Pivarubicin Is More Effective Than Doxorubicin Against Triple-Negative Breast Cancer In Vivo.

Triple-negative breast cancer (TNBC) is unresponsive to antiestrogen and anti-HER2 therapies, requiring the use of cytotoxic drug combinations of anthracyclines, taxanes, cyclophosphamide, and platinum compounds. Multidrug therapies achieve pathological cure rates of only 2040%, a consequence of drug resistance and cumulative dose limitations necessitated by the reversible cardiotoxic effects of drug therapy. Safer and more effective treatments for TNBC are required to achieve durable therapeutic responses.

Cardioselective beta-blocker treatment of hypertension in patients with asthma: when do benefits outweigh risks?

Background: Benefits outweigh risks of cardioselective beta-blocker therapy in patients with nonsevere asthma and a history of heart failure or myocardial infarction (MI). This review summarizes the risks versus benefits of using cardioselective beta-blockers in the treatment of hypertension in patients with asthma.

Methods: We searched the English literature from 1976 to 2011 via PubMed, EMBASE, and SCOPUS using the following search terms: "beta-blocker treatment of hypertension" AND "asthma"; "cardioselective beta-blockers" AND "asthma.

Esophageal electric fields are predictive of atrial defibrillation thresholds.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia characterized by disorganized cardiac electrical activity. Defibrillation electrode placement has been shown to affect the amount of energy and number of shocks required to defibrillate. The objective of this study was to investigate the relationship between esophageal electric fields (EEFs) and atrial defibrillation thresholds (ADFTs) to determine the feasibility of using EEFs during a low-strength shock to predict patient-specific defibrillation electrode placements.

Effects of paroxetine on the pharmacokinetics and pharmacodynamics of immediate-release and extended-release metoprolol.

Study Objective: To compare the effects of paroxetine on the pharmacokinetics and pharmacodynamics of the immediate-release (IR) and extended-release (ER) formulations of metoprolol.

Design: Prospective, randomized, open-label, 3-way crossover study.

Setting: General clinical research center.

Stressor states and the cation crossroads.

Neurohormonal activation involving the hypothalamic-pituitary-adrenal axis and adrenergic nervous and renin-angiotensin-aldosterone systems is integral to stressor state-mediated homeostatic responses. The levels of effector hormones, depending upon the degree of stress, orchestrate the concordant appearance of hypokalemia, ionized hypocalcemia and hypomagnesemia, hypozincemia, and hyposelenemia. Seemingly contradictory to homeostatic responses wherein the constancy of extracellular fluid would be preserved, upregulation of cognate-binding proteins promotes coordinated translocation of cations to injured tissues, where they participate in wound healing.

Carvedilol therapy after cocaine-induced myocardial infarction in patients with asthma.

Introduction: Cocaine-induced myocardial infarction (MI) is well documented. Current literature recommends avoiding beta-blockers in the acute care setting, but after discharge from the hospital, benefits of beta-blocker use may outweigh risks in patients with recent MI resulting from cocaine use. Cardioselective beta-blocker therapy has been demonstrated to be beneficial in post-MI patients with nonsevere asthma.

A dyshomeostasis of electrolytes and trace elements in acute stressor states: impact on the heart.

Acute stressor states are associated with a homeostatic activation of the hypothalamic-pituitary-adrenal axis. A hyperadrenergic state follows and leads to a dyshomeostasis of several intra- and extracellular cations, including K, Mg, and Ca. Prolongation of myocardial repolarization and corrected QT interval (QTc) of the ECG are useful biomarkers of hypokalemia and/or hypomagnesemia and should be monitored to address the adequacy of cation replacement.

Prevalence and predictors of abnormal cardiovascular responses to exercise testing among individuals with type 2 diabetes: the Look AHEAD (Action for Health in Diabetes) study.

Objective: We examined maximal graded exercise test (GXT) results in 5,783 overweight/obese men and women, aged 45-76 years, with type 2 diabetes, who were entering the Look AHEAD (Action for Health in Diabetes) study, to determine the prevalence and correlates of exercise-induced cardiac abnormalities.

Research Design And Methods: Participants underwent symptom-limited maximal GXTs. Questionnaires and physical examinations were used to determine demographic, anthropometric, metabolic, and health status predictors of abnormal GXT results, which were defined as an ST segment depression > or =1.

Adenosine deaminase in the diagnosis of tuberculous pericardial effusion.

Not long ago, primary tuberculosis was considered a rare disease; now with an increasing incidence worldwide, physicians should relearn many of its basic aspects and manifestations. Pericarditis is a rare finding seen with tuberculosis, but its prognosis is excellent with treatment, so early diagnosis is crucial. Pathogenesis is particularly important, and it must be taken in consideration when interpreting diagnostic tools.

Macro- and micronutrients in patients with congestive heart failure, particularly African-Americans.

Not all patients with heart failure, defined as a reduced ejection fraction, will have an activation of the RAAS, salt and water retention, or the congestive heart failure (CHF) syndrome. Beyond this cardiorenal perspective, CHF is accompanied by a systemic illness that includes oxidative stress, a proinflammatory phenotype, and a wasting of soft tissues and bone. A dyshomeostasis of calcium, magnesium, zinc, selenium, and vitamin D contribute to the appearance of oxidative stress and to compromised endogenous defenses that combat it.

Esophageal electric fields are correlated to atrial defibrillation thresholds: towards patient-specific optimization of external atrial defibrillation.

Studies have investigated the effect of defibrillator paddle position on the efficacy of external electrocardioversion of atrial fibrillation, without agreeing upon an optimal placement. We wish to investigate using esophageal electric fields (EEFs) to predict atrial defibrillation thresholds (ADFTs) on a patient-specific basis. We propose to (1) investigate the relationship between EEFs and ADFTs using computer simulations, (2) develop an esophageal probe that can accurately measure three-dimensional electric fields and (3) investigate the relationship between EEFs and ADFTs values in-vivo.

Exercise capacity and cardiovascular/metabolic characteristics of overweight and obese individuals with type 2 diabetes: the Look AHEAD clinical trial.

Objective: We examined associations of cardiovascular, metabolic, and body composition measures with exercise capacity using baseline data from 5,145 overweight and/or obese (BMI > or = 25.0 kg/m2) men and women with type 2 diabetes who were randomized participants for the Look AHEAD (Action for Health in Diabetes) clinical trial.

Research Design And Methods: Peak exercise capacity expressed as METs and estimated from treadmill speed and grade was measured during a graded exercise test designed to elicit a maximal effort.

Pharmacokinetic factors in the adverse cardiovascular effects of antipsychotic drugs.

Antipsychotics may cause serious adverse cardiovascular effects, including prolonged QT interval and sudden death. This review considers antipsychotic-induced cardiovascular events from three perspectives: high-risk drugs, high-risk individuals and high-risk drug interactions. Pharmacokinetic drug interactions involving the cytochrome P450 (CYP) enzymatic pathway and pharmacodynamic interactions leading to direct cardiotoxic effects are discussed.

Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans.

Study Objectives: To determine the effects of grapefruit juice on the pharmacokinetics of oral digoxin, a P-glycoprotein substrate not metabolized by cytochrome P450 3A4, in healthy volunteers, and to assess whether polymorphic multidrug-resistance-1 (MDR1) expression contributes to interindividual variability in digoxin disposition.

Design: Prospective, open-label, unblinded, crossover study.

Setting: University research center.

Aldosterone antagonists in congestive heart failure.

The role of aldosterone in the pathophysiology of congestive heart failure (CHF) has long been recognized. The recent RALES (Randomized Aldactone Evaluation Study) trial demonstrated early reduction in morbidity and mortality using spironolactone, an aldosterone receptor antagonist, in combination with angiotensin converting enzyme (ACE) inhibitor and loop diuretic, in patients with heart failure. This effect of spironolactone highlighted the importance of understanding the contributions of the renin-angiotensin-aldosterone system (RAAS) in the progression of CHF, and increased interest in the use of aldosterone antagonists.

Lower serum digoxin concentrations in heart failure and reassessment of laboratory report forms.

Serum digoxin concentrations (SDC) have been used clinically since the early 1970s. Whereas the therapeutic range for SDC is frequently cited as either 0.8 to 2.