Impaired neuroanatomic development in infants with congenital heart disease.

OBJECTIVES: We performed a regional volumetric study of the brain using 3-dimensional magnetic resonance imaging in infants with congenital heart disease to search for variables in anatomic development of the brain that may be associated with functional impairment. METHODS: Forty infants with congenital heart disease-17 infants with single ventricle physiology, 5 with transposition of great arteries, and 18 with ventricular septal defect-were studied prospectively by 3-dimensional magnetic resonance imaging of the brain several months after heart surgery. RESULTS: The global volume of gray matter was significantly reduced in the patients with congenital heart disease compared with normal controls (P < .001), whereas no significant difference in the volume of white matter was observed. Further, the decrease in gray matter volume was more apparent in the frontal lobe than in the temporal lobe, especially in infants with single ventricle physiology or transposition of the great arteries. Multivariate analysis revealed that preoperative hypoxia is strongly associated with decreased frontal gray matter volume (P < .01), as well as a diagnosis of hypoplastic left heart syndrome (P < .05). Of note, frontal gray matter volume, which includes the motor area, correlated weakly with psychomotor developmental index scores (P < .01). CONCLUSIONS: Brain developmental impairment occurs in many infants with congenital heart disease, especially in those who have preoperative hypoxia and critical congenital heart disease. This quantitative volumetric study encourages larger scale and longitudinal follow-up to elucidate the significance of impaired neuroanatomic development on functional outcome.

Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease.

OBJECTIVES: This study investigated patients with acute Kawasaki disease (KD) to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development. BACKGROUND: Both MRP-8 and -14, which are S100-proteins secreted by activated neutrophils and monocytes, bind specifically to endothelial cells and induce thrombogenic and inflammatory responses in a variety of disease conditions. METHODS: We investigated 61 patients with acute KD and examined sequential changes in serum levels of MRP-8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to circulating endothelial cells. RESULTS: The serum MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated during the early stage of acute KD, and decreased dramatically within 24 h of intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in 16 nonresponders both of these increased after the initial treatment. The number of MRP-8/MRP-14-positive circulating endothelial cells was higher in patients with acute KD than in control patients and increased significantly by 2 weeks after the onset of KD, especially in patients in whom coronary artery lesions developed. CONCLUSIONS: We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KD, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14-positive circulating endothelial cell may predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.