Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.
temic ventricular dysfunction is a significant medical problem for children and represents the reason for at least 50% of pediatric referrals for heart transplantation. 1 To date, there have been no large randomized controlled trials of any medication in children and adolescents with chronic heart failure. Treatment recommendations in children and adolescents with heart failure are extrapolated from the results of clinical trials conducted in adults, which may be problematic. 2 Although multiple studies in adults have demonstrated beneficial effects of -blockers on left ventricular function, symptoms, and survival, [3][4][5][6][7]
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Doxorubicin (former generic name, adriamycin), a highly effective anticancer drug, produces cardiotoxicity, which limits its therapeutic potential. The mechanism of this cardiotoxicity has remained elusive. Our data suggest that this toxicity could involve doxorubicinol, the primary circulating metabolite of doxorubicin. Doxorubicinol was markedly more potent than doxorubicin at compromising both systolic and diastolic cardiac function. Similarly, doxorubicinol was much more potent than doxorubicin at inhibiting the calcium pump of sarcoplasmic reticulum [ATP phosphohydrolase (Ca2+-transporting), EC 3.6
Postmortem studies of three ostensibly healthy persons whose unheralded death occurred incidental to strenuous exercise revealed an obstructed but mural left anterior descending (LAD) artery, diminished vascularity to the posterior left ventricle and ventricular septum, and morphologic evidence of patchy, ischemic necrosis of the ventricular septum in different stages of healing. Although mural coronary arteries are considered a normal anatomic variant, our observations, coupled with reported clinical studies, strongly suggest that systolic constriction of the LAD artery may precipitate death in selected subjects.
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