A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial. / Arterial access is a major site of complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients decreasing hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using Angio-Seal for the incidence of arterial puncture site complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. This study is a unicentric, non-inferiority clinical trial where two hundred and forty patients with non-ST-segment elevation acute coronary syndrome were randomized to either radial or femoral access using Angio-Seal. The primary outcome was the occurrence of complications at the arterial puncture site until 30 days after the procedure, including major bleeding, hematoma >= 5 cm, retroperitoneal hematoma, compartment syndrome, pseudoaneurysm, arteriovenous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgery repair. With respect to demographic and clinical characteristics, there were differences only in terms of gender, with greater presence of female patients in the radial group (33.3% versus 20.0%, p = 0.020). There were no differences between the groups regarding the diagnosis of admission, ischemic changes present in the electrocardiogram, elevation of myocardial necrosis markers or risk scores, as well as the adjunct antithrombotic pharmacotherapy and features of the percutaneous coronary intervention. Hemostasis was achieved in the entire radial group with the use of selective radial compressor TR Band and in 95% of the procedures performed by femoral technique with Angio-Seal (p = 0.029). Except for a higher incidence of arterial occlusion in the radial group compared to the femoral, there were no differences among the other outcomes analyzed. According to the non-inferiority test for arterial access site complications in 30 days, it was found that the use of Angio-Seal not produced results inferior to the radial approach, considering the margin of 15% (12.5% vs. 13.3%, difference -0.83%, 95% CI -9.31 - 7.65, p for noninferiority <0.001). The main results of this study demonstrated that in a population of patients diagnosed with non-ST segment elevation acute coronary syndrome, who underwent invasive risk stratification, the use of the Angio-Seal vascular closure device confers to the femoral approach noninferiority in the incidence of arterial puncture site complications at 30 days when compared to the radial approach.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22346号 / 医博第4587号 / 新制||医||1042(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 森本 尚樹, 教授 福原 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Tesis para optar al grado de magíster en ciencias de la nutrición mención promoción de la salud y prevención de enfermedades crónicas no transmisibles / Introducción: La estimación de la estatura a partir del largo del fémur es relevante para distintos campos profesionales como ciencias forenses e identificación y salud pública. Problema: La población chilena pasa por un cambio secular pondo-estatural y las fórmulas utilizadas para estimar estatura desde largos óseos no se adecúan a la realidad actual. Asimismo es difícil acceder a largos óseos y/o muestras actuales esqueletizadas con estatura conocida y debidamente estimada. Objetivo Gral.: El objetivo de esta investigación fue desarrollar una nueva fórmula para estimar estatura a partir del largo del fémur en población chilena actual, utilizando imágenes DEXA (Absorciometría de Doble Energía Radiológica). Metodología: Estudio transversal y muestra de 176 individuos (95 hombres y 81 mujeres entre 16-18 años) provenientes de una cohorte estudiada por el Instituto de Nutrición y Tecnología de los Alimentos (INTA) y la Universidad de Michigan (Financiado por Proyecto NIH), cuya estatura es conocida y poseen imágenes DEXA de cuerpo entero. El largo del fémur se estimó mediante el método Linear Pixel Counter (LPC) a partir de imágenes DEXA (Lunar iDXA EnCORE 2011 Versión 13.60.033 Copyright © 1998-2010; Lunar DPX-LIQ; Lunar Corp., Madison, WI, USA). Variable dependiente: Estatura. Variable independiente: Largo máximo del fémur. Resultados: Nuevo modelo de regresión lineal simple para estimar estatura a partir del largo del fémur en población chilena actual. Conclusiones: La estatura estimada mediante la nueva fórmula no presenta diferencias significativas respecto de la estatura real del individuo (Suma de Rangos de Wilcoxon p>0,05). Las otras fórmulas tradicionalmente empleadas: Trottrer y Gleser (1958); Genovés (1967); Del Angel y Cisneros (2004); Ross y Manneschi (2011 y 2012) presentan al menos un sexo cuya estatura difiere significativamente de la estatura real del individuo (Suma de Rangos de Wilcoxon p<0,05).

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Discoveries made with KCl-induced contractions have elucidated the more complex reactions involved in GPCRs signaling; once the mechanisms of smooth muscle Ca2+ sensitization and desensitization are fully understood, then the development of advanced treatments for vascular disorders such as hypertension, cerebral and coronary vasospasm, and vascular hyporeactivity following hemorrhagic shock may be possible. Studies have shown that KCl-induced contractions induce Ca2+-sensitization. Therefore, we tested the hypothesis that KCl induced Ca2+-sensitization is due to ROK activation by the increase in [Ca2+]i. To test this hypothesis, rabbit femoral arteries were permeabilized with 20µg/ml α-toxin and 1% Triton X-100 and subjected to different calcium concentrations in the presence or absence of various ROK inhibitors. For a comparison we also used various PKC and MLCK inhibitors and repeated these experiments in intact tissues. We found that either [Ca2+]i alone does not directly activate ROK or the permeabilization technique itself disrupts the normal ROK signaling system. Secondary findings revealed that α-toxin activates PKC pathways; in both chemically permeabilized preparations proteases also appear to be activated and MLCK is the primary kinase responsible for contraction.

It is well known that the overlap between the thick and thin filaments in striated muscle is responsible for the single active length-tension (L-T) curve. With the lack of visible striations, a sarcomeric unit has not been identified in smooth muscle. Though once thought to function like striated muscle via a sliding filament mechanism of contraction, recent studies on length-adaptation (L-adaptation) in airway smooth muscle (ASM), in which increased tension is generated with repeated contraction, have led to the hypothesis of a dynamic L-T curve in smooth muscle. Although more established in ASM, two studies have shown L-adaptation in vascular smooth muscle (VSM). In this project, the L-T curve over a 3-fold length range in rabbit femoral artery was investigated and the presence of more than one active and passive L-T curve was identified. The third of three repeated KCL-induced contractions at a single, shortened length resulted in L-adaptation in which the phasic and tonic phases of contraction demonstrated a 10-15% increase in active tension (Ta) relative to the first contraction. Experiments investigating possible mechanism(s) responsible for this phenomenon demonstrated that neither an increase in [Ca2+]i nor an increase in MLC20 phosphorylation was responsible for the increased tension. However, actin polymerization did appear to play a role in the L-adaptation of both phases of contraction. Thus directions for future research could include further study of actin polymerization in VSM that contributes to L-adaptation and may ultimately result in artery remodeling.

Osteoarthritis (OA) is a chronic disease that affects the joints, most commonly hands, hips, knees, feet, and spine (Litwic et al. 2013). The disease becomes more common with advanced age and is one of the most prevalent causes of disability in older populations. Currently there is no cure besides total joint replacement surgery, and there will be approximately 4 million Americans living with a hip replacement by the end of the next decade (Maradit Kremers et al. 2015). Osteoarthritis was classically characterized as a disease of progressive articular cartilage degradation, but the degeneration involves all tissues of the synovial joint including the periarticular muscles, joint capsule, synovium, ligaments, and subchondral and metaphyseal bone. The cause of pain in OA is not well understood, but it is known that bone marrow lesions (BMLs) identified in subchondral bone by MRI are an important determinant of pain (Felson et al. 2001; Kumar et al. 2013). Abnormal blood vessel growth may be responsible MRI signature of BMLs, and the commonality between pathways for angiogenesis and neurogenesis suggests this pathologic process may be the source of pain in OA. The objective of this study was to characterize the histologic nature of subchondral cysts identified by micro computed tomography (μCT) which had been registered with MRI images in which marrow lesions were identified. Femoral heads were collected from 10 patients (6 females and 4 females; age 29-80) who underwent total hip arthroplasty. All patients had MRIs performed within 6 months prior to surgery. The heads were fixed and scanned with μCT to identify cysts in the subchondral bone. A block of the femoral head containing the cyst of interest was resected and processed for histologic analysis. The sections were stained with either Safranin-O and Fast Green or hematoxylin and eosin to view the nature and composition of the tissue. A two-dimensional image from the μCT that corresponded to the histologic slice was matched with a coronal view from the MRI. The primary compressive group was reliably identified on μCT images and served as good indicator for orienting the CT to match with the MRI. The subchondral cysts that were matched to MRI all consisted of predominantly fibrous bone marrow and frequently had a large number of blood vessels within the tissue. Three of the eight cysts had cartilage intrusions that were located mostly within peripheral trabecular bone, though one cyst contained a nodule of cartilage surrounded by organized fibers with the texture of granulation tissue. The process of image registration was mostly performed manually, but the development of this process will contribute to a more refined, semi-automated process in the future. The ability to correlate the histopathology of CT-identified lesions with a signature patter on MRI will be an important tool for better characterizing the nature of BMLs and understanding the pathogenesis of OA.

A resistência elástica é aplicada amplamente em programas de fortalecimento muscular nos processos de reabilitação física. No entanto, as conseqüências biomecânicas para o músculo exercitado com esta forma de sobrecarga são pouco estudadas. A ausência de fundamentação científica no que tange a aplicação da resistência elástica fez com que surgissem algumas suposições a respeito de sua caracterização biomecânica. Uma delas sugere que o exercício com resistência elástica pode ser caracterizado como sendo isocinético. Neste contexto, o objetivo global deste trabalho foi o de caracterizar o comportamento biomecânico do músculo quadríceps femoral frente ao exercício com resistência elástica. Tal caracterização foi realizada através da utilização de um modelo biomecânico bidimensional da articulação do joelho. O seu comportamento mioelétrico também foi avaliado. Conclui-se de uma forma geral, que o desenvolvimento deste estudo permitiu um entendimento a respeito da interação biomecânica entre o músculo e a resistência elástica durante o exercício. Permitindo dessa forma elucidar algumas questões ligadas a aplicação clínica desta modalidade de exercício / The elastic resistance is applied in programs of muscular fortification in processes of physical rehabilitation. However, the biomechanicals consequences for the muscle exercised with this resistance form aren’t very studied. The low scientific fundamentation for the application of the elastic resistance, results in some suppositions about its biomechanic characterization. One of them suggests that the exercise with elastic resistance can be characterized as isokinetic. In this context, the global objective of this work was characterizing the biomechanic behavior of the quadriceps muscle front to the exercise with elastic resistance. Such characterization was accomplished through the use of a bidimensional biomechanic model of the knee joint. The electromiographic behavior was also evaluated. In a general conclusion, the development of this study allowed an understanding of the biomechanic interaction between the muscle and the elastic resistance during the exercise. Allowing to elucidate some subjects of the clinical application of this exercise modality

O presente estudo objetivou comparar biomecanicamente, por meio do ensaio de compressão excêntrica, a resistência dos implantes Clamp and Rod Internal Fixation (CRIF) 5,0 mm versus placa de reconstrução 3,5 mm na fixação de fratura distais de fêmur de cão. Tais implantes foram subdividos em dois grupos, denominados grupo CRIF (GC) e grupo placa (GC). Foram utilizados 22 fêmures de 10 cadáveres de cão entre 2 e 7 anos de idade e peso corporal entre 20 e 40 kg, que foram distribuídos aleatoriamente a serem testados ambos os implantes em cada um dos membros dos pares. Para realização dos testes, foi simulado uma fratura distal nos corpos de prova, através de uma osteotomia de até 0,5 cm, realizada por meio de serra oscilatória, imediatamente proximal ao início da tróclea. Os implantes foram fixados segundo os padrões AOSIF, lateralmente ao fêmur, sendo utilizados três parafusos distais e cinco proximais ao foco de fratura. Foi utilizado o programa de computador PMI para calcular o ponto máximo de resistência antes da falha e avaliadas as variáveis força máxima, deformação máxima real, rigidez, força intermediária e deformação intermediária real. Não foram encontradas diferenças estatisticamente significativas entre os GC e GP quantos as variáveis avaliadas / This study aims to compare the biomechanical properties, through eccentric compression test, of the resistance of the 5.0 mm Clamp and Rod Internal Fixation Implants (CRIF) and 3.5 mm reconstruction plate in fixing dog femur distal fracture. Such implants were subdivided into two groups, called CRIF Group (CG) and plate group (CG). It was used 22 femurs from 11 dog cadavers with age between 2 and 7 years old and body weight between 20 and 40 kg, which was randomly assigned to test both implants in each member of the pair. A distal fracture in the specimens with a gap of 0.5 cm osteotomy, it was simulated to perform the test, performed by the oscillating saw, just proximal to the beginning of the trochlea. Bound the distance from the gap to the distal femur limit was equivalent to the distance between the femoral condyles. The implants were fixed by the standards AO / SIF, laterally to the femur, being used three distal screws and five proximal to the fracture site. The bone was placed longitudinally, and the femoral neck coupled to a concave surface simulating an acetabular device. PMI computer program was used to calculate the maximum point of resistance before failure and evaluated the variables maximum strength, real maximum deformation, stiffness, intermediate strength and real intermediate deformation. No statistically significant differences were found between the GC and GP as the variables evaluated