Improvement in glycemic control through changes in insulin regimens: findings from a Japanese cohort of children and adolescents with type 1 diabetes.

OBJECTIVE: Although insulin analogs have dramatically changed diabetes treatment, scarce evidence is available on those effects. We aimed to explore whether glycemic control had improved, the use of insulin analogs had been increased, and hypoglycemic events had decreased over time in Japanese pediatric patients with type 1 diabetes (T1D). METHODS: Glycated hemoglobin A1c (HbA1c) values, proportion of insulin regimens, incidence of severe hypoglycemic events, and pubertal increase in HbA1c were compared in three cohorts of childhood-onset Japanese T1D patients (567 subjects in the 1995 cohort, 754 subjects in the 2000 cohort, and 806 subjects in the 2008 cohort). RESULTS: Mean HbA1c values tended to decrease [78.5 mmol/mol (9.33%) in the 1995 cohort, 68.2 mmol/mol (8.39%) in the 2000 cohort, and 61.2 mmol/mol (7.75%) in the 2008 cohort; P < .0001]. The proportion of patients who received basal-bolus treatment tended to increase with statistical significance, as did the proportion on insulin analogs. The incidence of severe hypoglycemic events (events/100 patients/y) had decreased (19.1 in the 2000 cohort and 8.7 in the 2008 cohort; P = .02). The pubertal increase in HbA1c tended to decrease [males, 12.0 mmol/mol (1.10%) in 1995, 9.4 mmol/mol (0.85%) in 2008, and 9.4 mmol/mol (0.86%) in 2008; P = .55; females, 14.0 mmol/mol (1.28%) in 1995, 10.3 mmol/mol (0.94%) in 2000, and 4.2 mmol/mol (0.38%) in 2008; P = .0003]. CONCLUSIONS: Glycemic control and incidence of severe hypoglycemic events were chronologically improved, especially in female adolescents.

High-dose Cepharanthin for pediatric chronic immune thrombocytopenia in Japan.

BACKGROUND: A nationwide, multicenter and observational study was retrospectively conducted to evaluate the clinical utility of Cepharanthin (CEP) for pediatric patients with chronic immune thrombocytopenia (ITP). METHODS: Clinical and laboratory data for 46 Japanese patients aged <16 years who were diagnosed as having chronic ITP in 14 hospitals during 2001-2011, and were treated with CEP for >12 months, were analyzed. RESULTS: Median daily CEP dose was 1 mg/kg (range, 0.12-2 mg/kg). Median platelet count prior to CEP was 20.5 × 109 /L (IQR, 8.3-53.0 × 109 /L), and then significantly increased to 58.5 × 109 /L (IQR, 22.8-115.0 × 109 /L) and 69.0 × 109 /L (IQR, 23.0-134.0 × 109 /L) at 12 and 24 months of treatment, respectively. No life-threatening bleeds or moderate-severe adverse events were reported. Of 38 patients who received both corticosteroids (CS) and CEP, 17 patients (45%) were weaned from CS, and 15 patients (39%) attained the reduced dose of CS. The duration from the start of CEP to the stopping of CS was a median of 413 days (range, 49-1734 days) in patients who were weaned from CS. CONCLUSIONS: CEP alone or combined with CS was useful for the management of pediatric chronic ITPs.

Higher dose of methimazole causes frequent adverse effects in the management of Graves' disease in children and adolescents.

OBJECTIVE: Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves' disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment. DESIGN: Retrospective and collaborative study. SETTING: Nine facilities in Chiba prefecture, Japan. PATIENTS: Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4±0.1 mg/kg (mean±SD, n=11); group B, 0.7±0.2 (n=37); group C, 0.9±0.2 (n=16). MAIN OUTCOME MEASURES: The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12). RESULTS: Mean duration of times for normalization of T4 was 1.9±1.5 months in group A, 1.6±0.9 in group B and 1.9±1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups. CONCLUSIONS: Higher doses of MMI are harmful for initial use in children and adolescents with GD.

Screening and treatment of childhood type 1 and type 2 diabetes mellitus in Japan.

A large number of children with type 2 diabetes mellitus (T2DM) and a small number with a slowly progressive form of type 1 diabetes mellitus (SPT1DM) have been detected by a urine glucose screening program conducted at Japanese schools since 1974. The incidence of T2DM in children has increased over the last 3 decades and is estimated to be approximately 3.0/100,000/year, which is twice as that of T1DM. In contrast, SPT1DM in children is more prevalent in Asians, particularly Japanese, and exhibits unique clinical features that differ from those of the rapid onset form of T1DM, usually seen in Caucasians. In the first part of this review, we summarize the urine glucose screening program conducted at Japanese schools and clinical characteristics of the 2 diabetic subtypes in Japanese children. In recent years, concerns regarding childhood diabetes in Asian countries, including Japan, have risen, and medical care for the same is exceedingly developing. Intensive insulin therapy such as basal-bolus therapy by multiple daily insulin injections and pump therapy, both using insulin analogs, has been increasing in pediatric patients with T1DM. In addition, various antidiabetic medications have been introduced for children with T2DM. In the second part of this review, we describe treatment of Japanese children with T1DM and T2DM and changes in glycemic control as a result of development of the treatment.

Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: efficacy and adverse reactions during initial treatment and long-term outcome.

OBJECTIVE: The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI). DESIGN, SETTING AND PARTICIPANTS: Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (> or = 0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (> or = 7.5 mg/kg, n=45). MAIN OUTCOME MEASURES: The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared. RESULTS: Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40). CONCLUSIONS: PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Health-related and diabetes-related quality of life in Japanese children and adolescents with type 1 and type 2 diabetes.

BACKGROUND: The aim of this study was to assess (i) the health-related quality of life (HR-QOL) of primary, junior and high school children with type 1 and type 2 diabetes and to compare it with that of healthy school children; and (ii) to compare the diabetes-related QOL (DR-QOL) and the QOL of parents of children with diabetes, between type 1 and type 2 diabetes in Japan. METHODS: Overall, 471 patients aged 9-18 years (368 with type 1 and 103 with type 2 diabetes) and their parents were involved. QOL was assessed using a self-administered questionnaire. RESULTS: The total score for HR-QOL of primary and junior school children with type 1 diabetes was significantly higher than that of those with type 2 diabetes and healthy controls. However, there were no significant differences in high school children. Some subscales regarding HR-QOL were significantly lower for children with type 2 diabetes than for children with type 1 diabetes or healthy controls. The DR-QOL of children with type 1 and type 2 diabetes did not significantly differ. The Family Burden and Family Involvement were significantly greater in parents of children with type 1 diabetes. There were significantly positive correlations between HR-QOL and DR-QOL in both groups. In type 1 diabetes only, there were significant negative correlations between glycated hemoglobin and some subscales of the HR-QOL and QOL of parents of children with diabetes, and weak positive correlation between glycated hemoglobin and Family Burden. CONCLUSIONS: The HR-QOL of school children with type 1 diabetes was higher than that of those with type 2 diabetes and healthy school children. The QOL of school children with type 1 diabetes was not impaired.

Increasing secular trends in height and obesity in children with type 1 diabetes: JSGIT cohort.

BACKGROUND: Recently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change. OBJECTIVE: To examine secular trends in patients' anthropometric indices. SUBJECTS: Japanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. METHODS: We analysed serum haemoglobin A1c (HbA1c) levels, the incidence of severe hypoglycaemic events, the types and doses of insulin, height standard deviation scores (SDS), body mass index (BMI) percentiles compared with healthy Japanese children and obesity prevalence over time. We also stratified the patients according to glycaemic control levels of <58 mmol/mol (optimal), 58-75 mmol/mol (suboptimal) and ≥75 mmol/mol (high-risk). RESULTS: Data for 513-978 patients from each of the cohorts were analysed. The incidence of severe hypoglycaemic events decreased over time (from 21 to 4.8/100 patient-years), while the proportion of insulin analogue doses increased (14.6% to 98.6%). In addition, patient height SDS (-0.22 to +0.17), BMI percentile (52.1 to 58.7) and obesity prevalence (2.1% to 5.1%) increased. Height SDS increased in all of the glycaemic control subgroups, while BMI percentile and obesity prevalence increased in the suboptimal and high-risk groups. CONCLUSIONS: Since 1995, the average height of children with T1DM has increased in parallel with increasing insulin doses. Clinicians should be aware of increased BMI in these patients and the associated risk of developing cardiovascular disease in the future.

OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.

CONTEXT: Orthodenticle homeobox 2 (OTX2) is a transcription factor necessary for ocular and forebrain development. In humans, heterozygous mutations of OTX2 cause severe ocular malformations. However, whether mutations of OTX2 cause pituitary structural abnormalities or combined pituitary hormone deficiency (CPHD) has not been clarified. OBJECTIVES: We surveyed the functional consequences of a novel OTX2 mutation that was detected in a patient with anophthalmia and CPHD. PATIENT: We examined a Japanese patient with growth disturbance, anophthalamia, and severe developmental delay. He showed deficiencies in GH, TSH, LH, FSH, and ACTH. Brain magnetic resonance imaging revealed a small anterior pituitary gland, invisible stalk, ectopic posterior lobe, and Chiari malformation. RESULTS: Sequence analysis of OTX2 demonstrated a heterozygous two bases insertion [S136fsX178 (c.576-577insCT)] in exon 3. The mutant Otx2 protein localized to the nucleus, but did not activate the promoter of the HESX1 and POU1F1 gene, indicating a loss of function mutation. No dominant negative effect in the presence of wild-type Otx2 was observed. CONCLUSION: This case indicates that the OTX2 mutation is a cause of CPHD. Further study of more patients with OTX2 defects is necessary to clarify the clinical phenotypes and endocrine defects caused by OTX2 mutations.

Quality of life of young adults with congenital hypothyroidism.

BACKGROUND: The aim of the present study was to investigate health-related quality of life (HRQOL) and the living conditions of young adults with congenital hypothyroidism (CH) detected on newborn screening. METHOD: Among medical institutions that care for CH patients in Japan and were approached to in the present study, 78 institutions agreed to participate. The World Health Organization Quality of Life-26 (WHO/QOL-26) was used for measurement of HRQOL. CH patients who gave consent after receiving an explanation from their physicians filled in questionnaires at home and sent them by mail. This survey involved 51 CH patients (15 male; 36 female) whose mean age was 21.1 +/- 2.7 years (+/-SD; range, 18-27 years). The data from WHO/QOL-26 forms completed by 43 patients (12 male; 31 female) were compared with those for healthy individuals. RESULTS: Mean WHO/QOL-26 scores were 3.51 +/- 0.43 for male patients and 3.59 +/- 0.42 for female patients, and there were no significant differences between them and healthy individuals (men, 3.32 +/- 0.42; women, 3.35 +/- 0.49). No significant difference was observed between patients and healthy individuals on any domain of the WHO/QOL-26. Their degree of educational attainment was not poor. CONCLUSIONS: The HRQOL of young adults with CH detected on newborn screening was not poor.

Responses in children to measles vaccination associated with perirenal transplantation.

BACKGROUND: Measles infection can be fatal in pediatric patients with chronic renal failure or in patients who have undergone renal transplantation, both of whom are in the immunosuppressed state. The efficacy of single, live measles vaccination in preventing infection was examined. METHODS: Of 156 children with renal failure who underwent renal transplantation, the changes in antibody titer were investigated before and after renal transplantation in 125 children whose measles antibody titer could be examined, together with disease and vaccination histories. Live measles vaccine was administered to 42 children with negative antibody titer. The antibody seroconversion rate was then investigated in these children, along with rate of antibody maintenance and degree of antibody titer elevation. RESULTS: Seroconversion rate was 97.6%. Antibody titers measured on HI and EIA were 72 +/- 118 fold (HI) and 36.9 +/- 31.3 (EIA), respectively. The geometric mean of the increase in antibody titer 6 months after vaccination was 15. No side-effects of vaccination were observed in any of the children. CONCLUSIONS: Live measles vaccination of children with chronic renal failure is effective and safe, because the seroconversion rate, rate of antibody titer maintenance and degree of antibody titer elevation in children with chronic renal failure were all equivalent to those of healthy children.

Title: Health-related and diabetes-related quality of life (QOL) in Japanese children and adolescents with type 1 and type 2 diabetes.

Background: To assess 1) the HR-QOL of primary, junior and high school children with type 1 and type 2 diabetes and to compare them with healthy school children and 2) To compare the DR-QOL and parents' QOL between type 1 and type 2 diabetes in Japan. Methods: Overall, 471 patients aged 9-18 years (368 with type 1 and 103 with type 2 diabetes) and their parents were involved. QOL was assessed by self-administered questionnaire. Results: The total score of HR-QOL for primary and junior school children with type 1 diabetes was significantly higher than that of those with type 2 diabetes and healthy controls. However, there were no significant differences in high school children. Some subscale of HR-QOL were significantly lower for children with type 2 diabetes than for children with type 1 diabetes or healthy controls. The DR-QOL of children with type 1 and type 2 diabetes did not significantly differ. The Family Burden and Family Involvement were significantly greater in parents of children with type 1 diabetes. There were significantly positive correlations between HR-QOL and DR-QOL in both groups. In type 1 diabetes only, there were significant negative correlations between HbA1c and some subscales of the HR-QOL and PDQOL, and weak positive correlation between HbA1c and Family Burden. Conclusions: The HR-QOL of school children with type 1 diabetes was higher than that of those with type 2 diabetes and healthy school children. The QOL of school children with type 1 diabetes was not impaired.

Analysis of weight at birth and at diagnosis of childhood-onset type 2 diabetes mellitus in Japan.

BACKGROUND: The prevalence of childhood-onset type 2 diabetes mellitus (T2DM) has increased dramatically over the past two to three decades in Japan, but epidemiological and clinical data remain limited. Several epidemiological studies stress the importance of elucidating the pathophysiology of prenatal nutrition and other intra-uterine environmental factors and the risk of T2DM in each of the different populations. We examined the associations of weight at birth, weight at diagnosis of T2DM, and clinical characteristics of childhood-onset T2DM. METHODS: Clinical data sheets were sent to councillors of the Japanese Society for Pediatric Endocrinology (JSPE) and members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) in June 2003. Clinical data on 259 children (9-17 yr of age) categorized as T2DM by pediatric endocrinologists, who are members of the JSPE and/or JSGIT, using 1999 Japan Diabetes Society criteria were analyzed. Degree of overweight was assessed by percent overweight and standard deviation score-body mass index. RESULTS: The age (mean +/- SD) of the 259 patients recruited (121 boys and 138 girls) was 11.9 +/- 2.1 yr at diagnosis and 14.4 +/- 2.0 yr at the time of the survey. Sixty-nine percent of all patients were obese (percent overweight >or=20%) at the time of diagnosis. Obese patients were older at the time of diagnosis and had a higher level of hemoglobin A1c (HbA1c) at diagnosis than non-obese patients (p < 0.05), and there were fewer girls than boys. Twenty two (11.3%) of 195 patients had low birth weights (<2500 g) and 19 (9.7%) had high birth weights (>or=4000 g). The frequencies of low and high birth weights were higher among patients with T2DM than among a control group, producing a U-shaped distribution (p < 0.05). The frequency of a family history of diabetes was lower among low-birth weight patients. In contrast, high-birth weight patients had a higher prevalence of diabetic mothers and medication including insulin therapy (p < 0.05). CONCLUSIONS: Obesity was shown to be a major risk factor for childhood-onset T2DM in Japan. The frequencies of low and high birth weights were higher among patients with T2DM, and differences in clinical characteristics, such as family history of diabetes, were recognized among patients with T2DM with low, normal, and high birth weights.

Effects of bodyweight on health-related quality of life in school-aged children and adolescents.

BACKGROUND: The purpose of the present study was to investigate the effects of bodyweight on health-related quality of life (QOL) in children. METHODS: A questionnaire to assess health-related QOL was developed and completed by 242 primary school children and 180 junior high school students in Morioka, Japan. Subjects were classified by obesity index into three groups as follows: underweight, /=+20% (n = 55). The overall QOL score and the score of each domain were compared among the three groups and in each gender. RESULTS: Overall QOL scores did not differ significantly among the three groups. The scores for the domain of 'strength, diligence and self-esteem' in the underweight and overweight groups were significantly lower than those for the normal-weight group overall and for girls (P < 0.01). Scores for the 'school' domain in the underweight group were significantly lower than those for the overweight group overall and for boys (P < 0.05). CONCLUSIONS: Children, except those of normal bodyweight, have low scores in some domains of health-related QOL, suggesting the importance of considering the effects of bodyweight on QOL in programs aimed at further understanding under- or overweight children and adolescents.

The incidences of and risk factors for severe retinopathy requiring photocoagulation and albuminuria in Japanese patients with childhood-onset type 1 diabetes.

The aim of this study was to clarify the incidences of and the risk factors for severe retinopathy requiring photocoagulation therapy and albuminuria in Japanese patients with childhood-onset type 1 diabetes mellitus. A total of 756 patients from a cohort study by the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes were included in the study. Patients were registered in 1995 or 2000, and HbA1cwas measured every 4 months and analyzed in central hospital for an average of 6 years. The presence of severe retinopathy requiring laser photocoagulation and the presence of albuminuria was checked for during the period 2010-2011. During a median of 18 (range: 15-21) years, 34 out of 756 patients underwent laser photocoagulation and 57 out of 605 patients developed albuminuria. A Cox proportional hazards model showed that the risk of severe retinopathy requiring laser photocoagulation increased by 1.15 (95% confidence interval [CI] 1.03-1.29, p = 0.012) with each increase of a year in the age at onset, by 4.03 (95% CI 1.20-13.5, p = 0.024) in females, and by 2.05 (95% CI 1.69-2.49, p < 0.0001) with each increase of 1% in HbA1c. The risk of albuminuria increased significantly, by 1.09 (95% CI 1.01-1.18 p = 0.037), with each increase of a year in the age at onset and by 2.38 (95% CI 1.93-2.97 p < 0.0001) with each increase of 1% in HbA1c. In Japanese patients with childhood-onset type 1 diabetes, older age at the onset of diabetes, female rather than male gender, and higher HbA1c were found to increase the risk of requiring photocoagulation. No patients with HbA1c < 7.5% developed severe retinopathy requiring photocoagulation therapy. The risk of developing albuminuria increased with age at onset of diabetes and HbA1c. Female gender was a strong risk factor for severe retinopathy requiring photocoagulation, but not for albuminuria.

Treatment for childhood-onset Graves' disease in Japan: results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists.

OBJECTIVE AND DESIGN: To determine the present condition of treatment of childhood-onset Graves' disease in Japan, a nationwide questionnaire survey was conducted among councilors of the Japanese Society for Pediatric Endocrinology and the Japan Thyroid Association. MAIN OUTCOME: Responses were received from 125 individuals, and the rate of collection of questionnaires was 47%. Methimazole was selected for first-line initial antithyroid drug therapy by 92% of respondents. Antithyroid drugs tended to be given at larger initial doses and over longer periods of time to childhood-onset patients than to adult patients, and these tendencies were more pronounced for pediatric endocrinologists. Combination therapy with an antithyroid drug and thyroxine was used more frequently by pediatric endocrinologists. Thyroidologists had more experience with radioiodine therapy than pediatric endocrinologists. Opinions regarding preparation of guidelines for the initial dose of methimazole in childhood-onset Graves' disease were almost equally divided among the following: the dose of methimazole should be adjusted according to the severity of disease as in adult cases, methimazole should be started at a dose of 1mg/kg per day in all patients, and the dose should be determined based on results of a randomized study. CONCLUSIONS: The present condition of treatment of childhood-onset Graves' disease in Japan was clarified.

Arterial hemodynamics in patients after Kawasaki disease.

BACKGROUND: Histopathological findings in the acute stage of Kawasaki disease (KD) indicate widespread vascular inflammation that involves not only coronary arteries but also systemic arteries. This may cause changes in systemic arterial wall properties after KD, which could have adverse effects on arterial hemodynamics (an important predictor of cardiovascular morbidity and mortality). METHODS AND RESULTS: Systemic arterial hemodynamics were investigated by measuring aortic input impedance during cardiac catheterization in 42 KD patients who had developed coronary artery lesions (CALs) in the acute stage of KD. The KD patients were subdivided into 2 groups according to the angiographic findings (group 1A, 26 patients with persistent CALs; group 1B, 16 patients with regressed CALs), and results were compared with those of 36 referents (group 2). Compared with referents, characteristic impedance was significantly higher for KD patients (137.0+/-5.1, 125.7+/-8.2, and 97.9+/-4.1 dyne x s x cm(-5) x m2 for group 1A, group 1B, and group 2, respectively), and total peripheral arterial compliance indexed to age-specific values was significantly lower for KD patients (group 1A 72.9+/-4.2% of normal; group 1B 70.6+/-5.9% of normal; group 2 97.7+/-4.0% of normal; for both variables, P<0.05 for each KD group versus group 2; P=NS between KD groups), which suggests that both central and peripheral arterial wall stiffness increase after KD regardless of persistence of CALs. Also, indices of arterial wave reflection (reflection coefficient, reflection factor, and augmentation index) were all significantly higher in KD patients than in referents (P<0.05), with the result that the aortic pressure waveforms of the present KD patients resembled those generally observed in the elderly. In addition, levels of circulating markers of endothelial dysfunction (ACE and von Willebrand factor) were associated with increased vascular stiffening in KD patients but not in referents. CONCLUSIONS: These results indicating abnormal arterial hemodynamics after KD highlight the importance of regular monitoring of the systemic arterial bed and potentially relevant cardiovascular events in long-term follow-up of KD.

[Childhood Graves' disease].

Because of the low frequency of childhood Graves' disease, detailed evidence-based clinical studies have not been reported. Practical clinical work has been performed on the basis of adult clinical references. Therapeutic management includes antithyroid drugs, surgical thyroidectomy and radiologic therapy. Recently in the U.S.A. radiotherapy has become the recommended course of action, even for childhood Graves' disease, whereas in Japan, antithyroid drug therapy is the primary course of action for childhood Graves' disease. In some cases, thyroidectomy is performed following drug therapy. Methimazole (MMI) and propylthiouracil (PTU) have been used, however, MMI is the preferred drug treatment. Compared to PTU, MMI is administered once a day and the frequency of side effects is lower than that of PTU. Evaluation of the TSH receptor antibody value before administration of antithyroid drugs is very useful in estimating the duration of the treatment. No appropriate index has been established guiding when to quit antithyroid drug therapy.

Ventricular afterload and ventricular work in fontan circulation: comparison with normal two-ventricle circulation and single-ventricle circulation with blalock-taussig shunts.

BACKGROUND: Recent studies have indicated that there are inherent limitations associated with Fontan physiology. However, there have been no quantitative analyses of the effects of right heart bypass on ventricular afterload, hydraulic power, and resultant overall hemodynamics. Methods and Results- During routine cardiac catheterization, aortic impedance and ventricular hydraulic power were determined, both at rest and under increased ventricular work induced by dobutamine, in 17 patients with Fontan circulation, 15 patients with a single ventricle whose pulmonary circulation was maintained only by Blalock-Taussig shunts, and 13 patients who had normal 2-ventricle circulation. Both vascular resistance (nonpulsatile load on the ventricle) and pulsatile components of ventricular afterload (represented by low-frequency impedance) were significantly higher in the Fontan group than in the other groups (P<0.01), and this was associated with decreased cardiac output in the Fontan patients. In addition, hydraulic power cost per unit forward flow was 40% lower in the 2-ventricle circulation than in the single-ventricle circulation, suggesting lower ventricular efficiency in single-ventricle circulation attributable to the lack of a pulmonary ventricle. Furthermore, in the Fontan group, beta-adrenergic reserve was markedly decreased because of a limited preload reserve. CONCLUSIONS: Fontan physiology is associated with disadvantageous ventricular power and afterload profiles and has limited ventricular reserve capacity. Thus, to improve the long-term prognosis of patients after Fontan surgery, future research should be conducted into medical interventions that can overcome these limitations inherent in Fontan circulation.

Past 10-year status of insulin therapy for preschool-age Japanese children with type 1 diabetes.

The aim of this study was to evaluate the past 10-year status of insulin therapy for preschool-age children with type 1 diabetes in Japan. One-hundred and forty-two patients who had been diagnosed at less than 5 years of age within the past 10 years (1993-2002) at 36 hospitals were registered in this study on April 2003. The methods of daily insulin therapy and episodes of severe hypoglycemia during the preschool period were investigated. Eighty-six (60.6%) children were treated with a pen-type device and 56 (39.4%) were treated with a syringe-type device. The once-a-day insulin regimen was used for 2, a twice-a-day regimen for 104, a three-times-a-day for 28 and a four-times-a-day for 8. Episodes of severe hypoglycemia were recorded in nearly half of the subjects, and one-fourth of the subjects had repeated episodes. One hundred and eleven of their parents were questioned regarding the degree of psychosocial stress experienced during the care of their children. Most parents worried about the glycosylated hemoglobin value at each hospital visit. They were next very afraid of nocturnal severe hypoglycemia, independent of any actual experience. These results suggest that although insulin therapy can involve various methods, the important point is to simultaneously provide good glycemic control and prevent severe hypoglycemia, especially during this age.

Distribution of Chlamydia trachomatis serovars among female prostitutes and non-prostitutes in Thailand, and non-prostitutes in Japan during the mid-90s.

The distribution of Chlamydia trachomatis serovars in Thailand and Japan during the same period of the mid-90s was determined. Seventy-one C . trachomatis specimens isolated from female patients who visited the Venereal Diseases Center at Bangkok, Thailand in 1994 were used in this study. Of these, 56 patients were prostitutes. Forty-seven specimens obtained from female non-prostitutes who attended the Department of Obstetrics and Gynecology, Saitama Medical School, Japan during the period from 1993 to 1995 were also used in this study. DNA was extracted from these specimens and typing of C. trachomatis serovars was performed by the polymerase chain reaction-restriction fragment length polymorphism method. The identified serovars among prostitutes of Thailand (n = 56)/non-prostitutes of Thailand (n = 15)/non-prostitutes of Japan (n = 47) were as follows: Ba 1/0/2, D 8/1/15, E 11/2/8, F 16/9/8, G 4/0/7, H 3/2/3, I 1/0/1, J 3/0/0, and K 10/1/4. Serovar F was most prevalent (35.2%) in both prostitutes and non-prostitutes from Thailand, followed by serovar E (18.3%). On the other hand, serovar D was the most frequent serovar in non-prostitutes in Japan (31.9%) followed by serovars F (17.0%) and E (17.0%). A difference in the distribution of C. trachomatis serovars of Thailand and Japan was noted.