[Partial anomalous pulmonary venous drainage to the high superior vena cava; repair by direct anastomosis between the superior vena cava and the right atrial appendage; report of a case].

A 10-year-old boy with partial anomalous pulmonary venous connection to the high superior vena cava (SVC) underwent surgical repair by Williams method. The SVC was divided above the orifice of the anomalous pulmonary vein. The proximal end of the SVC was closed and the distal end of the SVC was anastomosed to the right atrial appendage (RAA). The anomalous pulmonary vein was rerouted to the left atrium via the SVC and the surgically enlarged central type atrial septal defect (ASD). The postoperative course was uneventful except transient sinus bradycardia and catheter study showed no stenosis of the SVC and the RAA.

Correlation of genetic etiology with response to beta-adrenergic blockade among symptomatic patients with familial long-QT syndrome.

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome.

BACKGROUND: Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. METHODS AND RESULTS: DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C-->T mutation was identified at nucleotide 362 of alpha-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T-->A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A-->G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. CONCLUSIONS: These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, alpha-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.

Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications.

BACKGROUND: To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (IVGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD). METHODS: A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for 2-5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG). IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis. RESULTS: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG z-score (< -0.7485 vs > or = -0.7485), was 30.3 (95% confidence interval, 3.8-243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion. CONCLUSIONS: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.

Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.

BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.

[A quantitative study of regional cerebral blood flow in childhood using 123I-IMP-SPECT: with emphasis on age-related changes].

Single photon emission computed tomography (SPECT), using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) was used for quantitative analysis of regional cerebral blood flow (rCBF) on 26 individuals between 0 and 19 years of age. The rCBF showed age-related changes; it was low in early infancy, increased in late infancy through early childhood, and decreased and remained constant after puberty. The rCBF through cerebral cortex varied more greatly than through thalamus and cerebellum, and seemed to depend more closely on age. In the case of 4 months of age rCBF was very low at the frontal region and was very high at the occipital region. In more older cases, rCBF in the cerebral cortex was higher than in the thalamus. In childhood, rCBF was very inconsistent and showed a great inter-individual variance.

Successful percutaneous closure of a coronary artery fistula with a detachable balloon.

Percutaneous transcatheter closure technique of a coronary artery fistula with a detachable balloon was performed for a 14 year old male student. Complete closure of the fistula without any complications was confirmed by angiography after the procedure. When the patient underwent a second angiography 6 months after the closure, it was confirmed that the position of the balloon had not changed, that the interruption of the flow of the fistula had been maintained and that the diameter of the left coronary artery and the fistula were reduced. Percutaneous closure technique using a detachable balloon may become the primary treatment for a coronary artery fistula in place of surgical ligation.

Histopathologic and coronary angiographic assessment of effectiveness of aspirin or aspirin-and-gammaglobulin in Kawasaki disease.

Coronary angiography and right ventricular endomyocardial biopsy were performed in 36 children during convalescence (days of illness 23-86; mean = 41.5 days) following acute Kawasaki disease. Treatment of the acute stage was not randomized; it consisted of aspirin alone in 14 subjects (during the years 1980-88), and gammaglobulin and aspirin in 22 subjects (1984-91). The dosage of aspirin was 30 mg/kg orally during the acute febrile stage and 5-10 mg/kg orally after lysis of fever. The dosage of gammaglobulin was 200 mg/kg x 5 days in 19 patients, 200 mg/kg x 3 days in one patient, 200 mg/kg x 1 day + 400 mg/kg x 4 days in one patient and 200 mg/kg x 4 days + 400 mg/kg x 4 days in one patient. Among the 14 patients treated with aspirin alone, large coronary aneurysms were noted in four, moderate aneurysms in three and transient aneurysms in one. Among 22 patients treated with gammaglobulin, only five had aneurysms and these were transient. The histopathological (HP) score based on myocardial disarrangement, degeneration and hypertrophy; interstitial edema, large mononuclear cell infiltration and fibrosis; and endocardial abnormalities was higher in the aspirin group than in gammaglobulin group. Moderate to severe HP changes were noted in five subjects in the aspirin group, while moderate HP changes were found in only two subjects in the gammaglobulin group. Gammaglobulin therapy not only reduced the incidence of the coronary arterial lesions but also reduced the severity of myocardial damage from moderate or severe to mild in Kawasaki disease.

[Successful operation for isolated cardiac rhabdomyoma of the right atrium].

A 12-year-old girl has experienced palpitation and dizziness, and presented atrial flutter with maximal heart rate of 220/min. Two-dimensional echocardiogram and chest MRI revealed a mass attached to the inter-atrial septum. Complete excision of the tumor including the atrial septum was performed without damage to tricuspid valve. The interatrial septal defect was closed primarily. Histology of the tumor was compatible with cardiac rhabdomyoma. Sinus rhythm was present and no tachycardia occurred in the postoperative period. On the literature, only one case of isolated cardiac rhabdomyoma developing in the atrium was reported and this is considered as the oldest operative case in Japan.

A longitudinal study of blood pressure, cholesterol and left ventricular muscle volume in children: the Shimane Heart Study.

Three hundred and forty-four healthy schoolchildren living in Izumo City, Shimane Prefecture, Japan, were assessed at 3 year intervals from 6 to 15 years, starting in 1978 (Cohort 1) or 1981 (Cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y - z)/N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1, there is positive tracking. For systolic blood pressure (SBP) measurements (except at 6 years old) and serum cholesterol levels, all Ti were greater than 1.0 regardless of the time when tracking was commenced. Tracking indices were slightly greater in the serum cholesterol levels than in the SBP measurements. Left ventricular muscle volume indices (LVMVI) were calculated by echocardiographic measurements. In girls, the LVMVI was larger only in the above-median SBP group at the age of 12 years (P < 0.01), but the LVMVI of the higher SBP (above median) group was larger than in the lower (below median) group at every age in boys; the difference was statistically significant (P < 0.05) at 12 and 15 years of age. Left ventricular mass enlargement may occur in the prehypertensive stage in humans as well as in rats.

Methacholine inhalation challenge in children with idiopathic chest pain.

Bronchial reactivity to inhaled methacholine (MCH) was evaluated in 32 patients with 'idiopathic' chest pain. Each pain was recurrent in nature. The incidence of cases with a provocative concentration causing a 20% fall in the forced expiratory volume in 1 sec (PC20) of 10 mg/ml or less was 62.5% (20 cases), while it was only 11.1% (three cases) in 27 healthy controls. Seventeen patients had no personal history of allergic diseases, elevated serum IgE level or positive house dust mite-specific IgE antibody. Among these 17, eight (47.1%) had a PC20 of 10 mg/ml or less, the incidence of which was also higher than that of the healthy controls. During the challenge, eight patients complained of chest pain similar to that experienced before. The present results indicate that bronchial hyper-reactivity is an important cause of 'idiopathic' chest pain. Patients with unexplained chest pain should be considered for inhalation challenge.

Quantitative analysis of the tracking of blood pressure and relative factors in childhood: Shimane Heart Study.

1. In order to clarify the predictive factors of cardiovascular diseases caused by hypertension and hypercholesterolaemia in adults, a longitudinal epidemiological study was started in 1978. 2. This paper reports the results of research carried out from a quantitative analysis of the tracking of blood pressure and anthropometric parameters in children and adolescents using a tracking index. The index was calculated according to the changes in blood pressure quintiles for the whole population during the observation period. 3. The study population consisted of 5148 Japanese children living in the city of Izumo, who were examined every 3 years between the ages of 6 and 15 years old. 4. Although systolic blood pressure tracked weakly during childhood and adolescence, there was no significant relation between the tracking of systolic blood pressure and a family history of hypertension. 5. The tracking indices of the anthropometric parameters were better than those of systolic blood pressure, but the index of the left ventricular mass was similar to that of systolic blood pressure. 6. In conclusion the tracking of blood pressure might be determined by the tracking of bodyweight and height.

Chronic alpha 1 blockade in a patient with Eisenmenger syndrome.

In an 18-year-old male with Eisenmenger syndrome cyanosis and erythrocytosis were increasing. The erythrocytosis diminished following oral bunazosin and phlebotomy was not needed during the treatment. When bunazosin was stopped, the erythrocytosis increased, but when it was resumed, the erythrocytosis and general fatigue diminished.

Left ventricular diastolic function of children in high blood pressure tracking group.

The purpose of this study was to determine whether left ventricular (LV) diastolic function in children with high blood pressure (BP) is abnormal. We measured the corrected LV isovolumic relaxation time (IRT), peak velocity of increase in LV dimension (dD/dt) and the LV muscle volume in a high systolic BP tracking group (10 boys and 22 girls) and a low BP tracking group (22 boys and 11 girls) at 3-year intervals from the ages of 6 to 15. The corrected IRT of the high BP tracking group was significantly longer than the low BP tracking group. Left ventricular dD/dt/D of the high BP tracking group was significantly lower than the low BP tracking group from the ages of 12 in boys and 9 in girls. The left ventricular muscle volume index of both groups, however, was not significantly different. Both corrected IRT and dD/dt/D were well correlated with diastolic BP. These data suggest that children in the high BP tracking group might have LV diastolic abnormalities from age 12 or 15, in contrast to children of the low BP tracking group, without increased LV muscle volume. Therefore, it might be useful to examine BP and LV function of children from ages 12 or 15 for prevention of hypertension.

Japan: perspectives in school health.

In Japan, the original Law of School Health was established some 65 years ago to improve the environment and to prevent infectious diseases in school. Most recently, new environmental problems and behavioral issues have emerged. In addition to environmental health and health education, a major aspect of school health has been the development of a mass screening system both to detect present problems and to prevent adult diseases. In this article, the school health system in Japan is described and the application of mass screening by reference to heart disease as detected in Shimane Prefecture is illustrated. In the future, mass screening may be combined with a computer-based analysis system for managing data on new kinds of problems. New disciplines may become involved and improved programs developed, based on the lessons already learned from mass screening.