Masayuki Teraguchi

Evaluation of Preclinical Atherosclerosis by Flow-Mediated Dilatation of the Brachial Artery and Carotid Artery Analysis in Patients with a History of Kawasaki Disease

Cardiac sequelae of Kawasaki disease are an important cause of ischemic heart disease in young adults. The possibility of early progression of atherosclerosis following Kawasaki disease is therefore of great concern. We examined whether preclinical atherosclerotic changes are seen in patients with a history of Kawasaki disease, and whether these changes appear in all or in only a proportion of patients. Sixty-five patients with a history of Kawasaki disease, aged 13.1 ± 2.1 years, and 20 aged-matched controls participated in the study. All subjects underwent flow-mediated dilatation (FMD) of the brachial artery and analysis of carotid artery size and pulse-wave transmission. Patients were classified into four groups depending on the severity of the maximum coronary artery lesion: group 0 (normal), group 1 (mild), group 2 (moderate), and group 3 (severe). There was no statistical difference in the carotid artery analyses between the four groups. FMD (mean ± SD) was significantly lower in groups 2 and 3 than in groups 0 and 1 and the control group (group 0, 19.4 ± 3.9%; group 1, 19.5 ±4.1%; group 2, 8.9 ± 2.8%; group 3, 4.2 ± 1.5%; control group, 18.8 ± 2.8%; p < 0.0001). There was a significantly negative correlation between the severity of the coronary artery lesion and FMD (p < 0.0001 for both). Endothelial dysfunction was revealed by FMD in patients with persistent coronary artery lesions subsequent to Kawasaki disease. Preclinical atherosclerosis may be present only in patients with coronary aneurysms.

Polymorphism of Fcγ RIIa May Affect the Efficacy of γ-Globulin Therapy in Kawasaki Disease

We evaluated whether there is a possible relationship between the effectiveness of γ-globulin treatment for patients with Kawasaki disease (KD) and the polymorphism of Fcγ RIIa, IIIb, and IIIa. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received γ-globulin treatment. The genotypes for Fcγ RIIIb-NA(1, 2), Fcγ RIIa-H/R131, and FcγRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions (CALs). Twenty-three percent of patients with the HH allele for the Fcγ RIIa polymorphism progressed to CALs, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of CALs in KD before the initiation of γ-globulin therapy.

Multiple Hepatoblastomas Associated with Trisomy 18 in a 3-Year-Old Girl

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.

Plasma Levels of Nitrate in Congenital Heart Disease: Comparison with Healthy Children

Nitric oxide (NO) is an endothelium- derived relaxing factor, and plasma nitrate is the stable end product of NO production. The aim of this study was to investigate the change in levels of plasma nitrate according to age and to elucidate the effect of pulmonary hypertension (PH) associated with congenital heart disease on NO production. We measured plasma levels of nitrate in 48 healthy children aged 5 days to 12 years to establish the normal range. Forty-six preoperative patients aged 4 months to 12 years with congenital heart disease were studied by cardiac catheterization. Plasma nitrate in healthy children decreased with age, from 1 month to 1 year, and then remained almost constant until the age of 12 years. Plasma nitrate was significantly increased in 22 preoperative patients with PH (mean pulmonary arterial pressure >?25 mmHg) compared with age-matched normal controls: (mean 56.9 vs 33.5 µmol/L, p<0.05) and was significantly correlated with pulmonary to systemic pressure ratio (r= 0.83, p < 0.0001). There was no significant difference between plasma nitrate levels in 24 preoperative patients without PH and those in the age-matched normal control (mean 25.6 vs 24.9 µmol/L). In 10 patients with preoperative PH who were examined before and after surgery, plasma nitrate levels remained high in the cases with residual PH but decreased to the normal range in the cases without residual PH. Plasma nitrate level is useful for evaluating PH both before and after operation in patients more than 4 months of age, and it is important to note differences in normal plasma nitrate levels according to age.

Pulmonary infarction and deep venous thrombosis in a 13-year-old boy with Churg–Strauss syndrome

childhood, such as anaphylactoid purpura and Kawasaki disease, there are some rare but important disorders affecting children. Churg–Strauss syndrome (CSS) is one of these and is characterized by hypereosinophilia and systemic vasculitis that develops in patients with allergic disorders.1 Some patients with CSS have multisystemic involvement and often have various complications.2,3 The purpose of this report is to describe a case of CSS associated with pulmonary infarction and deep venous thrombosis and to summarize the patients in childhood previously reported.

A case of Kawasaki Disease associated with syndrome of inappropriate secretion of antidiuretic hormone

Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Plasma Nitric Oxide Products Correlate with Cardiac Index of Congenital Heart Disease

Abstract. We wished to determine the relationship between circulating levels of nitric oxide (NO) and cardiac index (CI) in children with congenital heart diseases. We measured the plasma levels of nitrate/nitrite (NOx), the stable end products of NO production as well as tumor necrosis factor-α (TNF-α), atrial natriuretic peptide (ANP), and brain natriuretic peptide in relation to various parameters determined simultaneously.The plasma NOx levels correlated negatively with CI (r=−0.541, p < 0.05). No correlation was observed between NOx and cardiac output. TNF-α correlated with NOx levels (r= 0.593, p < 0.005) but not with either CI or cardiac output. Plasma levels of ANP and TNF-α were higher in atrial septal defect than those in the control group (p < 0.001 and p < 0.05, respectively). Elevated plasma NOx could explain the increased basal release of endothelial NO due to high pulmonary blood flow. Plasma NOx correlate negatively with CI in young patients with left-to-right shunt congenital heart diseases.

Early changes in plasma brain and atrial natriuretic peptides in premature infants: correlation with pulmonary arterial pressure

To define the change in plasma natriuretic peptides in newborns, we prospectively studied 10 premature infants. They were followed sequentially during the first week of extrauterine life by two-dimensional and pulsed Doppler echocardiography, and studied for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We estimated mean pulmonary arterial pressure (MPAP) and measured blood pressure on days 1, 2, 3, 5, 7, respectively. Plasma ANP levels were 81.7 +/- 11.4 pg/ml on day 1 and 67.9 +/- 6.0 pg/ml on day 7, respectively. Between day 2 and day 7, there was a fall in MPAP, i.e. from 37 +/- 4 mmHg to 22 +/- 2 mmHg (P < 0.01), which was associated with a significant decrease in plasma BNP (41.8 +/- 10.1 pg/ml on day 2 vs. 10.4 +/- 0.9 pg/ml on day 7, P < 0.01). There was a positive correlation between MPAP and plasma BNP level (r = 0.643, P < 0.0001), but there was no correlation between MPAP and plasma ANP level. These data suggest that the pattern of secretion of BNP is different from that of ANP and that BNP levels reflect the changes of pulmonary arterial pressure in the neonatal period in premature infants.

Idiopathic CD4+ T-lymphocytopenia in a boy with down syndrome: Report of a patient and a review of the literature

Idiopathic CD4+ T-lymphocytopenia (ICL) has been supposed to be a rare syndrome characterised by a decreased number of CD4+ T-lymphocytes (<300 CD4+ cells/ll or a CD4+ count <20% of total T cells) on two occasions and clinically manifested by opportunistic infections [11]. Also, any defined immunodeficiency disorder must be excluded such as human immunodeficiency virus (HIV), Epstein-Bar virus, and cytomegalovirus infection. We report on a boy with Down syndrome who was found to have ICL. A 6-year-old boy with Down syndrome was admitted because of an induration of subcutaneous tissue in the left lower abdominal wall. At 5 years and 1 month of age, a suture granuloma was excised which was caused by a silk string left after orchiectomy performed 3 years before for epididymitis. Ten months later a mass developed in the same region. Although he responded temporarily to oral antibiotics, the mass reappeared. Blood culture grew Stenotrophomonas maltophilia. On admission, the leukocyte count was 4,400/ll with 55.5% lymphocytes. C-reactive protein was negative, but the erythrocyte sedimentation rate was 54 mm/1 h. IgG antibody to Epstein-Bar virus capsid antigen was present in a titre of 1:40. Serum cytomegalovirus antibody was negative. Serum HIV-1 and HIV-2 antibodies were negative. Flow cytometric analysis showed the following: CD3+ T-lymphocyte counts (/ll) (% of total lymphocyte count), CD19, CD4, and CD8 were 1,709 (70.0%), 168 (6.9%), 530 (21.7%), and 1,424 (58.3%), respectively. Debridement was performed and the wound was left open after intravenous ceftazidime treatment. The postoperative course was uneventful. The CD4+ T-lymphocyte counts were persistently low for 1 year and 4 months and were less than 20% of total lymphocytes on four occasions (18.8%, 16.7%, 18.6%, and 19.7% at the age of 6 years and 4 months, 6 months, 8 months, and 10 months, respectively). Slightly reduced CD45RA expression (53.1%), slightly enhanced CD45RO expression (28.7%), and distinctly enhanced CD95 expression (71.0%) on CD4+ T cells were seen, compared to a control patient (70.6%, 15.9%, and 32.1%, respectively). Two patients were noted to have ICL among 22 patients with Down syndrome (male/female: 12/10, age 5 months to 31 years). One was a 25-year-old woman whose minimum CD4+ T-lymphocyte count was 278/ ll. The other was a 12-year-old, whose last two lymphocyte counts were 178 and 185/ll, respectively. Most patients reported with ICL are adults, but so far 28 children with ICL including our patient have been reported. The features of 18 symptomatic children with ICL are shown in Table 1. These children with ICL are thought to be at risk of developing opportunistic infections, but can be asymptomatic [7]. Stenotrophomonas maltophilia is a short to mediumsized straight gram-negative bacillus, which is isolated especially from immunocompromised hosts [9]. In the patient described here, the persistent tumour associated with Stenotrophomonas maltophilia infection prompted the immunological evaluation. Patients with Down syndrome are known to have immunological abnormalities including decreased numbers of CD4+ T-lymphocytes [5], but the extent of CD4+ T-lymphocytopenia is milder than that observed in ICL [1]. Genetic factors may cause ICL [2, 6], and the identification of trisomy 21 as a cause of ICL may aid in the identification of these genes.

Plasma levels of nitric oxide products and endothelin in pulmonary hypertension with congenital heart disease.

bral degeneration, severe seizures, psychomotor retardation and lens dislocation, and biochemically by increased quantities of sulphite, S-sulphocysteine, taurine and thiosulphate in urine, with cysteine being low, in the presence of normal serum urate. Xanthine dehydrogenase functions in the degradation of purines, isolated deficiency of which results in calculi in kidney and xanthine deposits in muscle, xanthinuria and hypouricaemia with no clinical symptoms (2, 3). In our patient, who exhibited the combination of some clinical and laboratory features of both enzymes, we showed deficient sulphite oxidase activity in cultured skin fibroblasts. A very low serum uric acid level indicated xanthine dehydrogenase deficiency, albeit indirectly (4). In MCD, no therapeutic attempts have been successful in reversing the clinical symptoms. Although the prognosis of MCD is unfavourable, correct diagnosis is still essential, when the availability of the prenatal diagnosis, by demonstrating sulphite oxidase deficiency in the chorionic villus samples or increased S-sulphocysteine in amniotic fluid, is considered (5, 6). Therefore, blood uric acid measurement should be included in the battery of tests to be performed in all refractory neonatal seizures.