京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21652号 / 医博第4458号 / 新制||医||1035(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 川村 孝, 教授 福原 俊一, 教授 佐藤 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Idiopathic tracheal stenosis (ITS) is a rare condition, and diagnosis of exclusion should be suspected in patients with exercise intolerance, wheezing, and dyspnea on exertion with a flow-volume loop suggestive of fixed airway obstruction. We report a case of a 32-year-old asthmatic woman with an existing diagnosis of vocal cord dysfunction and previous normal CT scan of the neck. She continued to have fixed upper airway obstruction on repeated flow-volume loops with persistent wheezing and cough along with occasional stridor and hoarseness of voice despite appropriate management of her asthma. She was finally diagnosed with ITS on a repeat CT scan of the neck for which she underwent laser surgery, steroid injection, and controlled radial expansion balloon dilation with a successful reduction of stenosis. This case illustrates the importance of clinical suspicion for early diagnosis of ITS in poorly controlled asthmatic patients and the relevance of non-surgical management of this condition.

Cardiovascular diseases (CVD) are the number one causes of death in the world. According to the world Health Organization (WHO) 17.5 million people died from cardiovascular disease in 2005, representing 30 % of all global deaths . Of these deaths, 7.6 million were due to heart attacks and 5.7 million due to stroke. If current trends are allowed to continue, by 2015 an estimated 20 million people will die annually from cardiovascular disease. The trends are similar in the United States where on an average 1 person dies every 37 seconds due to CVD. In 2008 an estimated 770,000 Americans will experience a new heart attack (coronary stenosis) and 600,000 will experience a first stroke. Although the exact causes of cardiovascular disease are not well understood, hemodynamics has been long thought to play a primary role in the progression of cardiovascular disease and stroke. There is strong evidence linking the fluid mechanical forces to the transduction mechanisms that trigger biochemical response leading to atherosclerosis or plaque formation. It is hypothesized that the emergence of abnormal fluid mechanical stresses which dictate the cell mechanotransduction mechanisms and lead to disease progression is dependent on the geometry and compliance of arteries, and pulsatility of blood flow. Understanding of such hemodynamic regulation in relation to atherosclerosis is of significant clinical importance in the prediction and progression of heart disease as well as design of prosthetic devices such as stents. The current work will systematically study the effects of compliance and complex geometry and the resulting fluid mechanical forces. The objective of this work is to understand the relationship of fluid mechanics and disease conditions using both experimental and computational methods where (a) Compliance effects are studied in idealized stenosed coronary and peripheral arteries using Digital Particle Image Velocimetry (DPIV), (b) Complex geometric effects of stented arteries with emphasis on its design parameters is investigated using CFD, Also (c) a novel method to improve the accuracy of velocity gradient estimation in the presence of noisy flow fields such as in DPIV where noise is inherently present is introduced with the objective to improve accuracy in the estimation of WSS, which are of paramount hemodynamic importance. The broad impact of the current work extends to the understanding of fundamental physics associated with arterial disease progression which can lead to better design of prosthetic devices, and also to better disease diagnostics. / Ph. D.

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