The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

The study was performed to evaluate the relationships among serum free and total insulin-like growth factor (IGF)-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and insulin concentrations in prepubertal children with idiopathic short stature (ISS). Eighteen children with ISS and 15 age-matched controls were included in the study. All short children had a height standard deviation score of more than 2 below the mean, and maximum stimulated GH levels greater than 10 microg/l after two standard provocation tests. The serum levels of free IGF-I were significantly lower in short children (1.6 +/- 0.3 microg/l) than in the controls (2.8 +/- 0.6 microg/l, P<0.05), while total IGF-I levels were slightly, but not significantly, lower in short children than in controls. The serum levels of IGFBP-1 were significantly higher in the ISS group (124.6 +/- 5.6 microg/l) than in controls (80.0 +/- 8.7 microg/l, P < 0.0001). The fasting insulin and IGFBP-3 levels were similar in both groups. A stepwise regression analysis for all subjects revealed that IGFBP-1 is the only independent predictor of log free IGF-I (R2 = 0.23, P<0.01). The present study shows that the serum levels of free IGF-1 are significantly lower and insulin-like growth factor-binding protein-1 levels are higher in prepubertal children with idiopathic short stature, as compared with age-matched controls. The high IGFBP-1 may contribute to growth retardation in a subgroup of idiopathic short stature through a decrease in free IGF-1.

OBJECTIVESimple obesity is characterized by normal or accelerated growth in the presence of reduced serum levels of GH, whereas its detailed mechanism remains unknown. We, therefore, evaluated interrelationships among serum levels of insulin, IFG‐I, IGF binding protein (IGFBP)‐1 and ‐3 and growth hormone binding protein (GHBP) in prepubertal obese children.SUBJECTSPrepubertal 20 obese children and 20 age‐matched control children were included in the study.RESULTSSerum levels of insulin, IGF‐I and IGFBP‐3 in obese children did not differ from those in controls. The serum level of IGFBP‐1 was significantly lower in obese children (22.1 ± 18.4 μg/l, P<0.001) than in control children (76.0 ± 62.9 μg/l). No relationship was found between the serum levels of insulin and IGF‐I, IGFBP‐1, or IGFBP‐3 in obese subjects. The serum level of GHBP in obese children was significantly elevated as compared with that in controls and was positively correlated with body mass index (BMI). No relationship was found between the serum levels of GHBP and IGF‐I in obese subjects.CONCLUSIONSThe present study showed for the first time that the fasting IGFBP‐1 level was suppressed in prepubertal obese children with fasting normoinsulinaemia. We speculate that the hyperinsulinaemia which cannot be detected in the fasting state may have suppressed hepatic production of IGFBP‐1. Alternatively, the reduced IGFBP‐1 is likely to be a compensatory response to impaired insulin sensitivity. Thus, the IGFBP‐1 level may be a useful predictor for the early identification in the development of insulin resistance in prepubertal obese children.

IT has been indicated that slipped capital femoral epiphysis (SCFE), Perthes' disease and scoliosis may develop or worsen due to rapid growth caused by GH therapy in children with GH deficiency. In this study, the association between these skeletal disorders and GH deficiency or GH therapy was analyzed, based on the large database provided by the International Cooperative Growth Study (ICGS) Japan.

OBJECTIVE:To evaluate the relationship between serum levels of leptin and insulin in prepubertal lean, obese and insulin-dependent diabetes mellitus (IDDM) children. SUBJECTS AND MEASUREMENTS:Prepubertal children, 16 lean, 17 obese and 16 IDDM were included in the study. Fastang serum leptin and insulin concentrations were measured by radioimmunoassays. RESULTS:The serum level of leptin was significantly higher in obese children than in lean and IDDM children (P < 0.0001 and P < 0.0001, respectively), and showed a positive correlation with body mass index (BMI) for the combined group (lean, obese and IDDM; r = 0.77, P < 0.0001). In addition, the serum leptin level was higher in IDDM children than in lean controls (P < 0.01), whereas no difference was found in BMI between the two groups. The mean fasting serum levels of insulin were significantly elevated in IDDM children as compared with lean controls (P < 0.01). A significant positive correlation was found between serum insulin and leptin levels for the combined group (r = 0.37, P < 0.01). When a multiple regression analysis for all subjects was performed, the total contribution of all parameters, including gender, BMI and log insulin, accounted for 75% of the leptin variation. BMI (57.8%), log insulin (14.0%) and gender (3.2%) contributed significantly to this variation. CONCLUSIONS:The elevated concentration of leptin in insulin-dependent diabetic children, independent of body mass index, was probably caused by chronically increased serum insulin levels. We demonstrated that not only body mass index but also insulin was a significant independent predictor of serum leptin concentrations. It is therefore suggested that insulin might play an important role in regulating serum leptin concentrations independent of adiposity.

The Foundation for Growth Science has been controlling the use of GH by its registration system, which includes a scoring system for the eligibility for GH treatment according to the diagnostic criteria for GH deficiency (GHD) established by the Study Group for Hypothalamo-pituitary Disorder of the Ministry of Health and Welfare. Until 1995, 28,876 patients with GHD (19,432 boys and 9,444 girls) had been registered as eligible for GH treatment. The number of patients registered in a year increased gradually till 1990 due to the unlimited hGH supply by recombinant techniques and the change in the criteria for GH treatment and the number registered became stable after 1990. The frequency of GH-treated patients is calculated to be 55.2/100,000 persons (72.2/100,000 in boys and 37.1/100,000 in girls) in patients born between 1960 and 1990. The highest frequency was 148.4/100,000 persons (191.7/ 100,000 boys and 103.7/100,000 girls) in 1981, when 2,278 patients (1,508 boys and 770 girls) were born. Eligibility for GH treatment is assessed according to the scoring system which is basically dependent on peak GH values in provocation tests so that standardization of GH values measured with the various commercial GH kits is required to avoid inequality of patients' access to the treatment. In samples obtained by GRF test in 10 normal volunteers, hGH was measured with seven human GH (hGH) kits at a laboratory center. Since the RIA value has been used historically for the diagnosis of GHD, the mean of two RIA measurements was selected as the basis for the standardization procedure and the linear regression formula was used for each hGH kit. After the freely available supply of hGH obtained by recombinant DNA techniques, the role of the Foundation for Growth Science has changed to avoid hGH abuse. Even with this regulation, the frequency of registered patients may indicate a tendency to GH overuse.

Growth response to GH therapy in prepubertal patients with idiopathic GH deficiency (GHD) was analyzed in terms of the chronological age at the start of GH treatment and the GH secretory capacity, by using the large database provided by the International Cooperative Growth Study (ICGS) Japan. 1192 patients, aged from 3 to 10 years were divided into three groups with the following maximum GH values in GH stimulation tests: Group A: both < or = 5 ng/ml, group B: both 5-10 ng/ml, group C: one > 10 ng/ml. Analysis of age-related growth response using with delta height SDS (delta height SDS) as a response variable revealed that the group A patients responded better to GH, while there was no differences between the other groups. Simple and multiple regression analysis showed that IGF-I and chronological age (CA) negatively correlated with growth response, and target height SDS-height SDS positively correlated. These three most important predictors accounted for 49% of the variation in the growth response in group A, whereas six variables such as CA, frequency of GH injection, % overweight, GH dose, target height-height SDS, and pretreatment height velocity SDS accounted for only 28% of those in groups of B and C. These results lead us to conclude that growth response to GH is related to the degree of GH impairment with its cut-off level of 5 ng/ml. From these findings it might be suggested that treatment regimen should be tailored to individual requirements according to the degree of GHD.

We describe an infant with congenital cytomegalovirus infection who developed the syndrome of resistance to thyroid hormone at three weeks of age, presenting with elevated thyroxine levels and non‐suppressible thyroid‐hormone‐stimulating hormone secretions without any features of thyrotoxicosis. The resistance was present at the peripheral and pituitary levels and resolved spontaneously by 18 months of age. Cytomegalovirus infee tion was confmed by the positive urine culture of this virus. This case demonstrates for the fit time a possible association of thyroid hormone resistance with congenital cytomegalovirus infection.

We describe a 2‐year‐old boy with a non‐palpable right radial pulse associated with underdevelopment of the arm. An arteriogram showed a narrowing of the distal part of the right subclavian, axillary and brachial arteries, and poor collateral circulation. This patient illustrates a rare cause of an absent radial pulse, other than Takayasu's disease.

Clinical and cytogenetic aspects of a female infant with trisomy 21 and the fragile X [fra(X)] chromosome are reported. Most of the facial characteristics of the patient are those observed in Down syndrome, but some features such as long face with prominent forehead and lower jaw, and large ears are related to the fra(X) syndrome. The origin of an additional chromosome 21 may be ascribed to maternal first meiotic nondisjunction in our case. It has been suspected that female carriers of the fra(X) chromosome may be predisposed to meiotic nondisjunctional events. However, there is probably no relationship between the two chromosomal abnormalities in our case because of the maternal age at the delivery.

A 2-year-old Japanese male whose clinical features included intrauterine and postnatal growth retardation, mild mental retardation, microcephaly and characteristic facial appearance including sloping forehead, blepharophimosis, ptosis of unilateral eyelid, broad nasal bridge, dysplastic auricles, and retrognathia, is presented. The clinical findings of this patient are strikingly similar to those of patients with the Dubowitz syndrome. However, all reported cases with the Dubowitz syndrome are Caucasians. This syndrome may be diagnosed even in sporadic cases of any ethnic groups based on the characteristic features.

A 2‐year‐old boy, whose clinical abnormalities included growth retardation(3rd percentile), mild mental retardation (DQ = 67), microcephaly, hypertelorism, strabismus, prominent nasal bridge, stubby nose, pointed chin, undescended testes and hydronephrosis, had a ring chromosome 10. Using high‐resolution banding technique, the breakpoints were decided at p15.3 and q26.3 of chromosome 10. The clinical features observed in this case were common in 8 other cases with ring chromosome 10 previously reported. Thus, the terminal deletion of both arms of chromosome 10 seems to be the cause of the specific clinical abnormalities. When a patient has the clinical common abnormalities above mentioned, ring chromosome 10 syndrome will be suspected before chromosome analysis.

PyONYOSITIS, single or multiple abscesses in skeletal muscles, has traditionally been considered a tropical disease. In temperate climates its incidence is low; a Norwegian study reported four cases anaong 20,000 autopsies? In the past decade, 20 cases of pyomyositis, which included 14 children, have been reported in the United States. 2-7 The diagnosis of this disease poses difficulties which arise from a lack of familiarity by clinicians and the absence of classical inflammatory signs on the overlying skin. The muscle fascia prevents the inflammatory process in the muscle from extending into the subcutaneous or cutaneous tissues. The initial diagnosis is often a hematoma, cellulitis, osteomyelitis, arthritis, polymyositis, or neoplasm. Often one to four weeks elapse before a correct diagnosis is made and appropriate treatment is instituted, in four cases, a soft tissue sarcoma was Suspected, resulting in resection of the involved muscle?. ~ Since abscesses may often occur in multiple sites, a search for occult muscle abscesses is necessary. Gallium 67 citrate scintigraphy, originally introduced for the purpose of detecting neoplasms, has been proven to be useful in tracing occult abscesses. 8, ' We report three children With the histologic diagnosis of pyomyositis, in whom a gallium 67 scan was helpful in the early detection and localization of occult abscesses.