Thesis (Ph. D.)--University of Wisconsin--Madison, 1967. / Typescript. Vita. Description based on print version record. Includes bibliographical references.

OBJECTIVE: To determine if applying electroacupuncture at ST 36-37 will lower the systolic, diastolic, and mean blood pressures of chronic hypertensive rats. DESIGN: A 12 week study on the effect of electroacupuncture was conducted from September 2014 to December 2014. The total number of rats used in the study was 16 (n=16). The rats were divided into four groups: Electroacupuncture, Sham-EA, Hypertensive control, and Normotensive control. All of the rats, expect for those in the Normotensive group, were housed in the cold room to induce chronic hypertension. After 8 weeks in the cold room, the rats in the Electroacupuncture group received electrical stimulation twice a week for 30 min. Needles were also inserted into the rats in the Sham-EA group, but there was no electric current. The blood pressures of all of the rats were measured once a week for 12 weeks. Lastly, the data was analyzed using SigmaStat to perform One Way ANOVA and T-tests. RESULT: The initial blood pressures between the 4 groups were similar with a difference of less than 5 mmHg. The groups placed in cold rooms showed a significant difference of more than 20 mmHg compared to their initial blood pressures (P≤0.05) at week 7. Finally, the blood pressures of the Sham-EA and Hypertensive control group did not lower at 12 weeks compared to week 7. However, the systolic, mean, and diastolic blood pressures in the EA group lowered with a significant difference of greater than 20 mmHg at week 12 compared to week 7. There was no significant change between the initial and final blood pressures for those in the Normotensive group. CONCLUSION: The data showed that systolic, diastolic, and mean blood pressures in the Electroacupuncture group lowered significantly at week 12 or after 5 weeks of treatment. Thus, we can conclude that electroacupuncture does have a beneficial effect in lowering blood pressure in chronically hypertensive rats.

Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated, and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically-inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Further, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects. This work suggests that Wnt/β-catenin maintains a subpopulation of valve mesenchyme in a less-differentiated, progenitor-like state that allows these cells to respond to mitogens and morphogens. The coordinated interplay of signals with distinct effects on a “progenitor cell” pool is a common logic mechanism for balanced tissue growth and differentiation in many biological contexts. Inspired by epithelial organ homeostasis processes, we identified specific and dynamic expression of the well-established quiescent stem cell marker Lrig1 in the developing valves. Endocardial Lrig1 likely moderates ErbB2 levels and thereby signaling output to prevent excessive EMT and resulting pathologically enlarged valves. Finally, we use Cre-mediated lineage labeling to show that the cusps of the semilunar valves have differential mesenchymal origins and that the localization of said distinct mesenchyme may account for the discretely patterned extracellular matrix of mature valves. This dissertation includes previously published and unpublished coauthored material. / 10000-01-01

The ablative management of atrial fibrillation, despite a number of landmark discoveries, remains one of the most challenging fields in interventional electrophysiology. It is generally accepted that successful isolation of the pulmonary veins is a highly effective way of managing paroxysmal forms of AF. However, despite almost a decade of research into alternative lesion patterns, the solution to persistent AF remains beyond our grasp. A variety of strategies have been proposed to target key areas in the atria; these use various complex mapping systems, usually based on tailored lesion sets to try and improve outcomes. None have proven to be the golden bullet. We have investigated the role of a lesion set intended to alter the electrical properties of the posterior wall of the left atrium. Commonly known as the ‘box-set’, this pattern has shown promise in early studies and may provide some key insights into future developments. Surgical ablation using the Epicor system aims to deliver the box-set lesion, outcomes have previously been documented but each series has its limitations. In our series, very late outcomes are reported to show an 80% freedom from AF rate in patients with paroxysmal AF pre-operatively and only 20% in those with long-standing persistent forms. The reason behind this dramatic variation is explored through the invasive electrophysiologal assessment of both successful and unsuccessful cases. We report a clear correlation between the successful isolation of the posterior wall and long-term freedom from AF. Though surgical ablation may be an acceptable approach for some, the ultimate goal is a lesion set that can be delivered purely endocardially. We explore the outcome of one such empirical pattern based on the box-set concept delivered through linear catheter technology and report outcomes broadly similar to alternative patterns.

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No description available.

<p><strong>Background:</strong> Syncope is estimated to account for 1% to 3% of emergency department (ED) annual visits in North America. Although most potential causes of syncope are benign and self-limited, others are associated with serious morbidity and substantial mortality. Recent efforts have focused on prospective identification of ED patients with syncope who are at high risk for early serious adverse outcomes in an attempt to hospitalize them at their first visit to the ED.</p> <p><strong>Objective: </strong>The purpose of this thesis is to describe the methodological issues related to the design of a study to determine whether the Revised Strategy of Syncope Diagnosis in the Emergency Room at the General Hospital Structured Care Pathway (RESASTER-SCP) is superior to usual care in identifying patients at low risk for serious adverse outcomes presenting to the ED who can be safely discharged home. <strong></strong></p> <p><strong>Design and Methods: </strong>A cluster randomized trial will be conducted with EDs (16 teaching and 46 non-teaching general hospitals) as the unit of randomization and patients presenting with syncope (TLOC) as the unit of analysis. Study participants will be followed at 1, 3, 5, and 12 months after the intervention (RESASTER-SCP vs. usual care) has been applied in the ED. Intention to treat analysis will be used. The analysis will be conducted at the individual level using proportions. Alpha level will be set at 0.05 with a power of 0.80 for the primary outcome.<strong></strong></p> <p><strong>Conclusion: </strong>This thesis describes some of the methodological issues concerning the design of a cluster randomized trial to determine whether or not RESASTER-SCP is superior to usual care in identifying patients presenting with syncope to the ED who can be safely discharged home.</p> / Master of Science (MSc)

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

This thesis details the measurement and simulation of patient skin doses arising from X-ray exposure during interventional cardiology procedures. Interventional cardiology procedures can be long and complex resulting in high skin doses, to the extent that radiation burns may be produced. Twenty patients were used in the study consisting of 10 coronary angiogram and 10 coronary angioplasty procedures. Radiochromic films were used to measure skin dose directly. The Gafchromic® XR-RV2 film was chosen for its suitability for this project. The key characteristics of this film were experimentally determined including: dose response, energy dependence, polarisation and post-exposure growth. The dose range was found to be ideally suited for the doses encountered in this study. Energy dependence was found to be ~14% between 60 and 125 kVp at 1 Gy and introduced an unavoidable uncertainty into dose calculations from unknown beam energies. Document scanner characteristics were also been investigated and a scanning protocol is determined. A mathematical model was created to use the geometry and exposure information encoded into acquisition files to reconstruct dose and dose distributions. The model requires a set of study files encoded according to the DICOM format, as well as user input for fluoroscopic estimations. The output is a dose map and dose summary. Simulation parameters were varied and results compared with film measurements to provide the most accurate model. From the data collected the relation between dose area product, maximum skin dose and fluoroscopic time were also investigated. The results demonstrated that a model based on acquisition information can accurately predict maximum skin dose and provide useful geometrical information. The model is currently being developed into a standalone program for use by the Medical Physics and Bioengineering department.

No description available.