Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22695号 / 医博第4639号 / 新制||医||1045(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 髙橋 良輔, 教授 Shohab YOUSSEFIAN, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Made available in DSpace on 2016-01-26T12:51:52Z (GMT). No. of bitstreams: 1 salomonrajas_tese.pdf: 1978465 bytes, checksum: ca15f774abde6ac24567685d49084f3a (MD5) Previous issue date: 2003-05-29 / Introduction: The surgical treatment of the aneurysm of descending thoracic and thoracoabdominal aorta are related with risk of spinal cord ischemic, as well as, coagulation and renal function disorders. Among the spinal cord protection methods, there are liquor drainage, temporary bypass, intercostal arteries implant, deep hypothermia, selective cooling of spinal cord and drugs. Objective: The goal of this paper is to show the viability of using extracorporeal circulation from left atrium to ascending aorta with deep hypotermia for surgical treatment of the thoracic and thoracoabdominal aneurysms. Material and Methods: From January 1994 to July 2001, thirty eight patients were operated, 26 male with mean age of 54.6±12.7. Twelve patients (31.6%) were submitted to correction of thoracoabdominal aneurysm and twenty six to correction of descending aorta aneurysm. The etiologies were: post-trauma in one patient, dilatation after correction of coarctation of the aorta in four patients, syphilitic aortite in two , atherosclerotic in ten patients and aortic dissection in twenty one patients. After extracorporeal circulation installed, the patients were cooled, the faryngeal temperature ranged from 15° and 25°C (20.6±3.2°C). The total circulatory arrest time from nine to thirty six minutes (21.3±6.7). The aortic diameter ranged from 4 to 10.5 cm (8.1±1.5 cm). Results: As neurological complications, paraplegia ocurred in two cases (5.3%) and in one of them there was stroke associated. One patient had paraparesis in inferior members and one, had seizure. The respiratory complications ocurred in twelve (31.6%) patients and tracheostomy was necessary in two cases por delayed ventilaroty support. Two patients from this group (16.7%) died. Two patients had transitory elevation of creatinine but dialysis was not necessary. Emergency operation was performed in two cases and both died. The overall mortality was seven patients (18.4%) and the causes were: bleeding in one patient, respiratory insufficiency in two patients, sudden death in two, heart failure in one and failure of weaning from extracorporeal circulation. Conclusion: Surgical correction of descending thoracic aorta and thoracoabdominal aneurysms during deep hypothermia using extracorporeal circulation with cannulation of left atrium and ascending aorta is a safe method, with low mortality. The complications such as neurologic, respiratory and renal were according to the literature. / O tratamento cirúrgico dos aneurismas da aorta torácica descendente e toracoabdominal estão associados com risco de isquemia medular, como também, a distúrbios de coagulação e alterações da função renal. Dentre os métodos de proteção medular estão, a drenagem do líquido cefalorraquidiano, o bypass temporário, o reimplante das artérias intercostais, a hipotermia profunda, o esfriamento seletivo da medula espinhal e o uso de agentes farmacológicos. Objetivo: O objetivo deste trabalho é demonstrar a viabilidade do uso da circulação extracorpórea (CEC) estabelecida entre o átrio esquerdo e aorta ascendente para indução da hipotermia profunda na correção dos aneurismas torácicos e/ou toracoabdominais. Casuística e Método: No período de janeiro de 1994 a julho de 2001, foram operados 38 pacientes, sendo 26 do sexo masculino, com média de idade 54,6±12,7 anos. Doze pacientes (31,6%) foram submetidos a correção de aneurisma toracoabdominal e 26, a aneurismas torácicos descendentes. O diagnóstico etiológico foi pós-trauma em um paciente; pós-coarctação da aorta (corrigida ou não) em quatro; aortite sifilítica em dois; aterosclerótico, dez pacientes e dissecção de aorta em 21 pacientes. Os pacientes foram induzidos a hipotermia profunda por meio de CEC, com temperatura faríngea variando entre 15 e 25°C (20,6±3,2°C). O tempo de parada circulatória variou de nove a trinta e seis minutos (21,3±6,1 minutos). O diâmetro da aorta dos pacientes variou de quatro a 10,5 cm (8,1±1,5 cm). Resultados: Dentre as complicações neurológicas, a paraplegia ocorreu em dois casos (5,3%), sendo que em um paciente houve quadro associado de acidente vascular cerebral. Um paciente evoluiu com paraparesia de membros inferiores e um, com quadro de convulsão. As complicações respiratórias estiveram presentes em 12 pacientes (31,6%), sendo que dois (5,3%) necessitaram de traqueostomia por necessidade de ventilação mecânica por tempo prolongado, com mortalidade de 16,7% (dois pacientes). Dois pacientes apresentaram elevação transitória nos níveis de creatinina, sem indicação de diálise. Dois pacientes foram operados em caráter de urgência, evoluindo para óbito. A mortalidade total da casuística foi de sete pacientes (18,4%), sendo um por sangramento, dois por complicações respiratórias, dois por morte súbita, um por insuficiência cardíaca e um por dificuldade de saída de CEC. Conclusão: A correção dos aneurismas da aorta torácica descendente e toracoabdominal com o emprego da hipotermia profunda de indução interna pela circulação extracorpórea estabelecida entre o átrio esquerdo e a aorta ascendente, demonstrou ser um método viável para o tratamento cirúrgico dos aneurismas torácicos e toracoabdominais apresentando: mortalidade, complicações neurológicas, renais e respiratórias compatíveis com os achados da literatura da época.

Introdução: O acesso pterional é uma das craniotomias mais utilizadas. Entretanto, apresenta algumas desvantagens, como a dissecação ampla do músculo temporal, que pode causar atrofia e deformidade do contorno facial. A craniotomia minipterional descrita em 2007 propiciou exposição anatômica semelhante a da craniotomia pterional clássica. Objetivos: Comparar os resultados clínicos, funcionais e estéticos dos dois acessos cirúrgicos destinados ao tratamento de aneurismas da circulação anterior. Métodos: Cinquenta e oito doentes, com aneurismas rotos (40) e não rotos (18) foram admitidos no estudo. No grupo A, 28 indivíduos foram submetidos à craniotomia minipterional. No grupo B, 30 doentes foram operados com a craniotomia pterional clássica. Doentes com hematomas intracranianos, aneurismas do segmento oftálmico e aneurismas gigantes foram excluídos. Os resultados estéticos foram analisados por meio de dois métodos. No primeiro, uma autoavaliação utilizava uma régua escalonada de 0 a 100, na qual o zero representou o melhor resultado e 100 o pior resultado na percepção do próprio doente. Fotografias dos doentes foram mostradas a dois observadores independentes. Os resultados foram classificados como ótimo, bom, regular e mau (de acordo com uma escala pré-determinada). A gradação da atrofia foi mensurada por meio de três métodos, utilizando a tomografia computadorizada de crânio. No primeiro, observou-se a percentagem de redução do complexo músculo temporal, tecido subcutâneo e pele. No segundo método, a percentagem de redução da espessura do músculo temporal foi analisada isoladamente. O terceiro método foi a mensuração da volumetria do músculo temporal, tecido subcutâneo e pele calculados a partir da margem superior do arco zigomático até a linha temporal superior utilizando-se o software OsiriX (Pixmeo Sarl Geneva/ Suíça OsiriX). Para os resultados clínicos e funcionais, foi utilizada a Escala de Rankin modificada. Outras variáveis, como paralisia do ramo frontal do nervo facial, hemorragia pós-operatória, fistula liquórica, hidrocefalia e mortalidade, também foram analisadas. Resultados: Em ambos os grupos, os dados demográficos e as características pré-operatórias foram similares. A satisfação com o resultado estético foi observada em 79% (19) no grupo A e 52% (13) no grupo B (p=0,07). O valor médio da régua foi 27 no grupo A e 45,8 no grupo B (p=0,03). Quando somente doentes classificados como Rankin modificado 0 ou 1 foram analisados, o valor médio da régua foi de 25,2 no grupo A e 39,4 no grupo B (p=0,11). Dois avaliadores independentes analisaram as fotografias dos doentes e o coeficiente de correlação kappa para os resultados estéticos foi de 0,73. De acordo com os mesmos ótimo e bom, foram observados em 87% (21) no grupo minipterional e 48% (12) no grupo pterional. A percentagem de redução do músculo temporal, subcutâneo e pele (método 1) foi de 14,9% no grupo A e 24,3% no grupo B (p=0,01). Quando somente o músculo temporal foi analisado (método 2), a percentagem de redução foi de 12,7% no grupo A e 22% no grupo B (p=0,005). A redução volumétrica das estruturas (método 3) foi de 14,8% no grupo A e 24,5% no grupo B (p=0,012). Na avaliação clínica no 6? mês, os valores da Escala de Rankin modificada foram similares (p=0,99). O óbito ocorreu em 4 doentes no grupo A e 5 doentes no grupo B (p=1,0). Conclusão: Os resultados clínicos demonstraram que a craniotomia minipterional é um procedimento seguro, com prognóstico similar ao da técnica convencional. Os resultados cosméticos foram melhores com menor deformidade no contorno facial, uma vez que a percentagem de redução da espessura, do volume do músculo temporal, do tecido subcutâneo e da pele foi menor com a técnica proposta. A craniotomia minipterional foi a melhor alternativa em relação à craniotomia pterional clássica para tratar aneurismas rotos e não rotos da circulação anterior / Introduction: The pterional approach is one of the most commonly used craniotomy. However it has disadvantages, such as complete dissection of the temporalis muscle. This may lead to muscular atrophy and facial deformity. The minipterional craniotomy was described in 2007 and the anatomic exposure provided by the pterional and minipterional approaches were similar in the total area of exposure and angular view. Objectives: This prospective randomized study was designed to compare the clinical, functional and aesthetic results of two surgical techniques for microsurgical clipping of anterior circulation aneurysms. Methods: Overall, 58 eligible patients admitted with ruptured and unruptured anterior circulation aneurysms were enrolled in the study. In group A, 28 patients were operated with the minipterional technique. In Group B 30 patients were operated according to the classical pterional craniotomy. Patients with intracranial haematomas, ophthalmic aneurysms and giant aneurysms were excluded. The aesthetic results were analyzed with 2 methods. In the first, the patients were showed to a rule, with a scale from 0 to 100, in which 0 mean the best result and 100 the worst result. Photos were taken and showed to two independent observers, the results were classified as excellent, good, regular or poor, according to a pre-determined scale. The degree of atrophy was measured with three methods. In the first one, the authors observed the percentage of thick reduction in the temporal muscle, subcutaneous tissue and skin. In the second method the percentage of thick reduction of the isolated temporal muscle was observed and the third the volumetric analysis of the temporal muscle, subcutaneous tissue and skin was calculated from the superior edge of zygomatic arch to superior temporal line using the OsiriX software (OsiriX - Pixmeo Sarl Geneva/Suíça). The functional results were compared using the Modified Rankin Score. Others variables such frontal facial palsy, post-operative hemorrhage, cerebrospinal fistulas, hydrocephalus and mortality were also analyzed. Results: In both groups the demographic and pre-operative characteristics were similar. The satisfaction with aesthetic results were observed in 79% (19) in group A and 52% (13) in group B (p=0,07). The mean value observed in the rule was 27 in group A and 45,8 in group B (p=0,03). When patients classified as Rankin Modified Score of 0 or 1 only were included the mean value observed in the rule was 25,2 in group A and 39,4 in group B (p=0,11). Two independent observers analyzed the patients photos and the kappa coefficient correlation for the aesthetic results was 0,73. According to them excellent and good results were observed in 87% (21) in minipterional group and 48% (12) in the pterional group. The degree of atrophy of temporal muscle, subcutaneous tissue and skin (method 1) was14,9% in group A and 24,3% in group B (p=0,01). The measurement of temporal muscle (method 2) revealed that the degree of atrophy was 12,7% in group A and 22% in group B (p=0,005). The volumetric reduction of the structures (method 3) was 14,8% in group A and 24,5% in group B (p=0,012). Rankin Modified Score was similar in both groups in the 6-month evaluation (p=0,99). Mortality occurred in 4 patients in group A and 5 patients in group B (p=1,0). Conclusion: These clinical results indicate that the minipterional is a safe procedure. We can estimate the better cosmetic results with less facial contour deformity since the percentage of thick and volumetric reduction in temporal muscle, subcutaneous tissue and skin were demonstrated. It can be an excellent and better alternative to the classical pterional approach

Cerebral aneurysm formation, growth, and rupture are active areas of investigation in the medical community. To model and test the mechanical processes involved, small aneurysm (< 5 mm) segmentations need to be performed quickly and reliably for large patient populations. In the absence of robust automatic segmentation methods, the Vascular Modeling Toolkit (VMTK) provides scripts for the complex tasks involved in computer-assisted segmentation. Though these tools give researchers a great amount of flexibility, they also make reproduction of results between investigators difficult and unreliable. We introduce a VMTK pipeline protocol that minimizes the user interaction for vessel and aneurysm segmentation and a training method for new users. This protocol allows for decision tree handling for CTA and MRA images. Furthermore, we investigate the variation between two expert users and two novice users for six patients using shape index measures developed by Ma et al. and Raghavan et al.

This thesis focuses on special arterial fluid mechanics techniques developed for patient-specific computer modeling of blood flow in cerebral arteries with aneurysm and stent. These techniques are used in conjunction with the core computational technique, which is the space–time version of the variational multiscale (VMS) method and is called “DST/SST-VMST.” The special techniques include using NURBS for the spatial representation of the surface over which the stent mesh is built, mesh generation techniques for both the finite- and zero-thickness representations of the stent, techniques for generating refined layers of mesh near the arterial and stent surfaces, and models for representing double stent. We compute the unsteady flow patterns in the aneurysm and investigate how those patterns are influenced by the presence of single and double stents. We also compare the flow patterns obtained with the finite- and zero-thickness representations of the stent.

Motivated by the need to design minimally-invasive treatments for wide-necked cerebral aneurysms, we used computational modeling to assess aneurysm hemodynamics, examined in vitro cellular responses arising from mechanical and chemical stresses, and designed novel materials that cooperatively adhere to the endothelium. We first hypothesized that because aneurysm geometry plays an important role in hemodynamics, changes in flow patterns may affect the shear stress experienced on the aneurysm wall. We defined flow regimes based on aneurysm hemodynamic and geometric parameters, which may correlate with aneurysm rupture. Because of the direct contact between endothelial cells (ECs) and blood flow, we then evaluated how changes in hemodynamics and inflammatory cytokines affect the expression of cell adhesion molecules (CAMs) and matrix remodeling factors on ECs. We subsequently designed biomaterials that complement the dynamic EC surface and have the ability to conform to any geometry through in situ crosslinking. Antibody-conjugated hydrogels facilitated synergistic EC adhesion using cooperativity as an adhesion strategy. We optimized the presentation of antibodies to inflammatory CAMs on polyvinyl alcohol (PVA) and alginate hydrogels to achieve strong adhesion to inflamed ECs. We synthesized photocrosslinkable, aminated PVA hydrogels and determined the effect of substrate stiffness on cell adhesion. We also evaluated the effects of antibody presentation on cell adhesion strength and dynamics using alginate hydrogels. Taken together, the results of this work may be used to design hydrogels for vascular remodeling applications under shear stress, including embolic agents for cerebral aneurysms. / Engineering and Applied Sciences

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a mouse model of adipocyte AT1aR deficiency using the Cre/LoxP system. Adipocyte-AT1aR deficiency confers no protection from the development of obesity or obesity- associated parameters. However, low fat fed adipocyte-AT1aR deficient mice exhibit remarkable adipocyte hypertrophy and reductions in adipocyte differentiation. These results demonstrate that AngII is a stimulus for adipocyte differentiation and adipocyte hypertrophy alone is insufficient to initiate obesity- associated disorders. In hypercholesterolemic mice, adipocyte AT1aR deficiency conferred no protection from diet or AngII-induced vascular diseases. Overall these studies suggest the primary role of adipocyte AT1aRs is to promote adipocyte differentiation and the development of small adipocytes.