It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

The planned MADIT-CRT trial is designed to determine if CRT-D will reduce the risk of mortality and HF events by approximately 25% in subjects with ischemic (NYHA class I-II) and non-ischemic (NYHA class II) cardiomyopathy, left ventricular dysfunction (EF ≤ 0.30), and prolonged intraventricular conduction (QRS duration ≥ 130 ms). A.N.E. 2005;10(4)Supplement:34-43MADIT; cardiac resynchronization therapy; heart failure Heart failure (HF) with its associated morbidity and mortality remains a major unresolved public health problem in the United States and throughout the world. It is estimated that HF affects nearly 5 million people in the United States alone and claims more that 300,000 lives annually. 1 The MADIT-II trial demonstrated improvement in overall survival with an implantable cardioverter defibrillator (ICD) in high-risk subjects with prior myocardial infarction and advanced left ventricular dysfunction (ejection fraction ≤0.30) despite the occurrence of HF in this population.2 Similar results were found in the recently published SCD-HeFT and DEFINITE trials.3,4 Cardiac resynchronization therapy (CRT) with biventricular pacing is effective as adjunctive therapy to pharmacologic management of patients with severe HF and intraventricular conduction delay, with improvement in ven-

The purpose of this study was to identify and validate novel serological protein biomarkers of human colorectal cancer (CRC).The PSME3-containing spot on tumor gels showed no visible difference to the corresponding spot on matched control gels. MS analysis revealed the presence of two proteins, PSME3 and annexin 4 (ANXA4) in one and the same spot on tumor gels, whereas the matched spot contained only one protein, ANXA4, on control gels. Therefore, dysregulation of PSME3 was masked by ANXA4 and could only be recognized by MS-based analysis but not by image analysis. To validate this finding, antibody to PSME3 was developed, and up-regulation in CRC was confirmed by Western blot analysis and immunohistochemistry. Finally by developing a highly sensitive immunoassay, PSME3 could be detected in human sera and was significantly elevated in CRC patients compared with healthy donors and patients with benign bowel disease. We propose that PSME3 be considered a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Further studies are needed to fully assess the potential clinical value of this marker candidate.

Aims: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. Methods and results: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. Conclusions: The CHARM Programme provides the largest and most detailed comparison to date of patients low-and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.