Publications

Mammalian myocardial infarction is typically followed by scar formation with eventual ventricular dilation and heart failure. Here we present a novel model system in which mice constitutively expressing cyclin A2 in the myocardium elicit a regenerative response after infarction and exhibit significantly limited ventricular dilation with sustained and remarkably enhanced cardiac function. New cardiomyocyte formation was noted in the infarcted zones as well as cell cycle reentry of periinfarct myocardium with an increase in DNA synthesis and mitotic indices. The enhanced cardiac function was serially assessed over time by MRI. Furthermore, the constitutive expression of cyclin A2 appears to augment endogenous regenerative mechanisms via induction of side population cells with enhanced proliferative capacity. The ability of cultured transgenic cardiomyocytes to undergo cytokinesis provides mechanistic support for the regenerative capacity of cyclin A2.

A pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus (hMPV) strain associated with a critical respiratory tract infection in an elderly adult with chronic lymphocytic leukemia. This infection had previously eluded diagnosis despite extensive microbiological testing for possible etiologic agents. The patient's hMPV strain did not grow in viral culture, and only one of five specific reverse transcription-PCR assays for hMPV was positive.

BACKGROUND

Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co-morbidity and advanced disease. Further, this effect may be worse in women.

OBJECTIVE

To determine whether the effect of diabetes on outcomes and the sex-related variation persisted in a propensity score-matched HF population, and whether the sex-related variation was a function of age.

METHODS

Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non-parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non-diabetic patients.

RESULTS

All-cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex-diabetes interaction (overall adjusted p<0.001) was only significant in patients > or = 65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk-adjusted HR (95% CI) for all-cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex-diabetes interaction (p = 0.011).

CONCLUSIONS

Diabetes-associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex-related differences in outcomes were primarily observed in elderly patients.