Motoki Fujiwara

CD14+CD16+ monocyte subpopulation in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring in early childhood. We have demonstrated that the activation of monocytes/macrophages plays a central role during acute KD. Recently, it has been reported that the CD14+CD16+ monocyte subpopulation plays a more important role in inflammation. In this study, we investigated the peripheral blood CD14+CD16+ monocyte subpopulation by flow cytometry, and serum levels of IL‐10 and IL‐12 using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation in patients with bacterial infections, mononucleosis and anaphylactoid purpura, since the cause of KD remains unknown. We observed an increase in the number of CD14+CD16+ monocytes with acute KD, which was a positive correlation with C‐reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. In addition, we found that the serum levels of IL‐10, but not IL‐12, were higher during acute KD. These data suggest that increased peripheral blood CD14+CD16+ monocytes are part of the regulatory system of monocyte function during acute KD.

Decreased interferon-gamma (IFN-γ)-producing T cells in patients with acute Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of early childhood, in which the activation of monocytes/macrophages plays a central role in the development of vasculitis during the acute stage of disease. In this study we investigated peripheral blood T cells of 10 patients with KD, focusing on the Th1 and Th2 imbalance, using intracellular cytokine staining and analysis of the cytokine‐producing T cells by flow cytometry. We observed a decrease in the numbers of IFN‐γ‐producing, but not IL‐4‐producing, CD3+ T cells, during the acute stage. Our results suggest that there is an imbalance of Th1 and Th2 subsets during the acute stage of KD.

Congenital Aneurysm of the Muscular Interventricular Septum in a Fraternal Case Diagnosed by Fetal Echocardiography

Abstract. Two siblings with aneurysms of the muscular ventricular septum are presented. Case 1 (the older brother) underwent fetal echocardiography at 26 weeks of gestation. Initially, it was thought that he had a muscular ventricular septal defect; however, postnatal echocardiography revealed an aneurysm of the muscular portion of the ventricular septum. Retrospective review of the 26-weeks gestation fetal echocardiogram confirmed this diagnosis. Case 2 (a younger brother of the first case) was also diagnosed as having an aneurysm of the ventricular septum by fetal echocardiography at 28 weeks of gestation. Postnatal echocardiography confirmed this diagnosis.

CD8+ T-lymphocytes infiltrate the myocardium in fulminant herpes virus myocarditis.

We report two cases of fulminant viral myocarditis in previously healthy children. They were caused by herpes simplex virus (HSV)-I (in a boy aged 3 years) and Epstein-Barr virus (EBV) (in a boy aged 12 months). We obtained the diagnosis of HSV-l myocarditis by immunohistochemistry and the diagnosis of EBV myocarditis by in situ hybridization. Histologic examination of heart tissue from the two boys revealed mononuclear cell infiltration of the myocardium. Immunohistochemical staining identified these cells as CD8+ T-lymphocyles. CD8+ T-lymphocytes induced by herpes virus infections may play an important role in the damage to heart muscle fibers seen in fulminant myocarditis in previously healthy children. To our knowledge, this is the first report of HSV-l or EBV myocarditis (at least in children) in which viral infection has been demonstrated in the myocardium.

CTLA-4 (CD152) expression in peripheral blood T cells in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of early childhood caused by vasculitis. Whether or not peripheral blood T cells are activated in acute KD remains uncertain, as some reports have presented evidence of peripheral blood T cell activation, whereas others suggest that the level of peripheral blood T cell activation is low during acute KD. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4, CD152) is a surface molecule of activated T cells. We therefore investigated intracellular CTLA‐4 expression in the peripheral blood T cells of patients with acute KD as a marker of T cell activation. We collected blood samples from 20 patients with KD and six with Epstein–Barr virus infectious mononucleosis (EBV‐IM) who were admitted to our hospital, as well as 13 healthy children. We determined the intracellular expression of CTLA‐4 in T cells by flow cytometry. We demonstrated that the intracellular expression of CTLA‐4 is up‐regulated in peripheral blood CD3+ T cells, CD4+ T cells and CD8+ T cells at the early part of the acute stage in KD. However, the mean percentages of intracellular T cells expressing CTLA‐4 in EBV‐IM patients were about fourfold higher than those in T cells from patients with acute KD. Our results suggested that the level of activation of peripheral blood T cells is very low during acute KD.

Prenatal diagnosis and management for a large fetal cardiac tumor complicated with hydrops fetalis

Fetal cardiac tumor is a rare disease, and its prognosis varies in relation to the complications such as arrhythmia and out‐flow obstruction. Hydrops fetalis is one of severe complications that result in an unfavorable outcome. A case is presented herein of a large fetal cardiac tumor diagnosed at 28 weeks gestation. At 30 weeks gestation, the fetus complicated with hydrops fetalis because of impaired cardiac function. Increased peak systolic velocity in the ascending aorta and marked reversed flow in the ductus venosus were observed. Oral digoxin therapy was administered to the mother as a cardiotonic agent and the hydropic condition was immediately diminished. After normal delivery, the cardiac tumor gradually decreased in size and the infant developed normally, but required an antiarrhythmic drug. The case indicates that the in utero digoxin therapy could be a choice for hydrops fetalis caused by cardiac tumor.

Successful Treatment of Supraventricular Tachycardia Exhibiting Hydrops fetalis with Flecainide Acetate

Background: The efficacy of flecainide acetate for the treatment of fetal supraventricular tachycardia with hydrops fetalis and changes in venous blood flow patterns in the fetus during treatment are reported. Case: Oral flecainide administration was started at 30 weeks of gestation. Cardioversion was achieved 6 days after treatment. Sustained abnormal venous Doppler indices were shown and complete normalization of venous returns was observed 6 days after cardioversion. A vigorous male baby was born, and he is now 1 year of age and in good condition with no medication. Conclusion: Reversible cardiac dysfunction was observed even after cardioversion in the fetus with supraventricular tachycardia, which could be assessed precisely by venous Doppler analysis.

MBP deposition in eosinophilic gastroenteritis

can exclude that the persistence of IgE to this drug was due to other drugs crossreacting with cefaclor because during this period of time the child did not take any drugs. However, an uncontrolled or hidden contact, as with b-lactams, can occur in subjects with hypersensitivity to these drugs (7). Therefore, in our patient, an uncontrolled or hidden contact with cefaclor could have maintained the production of speci®c IgE to cefaclor. Other possible explanations for the persistence of IgE to cefaclor are 1) the ingestion of foods that might have allergenic peptides in common with cefaclor 2) the presence of genetic factors which might be responsible for the continuous production of speci®c IgE to cefaclor without the presence of a speci®c stimulus 3) the intrinsic peculiarity of cefaclor to induce a persistent IgE immune response. All these are only hypotheses because there are no studies on this matter. In conclusion, this case shows that IgE to cefaclor may persist for many years after the last administration. It is thus important to advise the cefaclor-allergic patient strictly to avoid the administration of this drug in later years. Further studies are needed to evaluate the persistence of speci®c IgE to cefaclor in subjects with cefaclor allergy.

Eosinophilic gastroenteritis associated with Epstein-Barr virus infection in a young boy

Eosinophilic gastroenteritis (EOG) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract, usually associated with eosinophilia in the peripheral blood (1). Its origin remains unknown, but several studies of adult cases indicate that eosinophil accumulation and release of eosinophil granule proteins such as major basic protein lead to damage of the gastrointestinal mucosa (2,3). Viral infection has been detected in a small number of patients with EOG (4), but there have been no reports of patients with Epstein-Barr virus (EBV) infection. We previously reported the immunohistopathologic findings of massive major basic protein deposition in the gastroduodenal mucosa of a child with EOG (5). We further examined the gastroduodenal biopsy specimens and found that the gastroduodenal damage observed in this case was associated with EBV infection.

Exercise- or dipyridamole-loaded QGS is useful to evaluate myocardial ischemia and viability in the patients with a history of Kawasaki disease.

Abstract Background : Evaluation of myocardial ischemia and viability is very important for the management of patients with a history of Kawasaki disease (KD). 99mTc‐tetrofosmin myocardial perfusion scintigraphy combined with quantitative gated single photon computed emission tomography (QGS) gives us information, not only about perfusion, but also the percentage change in left ventricular wall thickness (%WT) and relative changes in left ventricular wall motion (LVM).