Publications

OBJECTIVES

The purpose of this work was to determine the prognostic value of normal exercise myocardial perfusion imaging (MPI) tests and exercise echocardiography tests, and to determine the prognostic value of these imaging modalities in women and men.

BACKGROUND

Exercise MPI and exercise echocardiography provide prognostic information that is useful in the risk stratification of patients with suspected coronary artery disease (CAD).

METHODS

We searched the PubMed, Cochrane, and DARE databases between January 1990 and May 2005, and reviewed bibliographies of articles obtained. We included prospective cohort studies of subjects who underwent exercise MPI or exercise echocardiography for known or suspected CAD, and provided data on primary outcomes of myocardial infarction (MI) and cardiac death with at least 3 months of follow-up. Secondary outcomes (unstable angina, revascularization procedures) were abstracted if provided. Studies performed exclusively in patients with CAD were excluded.

RESULTS

The negative predictive value (NPV) for MI and cardiac death was 98.8% (95% confidence interval [CI] 98.5 to 99.0) over 36 months of follow-up for MPI, and 98.4% (95% CI 97.9 to 98.9) over 33 months for echocardiography. The corresponding annualized event rates were 0.45% per year for MPI and 0.54% per year for echocardiography. In subgroup analyses, annualized event rates were <1% for each MPI isotope, and were similar for women and men. For secondary events, MPI and echocardiography had annualized event rates of 1.25% and 0.95%, respectively.

CONCLUSIONS

Both exercise MPI and exercise echocardiography have high NPVs for primary and secondary cardiac events. The prognostic utility of both modalities is similar for both men and women.

Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF), and CHF has been shown to be associated with atrial structural remodeling resulting in fibrosis. Atrial interstitial fibrosis has been seen in patients with CHF and in animal models of pacing-induced heart failure. With atrial fibrosis, conduction abnormalities result in increased AF vulnerability. The mechanism of AF associated with CHF is under debate, as both focal and reentrant mechanisms have been observed in animal models of CHF. However, recent studies using frequency-domain analysis have shown that the AF within this model is characterized by discrete, stable, high-frequency areas. The precise signaling processes involved in the development of atrial fibrosis are unknown. Angiotensin appears to play a role, as inhibition of angiotensin-converting enzyme (or angiotensin-receptor blocker) blunts atrial fibrosis in animal models of heart failure and decreases the incidence of AF in patients with heart failure. Transforming growth factor-beta (TGF-beta) also appears to play an important role. Mouse models that overexpress TGF-beta1 have profound atrial fibrosis and AF (with normal ventricles). Heart failure in canine models also produces increases in atrial TGF-beta1 expression, and inhibition of this expression prevents atrial fibrosis and the development of a substrate for AF. Atrial fibrosis appears to play a role in the development of a vulnerable substrate for AF, especially in the setting of CHF.

PURPOSE

Tumor oxygen level plays a major role in the response of tumors to different treatments. The purpose of this study was to develop a method of determining oxygen transport properties in a recently developed 3D model of tumor parenchyma, the multicellular layer (MCL).

METHODS

OCM-1 human choroidal melanoma cells were grown as 3D MCLs on collagen-coated culture plate inserts. A recessed-cathode oxygen microelectrode was used to measure oxygen tension (PO(2)) profiles across 8 different MCL from the free surface to the insert membrane. The profiles were fitted to four different one-dimensional diffusion models: 1-, 2-, and 3-region models with uniform oxygen consumption (q) in each region and a modified 3-region model with a central region where q=0 and PO(2)=0.

RESULTS

Depending upon the presence of a central region of anoxia, the PO(2) profiles were fitted best by either the two-region model or the modified 3-region model. Consumption of tumor cells near the insert membrane was higher than that of cells close to the free surface (33.1+/-13.6 x 10(-4) vs. 11.8+/-6.7 x 10(-4) mm Hg/mum(2), respectively).

CONCLUSIONS

The model is useful for determining oxygenation and consumption in MCL, especially for cell lines that cannot be grown as spheroids. In the future, this model will permit the study of parameters important in tumor oxygenation in vitro.

Homelessness annually affects an estimated 2.3 million to 3.5 million individuals living in the United States. Homeless people face difficulties in meeting their basic needs. Many have substance abuse problems and mental illness, lack social support, and have no medical insurance. These challenges complicate the homeless patient's ability to engage in end-of-life advanced planning, adhere to medications, and find an adequate site to receive terminal care. Employing a multidisciplinary team to care for homeless patients can help address their needs and improve care. For patients who continue to use illicit substances while receiving end-of-life care, experts recommend scheduling frequent clinic visits, using long-acting pain medications, dispensing small quantities of medications at a time, and using a written pain agreement. Homeless people are less likely to have a surrogate decision maker. Clinicians should have frequent, well-documented conversations with these patients about end-of-life wishes. Homeless people can rarely use hospice services because they lack the financial resources for inpatient hospice and have neither the home nor the social support required for home hospice. Developing inpatient palliative care services at hospitals that serve many homeless people could improve the end-of-life care homeless people receive.

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.