Search

We assessed the bioequivalence of a single dose of 5-mg of esaxerenone administered as an orally disintegrating tablet (ODT) with the conventional oral tablet in healthy Japanese men. This single-center, open-label, randomized, two-drug, two-stage crossover, single-dose study was conducted in two parts. In study 1, both formulations were taken with water. In study 2, only the ODT formulation was taken without water. The primary outcome was the evaluation of bioequivalence of the ODT and conventional tablet using the pharmacokinetic (PK) parameters maximum plasma concentration (C

Levocetirizine is classified as a second‐generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate‐release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.

Purpose MB02 is a biosimilar to bevacizumab that has demonstrated similar physicochemical and functional properties in in vitro studies to the reference bevacizumab (Avastin®). This study aims to assess the pharmacokinetic (PK) similarity of MB02 to the reference bevacizumab in Japanese population. Methods This double-blind, randomized, parallel-group, single-dose PK study, was performed in healthy Japanese male volunteers. Subjects were equally randomized (1:1) to receive a single (3 mg/kg) IV dose of MB02 or reference bevacizumab. PK assessments were done up to 70 days post-dose. Non-compartmental parameters were calculated. PK similarity was determined using predefined equivalence range (0.80–1.25) for the area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC0–∞). Immunogenicity samples were taken pre-dose and up to day 70. Safety was assessed throughout the study. Results In total, 48 subjects (24 in each treatment group) were dosed. Consequently to the observed similar PK profile, the 90% confidence interval for the geometric means ratio for the primary PK endpoint, AUC0–∞, was within the predefined equivalence range (0.981–1.11). Forty-seven treatment-emergent adverse events (TEAEs) were reported in 20 subjects (41.7%) with comparable incidence among MB02 and reference bevacizumab groups (22 and 25, respectively), none of them was severe or serious. Anti-drug antibodies incidence was low and similar between treatment groups. Conclusions Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650.

Students have become more familiar with cancer because of media, such as television or the Internet, reporting on celebrity cancer cases. Moreover, with Japan's increasing age and cancer rates, the number of students whose parents/relatives develop cancer is likely to increase. This study examined cancer awareness and understanding among students aged 10 to 16 or more. A cross-sectional nationwide survey was conducted using a self-administered questionnaire. Cancer awareness and cancer understanding were assessed using a self-administered questionnaire. We collected a total of 9139 questionnaires and excluded those with missing data. Thus, we analyzed the responses of 8701 students: 2135, 2902, and 3664 from elementary, junior, and high school, respectively. Data were analyzed using a multivariable model adjusted for gender and grade. Approximately 30% of respondents had parents/relatives with cancer. In addition, there was a significant association between having parents/relatives with cancer and cancer awareness; however, students having parents/relatives with cancer had more negative awareness (i.e., "I think cancer is scary," "I think I will get cancer in the future," and "I think cancer is preventable"). Furthermore, there was a significant association between cancer understanding and awareness. These findings suggest that cancer education could have a desirable effect on students whose parents/relatives have cancer. Further, cancer education offers benefits to students who are naive about cancer and ill prepared to cope when a family member discloses a cancer diagnosis.

The purpose of this study was to describe the cancer-screening intention, sources of cancer information, and cancer understanding among Japanese adolescents. A cross-sectional nationwide survey involving a self-administered questionnaire was conducted. Response rates of the target schools were 46.4 % (n = 103) for junior high schools and 55.8 % (n = 116) for high schools. From these, we analyzed the data of 2960 junior high school students (1520 males, 1440 females) and 3703 high school students (1546 males, 2157 females) to examine the association between cancer-screening intention and sources of cancer-related information and understanding. A significant association between cancer-screening intention and sources of cancer information and cancer understanding was observed. The screening intention group identified more sources of cancer information than the no-screening intention group did. Understanding about cancer was reported by a higher proportion of students in the screening intention group compared with the no-screening intention group. Recognition that healthy people must take part in cancer screening was significantly associated with screening intention in both junior high (odds ratio (OR), 1.859; 95 % confidence interval (CI), 1.582–2.185; P

On March 11, 2011, Kawauchi Village, in Fukushima Prefecture, was struck by both the Tohoku earthquake and the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, with subsequent evacuation. One year later, in April 2012, villagers began to return. In the previous studies, increases in metabolic diseases were noted; here, we compared the prevalence of metabolically unhealthy conditions among evacuee and non-evacuee populations located nearby, namely Miharu and Ono Towns. This is a retrospective study using health examination data comparing health and health changes prior to the 2011 disaster (2008–2010: baseline) to the post-disaster period (2012–2015). 3451 residents who attended annual health checkups both between 2008 and 2010 and after 2011 made up the study population (599 evacuees and 2852 non-evacuees, collectively “baseline”). Disease states examined in this study included diabetes mellitus (DM) and borderline DM, polycythemia, hypertension, obesity, as well as exercise and smoking habits. We confirmed increases in the prevalence of obesity, diabetes, and polycythemia, which continue even 4 years after the FDNPP accident in the evacuee population, when compared to age- and gender-matched neighborhood populations. On qualitative questionnaire, evacuees were noted to have a higher rate of habitual exercise. The reasons for this shift in population health remain under investigation, but may involve a shift from active to sedentary lifestyle in the evacuee population that cannot be compensated for by increased exercise habit.

Von Recklinghausen disease is an autosomal domi- nant neurocutaneous disorder, characterized by cuta- neous neurofibromas, accompanied by café-au-lait spots. We report a case of a 51-year-old man with von Recklinghausen disease who had been operated on for thoracic and spinal neurofibroma. Exploratory thoracotomy was performed under general anesthesia combined with epidural anesthesia. After tracheal intubation with spiral tube, one lung ventilation was performed using blocker tube. General anesthesia was maintained by inhalation of oxygen, air, and desflurane and the continuous infusion of remifentanil. The opera- tive course was uneventful. The patient emerged from general anesthesia smoothly, and was extubated safely. There was no neurological abnormality after operation. Preoperative evaluation of airway status and neuro- logical findings are essential in the anesthetic management of the patient with von Recklinghausen disease. This case suggests that we must take the complication into account for anesthetic management and select the appropriate anesthetic method by routine preoperative estimation. It is of great importance that anesthesiologists evaluate the airway status and neurological find- ings of patients with von Recklinghausen disease.

Aims Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) in people with type 1 diabetes mellitus. Methods In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20–65 years) and 24 European participants (aged 18–65 years) with glycated haemoglobin levels ≤9.0% (≤75 mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9 U/kg (0.9 U/kg in the European study only), and Gla-100, 0.4 U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing. Results The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300. Conclusions Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36 h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes.

Background: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. Methods: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. Results: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. Conclusions: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression.

Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce the risk of hypoglycaemia, possibly through augmentation of glucose-dependent insulinotropic polypeptide (GIP) action, but not that of glucagon-like peptide-1 (GLP-1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP-4 inhibitor linagliptin on glucagon and other counter-regulatory hormone responses to hypoglycaemia were evaluated and compared with those of the GLP-1 receptor agonist liraglutide in a multi-centre, randomized, open-label, 2-arm parallel comparative, exploratory trial. Three-step hypoglycaemic clamp glucose tests preceded by meal tolerance tests were performed before and after 2-week treatment with the drugs. Glucagon levels were increased during the hypoglycaemic clamp test at 2.5 mmol/L. This increase was similar in the linagliptin and liraglutide groups, both before and after the 2-week treatment. Changes in other counter-regulatory hormones (ie, growth hormone, cortisol, epinephrine and norepinephrine) were also similar between the groups, but were suppressed substantially after 2-week treatment compared to baseline. In conclusion, we confirmed that the glucagon response to hypoglycaemia was not affected by linagliptin or liraglutide treatment in Japanese individuals with T2D.

Children are given visual acuity tests at school. The purpose of the tests is to facilitate school education. There are two types of visual acuity: far-vision and near-vision visual acuity. Far-vision visual acuity is required, for example, when reading something written on a white board in a classroom. On the other hand, near-vision visual acuity is needed when reading textbooks, notebooks, or when looking at computer screens. However, only far-vision visual acuity tests are stipulated in the "School Health Law". As a result, a near-vision visual acuity test is not typically included in medical examinations at public schools. However, we believe that a near-vision visual acuity test is necessary, and so in this paper we analyze some basic data about the relationship between children's near-vision visual acuity and their vision-related behavior. For the purposes of the paper, we examined both far-vision and near-vision visual acuity tests of elementary school children. We found that children whose far-vision visual acuity was under 1.0 had 4 vision-related behavioral problems, and that children whose near-vision visual acuity was under 0.8 had six such problems. Children whose far-vision visual acuity is found to be lacking are given remedial treatment to improve their eyesight. We therefore strongly recommend the addition of near-vision visual acuity tests in public schools so that children found to have near-vision acuity problems can be given treatment too.

With the developments in ICT society, means to get information has changed remarkably. In the scene of education, students study on VDT and use near visual acuity more than before. In order to teach students efficiently, we should inspect not only far visual acuity but also near visual acuity of students. We tested children's refaction, far and near visual acuity and questionnaire investigation at an elementary school, a municipal school in Urayasu city on May 2010. The purpose of those tests is to clarify the actual situation of the students who have poor near visual acuity. According to the far and near visual acuity test at the school, we found that there are children whose far visual acuity is "more than 1.0" and have near visual acuity "under 0.8" The percentage of them was 6.3% (22) for the right eye, and 5.6% (20) for left eye. And according to the refraction test at the school, we found that there are many children who have refractive myopia and refractive hyperopia. Their proportion was similar. In case of the children whose far visual acuity is "under 1.0", we found that there are many children who have low or moderate or high degree of myopia. A total percentage of them were 67.0% (132) for the right eye, and 64.4% (125) for left eye. The results show that the near visual acuity test is effective to preserve the sight of children who aren't found to have poor eyesight because who has good far-vision eyesight is good although they have hyperopia. We can conclude that far visual acuity inspection these days cannot manage near visual acuity. It is time to operate near visual acuity inspection.

We tested children's refraction and far and near visual acuity at "A" elementary school, a municipal school. The purpose of the test was to sort out the situation of the children who have poor near visual acuity. Then we recommended that the children whose near-vision eyesight was under0.8 contact an eye doctor. According to the refraction test at the school, we found that there are children who have poor near visual acuity and have low or high degree of hyperopia at the same time. The percentage of them was 31.8% (266) for the right eye, and 34.2% (286) for the left. On the other hand, there are those who hadn't been found to have low or high degree of hyperopia because they have far-vision eyesight of more than 1.0. The percentage of them was 27.8% (237) for the right eye and 34.2% (286) for the left. In addition, we found that there are children who have poor near visual acuity who have regulatory dysfunction. The results show that the near visual acuity test is effective to preserve the sight of children who aren't found to have poor eyesight because their good far-vision eyesight is good although they have hyperopia.

Recent studies suggest that the impairment of circadian clock function causes various pathological conditions, such as obesity, diabetes, and alcoholism, and an altered mRNA expression of clock genes was found under these conditions. However, it remains to be determined whether clock gene expression varies depending on metabolic conditions even in healthy people. To address this issue, we investigated the associations of metabolic parameters and alcohol consumption with mRNA expression of clock genes (CLOCK, BMAL1, PER1, PER2, and PER3) in peripheral blood cells obtained from 29 healthy non-obese elderly men (age 51-78 yrs) who adhered to a regular sleep-wake routine, through a single time-of-day venous blood sampling at approximately 09:00 h. There were significant correlations between (1) waist circumference and mRNA level of PER1 (r =-0.43), (2) plasma glucose concentration and PER2 (r =-0.50), (3) ethanol consumption and BMAL1 (r =-0.43), and (4) serum gamma-GTP concentration (a sensitive marker of alcohol consumption) and PER2 (r =-0.40). These results suggest mRNA expression of clock genes is associated with obesity, glucose tolerance, and ethanol consumption even in healthy people.

In February 2009, we tested the far-vision visual acuity and near-vision visual acuity of school children at "A" elementary school, a municipal school. The purpose of the test was to examine whether the present far visual acuity test could also identify the children whose near visual acuity is bad. Based on the past study, we set the standard of near visual acuity at 0.8. We recommended that children whose near visual acuity was under0.8 see an ophthalmologist. There were many children whose far visual acuity was under 1.0, more than half of all children, especially in the upper grades. This result shows that there is concern with the control of children's eyesight after the test.On the other hand, more than ten percent of the children of each grade scored less than 0.8 in uncorrected vision. We found children who have trouble seeing near objects who are overlooked in the present far visual acuity test. We have to check children's near visual acuity in order to find children who have trouble with near visual acuity.

We tend to overtax our eyes. It is because we daily watch TV, use PC, play video games and write e-mails on cell phones these days. When we continue using our eyes for hours, the ciliary muscles become abnormally tensed. As a result, we risk developing accommodative asthenopia. We can prevent the accommodative function decline by using a training stick to alternately focos on distal and proximal targets. We conducted training to reduce eye strain for about two months at an elementary school, among children in the first, third, and sixth grades. The sixth grade children did the training for only five weeks, because they had to participate in school events. We checked their near visual acuity before and after the training period in order to validate the evidence of the training. Then, we classified the children of each grade into two groups: children whose near visual acuity is more than 0.8 and children whose near visual acuity is less than 0.8. We analyzed the change of their near visual acuity. According to the analysis, for the first and the third grade children, the under 0.8 group progressed significantly. On the other hand, there was little progress seen in the 0.8 group. The sixth-grade children progressed little in either group. The result suggests an improvement in near visual acuity in the first and the third grade children. We are planning to validate the evidence of the effect of grade and of the training period.

Children are given only far-vision visual acuity tests at school, currently. We cannot identify children whose near-vision visual acuity isn't good through the test. Children whose near-vision visual acuity isn't good have difficulty in reading characters in their textbooks and notebooks, and on their PC screens. It is important to identify children whose near-vision visual acuity isn't good as early as possible in order to improve learning efficiency. There is a simple near-vision visual acuity test which can be given at school or home easily. Specifically, we use three indicators of near-vision visual acuity. First, we have the children practice at the "0.3" level. Secondly, we test at the "0.5" level for three-year-old children and "0.8" for children six years old and over. In case they have difficulty in seeing them, they should contact an eye doctor in order to find out the cause of their difficulty.

Children are given a visual acuity test at school. It has the purpose of facilitating school education. There are two types of visual acuity:far and near visual acuity. We need far visual acuity when we read letters on white boards in classrooms. On the other hand, we need near visual acuity when we read textbooks, notebooks, or computer screens. However, only far visual acuity tests are stipulated in the "Report of School Health Statistics". As a result, near visual acuity test is not a typical part of health research in public schools. We would like to introduce near visual acuity tests into health research in schools. We gathered fundamental data about near visual acuity in children and their vision-related behavior. We analyzed the data in order to find out the relationships between children's near visual acuity and vision-related behavior. Specifically, we examined near visual acuity of pre-school toddlers and took a survey of declining vision. As a result, we found that children whose near visual acuity was "under1.0" had some problems in vision-related behavior. We would like to introduce near visual acuity tests into health research on children before their enter elementary school. We firmly believe that children with poor eyesight can improve in near visual acuity before the beginning of compulsory education.

There are two types of visual acuity -distant and near vision visual acuity. We need distant visionvisual acuity when we read letters on white board in classrooms. On the other hand, we neednear vision visual acuity when we read textbooks, notebooks and letters on computer screens.However, only distant vision visual acuity tests as stipulated in the "Report of the SchoolHealth Statistics". As a result, near vision visual acuity tests are not a typical part of health researchin public schools. We would like to introduce near vision visual acuity tests into the healthresearch in schools.We gathered basic about near vision visual acuity in children and their rate of study. We analyzedthis in order to find out the relationships between children's visual acuity and the theirscores.We found that students whose poor near vision visual acuity had some problems studying efficiently.We should medically control poor near vision visual acuity when we discover underdevelopedvisual performance.In order to supply school education to all students equally, we're analyzing the significance of nearvision visual acuity tests to the school health check and introducing these tests from the viewpointof health education.

Regular checkups at school are conducted as a screening for rate of study. So, checkups have been improved as needed and visual acuity tests have also been improved as time has passed. However, we doubt if those changes truly reflect the reality of education. In addition to this, all the changes on visual acuity tests were limited to distant vision visual acuity" until now. Near vision visual acuity" has not been covered. It's possible that there are students who are thought to have little ability or to be lazy when in fact the largest cause of their difficulty in study is poor visual acuity. It is necessary to conduct visual acuity tests which help students who have visual function problems such as refractive error. The point of this study is to find students who have visual acuity problems which have not been discovered by visual acuity tests yet and to analyze their rate of study. The fundamental data will review new ways testing visual acuity which are effective in improving education. Our the research found, students who don't wear glasses although they have poor visual acuity and those who cannot see clearly although they wear glasses. They notice that they have problems seeing and in many cases there is relationship between their visual acuity and their rate of study. We should make consideration how to make physical checkups which have a greater impact on study.

Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type 2 diabetes mellitus is associated with both insulin secretion defect and insulin resistance. The primary metabolic defect leading to type 2 diabetes mellitus has been thought to be varied among populations, especially in Japanese and Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus using 102 affected Japanese sib-pairs to identify the genetic factors predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly, the 11p13-p12 region was reported to be a susceptibility locus for Japanese type 2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5 cM to D11S935 with the highest MLS in the previous linkage analysis reported. The only overlapped susceptibility region with suggestive evidence of linkage for Japanese type 2 diabetes mellitus was D11S935-D11S905 among the three reports including this study. These results taken together suggest that a susceptibility gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.

In this study, we assessed the effects of the prevaccination titer and age on the immunogenicity of a low dose of influenza vaccine in children less than 4 years of age. A total of 259 children received two vaccine doses (0.1 ml for 0-year-olds and 0.2 ml for children 1 year of age or older) 4 weeks apart during the 2005/2006 season. The hemagglutination inhibition antibody titers were measured before vaccination and 4 weeks after the first and second doses. The geometric mean titer, mean fold rise, seroresponse proportion (≥4-fold rise in titer), and seroprotection proportion (titer ≥1:40) were calculated for the prevaccination titer and age categories. A multivariate logistic regression analysis was performed using the seroresponse and seroprotection proportions as dependent variables and the prevaccination titer and age as explanatory variables. As for the seroresponse against the H1 antigen after the first dose, the adjusted odds ratios of the prevaccination titers (versus Ptrend< 0.001). Similar results were also obtained for the H3 and B strains. Significantly elevated odds ratios for seroprotection were observed with greater prevaccination titers and older ages for all strains. The prevaccination titer and age were independently associated with the antibody response in young children. The immune response was weaker in the younger children and those without preexisting immunity.

The objective of this study was to determine cancer understanding among Japanese primary and secondary school students. The study design was a cross-sectional nationwide survey using a self-administered questionnaire. The prefecture with the lowest student population was set to 1, and that with the highest student population was set to 18 for elementary schools and 19 for junior high and high schools based on the ratio of the student population. In this way, 213 elementary schools, 222 junior high schools, and 208 high schools were selected from all 47 prefectures in Japan, and questionnaires were sent to each school. The questionnaire listed the names of 15 cancers and asked respondents to choose one answer from three: “Never heard of,” “Heard of/Don’t understand,” or “Heard of/Understand.” Response rates for schools were 44.1 % (n = 94) for elementary schools, 46.4 % (n = 103) for junior high schools, and 55.8 % (n = 116) for high schools. A total of 8,876 questionnaires were used for the analysis. Our survey suggests that the most commonly understood types of cancer differed by grade, with lung cancer the most commonly understood in elementary school, leukemia in junior high schools, and breast cancer in high schools. Girls tended to demonstrate greater cancer understanding than boys, with particularly large differences by gender in rates of understanding of breast and uterine cancer at each assessed grade level. Here, we examined Japanese primary and secondary school students. Marked differences in cancer recognition by grade and gender suggest that educational efforts are needed at various grade levels and gender-specific cancer education. Further, more than 50 % of students at any school level were not familiar with most cancers. It suggests that cancer education is deficient.

Based on a questionnaire survey carried out in July 1996, this study aims to evaluate the effects of barefoot education of schoolchildren in elementary schools, with respect to behaviourmodification concerning safety and healthy lifestyle. The subjects were 571 schoolchildren, 420from a school which conducted barefoot education for seven months from April to October and151 from a school which did not. The 420 children in the former were divided into one group(N=289, 76.1%) who were always barefooted and another (N=91, 23.9%) who were not. The major findings were as follows. 1. The comparison between the two schoolchildren groups revealed that the barefoot educationgroup developed more safety and health behaviour such as avoidance against hazardous objects on the schoolyard and in the classroom, hand-washing, and cleaning of gymnastic wear. 2. Within the schoolchildren in the barefoot education school, the?galways berefooted" grouppaid more attention to hazardous objects and did hand-washing more frequently, though significantly different items between the two groups were fewer than those in the between-schoolcomparison. This study suggests advantageous effects of barefoot education on development of safety and healty behaviour in schoolchildren.

The purpose of this study was to develop a scale for measuring cognitive stress in order to assess mental health education program for high school students. First, the content of stressor was collected using the open-ended questionaaire from 1, 196 Korean high school students in Seoul, and 149 items were obtained. Next, stress magnitude of each stressor was appraised with 4-point rating scale by1, 188 Korean high school students in Seoul. On the basis of the results of principal component analysis and item analysis, subscales concerning daily hassles, e. g., home life, school life, future, friendship, social support, health and so on, were constructed. Eighteen items concerning life event were adopted as one subscale, which can be calculated in terms of 4-point rating scale. As a result, 36subscales consisted of 98 items were chosen. Moreover, 14integrated scales were constructed by a principal component analysis of these subscales. Lastly, percentile and T-score were prepared as a norm.

末梢型肺腺癌の腫瘍血管侵襲 (VI) 部位を組織学的に検討した.対象は腫瘍径3cm以下の切除例で, 問質弾性線維増生網 (EFW) の明らかな粘液非産生型末梢型肺腺癌で, 組織学的に血管内腫瘍細胞塞栓 (ITE) を明瞭に認めた22例である.腫瘍の間質形成所見を, 断裂したEFWからなる中心部線維化巣 (CF) と, その周囲肺胞を被覆増殖するreplacement growth (RG) に分け, CFは更に1) Type 1-like EFW, 2) collagenized EFW, 3) collapsed EFWに分けて, ITEの出現を部位別に検討した.結果;VIは15例35ヵ所でRGに, CF内では11例15ヵ所で1) に, 11例13ヵ所で2) に, 1例2ヵ所で3) にみられた.いずれもCF辺縁でRGとの境界部に多い.また, CF内での膠原化の程度に比例してRGでのVIの頻度が増加する傾向がみられた.CF内の血管病変はVIよりも器質化血管閉塞や破壊が多くみられた.この結果から, VIは末梢型肺腺癌の特有な腫瘍間質であるCF形成過程での微小環境循環障害で生ずる新生血管を機転として始まり, CF内の膠原化が進むと, より辺縁側の進展部 (RG) で腫瘍塞栓として観察されるようになると考えられた.

末梢型肺腺癌で中心部線維化巣 (central fibrosis: CF) を形成するType 2腺癌の, CF周囲肺進展部での腫瘍間質内弾性線維 (elastic fiber: EF) を画像解析した.検索症例のX線経過は, 約半年単位の短期経過で, 腫瘤径の増大が明瞭であった.このX線上の陰影増大経過は, 組織でのCF周囲進展部の広さに合致していた.CF周囲進展部のEF網は, たわみの乏しいThick EFが薄い肺胞壁をskipして構成されていて, 正常肺胞構築との類似性が強い.単位肺胞壁長あたりのEF量, EF長は正常肺胞でのそれより増大していたが軽度で, 2倍程度までに留まっていた.この結果, CF周囲腫瘍進展部肺胞壁は, Type 1腺癌でみられた強い肺胞壁の肥厚, 収縮等はみられず, 正常肺胞壁がそのままに腫瘍間質を形成していると考えられた.

末梢型肺腺癌 (Type 1) のWeigert染色で染まる弾性線維 (EF) 量を顕微鏡画像解析装置で解析した. 腫瘍間質には腫瘍腺腔に沿って波状に走行するThickEF (ThEF) と, 基底膜下に密在するFineEF (FiEF) とが識別できる. ThEFは形態的に正常肺胞壁内EFと同質とみなされ, FiEFはType1に特有のものであった. 一定区画内での腫瘍EF量は周囲肺に比し3～7倍多く, ThEFの区画内総長は同様, 1.5～3.3倍多かった. その比は単位壁長当たりでは, 腫瘍EF量で4.9～12.3倍, ThEF長で1.9～5.3倍と更に増大した. 後者は腫瘍間質の同部に存在した肺胞の収縮比とみなされる. この結果から, Type 1肺腺癌ではFiEFが新生する結果, 壁が肥厚し, 既存の肺胞がAirspaceを保ちつつ収縮し, 腫瘍間質が形成されると推測される. X線像の特徴である大きさは変わらず, 濃度が増加するのは, この腫瘍間質の肥厚収縮の結果と考えられる.

Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes. Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young non-diabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 age-matched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR. In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p

腫瘍径2cm以下の末梢型肺腺癌41例を腫瘍間質の弾1生線維増生様式から2大別し, 臨床病理学的, X線学的に検討した. 1型は腺癌細胞で被覆された肺胞壁が弾性線維増生を伴って肥厚しているが, 肺胞構築網は維持されている. 2型はその集簇や断裂がみられ, その結果不規則に破壊した肺胞構築網が形成されている. 2群問のX線像経過は腫瘍径と濃度変化に明らかな違いがみられ, 術後病理所見では2型にのみ胸膜, 脈管, リンパ節への侵襲傾向が著しかった. この区分けは早期腺癌と進行腺癌の違いを示唆していると推測される.

August 2015 e43 vs. PsA63% and 37%). The longest duration of biologic therapy was in AS patients (47 months). Regardless of diagnosis, 31% patients required switching to another biological due to non efficacy (94, 1%). TNFα inhibitors were switched in 73% cases and etanercept in 27% patients. Seven patients discontinued treatment due to complete remission, serious infection, chemotherapy, cerebrovascular insult, newly diagnosed psychiatric disorder, moving to another city and private reason. There were 21 adverse drug reactions: infections (16), leucopenia and anemia (4) and pharyngeal carcinoma (1). Conclusion: Six biologic agents with different mechanism of action (TNFα inhibitors (4), anti-CD20 (1) and IL6 inhibitor (1)) are used in treatment of RA. For AS and PsA, four TNFα inhibitors were used what is in accordance with Croatian clinical practice guidelines. More frequent switching between different TNFα inhibitors is consistent with similar reports.

A 26-year-old man presented with complaints of exertional dyspnea and cough. The patient has already been given corticosteroids at a previous hospital. Chest CT revealed small centrilobular nodules with diffuse ground-glass opacities in both lungs. Lung biopsy specimens at thoracoscopy revealed non-necrotizing granulomas, patchy foci of mononuclear cell infiltration and fibrous thickening of alveolar septa, and Masson's bodies in bronchioles. Sputum culture showed the growth of Mycobacterium avium complex (MAC). Culture of water from the bath tub of his home showed MAC. Administration of antituberculous drugs and corticosteroids, and avoidance of bathing at home resulted in the improvement of his symptoms and CT findings. We believe the case is hypersensitivity pneumonitis to MAC in an immunocompetent patient, simulating hot tub lung. Hypersensitivity pneumonitis caused by MAC is rare in Japan.

Background: The number of children with psychosomatic and psychosocial disorders has been increasing in Japan. There are, however, few trained pediatricians who have adequate knowledge of the treatment needed. The Research Group on the Promotion of Management of Children with Psychosomatic and Psychosocial Disorders carried out the present study to (i) disseminate knowledge about psychosomatic and psychosocial disorders of children; and (ii) establish a community-based network model to ensure effective communication among relevant institutions. Methods: To disseminate knowledge of the psychosocial and psychosomatic disorders, the Research Group compiled the Handbook for Psychosomatic Disorders of Children and distributed it to pediatricians throughout Japan. A follow-up questionnaire survey was then carried out. Also, in order to examine the current status of the communication network between pediatricians and the related institutions, the Research Group conducted a questionnaire survey on general pediatricians. Results: Sixty-five percent of the respondents indicated that they were actually using the Handbook. The topics in the Handbook that were most frequently referred to by the respondents were attention deficit hyperactivity disorders, school refusal, eating disorders, and orthostatic dysregulation. Thirty-seven percent of the participants indicated changes in their behavior towards psychosomatic and psychosocial problems. The results of the survey on communication networks found that the pediatricians generally collaborated with different institutions depending on the nature of the problems, such as school refusal and bullying, developmental disorders, child abuse and maltreatment, and others. Conclusion: Promotion of the Handbook would greatly contribute to improving the management of children with psychosomatic and psychosocial disorders, together with the construction of the basic network model for management of these children.

The ratio of glycated albumin to albumin concentration in serum is termed the glycated albumin (GA) value. The GA value provides a time-averaged index of the state of glycemic control for the previous 2 weeks. In this study, a dry chemistry system (GA monitor) via an enzymatic method was proposed in order to provide a GA value measurement for point of care testing (POCT). The GA monitor was made from three devices a set of test-tapes, a test-strip and an optical analyzer. A GA test-tape, a ketoamine test-tape and an albumin test-tape were enclosed in the fabricated test-strip. Time-course changes of the optical characteristics were evaluated using the test-strip. It was found that the three test tapes must be enclosed in the test-strip to create a dry chemistry system for small sample volumes (20 microl). A temperature control unit, which could hold the temperature of the GA test-tape at 45 degrees C and at 25 degrees C for the other two types of test-tape was incorporated into the optical analyzer. With the GA test-tape held separately and controlled at 45 degrees C, the analytical time decreased to one-third of the time taken for the three tapes at 25 degrees C. The analytical accuracy of the three types of test-tape showed favorable results, with R2 values of 0.96-0.98 and coefficients of variation (CV) of 2.4-6.8%. Compared with a commercially available liquid chemistry system, the analytical accuracy of the GA monitor exhibited a relatively favorable linearity of R=0.82. According to these results, a new GA value analytical system was realized, in which the GA value could be assayed within five minutes using only 20 microl of blood sample with a disposable test-strip. This system could potentially be used for clinical purposes as test equipment for rapid and efficient POCT.

Objectives We investigated the immunogenicity of the vaccine for H1N1pdm influenza, which became a global pandemic in 2009/2010. We reported the vaccination study outcomes based on the patients with rheumatoid arthritis, however we would like to know how much serological response who are exposed to H1N1 pdm, are expected in patients with rheumatoid arthritis under monoclonal antibody therapy, conventional DMARDs compared to healthy adults. Methods One hundred twenty-six patients (29 males and 97 females) with rheumatoid arthritis (RA) and thirty healthy volunteer were enrolled. In RA patients, conventional DMARDs, infliximab(INF), etanercept(ETA) and tocilizumab(TCZ) were treated by 59 patients, 27 patients, 18 patients, and 22 patients, respectively. Patients were vaccinated twice in September and October with the H1N1pdm influenza vaccine (Biken). Serum samples were taken prior to vaccination the first (S0) and second (S1) vaccinations, and in the fourth week after the second vaccination (S2), and serum antibody titres were measured using the haemagglutination inhibition (HI) assay. Using these data, we investigated the response rate (increase in HI titre ≥4-fold), seroprotection rate (HI titre ≥1:40), and seroconversion rate (increase in HI titre from pre-vaccination titre Results 1) The response rate at S1/S0 and S2/S0 are 59% and 69% in healthy volunteer, 60% and 74% in pts received DMARDs, 30% and 56% in pts received INF, 53% and 65% in pts treated ETA, and 77% and 76% in pts with TCZ. 2) Seroprotection rate at S1 and S2 are 34% and 45% in healthy volunteer, 40% and 47% in pts received DMARDs, 22% and 37% in pts received INF, 35% and 47% in pts treated ETA, and 50% and 48% in pts with TCZ. 3) Seroconversion rate at S1 and S2 are 55% and 66% in healthy volunteer, 59% and 68% in pts received DMARDs, 37% and 48% in pts received INF, 53% and 65% in pts treated ETA, and 64% and 71% in pts with TCZ. Conclusions In this research on the pandemic influenza vaccine, we found no inhibition of immunogenicity in patients receiving tocilizumab compared to healthy volunteer and patients with monoclonal antibody or DMARDs. Disclosure of Interest T. Tsuru Consultant for: USB, Employee of: Medical Co.LTA, M. Suzaki Employee of: Medical Co.LTA, K. Maeda: None Declared, H. Nakashima: None Declared, T. Eto Employee of: Medical Co.LTA, M. Ishibashi Employee of: Medical Co.LTA, J. Manabe Employee of: Medical Co.LTA, K. Terao Employee of: ChugaiPharmaceutical Co.,LTD., S. Irie Employee of: Medical Co.LTA

BACKGROUND Most peripheral lung adenocarcinomas form a characteristic central fibrosis; however, the mechanism of formation has not yet been clarified. METHODS The stromal elastosis of 176 patients with peripheral lung adenocarcinomas was studied histologically, morphometrically, radiographically, and clinicopathologically. RESULTS The tumors were classified into two types, according to the histomorphological pattern of the stromal elastosis: (1) a preserved framework composed of a uniformly thick stroma (Type 1; 20 patients) and (2) a disrupted framework in the central fibrosis in which many air spaces were collagenized or collapsed (Type 2; 156 patients). Around the central fibrosis in the Type 2 tumors, replacement growth took the form of a thin-walled, elastic framework. Image analysis disclosed that the elastotic framework had an increased elastic fiber volume (approximately three- to- nine-fold, compared with the normal alveolar wall), especially in Type 1 tumors, related to the contraction of the pre-existing alveolar wall. In Type 2 replacement growth, the amount of elastic fibers was slightly increased, which suggested mild reaction of the pre-existing alveolar wall. Radiographically, Type 1 tumors were characterized by a gradual increase of the density without enlargement, while the Type 2 tumors often enlarged within a short period. Recurrence was seen in 54% of the patients with Type 2 tumors, but in none of those with Type 1 tumors. CONCLUSIONS In the early development of peripheral adenocarcinoma, there is preservation of the elastotic framework (Type 1) of the stroma due to contraction and thickening of the alveolar walls. As the tumors grow, the elastotic framework is disrupted (Type 2), indicating stromal invasion. Based on the clinicopathologic findings and the outcome, Type 1 tumors may be in situ peripheral lung adenocarcinomas. Cancer 1996; 77:646-56.