In this thesis, a parallel solver was developed for the modelling of blood flow through a number of patient-specific geometries. A locally conservative Galerkin (LCG) spatial discretisation was applied along with an artificial compressibility and characteristic based split (CBS) scheme to solve the 3D incompressible Navier-Stokes equations. The Spalart-Allmaras one equation turbulence model was also optionally employed. The solver was constructed using FORTRAN and the Message Passing Interface (MPI). Parallel testing demonstrated linear or better than linear speedup on hybrid patient-specific meshes. These meshes were unstructured with structured boundary layers. From the parallel testing it is clear that the significance of inter-processor communication is negligible in a three dimensional case. Preliminary tests on a short patient-specific carotid geometry demonstrated the need for ten or more boundary layer meshes in order to sufficiently resolve the peak wall shear stress (WSS) along with the peak time-averaged WSS. A time sensitivity study was also undertaken along with the assessment of the order of the real time step term. Three backward difference formulae (BDF) were tested and no significant difference between them was detected. Significant speedup was possible as the order of time discretisation increased however, making the choice of BDF important in producing a timely solution. Followed by the preliminary investigation, four more carotid geometries were investigated in detail. A total of six haemodynamic wall parameters have been brought together to analyse the regions of possible atherogenesis within each carotid. The investigations revealed that geometry plays an overriding influence on the wall parameter distribution. Each carotid artery displayed high time-averaged WSS at the apex, although the value increased significantly with a proximal stenosis. Two out of four meshes contained a region of low time-averaged WSS distal to the flow divider and within the largest connecting artery (internal or external carotid artery), indicating a potential region of atherosclerosis plaque formation. The remaining two meshes already had a stenosis in the corresponding region. This is in excellent agreement with other established works. From the investigations, it is apparent that a classification system of stenosis severity may be possible with potential application as a clinical diagnosis aid. Finally, the flow within a thoracic aortic aneurysm was investigated in order to assess the influence of a proximal folded neck. The folded neck had a significant effect on the wall shear stress, increasing by up to 250% over an artificially smoothed neck. High wall shear stresses may be linked to aneurysm rupture. Being proximal to the aneurysm, this indicated that local geometry should be taken into account when assessing the rupture potential of an aneurysm.

Abstract Different metabolic and environmental factors affect the blood pressure level, constituting a cluster, especially in hypertensives, that leads to an increased risk of cardiovascular diseases. The present research was designed to determine the prevalence and the predictors of the metabolic syndrome and the role of insulin and blood pressure in carotid atherosclerosis in 600 treated male and female hypertensives aged 40-59 years and 600 age- and sex-matched controls. The prevalence of the metabolic syndrome in different population-based cohorts varied, depending on the definition, from 0.8% to 35.3%, being lowest in control men and women and highest in hypertensive men. 73.8% of a random, middle-aged, urban population showed at least one cardiovascular risk factor, and 91.3% of all hypertensive subjects showed at least one cardiovascular risk factor in addition to hypertension itself. The independent predictors of the metabolic syndrome were waist circumference, uric acid, total cholesterol and gamma-glutamyl transpeptidase. Hypertension had a significant effect on carotid intima-media thickness and the prevalence of plaques in men, but its effect in women was not significant. A long duration of hypertension resulted in greater intima-media thickness and a higher prevalence of plaques, particularly in men. There were significant associations between gamma-glutamyl transpeptidase and the components of the metabolic syndrome after adjustment for alcohol consumption and also in teetotallers. There were inconsistent associations between the different insulin measures and the intima-media thickness as a measure of carotid atherosclerosis. The exclusion of diabetic subjects did not change the results. In conclusion, a cluster of metabolic abnormalities related to hypertension is frequent among both controls and treated hypertensive subjects. Hypertensive subjects have higher prevalences of carbohydrate and lipoprotein aberrations and structural and functional cardiovascular complications than age- and sex-matched controls.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23607号 / 医博第4794号 / 新制||医||1055(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 溝脇 尚志, 教授 木村 剛, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20621号 / 医博第4270号 / 新制||医||1023(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 山下 潤, 教授 木村 剛, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Blunt carotid artery injury (BCAI), resulting primarily from automobile accidents, is a major contributor to the high mortality and morbidity rates associated with carotid artery dissection. More work is needed to characterize carotid artery injury mechanisms, quantify stages of damage, and elucidate failure modalities as a result of this type of injury. The present study examines the structure and mechanics of the carotid artery in the circumferential and axial directions by employing uniaxial tensile testing, high speed videography, interruption testing, scanning electron microscopy (SEM), histological analysis, real-time environmental SEM assessment, and atomic force microscopy (AFM). Results are as follows: (i) the carotid artery exhibits anisotropic, viscoelastic behavior; (ii) intimal failure precedes ultimate tissue failure, and the layers in order of increasing strength are intima, adventitia, and media; (iii) tissue damage accumulates as strain level increases, and failure occurs as a result of void nucleation, void growth, and void coalescence.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13584号 / 論医博第2304号 / 新制||医||1070(附属図書館) / (主査)教授 江木 盛時, 教授 湊谷 謙司, 教授 江藤 浩之 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

<p>UVOD: Vilisov poligon predstavlja najznačajniju rezervu kolateralnog protoka između ekstrakranijalnih arterija koje vaskularizuju mozak i ima sposobnost razvoja kolateranih puteva kod ekstrakranijalne karotidne bolesti. Ova anatomska struktura podložna je varijacijama koje uključuju i prekid kontinuiteta i nekompletnost kolateralizacije. CILJEVI: Cilj je bio da se utvrdi da li nekompletnost Vilisovog poligona utiče na če&scaron;će pojavljivanje neurolo&scaron;ke simptomatologije i ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Takođe cilj je bio i da se utvrdi da li cerebrovaskularna reaktivnost kod pacijenata sa asimptomatskom ekstrakranijalnom karotidnom bolesti zavisi od kompletosti Vilisovog poligona i na koji način hirur&scaron;ki tretman utiče na parametre cerebrovaskularne rezerve kod pacijenata sa kompletnim i nekompletnim Vilisovim poligonom. METOD: U retrospektivnoj studiji analiziran je nalaz MRA kod 211 pacijenata sa ekstrakranijalnom karotidnom bolesti i 102 pacijenta iz kontrolne grupe. U prospektivnoj studiji je kod 98 pacijenata sa asimptomatskom karotidnom bolesti pored MRA nalaza određivana cerebrovaskularna reaktivnost putem određivanja &bdquo;breath hold index&ldquo;-a (BHI) pre i nakon operativnog tretmana. REZULTATI: Nekompletan Vilisov poligon nađen je kod 25% asimptomatskih, 47,5% simptomatskih pacijenata sa karotidnom bolesti i kod 59% kontrolne grupe pacijenata, pri čemu su se razlike pokazale kao statistički značajne. Kod asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom BHI preoperativno iznostio je 0,62 a postoperativno 1,01 na strani lezije. U slučaju nekompletnog Vilisovog poligona preoperativna vrednost BHI iznostila je 0,88 a postoperativna 1,09 na strani lezije. Razlike su se pokazale kao statistički značajne između grupa i pre i posle operativnog tretmana. Porast je bio statistički značajno izraženiji u grupi asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom. Nisu zabeležene major operativne komplikacije (perioeprativni moždani udar,smrtni ishod) a na pojavu hiperperfuzionog sindroma najvi&scaron;e su uticali kompletnost Vilisovog poligona, vrednost BHI i preoperativni tretman hipertenzije. ZAKLJUČCI: Nekompletan Vilisov poligon predstavlja faktor rizika za pojavu neurolo&scaron;ke simptomatologije ili ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Kod asimptomatskih pacijenata nekompletan Vilisov pologon utiče na smanjenu cerebrovaskularnu reaktivnost i veći rizik od moždanog udara. Parametri cerebrovaskularne reaktivnosti signifikantno se pobolj&scaron;avaju nakon operativnog tretmana.</p> / <p>INTRODUCTION: Circle of Willis is the most important reserve of collateral flow between the extracranial arteries that supply the brain and has the ability to develop collateral pathways in extracranial carotid disease. This anatomical structure is subject to variations which include a disruption in the continuity and incompleteness of collateralisation. OBJECTIVES: was to determine whether the incompleteness of the Circle of Willis is more often associated with neurological symptoms and ishemic cerebral lesions in patients with extracranial carotid artery disease. Also, the objective was to determine whether cerebrovascular reactivity in patients with asymptomatic extracranial carotid artery disease depends on the completeness Circle of Willis and how surgical treatment affects the parameters of cerebrovascular reserve in patients with complete and incomplete Circle of Willis. METHODS: This study analyzed the findings of MRA in 211 patients with extracranial carotid artery disease and 102 patients in the control group. In prospective study in 98 patients with asymptomatic carotid artery disease in addition to the MRA findings cerebrovascular reactivity was determined by determining the &quot;breath hold index&quot; -a (BHI) before and after surgical treatment. RESULTS: Incomplete Circle of Willis was found in 25% of asymptomatic, 47.5% of symptomatic patients with carotid artery disease, and 59% of the control group patients, where the difference proved to be statistically significant. In asymptomatic patients with incomplete Circle of Willis BHI values were 0.62 preoperatively and 1.01 postoperatively on the side of the lesion. In the case of incomplete Circle of Willis preoperative BHI values were 0.88 preopertively and 1.09 postoperatively in asymptomatic patients. The differences are shown to be statistically significant between the groups before and after surgical treatment. The increase was significantly more pronounced in the group of asymptomatic patients with incomplete Circle of Willis. There were not recorded major operative complications (perioeprativni stroke, mortality) and the occurrence hyperperfusion syndrome was most affected by completeness of the Circle of Willis, a value BHI and preoperative treatment of hypertension. CONCLUSIONS: Incomplete Circle of Willis is a risk factor for the occurrence of neurological symptoms or ischemic brain lesions in patients with extracranial carotid artery disease. In asymptomatic patients incomplete Circle of Willis affects the reduced cerebrovascular reactivity and a higher risk of stroke. The parameters of cerebrovascular reactivity significantly improved after surgical treatment.</p>

INTRODUÇÃO: A estenose carotídea de origem aterosclerótica é um importante marcador de aterosclerose sistêmica avançada. A oclusão (obstrução completa da artéria) é rara e corresponde ao evento morfológico final da progressão da placa de ateroma na bifurcação carotídea. Muitos pacientes são sintomáticos no momento do diagnóstico e apresentam novos sintomas neurológicos na evolução apesar de tratamento clínico adequado. A literatura médica é escassa em determinar os principais fatores que podem levar a oclusão carotídea. A participação e intensidade das comorbidades e/ou fatores de risco, associados a dados demográficos peculiares foram pouco explorados. OBJETIVOS: Caracterizar o paciente com oclusão carotídea (OC) quanto a aspectos demográficos, doenças associadas e fatores de risco; detectar novos eventos neurológicos, cardiovasculares e óbitos no seguimento clínico destes pacientes. MÉTODO: Informações demográficas, clinicas e evolutivas de pacientes com oclusão carotídea e estenose carotídea não significativa foram recuperadas de um banco de dados compÍetado prospectivamente e complementadas com prontuário hospitalar e novos dados obtidos via convocação e/ou entrevista telefônica. RESULTADOS: No período de janeiro de 2005 a janeiro de 2013 foram analisados 213 pacientes portadores de OC e 172 portadores de estenose hemodinamicamente não significativa (ENS), ou abaixo de 50%. Foram analisados 4 dados demográficos e 9 fatores de risco, bem como sintomas neurológicos na apresentação e na evolução. No grupo OC predominaram indivíduos do sexo masculino, hipertensos, tabagistas, portadores de doença arterial obstrutiva periférica (DAOP), insuficiência renal crônica (IRC) com significância estatística em relação ao grupo ENS (p < 0,05).\\.Entre os pacientes com OC, 76,1% apresentaram sintomas neurológicos inicialmente contra 35,5% do grupo ENS (p = 0,000001). Quanto à evolução, os pacientes com OC apresentaram progressão significativa da estenose carotídea contralateral, quando comparada com a progressão da estenose nas carótidas do grupo ENS. (15,0% e 2,3%, p = 0,00011). O aparecimento de novos sintomas foi determinado pelo estado clínico de apresentação dos pacientes: 10,8% de novos sintomas nos inicialmente sintomáticos e 4,3% nos assintomáticos (p = 0,0218). Constatou-se maior número de óbitos na amostra OC (14,1%) do que na ENS (6,4%) com diferença significativa (p = 0,0150). CONCLUSÕES: OS pacientes portadores de OC apresentam maior prevalência de fatores de risco e comorbidades e maior mortalidade que o grupo ENS. No seguimento, os pacientes que se apresentavam sintomas neurológicos no momento do diagnóstico foram aqueles que mais desenvolveram novos eventos neurológicos. Este estudo representa um esforço em identificar uma amostra da população com estenose carotídea que pode necessitar de diagnóstico precoce e intervenção clínica vigorosa na prevenção de novos eventos e/ou óbitos / INTRODUCTION: Carotid stenosis is an important marker of severe systemic atherosclerosis. Internal Carotid occlusion (ICO) is rare and represents the final event when it comes to atherosclerotic plaque progression at the carotid bifurcation. Many patients are symptomatic when diagnosed with this condition and some of them will present more neurologic symptoms despite proper clinical management. So far only few studies have investigated if more comorbidities andjor risk factors, associated to demographic characteristics can lead to ICO. OBJETIVES: To identify the patient with ICO as regard to his demographic data, associated diseases and risk factors. Primary end-points were new neurologic events, cardiovascular symptoms and deaths during follow-up. METHOD: A prospective database was completed with demographic data and clinical information from patients with ICO and from a control group of patients with a non-significant stenosis (NSS), ar below 50%. Information was collected retrospectively from clínical records and missing data were completed with a medical appointment or teJephone interview. RESULTS: From [anuary 2005 to [anuary 2013, 213 patients with ICO and 172 patients with NSS were studied. Demographic data, risk factors for atherosclerosis and neurological symptoms at diagnosis and during follow-up were verified. Among patients with [CO there were more men and those with history of smoking, and more patients presenting with peripheral arterial disease (PAD) and chronic renal failure (CRF) than those in the NSS group (p < 0,05). At the time of diagnosis 76.1% of patients with ICO were symptomatic, while 35.5% in the NSS group (p=0.000001). Patients in the ICO group presented significant progression of the contralateral stenosis when compared to progression on any side in the control grouP\'\"(15.0% versus 2.3%, p = 0.00011). New symptoms were determined by the patient\'s clinical status. As regard to new neurological symptoms during follow-up, 10.8% of those initially symptomatic (both groups combined), presented new symptoms, opposed to 4.3% of those initially asymptomatic (p=0.0218). Number of deaths was significantly higher among patients in the ICO group (14.1% versus 6.4%, p=0.0150). CONCLUSIONS: Patients presenting with ICO have more risk factors and higher mortality by any cause. Those initially symptomatic will likely present more neurological symptoms during follow up. This study aims to identify those who are more at risk before the occlusion and could benefit of earJy diagnosis and vigorous c1inical intervention before new neurological events andjor death

INTRODUÇÃO: A estenose carotídea de origem aterosclerótica é um importante marcador de aterosclerose sistêmica avançada. A oclusão (obstrução completa da artéria) é rara e corresponde ao evento morfológico final da progressão da placa de ateroma na bifurcação carotídea. Muitos pacientes são sintomáticos no momento do diagnóstico e apresentam novos sintomas neurológicos na evolução apesar de tratamento clínico adequado. A literatura médica é escassa em determinar os principais fatores que podem levar a oclusão carotídea. A participação e intensidade das comorbidades e/ou fatores de risco, associados a dados demográficos peculiares foram pouco explorados. OBJETIVOS: Caracterizar o paciente com oclusão carotídea (OC) quanto a aspectos demográficos, doenças associadas e fatores de risco; detectar novos eventos neurológicos, cardiovasculares e óbitos no seguimento clínico destes pacientes. MÉTODO: Informações demográficas, clinicas e evolutivas de pacientes com oclusão carotídea e estenose carotídea não significativa foram recuperadas de um banco de dados compÍetado prospectivamente e complementadas com prontuário hospitalar e novos dados obtidos via convocação e/ou entrevista telefônica. RESULTADOS: No período de janeiro de 2005 a janeiro de 2013 foram analisados 213 pacientes portadores de OC e 172 portadores de estenose hemodinamicamente não significativa (ENS), ou abaixo de 50%. Foram analisados 4 dados demográficos e 9 fatores de risco, bem como sintomas neurológicos na apresentação e na evolução. No grupo OC predominaram indivíduos do sexo masculino, hipertensos, tabagistas, portadores de doença arterial obstrutiva periférica (DAOP), insuficiência renal crônica (IRC) com significância estatística em relação ao grupo ENS (p < 0,05).\\.Entre os pacientes com OC, 76,1% apresentaram sintomas neurológicos inicialmente contra 35,5% do grupo ENS (p = 0,000001). Quanto à evolução, os pacientes com OC apresentaram progressão significativa da estenose carotídea contralateral, quando comparada com a progressão da estenose nas carótidas do grupo ENS. (15,0% e 2,3%, p = 0,00011). O aparecimento de novos sintomas foi determinado pelo estado clínico de apresentação dos pacientes: 10,8% de novos sintomas nos inicialmente sintomáticos e 4,3% nos assintomáticos (p = 0,0218). Constatou-se maior número de óbitos na amostra OC (14,1%) do que na ENS (6,4%) com diferença significativa (p = 0,0150). CONCLUSÕES: OS pacientes portadores de OC apresentam maior prevalência de fatores de risco e comorbidades e maior mortalidade que o grupo ENS. No seguimento, os pacientes que se apresentavam sintomas neurológicos no momento do diagnóstico foram aqueles que mais desenvolveram novos eventos neurológicos. Este estudo representa um esforço em identificar uma amostra da população com estenose carotídea que pode necessitar de diagnóstico precoce e intervenção clínica vigorosa na prevenção de novos eventos e/ou óbitos / INTRODUCTION: Carotid stenosis is an important marker of severe systemic atherosclerosis. Internal Carotid occlusion (ICO) is rare and represents the final event when it comes to atherosclerotic plaque progression at the carotid bifurcation. Many patients are symptomatic when diagnosed with this condition and some of them will present more neurologic symptoms despite proper clinical management. So far only few studies have investigated if more comorbidities andjor risk factors, associated to demographic characteristics can lead to ICO. OBJETIVES: To identify the patient with ICO as regard to his demographic data, associated diseases and risk factors. Primary end-points were new neurologic events, cardiovascular symptoms and deaths during follow-up. METHOD: A prospective database was completed with demographic data and clinical information from patients with ICO and from a control group of patients with a non-significant stenosis (NSS), ar below 50%. Information was collected retrospectively from clínical records and missing data were completed with a medical appointment or teJephone interview. RESULTS: From [anuary 2005 to [anuary 2013, 213 patients with ICO and 172 patients with NSS were studied. Demographic data, risk factors for atherosclerosis and neurological symptoms at diagnosis and during follow-up were verified. Among patients with [CO there were more men and those with history of smoking, and more patients presenting with peripheral arterial disease (PAD) and chronic renal failure (CRF) than those in the NSS group (p < 0,05). At the time of diagnosis 76.1% of patients with ICO were symptomatic, while 35.5% in the NSS group (p=0.000001). Patients in the ICO group presented significant progression of the contralateral stenosis when compared to progression on any side in the control grouP\'\"(15.0% versus 2.3%, p = 0.00011). New symptoms were determined by the patient\'s clinical status. As regard to new neurological symptoms during follow-up, 10.8% of those initially symptomatic (both groups combined), presented new symptoms, opposed to 4.3% of those initially asymptomatic (p=0.0218). Number of deaths was significantly higher among patients in the ICO group (14.1% versus 6.4%, p=0.0150). CONCLUSIONS: Patients presenting with ICO have more risk factors and higher mortality by any cause. Those initially symptomatic will likely present more neurological symptoms during follow up. This study aims to identify those who are more at risk before the occlusion and could benefit of earJy diagnosis and vigorous c1inical intervention before new neurological events andjor death