Medicine and Health Sciences Commons^™

Cardiovascular Risk Associated With Interactions Among Polymorphisms In Genes From The Renin-Angiotensin, Bradykinin, And Fibrinolytic Systems, John P. Bentley, Folkert W. Asselbergs, Christopher S. Coffey, Patricia R. Hebert, Jason H. Moore, Hans L. Hillege, Wiek H. Van Gilst

Dartmouth Scholarship

Background: Vascular fibrinolytic balance is maintained primarily by interplay of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous research has shown that polymorphisms in genes from the renin- angiotensin (RA), bradykinin, and fibrinolytic systems affect plasma concentrations of both t-PA and PAI-1 through a set of gene-gene interactions. In the present study, we extend this finding by exploring the effects of polymorphisms in genes from these systems on incident cardiovascular disease, explicitly examining two-way interactions in a large population- based study.

Methodology/Principal Findings: Data from the population-based PREVEND study in Groningen, The Netherlands (n = 8,138) …

The Importance Of Examining Movements Within The Us Health Caresystem: Sequential Logit Modeling, Chioun Lee, Stephanie L L. Ayers, Jennie Jacobs Kronenfeld, Jemima A. Frimpong, Patrick A. Rivers, Sam S. Kim

Dartmouth Scholarship

Utilization of specialty care may not be a discrete, isolated behavior but rather, a behavior of sequential movements within the health care system. Although patients may often visit their primary care physician and receive a referral before utilizing specialty care, prior studies have underestimated the importance of accounting for these sequential movements. The sample included 6,772 adults aged 18 years and older who participated in the 2001 Survey on Disparities in Quality of Care, sponsored by the Commonwealth Fund. A sequential logit model was used to account for movement in all stages of utilization: use of any health services (i.e., …

Noninvasive Fluorescence Monitoring Of Protoporphyrin Ix Production And Clinical Outcomes In Actinic Keratoses Following Short-Contact Application Of 5-Aminolevulinate, Christine B. Warren, Sara Lohser, Lauren C. Wene, Brian W. Pogue, Philip Bailin, Edward Maytin

Dartmouth Scholarship

Topical 5-aminolevulinic acid (ALA) is widely used in photodynamic therapy (PDT) of actinic keratoses (AK), a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX (P_pIX) accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, P_pIX fluorescence measurements (5 replicates) were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic …

Identification Of Methylated Genes Associated With Aggressive Bladder Cancer, Carmen J. Marsit, E. Andres Houseman, Brock C. Christensen, Luc Gagne, Margaret R. Wrensch, Heather H. Nelson, Joseph Weimels, Shichun Zheng, John K. Wiencke, Angeline S. Andrew, Alan R. Schned, Margaret R. Karagas, Karl T. Kelsey

Dartmouth Scholarship

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $ 2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). …

Inspired Gas-Induced Vascular Change In Tumors With Magnetic-Resonance-Guided Near-Infrared Imaging: Human Breast Pilot Study, Colin M. Carpenter, Rebecca Rakow-Penner, Shudong Jiang, Bruce L. Daniel, Brian W. Pogue, Gary H. Glover, Keith D. Paulsen

Dartmouth Scholarship

This study investigates differences in the response of breast tumor tissue versus healthy fibroglandular tissue to inspired gases. Cycles of carbogen and oxygen gas are administered while measuring the changes with magnetic-resonance-guided near-infrared imaging in a pilot study of breast cancers. For two patients, analyses are performed with cross-correlation techniques, which measure the strength of hemodynamic modulation. The results show that the overall vasoresponse, indicated by total hemoglobin, of healthy tissue has approximately a 72% and 41% greater correlation to the gas stimulus than the tumor region, in two patients respectively, when background physiological changes are controlled. These data support …

Renin-Angiotensin System Activation Correlates With Microvascular Dysfunction In A Prospective Cohort Study Of Clinical Sepsis, Kevin C. Doerschug, Angela S. Delsing, Gregory A. Schmidt, Alix Ashare

Dartmouth Scholarship

Microvascular dysregulation characterized by hyporesponsive vessels and heterogeneous bloodflow is implicated in the pathogenesis of organ failure in sepsis. The renin-angiotensin system (RAS) affects the microvasculature, yet the relationships between RAS and organ injury in clinical sepsis remain unclear. We tested our hypothesis that systemic RAS mediators are associated with dysregulation of the microvasculature and with organ failure in clinical severe sepsis.