The aim of this thesis is to evaluate the effect of doxycycline on the proteolytic and inflammatory processes in abdominal aneurysms. This data is essential for the development of pharmaceutical... Show moreThe aim of this thesis is to evaluate the effect of doxycycline on the proteolytic and inflammatory processes in abdominal aneurysms. This data is essential for the development of pharmaceutical strategies for the stabilization of an AAA. Such an approach could reduce the need for elective surgery and endovascular repair. It has repeatedly been shown that AAA progression and rupture is related to the failure of collagen in the aortic wall. Yet the exact mechanism underlying this failure remains unknown. Furthermore, the precise mechanism of activation of collagenases and their inflammatory mediators that are responsible for the collagen turnover of AAA are unknown. In this thesis we attempt to determine how collagen metabolism is balanced in aneurysmal diseases and contribute to the knowledge which collagenases and inflammatory mediators are involved in the destruction of the collagen network in AAA disease. Moreover, we evaluate some of the effects of doxycycline on the proteases and inflammatory mediators in AAA. Analyses showed that doxycycline inhibits specific MMPs and inflammatory pathways that are involved in the collagen balance and aneurysm growth. Together, these observations provide a rationale for a randomized clinical trial studying the effect of doxycycline on aneurysm growth. Show less
This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to... Show moreThis thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that overexpression of the breast cancer stem cell marker aldehyde dehydrogenase-1 in early stage breast cancer patients is inversely associated with age and is of prognostic importance. In part II, we have demonstrated proof-of-principle of intraoperative tumor detection and image-guided tumor resection by using the novel technique of near-infrared fluorescence imaging. We have performed two clinical trials to optimize the use of indocyanine green as a near-infrared fluorescence lymphatic tracer for the sentinel lymph node procedure in breast cancer patients. Show less
This thesis evaluates, using various methods, two important surgical procedures currently used in heart failure patients: surgical ventricular restoration and restrictive mitral annuloplasty. The... Show moreThis thesis evaluates, using various methods, two important surgical procedures currently used in heart failure patients: surgical ventricular restoration and restrictive mitral annuloplasty. The conductance catheter was used to analyze the hemodynamic effects of heart failure surgery invasively. It demonstrated improvement in systolic function of the left ventricle for both procedures at long term follow-up. Diastolic function demonstrated signs of impairment, although the functional effect remained limited, regarding limited or no increase in left ventricular end-diastolic pressure for SVR and RMA, respectively. Furthermore, assessment of left ventricular volumes demonstrated persistent reverse remodeling at follow-up. Clinical performance demonstrated significant improvement for both surgical procedures. The hemodynamic results together with the positive clinical outcome for both surgical procedures supports the use of these procedures in end-stage heart failure patients. Regarding the fact that using the conductance catheter is time consuming and can be burdensome for patients, a demand for less invasive methods was generated. Evaluation of alternative methods demonstrated that heart failure surgery can also be evaluated by single-beat analysis, a simplified method of the conventional conductance catheter method avoiding load interventions by temporary vena cava occlusions. Furthermore, echocardiography and to a certain extent, serum biomarker analysis can also be used. Show less
