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Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 236 (41.5%) who were involved with MCA.

N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine(bis-diamin e) (100 micrograms) dissolved in dimethylsulfoxide (DMSO) was administered to early developing chick embryos (Hamburger-Hamilton stage 9-21) in order to clarify the teratogenic effects on the cardiovascular system and to determine whether bis-diamine interferes with the migration of neural crest cells. Of 346 cases, 154 (44.5%) survived. The incidence of cardiovascular anomalies was 149 out of 154 cases (96.8%). Infundibular ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus were the primary cardiac anomalies observed in this study. A high percentage of these anomalies were accompanied by hypoplasia of the right 6th aortic arch artery and persistent left 4th aortic arch artery. Particularly, administration of bis-diamine to chick embryos at stage 13 resulted in a high incidence of persistent truncus arteriosus (64.3%). Bis-diamine has been suspected to inhibiting the migration of neural crest cells. However, neural crest cells were observed in the tunica media of the great arteries and the truncal valves of persistent truncus arteriosus produced by bis-diamine in chimeric embryos at stage 13. Morphological changes such as cell death were not observed.

Aneurysm of the vein of Galen is a rare anomaly. In the severe type, the first clinical manifestation of this anomaly is heart failure after birth. Prenatal diagnosis is important in preventing heart failure during the postnatal period. Here, we report the prenatal diagnosis of a case of aneurysm of the vein of Galen in which we used a pulsed Doppler unit combined with a fetal electrocardiogram-phonocardiogram unit.

The quail-chick chimera method was used to examine whether neural crest cells were associated with the formation of semilunar valves. From the metencephalon to somite 5, or from the otocyst to somite 3, left, right, or bilateral neural folds, including the neural crest, were transplanted. Among embryos used for the experiment, three into which left neural crest cells were transplanted, two into which right neural crest cells were transplanted, and two into which bilateral neural crest cells were transplanted had a morphologically normal heart. In these embryos, neural crest cells were found in all cusps of the aortic and pulmonary semilunar valves. Although neural crest cells have been thought to have no association with the formation of the semilunar valves, our experiment indicates that such association indeed occurs.

The case of a female neonate with truncus solitarius pulmonalis (TSP), a rare congenital heart anomaly, is reported. She died four days after birth. A single right ventricle with common atrioventricular (AV) valve was associated with (Collet & Edwards type II) truncus arteriosus communis, and appeared to have a single coronary artery with an abnormally high take-off near the origin of the right subclavian artery. However, the vessel that appeared to be the single coronary artery was in fact an extremely hypoplastic ascending aorta associated with aortic atresia and agenesis of the left ventricle and mitral valve.

A 12-month-old boy with clinical findings suggestive of homozygous familial hypercholesterolemia, who had no secondary causes of hypercholesterolemia, and whose parents had no lipid abnormalities, was reported. No abnormalities were noted in the low density lipoprotein (LDL) receptor activities of the fibroblasts from patient, parents and sibling.

The heredity of hypohidrotic ectodermal dysplasia (HED) has been considered to be X-linked recessive, autosomal recessive or autosomal dominant. In this report, a genetic analysis was carried out on a total of 57 patients with HED including 6 patients recently examined by the present authors and 51 patients reported in Japan before May, 1980. The morbidity varied depending on sexes, being significantly higher in men than in women (p < 0.001). Consanguinity was positive in 12.8% of the patients. The segregation ratio calculated, however, suggested that an autosomal recessive trait did not account for all the cases. The pedigree analysis and the segregation ratios revealed that HED was probably not autosomal dominant. It is finally pointed out that the heredity of all the patients with HED reported in Japan might be X-linked recessive.

In a study of risk factors for coronary heart disease (CHD) in Japanese schoolchildren, serum cholesterol and triglyceride were measured in 3813 fasting schoolchildren ages 6 to 18 years, and simultaneously serum high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in a randomly selected subsample of 2579 children. Mean and standard deviations as well as the fifth, 50th and 95th percentiles for serum cholesterol, triglyceride, HDLC and LDL-C for males and females were summarized by the age groups. The percentage of serum cholesterol levels higher than 200 mg/dl and triglyceride levels higher than 140 mg/dl by sex and age were also shown. In the light of the present results, it is concluded that the serum cholesterol, triglyceride, HDL-C and LDL-C levels are suggested to be on the same level with those in the United States. Accordingly, the present results also appear to emphasize the importance of further studies on the serum lipid and lipoprotein levels in Japanese children, as they are emphasized in the Western countries with high CHD mortality rates.

The influence of bis-diamine on truncoconal septation was studied by the administration of 200 mg of this drug to pregnant Donryu-strain rats on day 10 of gestation. Fetuses were removed at nine time periods from day 11 to 15. Some hearts were observed under a scanning electron microscope; others were serially sectioned and observed by light microscopy. In the treated group, the aorticopulmonary septum and the 6th aortic arch artery were hypoplastic or aplastic. Truncal swellings and conal ridges showed hypoplasia and failure to fuse. Various types of persistent truncus arteriosus were found in association with the degree of development of the 6th aortic arch artery and the aorticopulmonary septum. Fused 6th aortic arch arteries corresponded to Collett and Edwards' persistent truncus arteriosus type II, and non-fused arteries to type III. Aplastic arteries belonged to type IV or were unclassifiable.

Two cases with association of Hirschsprung disease and preaxial polydactyly occurring in siblings were reported. The proband was a female infant examined on the 12th day after birth. Major findings were as follows: growth retardation, mild microcephaly, rightanophthalmia, left exophthalmus associated with double disk and coloboma choroidae, ocular hypotelorism, cleft lip and palate, and bilateral preaxial polydactyly. CT scan of the brain revealed agenesis of the corpus callosum and atrophy of the cerebral cortex. Autopsy revealed alobar holoprosencephaly and agenesis of the corpus callosum, right optic nerve and olfactory nerve. Aganglionosis of the rectumwas noted at a site 10 cm from the anus. When her brother was born, bilateral preaxial polydactyly was found. He had Hirschsprung disease as well.

A case of incontinentia pigmenti achromians associated with mental retardation, epilepsy, short stature and ocular anomalies was reported. A study of this case together with a review of the 38 cases in the literature revealed that this entity has been associated with central nervous system involvements at a high frequency. It is necessary, therefore, to consider incontinentia pigmenti achromians as a neurocutaneous syndrome from the viewpoint of pediatric neurology.

A clinical study was made of 69 cases, 50 male and 19 female of squamous cell carcinoma of the lower gum treated at the Oral Surgery Department of Hokkaido University, School of Dentistry between 1970 January and 1983 December.Ages at first visit ranged from 29 to 83 years old but about 95% were over 50 years old. The majority had clinically advanced disease. Fifty four had radiologically abnormal findings of alveolar crest or mandible, and 30 had clinically metastasis lymph node at the first diagnosis.The three year absolute cure rate for all cases was 54.9%. In the comparison of treatment modality, the cure rate treated by surgery was clearly superior to that by radiation therapy and/or chemotherapy: The cure rate of the former was 75.0% and that of the latter was 21.1%. Post-operative tumor control rate was related to the radiological findings of the mandible. The recurrent rate of patients who had radiologically an irregular lytic destruction of the mandible was 42% and that of patients who exhibited an erosion or change of the alveolar crest or mandible was 15%. These results indicate that wide resection with plenty of safety margin is necessary in lower gum canccr that radiologically had irregular lytic destruction.

We encountered two children with chronic idiopathic myocarditis accompanied by marked right ventricular dilatation, who died of progressive right heart failure. A definitive diagnosis was made by histological examination of the myocardium at autopsy. The patients were both boys, aged 7 years and 1 year and 4 months, and a number of identical features were evident upon physical and laboratory examinations. No heart murmur was heard, and gallop rhythm was noted in distant heart sounds. Electrocardiogram revealed intraventricular block, low voltage QRS complex, and ST-T abnormality. Two-dimensional Doppler echocardiogram and right ventriculogram showed marked dilatation and decreased contractility of the right ventricle as well as tricuspid regurgitation. Thinning of the wall and marked dilatation of the right ventricle were confirmed at autopsy. Our observations showed that chronic myocarditis associated with tricuspid regurgitation may readily lead to marked right ventricular dilatation even exceeding the degree of left ventricular dilatation. Idiopathic myocarditis associated with such unusual features is relatively rare, and may present problems in differentiation from other congenital heart diseases causing dilatation and dysfunction of the right ventricle.

The incidence of 28 minor physical anomalies was examined in 118 patients with early infantile autism, 132 patients with 21 trisomy, and 237 normal subjects. Although the incidence of minor physical anomalies in children with early infantile autism was slightly higher than in the group of normal subjects, there was no significant difference between the groups. It was suggested from these findings that there is little possibility of the onset of early infantile autism being due to environmental insults at the embryonic period when minor physical anomalies are formed, and that there is no possibility of minor physical anomalies giving a clue as to the time of onset of early infantile autism. The incidence of minor physical anomalies in patients with 21 trisomy was significantly higher than in the group of normal subjects and of children with early infantile autism (p < 0.00l). Fra (X) was noted in two patients among 40 examined. These patients were not included among the subjects in the present study.

Since prostaglandin E1> (PGE1) has been used for congenital cyanotic heart diseases of PDA-dependent type due to its ductus dilatation effect, it is now possible to perform shunt operations with recovery of the general condition. Simultaneously, however, various side effects have been reported. In recent years, periosteal hypertrophy has been attracting attention as a side effect after long-term administration of PGE1. In this study, the authors administered 0.03 μg/kg/min of PGE1 intravenously to an infant with a single ventricle and pulmonary atresia from the 7th day after birth. On the 9th day after the onset of administration, swelling and pain appeared in the lower limbs and later in the upper limbs. X-rays of the lesions revealed hypertrophy of the periosteum. After administering PGE1 for 98 days, a shunt operation was performed, and a biopsy of the right tibia was conducted. Microscopic examination of the biopsy specimen showed marked new osteogenesis due to woven bones, and resorption, including osteoclasts, presumably attributable to a reaction specific to woven bones.

Of 1,235 patients (609 male; 626 female) with congenital heart disease for whom types, etiology and associated congenital anomalies were determinable, 129 patients (10.4%) had mental retardatin. Patients with congenital heart disease complicated by mental retardation included 70 (54.3%) with chromosome aberrations, three(2.3%) with single gene disorders, two (1.6%) caused by environmental insult, and two (1.6%) with other recognized syndromes. Among the remaining 52 patients, asphyxia at birt was noted in 16, including 12 complicated by multiple malformations, and 4 in whom mental retardedation was presumed to be due to the asphyxia. In the remaining 36 patients, the incidence of the complication of mental retardation in cyanotic congenital heart disese was significantly higher than that in acyanotic congenital heart disease was signicantly higher than that in acyanotic congenital heart disease. Patients with congenital heart disease of unknown etiology associated with mental retardation included those from two families considered to have new pedigree syndromes.

Levels of human growth hormone (hGH) in urine samples were determined by a highly specific and sensitive sandwich enzyme immunoassay, which had little cross-reaction with human luteinizing hormone, human follicle-stimulating hormone, human thyroid-stimulating hormone and human prolactin. The volume of urine samples used was 0.05 ml. Urine hGH levels in normal subjects, aged less than 2 yr, 2-5 yr, 6-15 yr and 28-35 yr (male) were 78-113, 19-51, 7.8-25 and 1.1-5.2 ng/g of creatinine, respectively. In dwarfism patients aged 6-15 yr, urine hGH levels were < 0.2-6.0 ng/g of creatinine.

One hundred body surface isopotential maps for 30 normal infants, ages three hours to seven days, were evaluated. Ventricular activation and recovery were examined. In the early and mid phase of QRS, the maximum moved from the center of the anterior chest to the lower right portion of the anterior chest. In the late phase, the maximum appeared on the back. The niche appeared earlier in normal newborn infants (19.6 +/- 3.9 msec) (mean +/- S.D.) than in normal children (25.7 +/- 4.6 msec) (P less than 0.001). The location of the maximum at the time of peak positive potentials gradually shifted leftward during the first week of life. The 100 T wave maps were classified into three types. During the first day of life, the T wave maps showed type I or II, changing to type II or III a few days after birth. All T wave maps were type III a week after birth. The ratio of type III gradually increased with age. We found that the QRS maps were different from those of normal children and that T wave maps changed within the first week of birth.

Administration of the antispermatogenic agent bis-diamine (N, N'-bis-(dichloroacetyl)-1, 8-octamethylenediamine) to pregnant rats produced a malformation complex resembling DiGeorge syndrome in man. The malformations consisted of hypoplasia or aplasia of the thymus, persistent truncus arteriosus, tetralogy of Fallot, aberrant subclavian artery and other cardiovascular anomalies, as well as hypoplasia of the parathyroid gland, thyroid gland, and the spleen. The malformation complex appeared with a high incidence when the drug was administered on day 9.5 or day 10 of gestation. Since the connective tissues of the thymus, aorticopulmonary septum, smooth muscles of the media of the aortic arch artery, and connective tissues of the parathyroid and the thyroid glands, are of neural crest origin, and since the time of their migration is around day 10 of gestation, we postulate that the action of bis-diamine might be involution of the migration of the neural crest cells and of its pathways. We further suggest from the findings of persistent atrioventricular canal and hypoplasia of the spleen, that the drug must have also affected the growth of mesenchymal cells, which originate from the endocardial epithelial cells.

Spleen cells from newborn rats with bisdiamine-induced congenital malformation were examined for subpopulation of lymphocytes and responsiveness of the lymphocytes to phytohemagglutinin (PHA), concanavalin A (ConA) and lipopolysaccharide (LPS). T cells, but not B cells, were significantly diminished in the drug-treated newborn rats. Proliferative response of the lymphocytes to PHA and ConA, but not to LPS, was significantly depressed in the drug-treated newborns. Thus a defect in cell-mediated immunity was suggested to be associated with the congenital anomaly. It is tempting to consider that this bisdiamine-induced malformation can be another animal model for the DiGeorge syndrome.

We found 12 patients with congenital heart disease of unknown etiology complicated with blepharoptosis during a period from Sept. 1, 1981 to April 30, 1989. All the patients with congenital heart disease were acyanotic, including 10 with short stature. Among these 10, abnormalities of high frequency were intrauterine growth retardation (5 cases), mental retardation (5), microcephaly (3), epicanthus (4), high arched palate (4), sacral dimple (4), and distal axial triradius (3). It is postulated that the association of congenital heart disease, blepharoptosis and short stature might indicate pathogenetic relationships.

The etiology of congenital heart disease was studied in 1,076 patients who were diagnosed in our outpatient clinic from September 1, 198 1 to February 29, 1984. In these patients, 9(0.8%) had single gene disorders and 63(5.9%) had chromosomal aberrations, of which 55(87.7%) were Down syndrome. The number of patients who had congenital heart diseases due to environmental insult was 2(0.2%), and those with a malformation syndrome of unknown etiology were 6(0.6%). The etiology of congenital heart diseases in the remaining 996 patients (92.6%) was not clarified. In these cases, the rates of consanguinity of parents, and paternal and maternal grandparents, the ages of the parents when the patients were born, and the number of minor anomalies, were compared with those in normal controls. The complications of major anomalies were also investigated. Further, the recurrence risks in patients' siblings were also calculated.

Four siblings presenting a combination of severe microcephaly, short and laterally downward slanting palpebral fissures, hypertelorism, micrognathia, and growth retardation are reported. The proband had congenital heart disease complicating these characteristic symptoms. The parents were not consanguineous. The karyotypes of the proband and parents were normal. The faces of three brothers of the proband were very much like that of the proband, but tvjo of them had cleft palates. Although it was confirmed that one of the three brothers did not have congenital heart disease, its presence in the other two could not be ascertained. All three older brothers died within one month after birth.

Three cases of criss-cross heart which we have observed during last five years are described. All of these cases were diagnosed by angiocardiography and two-dimensional echocardiography, and one of them was verified by autopsy. Two of them are unique among cases reported thus far. Case 1 shows ordinary criss-crossing with supero-inferior ventricle, and case 2, extreme crossing atrioventricular (A-V) valves, in which the right-sided right atrium connects to the left posteriorly positioned right ventricle through the tricuspid valve, and the left-sided left atrium to the right anterior left ventricle via a posteriorly positioned mitral valve. In case 3, the criss-cross appearance is secondary to displacement of the heart by compression caused by a diaphragmatic hernia. Findings in these cases suggest that criss-cross heart is caused not only by primary rotation of the ventricles during cardiac morphogenesiss but also by secondary rotation of a formed heart induced by extracardiac compression. The degree of rotation in these cases revealed a wide spectrum from minimal to extreme. In addition, subxiphoid two-dimensional contrast echocardiography is recommended as the only accurate method of non-invasive diagnosis of this condition.

A patient with the karyotype of 46,XY,der(11), (7;11) (p15;q25)mat is reported. The major clinical findings of the present case included psychomotor retardation, growth retardation after birth, wide anterior fontanel, left esotropia, sacral dimple, bilateral undescended testis, whorls on six fingers, unilateral palmar transverse crease, and bilateral high axial triaradius.

Anomalous origin of a single coronary artery from the pulmonary artery is exceedingly rare. Clinical and necropsy findings in a 17-month-old boy with anomalous origin of a single coronary artery from the pulmonary artery are described. In our case, no areas of infarction or ischemic changes were found as well as in 4 of the 5 previously reported cases. It is most important that surgical treatment be performed without delay.

A 21-month-old Japanese boy with Puretic syndrome (gingival fibromatosis with hyaline fibromas) was reported. On the basis of the present case and 17 cases in the literature, it was concluded that the disorder was a very rare connective tissue disease with an autosomal recessive mode of inheritance.

A 13-year-old girl developed viral myocarditis complicated by pulmonary thromboembolism. Marked dilatation and reduction in the contractility of the left ventricle were noted in a two-dimensional echocardiogram on admission. The thicknesses of the left ventricle and the interventricular septum were both 8 mm at this time, but increased after the 9th day of the illness to reach 2 cm by the 15th day, with a concomitant reduction in the left ventricular cavity. The myocardial thickening gradually decreased and the ejection fraction improved on serial echocardiographic evaluations, and the wall thickness and ejection fraction returned to normal by the 32nd day. The myocarditis resolved without sequelae. The implications of this transient myocardial thickening are discussed.

Noninvasive determination of right ventricular systolic pressure was attempted in 27 patients with ventricular septal defect based on the peak velocity of left-to-right shunt flow as measured in the right ventricle by a continuous wave Doppler technique. The systolic pressure gradient between the ventricles (delta p: mmHg) was calculated according to the simplified Bernoulli's formula, delta p = 4 V2, where V (m/sec) is the peak velocity of the left-to-right shunt flow. Right ventricular systolic pressure was determined by subtracting delta p from the systolic blood pressure measured in the upper arm, which was regarded as the left ventricular systolic pressure. The peak velocity of left-to-right shunt flow could be measured in all patients except one with muscular ventricular septal defect, and values ranged from 0.6 to 4.8 m/sec. The peak velocity of left-to-right shunt flow decreased inversely with the increase in right ventricular systolic pressure. The values of right ventricular systolic pressure determined by the continuous wave Doppler technique correlated highly (r = 0.820) with those determined by cardiac catheterization. The peak velocity of left-to-right shunt flow also showed high negative correlations with the pulmonary to systemic pressure ratio (r = -0.876) and pulmonary to systemic resistance ratio (r = -0.855). These results indicate that the continuous wave Doppler technique is clinically useful for determination of right ventricular systolic pressure as well as the pulmonary to systemic pressure ratio and pulmonary to systemic resistance ratio.

A 1-month-old male infant with a double outlet right ventricle complicated by left ventricular outflow tract obstruction due to a very small ventricular septal defect is described. The atrial septum was intact, but mitral stenosis was present .The characteristic finding in this patient was that the inherently small ventricular septal defect was further narrowed by abnormal adherence of the anterior mitral leaflet to the left ventricular septal surface below the defect . Intracardiac anatomical features other than the adherent mitral valve could be evaluated accurately by two-dimensional echocardiography. Because the atrial septum was intact, balloon atrioseptostomy was not possible. An attempt at surgical creation of an atrial septal defect was unsuccessful, and the patient died immediately after the operation. The autopsy findings of the heart are described, and diagnostic problems and the possibility of radical operation are discussed.