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Background There is little data on the long-term effects of continuous intravenous epoprostenol for children with idiopathic pulmonary arterial hypertension (IPAH) in Japan. Methods and Results Thirty-one IPAH patients younger than 18 years old who had begun epoprostenol therapy at Toho University Omori Medical Center between January 1999 and June 2004 were reviewed. During a mean follow up of 3.4 years, the rate of those who survived or did not undergo a lung transplantation among the 27 patients who received home infusion therapy of epoprostenol was 100% at 1 year, 96.3% at 2 years, and 79.4% at 3 years. In 82% of survivors, the World Health Organization functional class was changed from III or IV to II according to improvements in the plasma brain natriuretic peptide level and the distance walked in 6 min during the follow-up period. In most cases, mean pulmonary artery pressure and the ratio of pulmonary to systemic vascular resistance remained high, although the cardiac index had improved to within a normal range 1 year after the initiation of epoprostenol. Therefore, sildenafil was administered as an additional therapy to 16 patients who presented with sustained severe PAH. Conclusions Continuous IV epoprostenol certainly improves survival and exercise tolerance in childhood IPAH, although the improvement of pulmonary vascular resistance regardless of long-term epoprostenol therapy is insufficient. Therefore, the addition of a new drug, such as sildenafil, is recommended to be administered in adjunction with epoprostenol. (Circ J 2007; 71: 1785 - 1790)

Carbamazepine (CBZ), a widely used anticonvulsant, occasionally causes serious hematologic disorders. A 12-year-old boy was admitted because of a diffuse petechial rash and profound thrombocytopenia (10 x 10(9) platelets/l), after having been treated for epilepsy with CBZ for 12 days. Seven days following withdrawal of CBZ and initiation of prednisolone therapy, the platelet count recovered. In a subsequent challenge test with CBZ, platelet counts again decreased, and the levels of platelet-associated IgG and serum interleukin-6 increased. No antibodies against platelet glycoprotein IIb/IIIa or Ib were detected in plasma. We believe that this is the first reported occasion when CBZ-induced thrombocytopenia has been defined by a rechallenge test.

A small-for-gestational-age infant with cyanosis due to double outlet right ventricle with severe pulmonary stenosis and patent ductus arteriosus was treated with oral prostaglandin E1 derivative (OP-1206). The constricting ductus arteriosus dilated and the ductus-dependent pulmonary blood flow increased. The recommended dosage was 1.5-2.0 micrograms/kg/day which was lower than that of intravenous PGE1 or of oral PGE2. The administration interval was 6 hours, which was longer than that of oral PGE2. The patient was treated as an out-patient because continuous intravenous infusion was not necessary. Treatment was continued for 2 months without complication, at which time a Blalock-Taussig shunt operation was performed. Orally administered PGE1 derivative (OP-1206) was found to be equally effective to intravenous infusion of PGE1 for both short and long-term management of cyanotic heart disease in which the pulmonary blood flow is mostly dependent on the patency of the ductus arteriosus. Oral PGE1 derivative (OP-1206) may be a possible substitute for intravenous PGE1 infusion therapy.

We report here a case of neonatal hyperthyroidism born to a mother, whose pregnancy was complicated by poorly controlled Graves' disease. The patient demonstrated exophthalmos and marked goiter at birth, indicating the existence of thyrotoxicosis in utero. The mother's Graves' disease was well controlled in the third trimester, resulting in a slightly lower level of free thyroxine (FT4) in the umbilical cord blood serum; however, thyroid-stimulating hormone (TSH) was undetectable. Thyroid-stimulating hormone remained undetectable for 2 months, while FT4 levels varied in the course. This case suggests that severe and prolonged thyrotoxicosis in utero, due to poor control of pregnancy with Graves' disease, might induce unresponsiveness of the hypothalamo-pituitary system in the newborn.

SummaryKawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO) and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106 age-matched controls using ELISA. TPO values in the controls were 1.94 ± 0.69 fmol/ml (mean ± SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In the first week of KD, platelet counts were normal but TPO values increased (~ 15.5 fmol/ml). TPO levels peaked on day 6 ± 2 at 5.94 ± 2.64 fmol/ml and then fell gradually. When platelet counts peaked in the second to third weeks, TPO levels were still high or comparable with the controls. TPO levels in KD patients with normal platelet counts were significantly higher than control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL-11 nor leukemia inhibitory factor was detectable. These results suggest that TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase.

IL-5 play important roles in inflammatory responses in bronchial asthma, but little is known about serum levels and in vitro production of IL-5 in childhood bronchial asthma. We further examined serum IL-5 levels in children with bronchial asthma and the controls. IL-5 in serum was detected in all of asthmatic and disease-free individuals. Its values during asthma exacerbation were significantly higher than during remission of asthma. Serum IL-5 values did not significantly differ among groups divided by asthma severity. We studied IL-5 production by peripheral blood mononuclear cells cultured with or without Dermatophagoides farinae (Df) in children with mite allergy. IL-5 concentrations in culture supernatant from after stimulation with Df were significantly higher than those from asthmatic patients without stimulation and from the control subjects. In contrast, IL-5 levels in culture media from the controls were not significantly different between with and without stimulation with Df. Our results suggest that IL-5 may play roles in the pathogenesis of bronchial asthma.

Although, the efficacy of 2g/kg IVGG has been widely accepted, 1g/kg single administration of IVGG(1g-IVGG) alone is also effective in a certain number of acute Kawasaki disease(KD) patients(pts). To investigate the efficacy of 1g-IVGG in acute KD pts, we reviewed 136 pts started with IVGG (108 pts started with 1g/kg, and 28 pts started with 2g/kg). Among 108 pts, 1g-IVGG alone was effective in 68 pts(63%)(CRP: 7.7+/-3.7mg/dl), and 35(32%) of 40 pts(CRP:10.7+/-6.5mg/dl,p

Background: In acute phase Kawasaki Disease (KD), subclinical myocarditis is usually complicated. In recent studies, the heart-type fatty acid-binding protein (H-FABP) can be used as an early indicator of myocardial injury in adults. Objective: To investigate silent myocardial injury in patients with acute phase KD, we studied the serum levels of several biochemical markers for detecting evidence of myocardial injury. Patients M M/F=14/12). Results: The mean levels of H-FABP were 4.3 ±1.9 ng/ml before IVGG and decreased to 3.7 ±1.5 ng/ml (p

Background: Matrix metalloproteinases (MMPs) have been considered to play a pivotal role in extracellular matrix breakdown. The activity of MMPs is closely regulated by tissue inhibitors of metalloproteinases (TIMPs) under the pathophysiological conditions. In recent studies, the quantitative imbalance between certain MMPs and TIMPs may play an important role in the vascular remodeling process. Objective and Methods: To investigate the role of MMPs and TIMPs in vasculitis of patients with acute phase Kawasaki disease (KD), we sequentially measured the serum levels of MMP-1, 2, 3, TIMP-1, -2, and the plasma levels of MMP-9 using rapid one-step sandwich enzyme immunoassay before and after IVGG treatment. Nineteen patients (13 boys and 6 girls; 17.4±10.1 months of the mean age) with acute KD were studied. Results: The serum levels of MMP-1 and -3 before treatment were slightly elevated compared to normal range of adults reported in previous literatures and returned to normal range after 1 month. MMP-2 levels were slightly elevated before treatment and remained that level through 1 month later (p