Wilson Gj

Natural history of dilated cardiomyopathy in children.

To assess the natural history and potential risk factors in childhood dilated cardiomyopathy, we investigated 25 patients (ages 9.6 +/- 4.4 years) who presented after they were 2 years old. All patients had symptoms of congestive heart failure and reduced contractility with a dilated left ventricle at presentation. Two factors at presentation were significantly different between patients who died less than 1 year after the presentation (n = 14) and those who survived for more than 1 year (n = 9); cardiothoracic ratio (65.1% +/- 6.8% vs 57.1% +/- 6.1%, p less than 0.01) and left ventricular ejection fraction (31.3% +/- 7.0% vs 40.0% +/- 6.2%, p less than 0.05). Irrespective of intensive medical therapy, dilated cardiomyopathy in children had a poor prognosis; the actuarial survival rate was 41% at 1 year and 20% at 3 years. Other forms of therapy should be considered in the early stages of dilated cardiomyopathy in this high-risk group.

Experience with repair of congenital heart defects using adjunctive endovascular devices

The use of endovascular devices as an adjunct to repair of congenital heart anomalies represents a novel but unproven therapeutic approach. Intraoperative implantation of pulmonary arterial stents (5 to 15 mm diameter) was done in 11 patients with pulmonary atresia with ventricular septal defect (n = 4), classic tetralogy of Fallot (n = 2), truncus arteriosus (n = 1), hypoplastic left heart syndrome (stage II [n = 1] and stage III [n = 1] Norwood procedure), and miscellaneous pulmonary arterial stenoses (n = 3), as well as in patients with congenital (n = 1) and postoperative (n = 3) pulmonary venous obstruction and in 1 patient with combined pulmonary arterial and venous obstruction. The stents were effective at achieving immediate patency in all patients. There were two early deaths, one related to acute thrombosis of a small-diameter left pulmonary artery stent. Reintervention because of stent-related pulmonary arterial stenosis was frequently necessary. In five of seven patients who survived more than 1 month after implantation of stent size 8 mm or smaller severe stent-related pulmonary arterial obstruction developed. In four of the five patients with pulmonary vein stent implantation intractable obstruction developed, resulting in death in all three patients who had bilateral pulmonary vein stent implantation. Intraoperative occlusion of apical muscular ventricular septal defect with use of a clamshell device inserted from the right atrial approach was accomplished in four patients. One patient who underwent associated aortic arch reconstruction died as a result of left ventricular hypoplasia. The results in the remaining three patients were favorable on the basis of absence of significant late residual intraventricular shunting, left ventricular dysfunction, or arrhythmia. We conclude that recurrent intraluminal obstruction as a result of neointimal hyperplasia appears to be an eventual certainty in currently designed small-diameter endovascular stents. For this reason, we would recommend standard surgical techniques for repair of obstructive lesions of the pulmonary arterial confluence to maximize growth potential. Device occlusion of muscular ventricular septal defects is feasible but probably only indicated for complex cases of ventricular septal deficiency that otherwise necessitate a left ventriculotomy.

Hypersensitivity myocarditis caused by an allergic reaction to cefaclor

An adolescent girl was seen with acute heart failure 6 days after the onset of a viral illness and otitis media treated with cefaclor. An endomyocardial biopsy specimen revealed active myocarditis with an eosinophilic infiltrate typical of hypersensitivity myocarditis. The patient showed dramatic improvement within 48 hours after withdrawal of the drug and administration of corticosteroids and immunoglobulin.

Cardiomyopathy : A late complication of hemolytic uremic syndrome

Abstract. This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS.

Evidence that increases in lymphocyte tyrosine phosphorylation precede cardiac allograft rejection: Effects of cyclosporine and potential use in clinical management

Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measured tyrosine phosphorylation in a porcine experimental transplant model to evaluate its utility in monitoring the allograft immune response. Using flow cytometry, we demonstrate a biphasic increase in phosphotyrosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and that increases are detectable as early as 1 day posttransplantation in untreated transplanted animals (n = 4). This biphasic response is likely result from the sequestration of ptyr+ cells from the periphery into the graft as graft-infiltrating lymphocytic cells show increased ptyr levels. This suggests possible lymphocyte trafficking between the peripheral compartment and the allograft. A 5-day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n = 4), but not at 10 mg/kg/day (n = 4), prevents graft rejection in this allograft model. Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day, suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells. Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and electrocardiographic signs of graft rejection, suggesting a potential diagnostic utility for measuring tyrosine phosphorylation in monitoring and managing transplant rejection.

Age-related differences in the effects of cyclosporine on lymphocyte intracellular free calcium

The effect of cyclosporine on lymphocyte intracellular free calcium [( Ca2+]i) is controversial, and potential age-related differences in lymphocyte CsA sensitivity have not been studied. We measured the mitogen-induced change in [Ca2+]i in peripheral blood lymphocytes (PBLs) following intravenous CsA infusion (5 mg/kg) in neonatal pigs and found a significantly reduced calcium response compared with control (P = 0.02). This was associated with an elevation in resting [Ca2+]i in the neonatal PBLs 24 hr following the CsA infusion (P = 0.02). These changes in lymphocyte [Ca2+]i were associated with suppression of cell proliferation. Neonatal PBLs in mixed lymphocyte cultures showed a greater PHA-induced change in [Ca2+]i (delta[Ca2+]i) compared with mature PBLs (P = 0.0007). The addition of CsA (1 microgram/ml) to mitogenic- and allogeneic-stimulated cultures did not affect resting [Ca2+]i or delta[Ca2+]i in either neonatal or mature PBLs. Our results demonstrate significant differences in calcium responses in neonatal lymphocytes following CsA infusion and allogeneic stimulation. This implies that there are age-related differences in CsA effects at or proximal to the level of calcium release and/or sequestration in the lymphocyte signal transduction pathway, and that elevated resting intracellular calcium levels may be indicative of reduced responsiveness, possibly through feedback inhibition of tyrosine kinase activity.