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Background: The role erectile dysfunction (ED) coupled with low testosterone levels as early markers of atherosclerosis is not well understood. Objectives: To analyze the relationship between serum testosterone levels with both ED and brachial artery flow-mediated vasodilation (FMD), in a primary prevention sample of men. Methods: We enrolled 802 asymptomatic, intermediate CV risk patients, according to the Framingham Risk Score, aged 40e80 years, who underwent the ultrasound examination of FMD, the evaluation of ED and the assessment of total serum testosterone levels. Results: Testosterone levels correlated both with FMD (r ¼ 0.85; p < 0.0001) and IIEF-5 score (rs ¼ 0.65; p < 0.0001). Multivariable logistic regression analyses revealed that lower serum testosterone levels were strongly associated (p < 0.001) with severe (OR 0.78; 95% CI: 0.62e0.86), and moderate ED (OR 0.85; 95% CI: 0.72 e0.97), while impaired FMD percentages were strongly associated (p < 0.001) with severe (OR 0.68; 95% CI: 0.59e0.79), moderate (OR 0.76; 95% CI: 0.63e0.83) and mild to moderate ED (OR 0.8; 95% CI: 0.69 e0.94). Mild ED resulted statistically associated with lower FMD (OR 0.94; 95% CI: 0.82 e 1.07; p ¼ 0.03) but not with serum testosterone levels. These relations were not substantially affected by adjustments for further potential confounders including smoking status, hypertension, diabetes mellitus and body mass index. Conclusions: lower total serum testosterone levels are associated with impaired FMD and ED in this sample of intermediate CV risk men according to the Framingham Risk Score

LETTER TO EDITOR

The occurrence of left bundle branch block (LBBB) is quite common in clinical practice. The changes in cardiac repolarization, caused by this disorder of electric conduction, may mask the presence of an acute myocardial infarction (AMI), delaying the diagnostic-therapeutic iter, with an important impact on prognosis. We describe the case of a woman of 59 years with LBBB, came to our observation for a constrictive chest pain associated with dyspnea. The diagnostic workup for suspected acute coronary syndrome (ACS), initially conducted only on the analysis of the electrocardiogram (negative TnI at entry), showed the presence of coronary arteries free of stenosis. However, the diagnostic confirmation of AMI was completed after the rise of cardiac markers and the electrocardiographic changes. This case confirm the difficulty about the diagnosis of AMI in patients with LBBB and stresses, however, as the use of some criteria proposed in the literature [1-3] can guide to its identification, directing patient to an appropriate treatment.

Purpose: This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors. Experimental Design: Part A of the study followed a multiple-ascending dose design to establish the maximum tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group, cohort-expansion phase to further assess tolerated doses. Safety, tolerability, and Src activity (immunohistochemistry and lysate-based methodologies) were assessed after 21 days of once-daily oral dosing. PK was assessed after single and multiple dosing. Results: In part A, 30 patients received once-daily saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175 mg (n = 19) of saracatinib. The most common grade ≥3 events considered to be treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was reduced following saracatinib treatment. The area under the concentration-time curve and Cmax of saracatinib increased with increasing dose. Saracatinib accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure after 10 to 17 days of dosing. The half-life was ∼40 hours. Conclusions: Saracatinib was well tolerated in patients with advanced solid malignancies. A reduction in tumor Src activity was observed. PK data show that saracatinib is suitable for once-daily oral dosing. Based on this study, the recommended dose for the phase II studies was chosen to be 175 mg/d. Clin Cancer Res; 16(19); 4876–83. ©2010 AACR.

Background: Chemotherapy cardiotoxicity is an emerging problem and it is very important to prevent cardiac dysfunction caused by anticancer drugs. The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years and to evaluate the cardioprotective role of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of cardiac dysfunction. Methods: A prospective study was carried out using patients with breast cancer (85 women; median age 57W12years) and other inclusion and exclusion criteria. On the basis of treatment, patients were divided into six groups: fluorouracil-epirubicincyclophosphamide, FEC (group A); FEC and trastuzumab (B); trastuzumab (C); FEC and taxotere (D); FEC, paclitaxel and trastuzumab (E); and chemotherapy and cardioprotective drugs (F). Cardiological evaluation including electrocardiogram and conventional echocardiogram with tissue Doppler imaging (TDI) was carried out at T0 (before starting chemotherapy), T1 (after 6months from the start of chemotherapy) and T2 (2 years after the end of chemotherapy). Results: Significant changes in the TDI parameters of systolic and diastolic function were observed at T1 and T2 in all patients. A significant reduction of left ventricular ejection fraction (LVEF) was observed only at T2. In the patients treated with ACEI (F), these changes were less significant than in other groups and they do not have significant changes in the indices of diastolic function. Conclusion: TDI is more sensitive than conventional echocardiogram in the early diagnosis of cardiac dysfunction and ACEIs seem to have an important role in the prevention of cardiotoxicity.