Citations

Cardiovascular disease (CVD) has been the number one killer in the United States. It has long been recognized that a high percentage of all cardiovascular disease is associated with the hardening of arteries or arteriosclerosis. Several imaging techniques, including x-ray angiography, ultrasound, magnetic resonance imaging (MRI), etc., are available for imaging atherosclerotic arteries. Most imaging techniques measure luminal diameter, wall thickness and plaque volume. However, no current imaging methods can measure elasticity of the arterial wall. Pulse wave velocity (PWV) is a simple and robust method to measure arterial stiffness. However, PWV can not evaluate the local arterial stiffness. We have developed a novel ultrasound method for estimating local elasticity of arteries by the wave speed dispersion. In this paper, we present a method to measure the wave speed dispersion by resonance. Theory was developed to calculate the wave speed in cylindrical tubes. Experiments were done on a rubber tube. The resonance of the tube was generated by an air-coupled ultrasound transducer. The resonance frequency was measured by a laser vibrometer. Theoretical and experimental wave dispersions were compared. This method may be useful in characterizing the elastic properties of arterial samples where the wave speed dispersion can not be easily measured.

Abstract Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (∼60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q. Cancer Res; 70(13); 5409–18. ©2010 AACR.

Complications related to endoscopic retrograde cholangiopancreatography (ERCP) include pancreatitis, hemorrhage, cholangitis, and perforation. ERCP-related perforation is uncommon, but mortality rates are high. Diagnosis requires a high clinical suspicion for early detection to allow optimal management of the perforation and a better prognosis. Treatment depends on the location and mechanism and increasingly involves nonoperative management. We report a case of successful nonsurgical treatment of a patient with extensive air involving the peritoneum, retroperitoneum, thorax, mediastinum, and subcutaneous tissues following an ERCP perforation.

Nucleoside and nucleobase uptake is integral to mammalian cell function, and its disruption has significant effects on the cardiovasculature. The predominant transporters in this regard are the equilibrative nucleoside transporter subtypes 1 (ENT1) and 2 (ENT2). To examine the role of ENT1 in more detail, we have assessed the mechanisms by which microvascular endothelial cells (MVECs) from ENT1−/−mice transport and metabolize nucleosides and nucleobases. Wild-type murine MVECs express mainly the ENT1 subtype with only trace levels of ENT2. These cells also have a Na+-independent equilibrative nucleobase transport mechanism for hypoxanthine (ENBT1). In the ENT1−/−cells, there is no change in ENT2 or ENBT1, resulting in a very low level of nucleoside uptake in these cells, but a high capacity for nucleobase accumulation. Whereas there were no significant changes in nucleoside transporter subtype expression, there was a dramatic increase in adenosine deaminase and adenosine A2areceptors (both transcript and protein) in the ENT1−/−tissues compared with WT. These changes in adenosine deaminase and A2areceptors likely reflect adaptive cellular mechanisms in response to reduced adenosine flux across the membranes of ENT1−/−cells. Our study also revealed that mouse MVECs have a nucleoside/nucleobase transport profile that is more similar to human MVECs than to rat MVECs. Thus mouse MVECs from transgenic animals may prove to be a useful preclinical model for studies of the effects of purine metabolite modifiers on vascular function.

Background— When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. Methods and Results— Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater increases in left ventricular end-diastolic pressure and was associated with blunted increases in heart rate, systemic vasodilation, and cardiac output. Exercise-induced pulmonary hypertension was present in 88% of patients with HFpEF and was related principally to elevated PCWP, as pulmonary vascular resistances dropped similarly in both groups. Exercise PCWP and pulmonary artery systolic pressure were highly correlated. An exercise pulmonary artery systolic pressure ≥45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity. Conclusions— Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure. Earlier and more accurate diagnosis using exercise hemodynamics may allow better targeting of interventions to treat and prevent HFpEF progression.