Resolution of sinus bradycardia, high-grade heart block, and left ventricular systolic dysfunction with rituximab therapy in Henoch-Schonlein purpura.

Henoch-Schonlein purpura (HSP) is a rare, typically self-limited, multi-organ vasculitis. Cardiac involvement with HSP carries high morbidity and mortality, thus requiring early aggressive immunosuppressive therapy. We report a case of HSP complicated with acute systolic left ventricular (LV) dysfunction, symptomatic sinus bradycardia and high-grade atrio-ventricular (AV) heart block. Cyclophosphamide, a commonly used agent in HSP, was contraindicated due to the patient's presentation with acute renal failure. Treatment with monoclonal antibody rituximab and corticosteroids was initiated with an improvement in and resolution of LV systolic dysfunction, sinus bradycardia and AV block. We believe this is the first published report on rituximab treatment in HSP with cardiac involvement manifesting with severe LV systolic dysfunction, sinus bradycardia and high-grade AV block.

The Extent of Mechanical Esophageal Deviation to Avoid Esophageal Heating During Catheter Ablation of Atrial Fibrillation.

OBJECTIVES: This study sought to determine the extent of lateral esophageal displacement required during mechanical esophageal deviation (MED) and to eliminate luminal esophageal temperature elevation (LETElev) during pulmonary vein (PV) isolation. BACKGROUND: MED is a conceptually attractive strategy of minimizing esophageal injury while allowing uninterrupted energy delivery along the posterior left atrium during PV isolation. METHODS: MED was performed using a malleable metal stylet within a plastic tube placed within the esophagus. Barium was instilled to characterize the trailing esophageal edge. For each MED attempt, the MEDEffective, defined as the distance from the trailing esophageal edge-to-ablation line, was correlated to occurrences of LETElev. RESULTS: In 114 consecutive patients/221 PV pairs undergoing MED (age 62.1 ± 11 years, 75% men, 62%/38% paroxysmal/persistent AF), esophageal stretching invariably occurred such that the esophageal edge trailed behind the plastic tube. MEDEffective distances of 0 mm to 10 mm, 10 mm to 15 mm, 15 mm to 20 mm or >20 mm were achieved in 60 (27.1%), 64 (29%), 48 (21.7%), and 49 (22.2%) attempts, respectively. Overall, LET elevation >38°C occurred in 81 of 221 (36.7%) PV pairs. The incidence of LETElev among the 4 groups was 73.3%, 35.9%, 25%, and 4.1%, respectively. MEDEffective distances were 9.1 ± 6.5 mm and 18 ± 7.6 mm in patients with and without LETElev, respectively (p < 0.0001). Three patients (2.6%) experienced clinically significant MED-related trauma, albeit only with a stiffer stylet. CONCLUSIONS: Mechanical esophageal deviation >20 mm from the PV ablation line prevents significant esophageal heating during PV isolation, but this level of displacement was difficult to safely achieve with this off-the-shelf mechanical stylet approach.

An Elusive and Deceptive Tachycardia.

A wide-complex tachycardia was induced with rapid atrial pacing, with intermittent ventriculoatrial block and QRS alternans. A short/negative HV interval was observed, and premature ventricular complexes resulted in the termination of the tachycardia. The findings at electrophysiology study were consistent with an antidromic re-entrant tachycardia involving a nodo-fascicular/ventricular connection.

Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart.

OBJECTIVE: The purpose of this study was to investigate whether resveratrol adds to the growth inhibitory effects of cisplatin and doxorubicin on ovarian and uterine cancer cells and to evaluate whether resveratrol diminishes the cardiac toxicity of doxorubicin in rodent heart. STUDY DESIGN: Human ovarian (OVCAR-3) and uterine (Ishikawa) cancer cells in culture were treated with cisplatin and doxorubicin, respectively, with and without resveratrol; and cell growth and viability were evaluated. Neonatal rat ventricular myocytes received doxorubicin in the presence and absence of resveratrol, and cell viability was evaluated. Mice received doxorubicin +/- resveratrol, and electrocardiograms were evaluated. Data were analyzed with analysis of variance and Scheffe's test. RESULTS: Resveratrol combined with cisplatin or with doxorubicin demonstrated an additive growth-inhibitory anticancer effect with a left shift of the cisplatin and doxorubicin dose/response curves. Resveratrol increased the viability of neonatal rat ventricular myocytes that were treated with doxorubicin and reduced doxorubicin-induced bradycardia and QTc interval prolongation in mice. CONCLUSION: Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in vitro and in mice.

AFPep: an anti-breast cancer peptide that is orally active.

BACKGROUND: We have synthesized a cyclic nonapeptide (AFPep) that is effective, after being administered by parenteral routes, for the treatment or the prevention of breast cancer. To test the hypothesis that AFPep remains safe and efficacious after oral administration, three different whole-animal bioassays were utilized, and the mechanism by which AFPep functions was investigated. METHODS: Using a human breast cancer xenograft model in mice for therapeutic activity, a carcinogen-induced breast cancer model in rats for prevention efficacy, and a mouse uterus growth inhibition model of anti-estrogenic activity, AFPep was administered by oral gavage (p.o.) and its effects compared to those following intraperitoneal (i.p.) and subcutaneous (s.c.) administration. Toxicity studies evaluated body weights and organ weights in mice and rats receiving AFPep. Preliminary mechanistic studies were carried out in T47D human breast cancer cells growing in culture and evaluated the effect of AFPep on estrogen-stimulated cell growth, phosphorylation of the estrogen receptor (ER), and on level of ER-related kinases. RESULTS: Orally administered AFPep stopped the growth of human tumor xenografts in mice, decreased the incidence and multiplicity of breast cancers in carcinogen-exposed rats, and inhibited the estrogen-stimulated growth of mouse uteri. In each of these systems, orally administered AFPep produced an effect similar to that obtained for AFPep administered by either i.p or s.c. routes. In rodents, no evidence of toxicity was seen for the peptide, even at very high doses. In culture, AFPep inhibited the estrogen-stimulated growth, but not the basal growth, of T47D cells, and it inhibited the estrogen-stimulated phosphorylation of Serine 118 in the ER of these cells, which was not explainable by early changes in ER-related kinases. CONCLUSIONS: Chronic oral administration of AFPep appears to be safe and effective for the treatment or prevention of breast cancer in animal models.