Hisaji Igarashi

Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on thyroid hormone status were studied in the peripheral blood of 36 breast-fed Japanese infants. Estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) from the breast milk significantly and negatively correlated with the levels of triiodothyronine (T3) and thyroxine (T4) in the blood of breast-fed babies. Therefore, exposure to background levels of the highly toxic organochlorine chemicals through the breast milk may cause some effects on thyroid hormone status in Japanese infants.

Postnatal exposure to chlorinated dioxins and related chemicals on lymphocyte subsets in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on lymphocyte subpopulations were investigated in the peripheral blood of 36 breast-fed Japanese babies. As a result, estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) equivalents from the breast milk positively and negatively correlated with the respective percentages of CD4+ and CD8+ lymphocytes in the blood of breast-fed babies. Consequently, the ratios of CD4+ to CD8+ T cells showed significant increasing tendency with the estimated total TEQ intakes. Therefore, our study suggests that exposure to background levels of the highly toxic organochlorine compounds through the breast milk influences the human neonatal immune system.

Spectrum of infective endocarditis during infancy and childhood: 20-Year review

SummaryThe medical records of the 29 patients under 18 years of age with infective endocarditis (IE) seen over a 20-year period by our department were reviewed to provide an overview of the spectrum of IE during infancy and childhood. None of the 29 patients had had previous cardiovascular surgery. The mean age at onset of IE was 7 years 2 months; 3 patients (10%) were under 2 years of age at onset. One patient during the early years died following 4 months of treatment with various antibiotics. Three patients underwent urgent surgery, and 17 patients with healed IE had elective surgery. All of the 20 patients who were operated on survived. The remaining 8 were followed with medical treatment alone. Positive blood cultures were obtained from 24 (83%) patients, and streptococci were still commonly found (38%). Ventricular septal defect (VSD) accounted for 66% of underlying heart diseases and rheumatic heart diseases for 14%. Vegetations were detected in 12 (67%) of 18 patients observed by echocardiography. Among these 12 patients, 1 with VSD underwent urgent tricuspid valve replacement and VSD closure because of worsening congestive heart failure due to progressive tricuspid regurgitation. Echocardiography identifies patients at high risk with IE, though the presence of a vegetation on echocardiography does not necessarily of itself dictate surgical intervention.

Life Expectancy and Social Adaptation in Individuals with Down Syndrome with and Without Surgery for Congenital Heart Disease

Life expectancy and social adaptation in 373 children with Down syndrome with and without congenital heart disease (CHD) were assessed retrospectively. Survival at age 24 years was 92.2% for patients without CHD (n=200), and 74.6% for those with CHD (n=173). Survival for those who underwent operation for cardiovascular lesions (n=95) was 87.8%, and for those not operated on despite hemodynamically significant cardiovascular lesions (n=39), it was 41.4%. Cardiac functional capacity was better in the children without congenital heart disease and in the group operated on, where most patients also attained good social adaptation. We conclude that children with Down syndrome with congenital heart disease should undergo early cardiac evaluation and surgery if indicated.

Long-Term Outcome of Coronary Abnormalities in Patients After Kawasaki Disease

From January 1973 through December 1992, a total of 302 patients (183 males, 119 females) with Kawasaki disease (KD) underwent coronary angiography. The age at onset of KD ranged from 2 months to 12.3 years (median 1.4 years). The age at the first angiographic evaluation ranged from 6 months to 17 years (median 3.5 years). Most of the patients (85%) had suffered from KD before 1985 and thus were treated without benefit of γ-globulin. Follow-up varied from 6 months to 25.8 years (median 13.6 years). Coronary abnormalities were confirmed in 71 (23.5%) of 302 patients; the left coronary artery (LCA) alone was involved in 36 cases, the right coronary artery (RCA) alone in 10 cases, and both arteries in 25 cases. Serial angiographic evaluation of the 42 cases revealed different attitudes in the progress of coronary abnormalities. All large aneurysms showed a tendency to regress, although some progressed to stenotic lesions. Moderate aneurysms stayed unchanged, regressed, or progressed to stenosis or obstruction. Small aneurysm never became stenotic and frequently regressed to normal internal diameter. aneurysms of the RCA tended to regress relatively early during the follow-up period, whereas those of the LCA gradually progressed to stenotic lesions. In 7 of 35 patients with RCA lesions, aneurysms progressed to complete obstruction and subsequent recanalization within 0.5 to 7.7 years (median 3.6 years) after the onset of KD. Most of the patients with coronary artery sequelae after KD remain asymptomatic. Serial angiographic observation is indicated for those patients who develop large coronary aneurysms during the acute phase of KD. The standard 12-lead electrocardiogram, chest roentgenogram, and exercise stress test are less sensitive for detecting and evaluating patients with coronary sequelae. For the screening of myocardial ischemia after KD, stress thallium 201 scintigraphy with dipyridamole infusion is recommended.

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease.

Abstract We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs=0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.

Long-term prospective study on the natural history of Wolff-Parkinson-White syndrome detected during a heart screening program at school

In the period 1985 to 1993, a total of 802 school‐aged children (284 first‐graders and 518 seventh‐graders) were referred to our hospital for further evaluation of electrocardiographic abnormalities. Among them, 57 (male 24 and female 33) children were confirmed as having Wolff‐Parkinson‐White (WPW) syndrome based on the findings of 12‐lead surface electrocardiograms (ECG). According to Lindsays criteria, the locations of the accessory pathways were as follows: Left‐lateral in 10 (18%), left‐posterior in 2 (4%), right‐free‐wall in 28 (49%), anterior‐septum in 13 (23%) and posterior‐septum in 3 (5%). One 12‐y‐old girl had multiple accessory pathways. Six patients had associated diseases: Ebsteins anomaly in 4, epilepsy in 1 and mental retardation with scoliosis in 1. Follow‐up periods ranged from 2.0 to 13.0 y (mean SD: 8.0 ± 3.3 y) for 23 first‐graders with WPW syndrome, and from 2.0 to 13.0 y (mean SD: 7.3 ± 4.2 y) for 34 seventh‐graders, respectively. Initially, 5 children had at least one episode of supraventricular tachycardia (SVT) by history and 6 children developed SVT during the follow‐up. One girl with multiple accessory pathways and recurrent SVT required long‐term drug therapy.

Discordance between thallium-201 scintigraphy and coronary angiography in patients with kawasaki disease: Myocardial ischemia with normal coronary angiogram

SummaryTo assess the usefulness of radionuclide tests in detecting coronary occlusive lesions in children with Kawasaki disease, we compared the results of stress thallium-201 myocardial single photon emission computed tomography with dipyridamole infusion and coronary angiography in 34 patients (19 males and 15 females). Perfusion defects on the stress image only were categorized as transient and were attributed to coronary vascular disease in the presence of redistribution on the delayed image. Others were classified as persistent, due to myocardial damage. Five of the seven children (71%) with severe stenosis on coronary angiography showed persistent and/or transient perfusion defects. However, six of the 11 children (55%) with aneurysms but no obvious stenosis, and four of the 16 children (25%) with normal angiography, showed persistent and/or transient defects. After analyzing 20 individual segments of perfusion defects in the 15 children, six segments (30%) were attributed to the stenosis of supplying coronary arteries, six segments (30%) were related to the coronary aneurysms, and eight segments (40%) were unrelated to any abnormalities on angiography. Thus, significant discordance between the radionuclide and angiographic studies was demonstrated. These results suggest that coronary lesions, as conventionally defined by angiography and supplemented by echocardiography, may not completely identify all Kawasaki patients who may develop myocardial ischemia in the future or who had ischemia in the past.

Serum hepatocyte growth factor combined with vascular endothelial growth factor as a predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

Abstract. We investigated the possible use of serum hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels as a predictive indicator for the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41 patients with KD and 25 afebrile controls. Serum HGF levels of patients in the acute phase of KD were significantly higher than those of afebrile controls (Pc<0.05) and decreased to lower levels during recovery (P<0.0001). Univariate analysis showed significant correlations between occurrence of CAL and five variables: duration of fever (P=0.018), serum C-reactive protein concentration (P=0.024), albumin concentration (P=0.009), serum VEGF level (P=0.009) and serum HGF level (P=0.035). Furthermore, multivariate analysis revealed that serum HGF and VEGF levels and presence of oedema were major risk factors for the occurrence of CAL. For prediction of the development of CAL, we established a new risk classification system with these three variables, which showed a sensitivity of 100% and a specificity of 94.4%. Conclusion: these data show that hepatocyte growth factor, together with vascular endothelial growth factor, might play an important role in the pathophysiology of Kawasaki disease and their serum levels could be a powerful predictor for the development of coronary artery lesions.

Central nervous system vasculopathy associated with neonatal lupus

Neonatal lupus erythematosus, characterized mainly by congenital heart block and transient skin lesions, is usually self-limited. A patient with history of neonatal lupus erythematosus and congenital heart block developed central nervous system vasculopathy resembling moyamoya disease and hypertension at 17 years of age. Careful examination and follow-up of possible central nervous system complications later in life might be important in infants with neonatal lupus erythematosus.