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Momotani N.,Tokyo Health Service Association.
Nihon rinsho. Japanese journal of clinical medicine | Year: 2012

In the treatment of pregnant patients with Graves' disease, propylthiouracil is preferred over methimazole in early pregnancy because of a possible teratogenicity of methimazole. Methimazole is preferable to propylthiouracil in other time of pregnancy on the basis of severe liver dysfunction occasionally caused by propylthiouracil. Fetal hypothyroidism can be avoided when maternal free T4 levels are maintained at or above the upper normal limit for non-pregnant subjects. However, maternal free T4 should be kept normal for pregnant reference range when pregnancy complications develop. Fetal hypothyroidism in this setting will not affect the infant's development as long as mothers are euthyroid and the infants recover from hypothyroid state within a short time after birth. In hypothyroid women, 1-T4 dose often needs to be increased in pregnancy. Maternal T4 deficiency in early pregnancy has been suggested to affect normal brain development in the offspring. However, it has recently been shown in iodine rich area that no adverse effect on neuropsychological development was seen irrespective of the severity of maternal T4 deficiency. Insufficient iodine intake in the mother can cause low T4 in pregnancy and also inadequate production of T4 in breast-fed infants when sufficient T4 is essential for normal brain development.


Kawata Y.,Tokushima University | Niki N.,Tokushima University | Ohmatsu H.,Tokushima University | Kusumoto M.,National Cancer Center Hospital East | And 4 more authors.
Medical Physics | Year: 2012

Purpose: Quantification of the CT appearance of non-small cell lung cancer (NSCLC) is of interest in a number of clinical and investigational applications. The purpose of this work is to present a quantitative five-category (, , and ) classification method based on CT histogram analysis of NSCLC and to determine the prognostic value of this quantitative classification. Methods: Institutional review board approval and informed consent were obtained at the National Cancer Center Hospital. A total of 454 patients with NSCLC (maximum lesion size of 3 cm) were enrolled. Each lesion was measured using multidetector CT at the same tube voltage, reconstruction interval, beam collimation, and reconstructed slice thickness. Two observers segmented NSCLC nodules from the CT images by using a semi-automated three-dimensional technique. The two observers classified NSCLCs into one of five categories from the visual assessment of CT histograms obtained from each nodule segmentation result. Interobserver variability in the classification was computed with Cohen's statistic. Any disagreements were resolved by consensus between the two observers to define the gold standard of the classification. Using a classification and regression tree (CART), the authors obtained a decision tree for a quantitative five-category classification. To assess the impact of the nodule segmentation on the classification, the variability in classifications obtained by two decision trees for the nodule segmentation results was also calculated with the Cohen's statistic. The authors calculated the association of recurrence with prognostic factors including classification, sex, age, tumor diameter, smoking status, disease stage, histological type, lymphatic permeation, and vascular invasion using both univariate and multivariate Cox regression analyses. Results: The values for interobserver agreement of the classification using two nodule segmentation results were 0.921 (P 0.001) and 0.903 (P 0.001), respectively. The values for the variability in the classification task using two decision trees were 0.981 (P 0.001) and 0.981 (P 0.001), respectively. All the NSCLCs were classified into one of five categories (type , n 8; type , n 38; type , n 103; type , n 112; type , n 193) by using a decision tree. Using a multivariate Cox regression analysis, the classification (hazard ratio 5.64; P 0.008) and disease stage (hazard ratio 8.33; P 0.001) were identified as being associated with an increased recurrence risk. Conclusions: The quantitative five-category classifier presented here has the potential to provide an objective classification of NSCLC nodules that is strongly correlated with prognostic factors. © 2012 American Association of Physicists in Medicine.


Kobayashi M.,Jikei University School of Medicine | Ohashi T.,Jikei University School of Medicine | Fukuda T.,Jikei University School of Medicine | Yanagisawa T.,Kitasato University | And 5 more authors.
Molecular Genetics and Metabolism | Year: 2012

Background: Fabry disease is an X-linked lysosomal disorder resulting from mutations in the α-galactosidase A (GLA) gene. Recent reports described that the E66Q mutation of GLA is not a disease-causing mutation. However, no pathological study was reported. We carried out pathological studies using a cardiac biopsy specimen from a patient with the E66Q mutation. Materials and methods: The case was a 34. year old male patient with end-stage renal failure and cardiomegaly. He was diagnosed with gout at 15. years of age and hemodialysis was started for gouty nephropathy from 31. years of age. He was suspected of having Fabry disease as the result of a screening study for Fabry disease in patients with end-stage renal failure and was referred to our hospital for mutation analysis of the GLA gene. We carried out enzymatic and genetic analysis for GLA and pathological studies of a cardiac biopsy specimen. Results: The patient had the E66Q mutation in the GLA gene. GLA activity in leukocytes was 36.2% of the average of normal controls. The pathological study of the cardiac biopsy sample showed no characteristic findings of Fabry disease. The immunohistochemistry for GL3 of the cardiac biopsy sample showed no positive cells. Conclusion: Although the E66Q mutation reduced enzyme activity, the characteristic pathological findings of Fabry disease and the abnormal accumulation of GL3 were not detected in cardiac tissues. The E66Q mutation of the GLA gene is thought to be a functional polymorphism based on enzymatic and pathological studies. © 2012 Elsevier Inc.


Kitagawa T.,Tokyo Health Service Association.
Pediatric Endocrinology Reviews | Year: 2012

In 1977, the Ministry of Health and Welfare (MHW) directed prefectural officials in charge of maternal and child health to start publicly funded newborn mass-screening (NBS) for phenylketonuria (PKU), maple syrup urine disease (MSUD), histidinemia, homocystinuria and galactosemia and a study group of MHW formulated the treatment guideline for the target diseases. In 1980, MHW launched the Japan Cooperative Project on Special Formula (JCPSF) to ensure a stable supply of special formula and also organized the committee for JCPSF. From 1977 to 2003, a study group of MHW conducted a follow-up study of the patients detected by the screening. From the follow-up it was concluded that dietary therapy was unnecessary for histidinemia and the screening for the disease was discontinued. In 1995, the guideline for the treatment of PKU was revised to keep lower blood phenylalanine levels. The guideline committee for the treatment of BH4 deficiency was establish in 1996 to obtain better prognosis. In 2012, the MHW decided to initiate publicly funded NBS using MSIMS for inborn errors of amino acid, organic acid, and fatty acid metabolism. The Japanese nationwide NBS has been performed for 35 years. This paper reviews the Japanese history of the development of NBS which has enabled more IEM patients to lead active and productive lives today.


Amemura-Maekawa J.,Japan National Institute of Infectious Diseases | Kikukawa K.,Saitama Prefectural University | Helbig J.H.,TU Dresden | Helbig J.H.,Nippon Medical School | And 14 more authors.
Applied and Environmental Microbiology | Year: 2012

Legionella pneumophila serogroup (SG) 1 is the most frequent cause of legionellosis. This study analyzed environmental isolates of L. pneumophila SG 1 in Japan using monoclonal antibody (MAb) typing and sequence-based typing (SBT). Samples were analyzed from bathwater (BW; n=50), cooling tower water (CT; n=50), and soil (SO; n=35). The distribution of MAb types varied by source, with the most prevalent types being Bellingham (42%), Oxford (72%), and OLDA (51%) in BW, CT, and SO, respectively. The ratios of MAb 3/1 positive isolates were 26, 2, and 14% from BW, CT, and SO, respectively. The environmental isolates from BW, CT, and SO were divided into 34 sequence types (STs; index of discrimination [IOD]=0.973), 8 STs (IOD= 0.448), and 11 STs (IOD=0.879), respectively. Genetic variation among CT isolates was smaller than seen in BW and SO. ST1 accounted for 74% of the CT isolates. The only common STs between (i) BW and CT, (ii) BW and SO, and (iii) CT and SO were ST1, ST129, and ST48, respectively, suggesting that each environment constitutes an independent habitat. © 2012, American Society for Microbiology.

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