001). Two studies (1 randomized, 1 non-randomized, n = 55) showed that preventive therapies lowered the average number of endoscopy dilatations (mean difference = -8.57, 95% CI = -13.88 to -3.25, p < 0,002). There were no significant differences in the 3 RCT studies (n=85) with regards to complication rates between patients with preventive therapies and those without (risk difference = 0.02, 95% CI = -0.09 to 0.14, p = 0.68). Conclusion: The use of preventive therapies after extensive ESD of the esophagus reduces the risk of stenosis and the number of endoscopic dilatations for resolution of stenosis without increasing the number of complications

Introdução: A deposição de cálcio junto aos folhetos valvares esta intimamente relacionada à fisiopatologia da estenose valvar aórtica degenerativa (EAD). A tomografia computadorizada com multidetectores (TCMD), além de possibilitar o delineamento tridimensional das estruturas cardíacas, permite a quantificação da intensidade da calcificação valvar. Atualmente, a relação entre a localização dos depósitos valvares de cálcio e a gravidade hemodinâmica na estenose aórtica permanece incerta. Objetivo: Avaliar se a topografia da calcificação valvar influencia a repercussão hemodinâmica na EAD. Métodos: Trata-se de estudo prospectivo, unicêntrico, incluindo 97 pacientes com EAD moderada ou importante. O escore de cálcio da valva aórtica foi calculado a partir da TCMD sem contraste. A topografia da calcificação valvar foi avaliada através de análise tomográfica específica com infusão de baixa dose de contraste endovenoso, objetivando uma detalhada segmentação anatômica dos planos valvares. A medida da atenuação, expressa em unidades Hounsfield (UH), foi utilizada para quantificar o conteúdo de cálcio na região central e periférica do plano valvar aórtico. Resultados: Pacientes com EAD importante apresentaram escore de cálcio valvar aórtico superior ao dos portadores de EAD moderada (3131 ± 1828 unidades Agatston [UA] e 1302 ± 846 UA, respectivamente; p < 0,001). Quanto à topografia da calcificação, pacientes com EAD importante exibiram atenuações significativamente maiores no centro do plano valvar do que em sua periferia (507,4 ± 181,7 UH vs. 449,8 ± 114,5 UH; p = 0,001). Inversamente, pacientes com EAD moderada apresentaram menor atenuação na região central do que na periferia valvar (308,7 ± 92,9 UH vs. 347,6 ± 84,2 UH, p < 0,001). A razão da atenuação centro/periferia também foi significativamente maior nos pacientes com EAD importante (1,14 ± 0,32 vs. 0,89 ± 0,13; p < 0,001), permanecendo significativamente associada à presença de EAD importante mesmo após ajuste para o grau subjacente de calcificação Resumo valvar. Conclusão: A gravidade da EAD parece resultar não apenas do grau de calcificação, mas também da localização dos depósitos valvares de cálcio / Introduction: The pathophysiology of degenerative aortic valve stenosis (AS) is intimately related to the development of calcific deposits in the valve structure. Multidetector computed tomography (MDCT), a reliable method to delineate the tridimensional heart geometry, has been shown to accurately quantify the global aortic valve calcium content. Currently, the relationship between calcium location and hemodynamic disease severity is poorly understood. Objective: The present prospective study was conducted to test the hypothesis of whether the location of valve calcification influences the functional severity of AS. Methods: Prospective, single-arm study including 97 patients with diagnosed moderate or severe AS. Aortic valve calcium score was calculated from nocontrast multidetector computed tomography (MDCT). \"Low-contrast- os \" MDCT images were acquired for segmentation of the cardiac anatomy, with the attenuation, expressed in Hounsfield units (HU), used to quantify the calcium content at the central and peripheral regions of the aortic valve zone. Results: The calcium score was higher among patients with severe AS compared to patients without severe AS (3131±1828 Agatston units [AU] vs. 1302±846 AU respectively; p < 0.001). Patients with severe AS had significantly higher attenuations at the center of the valve than at its periphery (507.4±181.7 HU vs. 449.8±114.5 HU; p=0.001). Conversely, patients without severe AS had lower attenuation at the center than at the periphery of the valve (308.7 ± 92.9 HU vs. 347.6±84.2 HU; p < 0.001). The center/periphery attenuation ratio was significantly higher for patients with severe AS than for those without severe disease (1.14±0.32 vs. 0.89 ± 0.13; p < 0.001), and remained significantly associated with the presence of severe AS even after adjusting for the underlying degree of valve calcification. Conclusion: The severity of degenerative aortic valve stenosis appears to result not only from the degree of calcification but also from the localization of the calcific deposits within the valve

Dor lombar é uma queixa comum especialmente entre os idosos. O termo estenose espinal é baseado no fato de que um espaço mínimo do canal vertebral é necessário para o funcionamento normal das estruturas nervosas e quando esse espaço torna-se estreito, resulta em sintomas como dor, dormência e fraqueza dos membros inferiores e claudicação neurogênica, que pioram com o esforço e melhoram com o repouso. Objetivos: Avaliar as alterações cinemáticas da marcha antes e após esforço físico em teste de esteira e correlacionar com a percepção de dor e com o grau de estenose do canal vertebral lombar obtido através do exame de ressonância nuclear magnética. Método: 14 pacientes com diagnóstico de estenose do canal vertebral lombar, com média de idade de 74,5 (9,8) anos e a área transversal média do canal vertebral foi de 43,86 (28,76) mm2. Para análise cinemática foram utilizados o sistema Vicon® MX 40 e o software Nexus® de reconstrução tridimensional das imagens. O exame constou de três fases: 1) Captura de seis ciclos de marcha após um período de descanso; 2) Caminhada em esteira durante um período máximo de 20 minutos; 3) Nova captura de outros 6 ciclos da marcha imediatamente após o esforço. A partir destes dados, as variáveis espaço temporais e angulares foram extraídas e analisadas individualmente e, em seguida, comparadas com a percepção da dor de cada paciente obtido pela escala visual analógica no inicio e ao final do exame e com a área transversal do canal vertebral medida em exames de ressonância nuclear magnética. Resultados: A maior parte das correlações se mostraram fracas e os resultados mais expressivos se referiram ao GDI onde notamos diminuição das medianas para ambos os membros com correlação negativa moderada com a percepção da dor pós-esforço, tanto para o membro esquerdo (r= -0,64, p=0,014) quanto para o direito (r= -0,53, p= 0,05), o que significa que existe uma diminuição significante da função geral dos membros inferiores conforme o sintoma da dor aumenta ( p= 0,002). Este fato pode ter reflexo na diminuição da cadência e da velocidade além dos tempos de apoio simples (significante para o membro esquerdo, p= 0,019) e balanço (significante para o membro direito, p= 0,013) como parte de uma estratégia de proteção contra a dor e o desequilíbrio. Conclusão: Há alteração da velocidade, cadência e dos tempos de apoio simples e duplo apoio para compensar a dor e a diminuição da função dos membros inferiores medida pelo GDI se correlaciona com o aumento da dor. Porém, as variáveis cinemáticas da marcha e a dor não tiveram correlação com tamanho da área transversal do canal vertebral / Back pain is a common complaint especially among older patients.The spinal stenosis term is based on the fact that a minimum space of the spinal canal is necessary for normal functioning of the nervous structures, and when this space becomes narrow, results in nerve compression symptoms such as pain, lower limbs numbness and weakness and neurogenic claudication, which increase with stress and decreases with rest. Objective: Evaluate kinematics changes of gait before and after physical effort in treadmill test, and correlate with the perception of pain and the lumbar stenosis degree obtained by nuclear magnetic resonance. Method: 14 subjects were evaluated with diagnostic of lumbar stenosis with a mean age of 74,5 (9,8) years and average size of the spinal canal was 43.86 (28.76) mm2. Were used for kinematic analysis Vicon ® MX 40 system and Nexus ® software for images three-dimensional reconstruction. The exam consisted of three phases: 1) Capture of six gait cycles after a rest period; 2) Walk on treadmill for a maximum of 20 minutes; 3) New capture of other 6 gait cycles immediately after the effort. From these data, temporal-spatial and angular variables were extracted and analyzed individually and compared to the pain perception obtained by visual analog scale at the beginning and the end of the exam and the cross-sectional area of the dural sac obtained from the nuclear magnetic resonance. Results: Most of the correlations were weak and the most significant results are reported to GDI when we observed decrease in medians for both lower limbs to moderate negative correlation when compared to pain perception after effort for both left (r = - 0.64, p= 0.014) and right limb (r= -0.53, p= 0.05), which means that there is a significant reduction in the global function of the lower limbs according the symptom of pain increases (p = 0.002). This fact may be reflected in decreased cadence and gait speed and also the times of single support (significant for the left limb, p= 0.019) and balance (significant for the right limb, p= 0.013) as a protection strategy against pain and imbalance. Conclusion: There is changing the speed, cadence and time of single and double support for compensation of pain and decreased function of the lower limbs measured by GDI correlates with increased pain. However, the kinematic variables of gait and pain did not correlate with the size of cross-sectional area of the spinal canal

Abstract The stem cell is a primitive cell that is capable of dividing to reproduce itself and can give rise to a selection of differentiated progeny. Stem cells are thought to be involved in or even main factors in many diseases. In postnatal humans, mesenchymal tissues have the capacity to regenerate from stem cells called mesenchymal stem cells (MSC). It is currently thought that these cells will become the basis of therapy for many diseases. In the present study, a novel in vitro method was developed to examine human bone marrow derived MSC differentiation into osteoblast lineage, and to study the role of MSC in a variety of mesenchymal diseases. The ability of MSCs to differentiate into osteoblasts was investigated during aging. In addition, the interindividual variability in the osteogenesis of MSCs and in the osteoblastic response of MSC to estrogen and testosterone was studied. Furthermore, an ex vivo model using a human aortic valve microenvironment was developed to explore whether the extracellular matrix influences the osteoblastic differentiation of the MSC. Finally, the role of MSC in neurofibromatosis type 1 (NF1) related congenital pseudarthrosis of the tibia (CPT) was studied. It was found that after menopause the osteogenic potential of MSCs does not decrease. It was also found that estrogen receptor (ER) alpha genotype confers interindividual variability of response to estrogen and testosterone in MSC derived osteoblasts. In addition, it was found that the non-calcified valves with living valve cells inhibited osteogenesis of co-cultured MSCs, whereas the calcified and devitalised valves promoted differentiation towards an osteoblastic lineage. Finally, MSCs from NF1-related pseudarthrosis showed altered NF1 gene expression, poor osteoblastic differentiation and bone formation. In conclusion, MSC can be easily isolated from the bone marrow and MSC has the capacity to regenerate tissue even at later stages of life. These results could help explain the contradictory effects of 17β-estradiol (E2) on osteoblasts in vitro and might also provide new insights into understanding the differences in responses to hormone replacement therapy. It seems that adult stem cells from bone marrow undergo milieu-dependent differentiation to express phenotypes that are similar to cells in the local microenvironment. Finally, the NF1 gene was shown to have a role in bone development and remodelling.

Abstract Calcified aortic valve disease represents a spectrum of disease spanning from mild aortic valve sclerosis to severe aortic valve stenosis (AS), being an actively regulated disease process and showing some hallmarks of atherosclerosis. The calcified aortic valve lesion develops endothelial injury and is characterized by inflammation, lipid accumulation, renin-angiotensin system activation and fibrosis. There is no approved pharmacological treatment available in AS. This study was aimed to characterize gene expression of endothelial factors in aortic valves in patients representing different stages of calcified aortic valve disease to reveal new targets for pharmacological interventions in AS. Aortic valves obtained from 75 patients undergoing valve replacement surgery were studied. Expression of natriuretic peptides (ANP, BNP and CNP), their processing enzymes (corin and furin), natriuretic receptors (NPR-A, NPR-B and NPR-C), endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE-1), endothelin receptors A and B (ETA and ETB), and apelin pathway (apelin and its receptor APJ) was characterized by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. AS was characterized by distinct downregulation of gene expression of CNP, its processing enzyme furin and the target receptor NPR-B. Furthermore, increased amount of ET-1 and its target receptor ETA as well as imbalance between ETA and ETB receptors and downregulated endothelial nitric oxide synthase (eNOS) gene expression were observed. Finally, gene expression of apelin and APJ receptor were significantly upregulated in stenotic valves when compared to controls in combination with disequilibrium between expression of angiotensin II receptors AT1 and AT2. The study provides a better understanding of molecular mechanisms associated with calcific aortic valve disease and suggest potential targets for novel therapeutic interventions.

Orientador: Ana Terezinha Guillaumon / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T09:17:18Z (GMT). No. of bitstreams: 1 Siqueira_LeticiaCristinaDalledone_M.pdf: 5041737 bytes, checksum: 615b5b4269f2f46490565662d28dfb21 (MD5) Previous issue date: 2015 / Resumo: Introdução: A espectroscopia próxima ao infra-vermelho (NIRS) é uma técnica não invasiva e de baixo custo que detecta as alterações hemodinâmicas teciduais. O NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ele pode ser utilizado a beira do leito e no centro cirúrgico. Objetivo: Avaliar o comportamento das possíveis alterações hemodinâmicas cerebrais, durante a endarterectomia, em pacientes com estenoses maiores que 70%, utilizando NIRS. Casuística e métodos: Foram avaliados 10 voluntários portadores de doença carotídea aterosclerótica com indicação de endarterectomia. Após a seleção dos pacientes que responderam um questionário com dados epidemiológicos e informações referentes a presença de comorbidades, a doença foi confirmada por métodos diagnósticos. No procedimento cirúrgico utilizou-se o NIRS para monitorização. Foram avaliadas as variáveis saturação de oxigênio (Sat O2) hemoglobina total (HbT), hemoglobina reduzida (HbR) e hemoglobina oxigenada (HbO) nos três tempos cirúrgicos pré, trans e pós-clampeamento carotídeo. Resultados: Utilizou-se p<0,05 como nivel de significância. A avaliação dos resultados obtidos através das medidas registradas pelo NIRS permite afirmar que as etapas da cirurgia diferem quanto ás variável HbR e SatO2. Durante a etapa do clampeamento, a variável HbR mostra valores mais elevados que nas outras duas etapas da cirurgia. De outra parte, a variável SatO2 mostra redução durante o clampeamento. Conclusão: O NIRS é um método viável e aplicável de monitorização intracerebral, não-invasivo e em tempo real, durante a endarterectomia carotídea, capaz de medir de forma precisa as mudanças das condições hemodinâmicas capilares intra-cerebrais / Abstract: Introduction: Near-infrared spectroscopy (NIRS) is a low-cost, non-invasive technique that detects tissue hemodynamic alterations. It enables continuous monitoring of the intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used beside a bed or in the operating room. Objective: To evaluate the use of NIRS for intra-surgical monitoring of the brain hemodynamic response, during an endarterectomy procedure of the atherosclerotic carotid artery. Casuistry and Methods: 10 patients with atherosclerotic carotid disease and recommended endarterectomy were evaluated. They were identified in a survey which provided epidemiologic data and the presence of comorbidities. Disease was confirmed by diagnostic methods. NRIS monitoring was used during the surgical procedure. Oxygen saturation (O2 Sat), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb) were the variables analyzed at the three carotid clamp stages: pre-, trans- and post-. Results: A p<0.05 value was considered statistically significant. The results obtained from the NIRS data reveal that the surgical stages differ in relation to the RHb and O2Sat variables. RHb presents higher levels during clamping when compared with the other two surgical stages. On the other hand, O2Sat is decreased during clamping. Conclusion: NIRS is a feasible, realtime and non-invasive intracranial monitoring method, during carotid endarterectomy, which measures accurately and reliably the changes of the intracerebral capillary hemodynamic conditions / Mestrado / Cirurgia / Mestra em Ciências

Para investigar se estresse oxidativo contribui para a progressão da calcificação/estenose valvar aórtica (VA), avaliamos a produção de espécies reativas de oxigênio (ERO) e efeitos dos antioxidantes tempol e ác. lipóico em modelo de calcificação VA em coelhos. Superóxido, H2O2 e 3-nitrotirosina aumentaram em células inflamatórias e principalmente nos núcleos de calcificação, juntamente com as subunidades p22phox, Nox2 da NADPH oxidase e da proteína dissulfeto isomerase, que co-localizam. PCR mostrou aumento da Nox4 em relação a Nox1. A calcificação foi menor com ác.lipóico e maior com tempol, coicidindo com resultados de modelo in vitro em células musculares lisas. VA humanas estenóticas tiveram aumento semelhante de ERO e da expressão protéica em torno da calcificação. Estresse oxidativo pode contribuir para a progressão da estenose aórtica. / To invetigate whether oxidative stress contributes to aortic valve (AV) calcification/stenosis progression, we assessed reactive oxygen species (ROS) production and effects of antioxidants tempol and lipoic acid in a rabbit AV calcification model. Superoxide, H2O2 and 3-nitrotyrosine increased in inflammatory cells and mainly in calcifying nuclei, coincident with NADPH oxidase subunits p22phox, Nox2 and protein disulfide isomerase, which co-localized. PCR showed switch from Nox1 to Nox4. Calcification was smaller with lipoic acid and greater with tempol, similar to an in vitro smooth muscle cell calcification model results. Human stenotic AV had analogous increase in ROS and protein expression around calcifying nuclei. Oxidative stress can contribute to AV stenosis progression.

No description available.

Introduction: Temporary QT-interval prolongation following intracranial hemorrhage and hydrocephalus has been repeatedly reported in adults. Case: We report a case of excessive QT prolongation with sudden bradycardia resulting in 2:1 atrioventricular conduction in a preterm infant most likely associated with a congenital hydrocephalus. Pathomechanisms are discussed. Conclusion: Congenital hydrocephalus predisposes to excessive QT prolongation in preterm infants.

No description available.