Measurements of Individual Radiation Doses in Residents Living Around the Fukushima Nuclear Power Plant

At the outset of the accident at Fukushima Daiichi Nuclear Power Plant in March 2011, the radiation doses experienced by residents were calculated from the readings at monitoring posts, with several assumptions being made from the point of view of protection and safety. However, health effects should also be estimated by obtaining measurements of the individual radiation doses. The individual external radiation doses, determined by a behavior survey in the "evacuation and deliberate evacuation area" in the first 4 months, were <5 mSv in 97.4% of residents (maximum: 15 mSv). Doses in Fukushima Prefecture were <3 mSv in 99.3% of 386,572 residents analyzed. External doses in Fukushima City determined by personal dosimeters were <1 mSv/3 months (September-November, 2011) in 99.7% of residents (maximum: 2.7 mSv). Thyroid radiation doses, determined in March using a NaI (TI) scintillation survey meter in children in the evacuation and deliberate evacuation area, were <10 mSv in 95.7% of children (maximum: 35 mSv). Therefore, all doses were less than the intervention level of 50 mSv proposed by international organizations. Internal radiation doses determined by cesium-134 (134C) and cesium-137 ( 137C) whole-body counters (WBCs) were <1 mSv in 99% of the residents, and the maximum thyroid equivalent dose by iodine-131 WBCs was 20 mSv. The exploratory committee of the Fukushima Health Management Survey mentions on its website that radiation from the accident is unlikely to be a cause of adverse health effects in the future. In any event, sincere scientific efforts must continue to obtain individual radiation doses that are as accurate as possible. However, observation of the health effects of the radiation doses described above will require reevaluation of the protocol used for determining adverse health effects. The dose-response relationship is crucial, and the aim of the survey should be to collect sufficient data to confirm the presence or absence of radiation health effects. In particular, the schedule of decontamination needs reconsideration. The decontamination map is determined based on the results of airborne monitoring and the radiation dose calculated from readings taken at the monitoring posts at the initial period of the accident. The decontamination protocol should be reevaluated based on the individual doses of the people who desire to live in those areas

A high-resolution measurement of air samples in polar ice core

第2回極域科学シンポジウム　氷床コアセッション 11月16日（水） 国立極地研究所 2階大会議室前フロ

チョウヘイソク オ キタシタ シキュウ ケイガン ショウチョウ テンイ ノ 1レイ

We report a patient of a metastatic small intestinal tumor from uterine cervical cancer. A 76 year-old woman admitted to our hospital because of dyspnea. She showed progressive acute renal failure with pulmonary edema. Abdominal CT showed an advanced uterine cervical tumor and bilateral hydronephrosis. She was treated with temporary hemodialysis and tube nephrostomy. 1 week after admission, she presented with severe nausea, vomiting and rapidly progressive abdominal distension. We diagnosed her as strangulated ileus of the small intestine and she underwent an emergency operation. Laparotomy revealed an isolated tumor of the ileum and dilatation of the proximal small intestine without peritoneal dissemination, and a partial resection of the ileum was performed. Histopathological findings showed that the tumor was composed of squamous cell carcinoma cells, indicating that it was metastasis from uterine cervical cancer. Metastatic small intestinal tumor from primary uterine cervical cancer is very rare. To our knowledge, only 5 cases have been reported in Japan, including the present case

イマチニブ ガ チョコウ シ チョウキ カンゼン カンカイ CR オ イジ シテ イル ショウチョウ GIST フクマク ハシュ サイハツ ノ 1レイ

We report the case of a patient with recurrent gastrointestinal stromal tumor （GIST） complicated with peritoneal dissemination who achieved long-term complete remission （CR） with imatinib mesylate therapy. A 64-year-old man was admitted to our hospital because of severe abdominal pain. Abdominal computed tomography （CT） showed free air and an intra-abdominal abscess. Perforation of the small intestine was diagnosed, and an emergency operation was performed. Two adjacent tumors （each,6cm in size）, one of which was ruptured, were found by laparotomy in the jejunum and as a peritoneal dissemination. Jejunojejunostomy with the two adjacent tumors was performed and as much of the disseminated tumors as possible were resected. Histopathological analysis indicated a high-risk GIST of the small intestine. Abdominal CT at 1.5 years after the initial operation showed multiple recurrent tumors due to peritoneal dissemination. The patient subsequently received imatinib mesylate therapy at 400mg/day, and 5 months later, abdominal CT showed no evidence of tumor recurrence. DNA analysis of the tumor revealed an exon 11 mutation in the c-kit gene. The patient continues to receive imatinib mesylate therapy （400mg/day）, and CR of the recurrent tumors has been maintained for 8 years and 7 months

Establishment of a new initial dose plan for vancomycin using the generalized linear mixed model

Background: When administering vancomycin hydrochloride (VCM), the initial doseis adjusted to ensure that the steady-state trough value (Css-trough) remains withinthe effective concentration range. However, the Css-trough (population mean methodpredicted value [PMMPV]) calculated using the population mean method (PMM) oftendeviate from the effective concentration range. In this study, we used the generalizedlinear mixed model (GLMM) for initial dose planning to create a model that accuratelypredicts Css-trough, and subsequently assessed its prediction accuracy.Methods: The study included 46 subjects whose trough values were measured afterreceiving VCM. We calculated the Css-trough (Bayesian estimate predicted value [BEPV])from the Bayesian estimates of trough values. Using the patients’ medical data, we createdmodels that predict the BEPV and selected the model with minimum information criterion(GLMM best model). We then calculated the Css-trough (GLMMPV) from the GLMM bestmodel and compared the BEPV correlation with GLMMPV and with PMMPV.Results: The GLMM best model was {[0.977 + (males: 0.029 or females: -0.081)] ×PMMPV + 0.101 × BUN/adjusted SCr – 12.899 × SCr adjusted amount}. The coefficients ofdetermination for BEPV/GLMMPV and BEPV/PMMPV were 0.623 and 0.513, respectively.Conclusion: We demonstrated that the GLMM best model was more accurate inpredicting the Css-trough than the PMM.九州保健福祉大学平成29年

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Making programs of the rapid intravenous injection of potassium preparations and anaphylactic shock for an emergency-care simulator system

我々は、救急ケアシミュレータを使用した薬物誤投与・病態変化の再現が可能なシミュレーションプログラムを作成した。救急ケアシミュレータはスタン&reg;を使用し、プログラムは操作専用パソコンを使用した。全身状態は、瞬き速度、心音、呼吸音および動脈温などでそれぞれ設定した。薬物誤投与に関しては、カリウム製剤急速静注の症状再現が可能となった。また、病態変化に関してはアナフィラキシーショックが再現可能となった。これらのプログラムはインターネットを介してダウンロードできる。救急ケアシミュレータを用いた薬物過量投与・病態変化の体験は、患者のバイタルサインの確認、薬効評価や薬物有害反応の確認に有用である。これらのプログラムの実行は、病院ではない学内において脈診、聴診、血圧測定、心電図所見といったバイタルサインの確認のトレーニングを可能にし、これらの技術の修得は薬学生の薬効評価や副作用の早期発見につながるであろう。We made simulation programs to enable the reproduction of drug misadministration / condition changes for an emergency-care simulator system. We employed a Stan&reg; simulator equipped with a personal computer. In these programs, the general clinical condition can be detected by blinking velocity, cardiac / respiratory sounds, heart / respiratory rate, body temperature and arterial blood pressure. As an example of drug misadministration, the simulation programs facilitated the reproduction of symptoms related to the rapid intravenous injection of potassium preparations. With respect to changes in clinical condition, it facilitated the reproduction of anaphylactic shock. These programs can be downloaded via the Internet. Experience of excess-dose drug administration / condition changes reproduced by the emergency-care simulator system is useful for checking patients\u27 vital signs, and eventually for evaluating the drug efficacy, and confirming adverse reactions to drugs. Application of these programs will help teach pharmacy students how to check for vital signs (pulse palpation, auscultation, blood pressure measurement, and electrocardiography) in a school setting, not a hospital setting. Mastering these techniques may also allow pharmacy students to determine the efficacy of drug and adverse reactions

細胞膜プレートを使用したサイトプローブ薬物の細胞膜透過性に関する基礎的検討

Drug efficacy depends on the amount of a preparation reaching the target tissue (grade of tissue transfer). In this experiment, we established the normal albumin concentration of a healthy adult (600 μ M) or a low-albumin state indicating marked liver hypofunction (100 μ M) on a cell membrane plate, and evaluated the cell membrane permeability of the probe agents. The cell membrane permeability of phenytoin or valproate depended on the concentration of albumin. Probe agent site-I and -II inhibitors, bucolome and oleic acid, respectively, increased the cell membrane permeability. In the future, the cell membrane permeability of probe agents should be further investigated to estimate the tissue transfer of agents based on various laboratory data (albumin, free fatty acids, uremic toxins, and bilirubin)