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We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.

Owing to improved technology and care for patients who need mechanical ventilation, the quality of life as well as the prognosis for long-term ventilator-assisted patients has improved significantly in recent years. However, the increased number of these patients has raised economic, ethical and medical problems. In order to assess the magnitude of these problems, we conducted the first nationwide survey on the status of long-term ventilator-assisted children in Japan. Questionnaires were mailed to 2524 pediatric departments at hospitals in Japan with more than 100 beds. At the time of the survey, 282 hospitals had 567 patients who had been ventilated for more than a month. Among these patients, 434 were younger than 20 years and had been ventilated for more than 3 months. The most common basic disorders were: various myopathies (n = 65), hypoxic-ischemic encephalopathy (n = 60), spinal muscular atrophy type 1 (Werdnig-Hoffmann disease, n = 55), chronic lung disorders of prematurity (n = 21), Ondine's curse (n = 22), drowning (n = 17) and congenital heart diseases (n = 16). Of these 434 patients, only 61 were ventilated at home. Although home care was considered suitable for chronic ventilator patients by many pediatricians who responded to the survey, its realization has been hampered by the lack of a system and regulations to support it. The fact that many pediatricians in Japan have actively prolonged the life of Werdnig-Hoffmann patients, from whom aggressive life saving measures have been withheld in most Western countries, has raised ethical as well as medical issues.

It is prerequisite for the pre-operative management of patients with congenital diaphragmatic hernia (CDH) to avoid the factors that increase pulmonary vascular resistance, because such patients easily fall into the state of persistent fetal circulation (PFC). In this paper, a new protocol is proposed for the perinatal management of CDH patients to prevent the PFC which is facilitated by the enlargement of hernia and the deviation of mediastinum caused by spontaneous breathing just after birth. We also describe the usefulness of this protocol based on our experience in which we successfully treated a patient with CDH with severe hypoplastic lungs that were diagnosed antenatally by ultrasonographic examination. In treating the CDH patient with severe hypoplastic lungs, it is effective for the respiratory control and the prevention of PFC to administer morphine and pancuronium to the neonate through the umbilical vein before the resection of the umbilical cord. In the case of Cesarean section, in addition to the direct administration of morphine to the patient, administration of morphine to the patient's mother just before the delivery is more effective to prevent PFC, which can be easily induced by the initial resuscitation at birth.

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patients showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.

The roles and characteristics of the ventricle were examined using mean ventricular pressure (MVP) in ventricular-vascular association. One hundred and two patients with congenital heart diseases who had undergone cardiac catheterization were studied. They were divided into five groups: Group 1, atrial septal defect without pulmonary hypertension (PH); Group 2, ventricular septal defect (VSD) without PH; Group 3, VSD with PH; Group 4, pulmonary valvular stenosis; and Group 5 as a control group. Then, we examined the relationships between mean pulmonary artery pressure (MPAP) and mean right ventricular pressure (MRVP), and also between mean systemic arterial pressure (MSAP) and mean left ventricular pressure (MLVP) among the five groups. Furthermore, we defined new indicators to express the ease of blood flow through each ventricle. They were referred to as a conductance of the right ventricle (CDR) and a conductance of the left ventricle (CDL), respectively. Then they were compared among the five groups. The values of MPAP/MRVP and MSAP/MLVP were kept constant to be about 1.3 and 1.7, respectively. Furthermore, CDR was different between each group according to the property of the pulmonary vascular bed, whereas CDL took almost the same value among the five groups. The ventricle works as a converter of atrial blood flow so that it can achieve efficient blood transport.

The Cooperative Program for Asian Pediatricians (CPAP) is a non-government organization established in 1989 to promote mutual understanding and friendship among young pediatricians in Asian countries. Unlike other government programs and non-government organizations, CPAP is solely facilitating mutual relationships among young inexperienced pediatricians who would otherwise have no chance to travel overseas. It has been funded by donations from members of the alumni association of the Department of Pediatrics at the University of Tokyo and many private companies and individuals. The Cooperative Program for Asian Pediatricians has so far invited 36 Asian pediatricians from 11 countries. By constructing a human network among Asian pediatricians, it is hoped that CPAP will contribute to making international cooperation in the Asian region easier and smoother.

A patient with partial trisomy for the distal segment of the long arm of chromosome 5 (q35.1-->qter) with partial 18q monosomy is presented. The mother of the patient was phenotypically normal and was proved to be a carrier of a reciprocal translocation of the long arm of chromosomes 5 and 18 46,XX,t(5;18)(q35.1;q23). The patient shows mild mental retardation, short stature, mild obesity, dysmorphic face, eczema, minor malformations of the extremities, and bilateral intracranial calcification in the basal ganglia. Most of the clinical manifestations of the patient are compatible with the previously reported clinical features of partial trisomy of the distal segment of 5q. However, the calcification of bilateral basal ganglia has not been reported for this chromosomal anomaly.

The status of chronic ventilator-assisted children admitted to university hospitals in Japan was investigated. Of 81 university hospitals which responded to the survey, 52 hospitals had admitted 102 patients requiring chronic ventilatory support. More than 60% of the patients were suffering from neurologic disorders. Werdnig-Hoffmann disease was the most common disease, followed by hypoxic-ischemic encephalopathy, congenital heart disorders and various myopathies. The average duration of ventilator care was 823 days. Only nine patients were weanable from the mechanical ventilation. Although the population of chronic ventilator-dependent patients was not large, the chronic nature of the basic disorders and the need for intensive care of the patients have raised serious social and medical issues.

A 17 year old male patient with Moebius syndrome with pituitary dwarfism and unilateral hypoplastic optic disc is presented. Although there have been several reports of an association of Moebius syndrome and pituitary dysfunction, growth hormone deficiency has not been reported previously. These associations may give some insight into the pathogenesis of Moebius syndrome.