Despite the development of radiotherapy machines and technologies, a proportion of patients suffer from radiation-induced enteritis or oral mucositis. It has been reported that hangeshashinto has been used for not only enteritis but also oral mucositis. This study reports the effect of hangeshashinto on enteritis or oral mucositis caused by radiotherapy. Three patients with enteritis and 5 patients with oral mucositis were treated with hangeshashinto at a dose of 7.5 g/day. The severity of enteritis or oral mucositis was evaluated using the Common Terminology Criteria for Adverse Events version 4 and Numerical Rating Scale both before and after hangeshashinto treatment. After the treatment with hangeshashinto, 3 of 5 patients with oral mucositis and 2 of 3 patients with enteritis showed apparent improvement. In conclusion, it is important to control the side effects of radiotherapy, which lead to improved tumor control rates. Prospective randomized studies are necessary to confirm the findings of this case series study.

In junior high school, educators with many different types of specialty jobs are involved in “education on the proper use of pharmaceutical products” and “drug-abuse resistance education”. Examples of these different jobs are physical education teachers, school nurses, school pharmacists. The aim of this study was to elucidate novel ideas and new directions in the future of medicine instructional education by clarifying the aims and thoughts of educators with different jobs on the education of pharmaceutical medicines and drug use. Based on the technique of Personal Attitude Construct (PAC) analysis, junior high school staff members involved in “education on the proper use of pharmaceutical products” and “drug-abuse resistance education” were interviewed regarding their aims and thoughts. Their responses were analyzed qualitatively. Five school pharmacists, five school nurses, and four physical education teachers were interviewed. The responses revealed that school pharmacists engaged in student education from the specialized perspective of pharmacology, school nurses engaged in student education from the perspective of imminent situations, and physical education teachers engaged in student education more from the perspective of student environment. This study suggested that “education on the proper use of pharmaceutical products” and “drug-abuse resistance education” should be a collaborative effort, so there were the different perspectives and aims of educators with different specialty jobs in the instruction of junior high school students on these subjects.

Nutritional profiles in middle-aged trained and untrained women were compared both before and after menopause. Subjects were assigned to one of four groups : (1) pre-menopausal trained (Pre-T: n=14, aged 43±5 years, running distance 56±27 km/week, Vo₂max 49±4ml/ kg/min, mean±SD), (2) pre-menopausal untrained (Pre-UT: n=25, 42±5 years, 34±5 ml/kg/ min), (3) post-menopausal trained (Post-T: n=19, 53±3 years, 49±17 km/week, 42±6 ml/ kg/min), (4) post-menopausal untrained (Post-UT: n=26, 54±3 years, 31±3 ml/kg/min) . There were no significant differences in hematocrit (range 38.7 to 39.3%), hemoglobin (12.8 to 13.1 g/dl) and total protein (6.9 to 7.1 g/dl) among the four groups. Serum iron concentrations in the post-menopausal women (Post-T: 97±30μg/dl, Post-UT: 106±29μg/dl) were relatively higher than in the pre-menopausals (Pre-T: 85±35 pg/dl, Pre-UT: 78±33 pg/dl) . Mean total iron binding capacity in Post-UT (326 pg/dl) was lower than other groups (352 to 361 pg/dl) . Higher serum ferritin levels were observed in the post-menopausal women (Post-T : 35.8±27.5 ng/ml, Post-UT : 60.4±47.1 ng/ml) than the pre-menopausals (Pre-T: 18.3±13.1 ng/ml, Pre-UT: 16.6±10.7ng/ml) . Intake levels of the four groups with regard to the major nutrients were sufficient as compared with the recommended dietary allowance appropriate for age, sex and physical activity level. Intakes of calcium, iron and vitamins B₁, B₂ and niacin were higher in the trained groups than in the untrained. Regularly performed endurance exercise resulted in higher protein and iron intakes associated with higher energy intakes both before and after menopause. These results suggest that nutritional status of middle-aged women who regularly perform vigorous endurance running could be adequate for maintaining their health in a good state.

Citrin defi ciency is an autosomal recessive disorder caused by mutation in the SLC25A13 gene. It has two major phenotypes: adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestatic caused by citrin defi ciency (NICCD). NICCD is characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with multiple amino acidemia and hypergalactosemia. NICCD is self-limiting in most patients. However, some patients may develop CTLN2 years later, which manifests as fatal hyperammonemia coma. We report three unrelated Malay children with genetically confi rmed NICCD characterised by an insertion mutation IVS16ins3kb in SLC25A13 gene. All 3 patients presented with prolonged neonatal jaundice which resolved without specifi c treatment between 5 to 10 months. Of note was the manifestation of a peculiar dislike of sweet foods and drinks. Elevated plasma citrulline was an important biochemical marker. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Malaysian infants regardless of ethnic origin.

    Clinical research is essential for the practice of evidence-based medicine. This study reports on our current practice of clinical research support in Mito Kyodo General Hospital and discusses future challenges. In April 2013, the University of Tsukuba hired a clinical research assistant to provide clinical research support in Mito Kyodo General Hospital. The clinical research assistant worked full-time in the hospital in collaboration with 3 university faculty members. The target population for this study comprised 450 medical personnel including doctors, nurses, and other medical staff. From April 2014, 1 of the 3 faculty members visited the hospital once a month to offer clinical research consultations and deliver a lecture on nursing research. We analyzed past records of clinical research support and conducted a questionnaire survey to explore the level of satisfaction of the medical personnel. Four-hundred and ninety records of 91 research topics proposed by 68 medical personnel were identified. Of these, 93.4% were proposed by doctors or nurses. Most studies employed an observational study design (64.8%) and were conducted in order to make a presentation at an academic conference (51.1%). The consultation sessions were held 1–5 times, for 40–405 min, and lasted from 1–84 days per research topic. Consultations mostly pertained to research design and protocol planning (57.1%). Forty-seven clients were invited to participate in the questionnaire survey, 30 of whom provided valid responses. The results showed that 96.6% of the clients were satisfied with the consultations. The number of clients who participated in the consultations comprised only 15.1% of the target population. These practice biases need to be addressed in future. However, nearly all respondents were satisfied with the consultations. These findings suggest that our clinical research support was beneficial to medical personnel.

Objective Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, OMIM 605814 ) is a novel autosomal recessive disease results from mutations in the gene SLC25A13 that encodes for citrin, a liver-type aspartate/glutamate cartier located in the mitochondrial inner membrane. Most of the Chinese NICCD patients diagnosed by genetic analysis had the sameSLC25A13 mutations as Japanese, however, in some cases, the known mutations were not detected. This research aimed to identify novel SLC25A13 mutations in Chinese NICCD patients and to explore the experimental conditions for their genetic diagnosis.Methods Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan (P757), Guangdong (P1194) and Hebei (P1443) Province of China, respectively; and all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced. Furthermore, the identified novel mutations were diagnosed by amplification with PCR, digestion with corresponding restriction endonuclease, and agarose gel electrophoresis.Results Three novel mutations identified in SLC25A13 gene of the 3 NICCD patients were an abnormal splicing IVS7-2A>G (P757), a missense A541D (c. 1622C > A, P1194) and a nonsense R319X (c. 955C > T, P1443). The PCR-RFLP procedures for their genetic diagnosis were also established, with specific fragments on electrophoresis after digestion of the PCR products with three different restriction endonucleases Msp Ⅰ, Hpy188Ⅰ and Taq Ⅰ, respectively.Conclusions The three novel mutations in SLC25A13 gene of Chinese NICCD patients were first identified, suggesting that SLC25A13 mutation distributed in Chinese population is somewhat different from that in Japanese. Moreover, the PCR-RFLP diagnostic procedures established in this research provide valuable tools not only for the genetic diagnosis of NICCD but also for further molecular epidemiologic investigations in Chinese population.Acknowledgement We are grateful to all research subjects and their family members for their cooperation, and to many members of medical staff who contributed much to this research. This study was financially supported partially by Guangdong Provincial Research Grant for Science and Technology (No. 2004B50301008) and the Major State Basic Research Development Program of China (No. 2007CB511901 ), and by Grants-in-Aid for Scientific Research (B: Nos. 16390100 & 19390096 ) and for Asia-Africa Scientific Platform Program (AASPP) from the Japan Society for the Promotion of Science.

OBJECTIVETo explore the major etiological features of cholestatic liver disease (CLD) in children, and to investigate the molecular epidemiological distribution of SLC25A13 mutations in CLD.

METHODA clinical cross-sectional investigation was performed on 63 CLD cases diagnosed from Oct. 2003 to Mar. 2009 in our department, including 36 males and 27 females. Their clinical data were collected, and etiology and prognosis were analyzed and summarized. Thirteen to 17 mutations in SLC25A13 gene were screened by means of procedures established previously by our group. Several SLC25AJ3 mutations were detected by direct sequencing of DNA fragments amplified by genomic DNA-PCR.

RESULTNo specific etiologies were identified in 24 of the 63 cases. Among the 39 cases with identified etiologies, inherited metabolic diseases were on top of the list, including 6 kinds and 27 cases in total, i.e., neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, 21 cases), transient galactosemia, tyrosinemia type I, galactose kinase deficiency, ornithine carbamoyl transferase deficiency and glycogen storage disease type I, followed by acquired causes (7 cases in total), such as total parenteral nutrition associated cholestasis (TPNAC), congenital syphilis and CMV hepatitis; and then biliary tract malformation (5 cases in total), including biliary atresia, Caroli's disease and gallbladder polyp, were the third. Ten of the 55 patients on follow-up have passed away, while the remaining 45 cases were improved or recovered clinically. SLC25A13 gene analysis were performed in 44 CLD subjects and 21 of them from 20 families (with 40 SLC25A13 alleles in total) were found to have mutations, and the seven mutations detected were 851-854del (23/40), IVS6 + 5G > A (6/40), IVS16ins3kb (3/40), 1638-1660dup (2/30), A541D (1/30), R319X (1/30) and G333D (1/30), respectively, and there were other 3 mutations (3/40) still needing identification in the remaining 3 alleles.

CONCLUSIONThe etiologies for CLD in some cases can not be identified. However, inherited metabolic diseases, including NICCD in particular, constitute common causative factors for CLD. Most of the CLD conditions can be improved, even recovered clinically, although some cases presented with poor prognosis. Seven mutations in SLC25A13 gene were detected, among which, 851-854del, IVS6 + 5G > A, IVS16ins3kb and 1638-1660dup were the leading four mutations, respectively.

Child ; Child, Preschool ; China ; epidemiology ; Cholestasis, Intrahepatic ; diagnosis ; epidemiology ; genetics ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mitochondrial Membrane Transport Proteins ; deficiency ; genetics ; Molecular Epidemiology ; Mutation ; Prognosis

Two clinical phenotypes for citrin deficiency (CD) have been reported. One is adult-onset citrullinemia type II (CTLN2) and another is neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). A child with CD and who had failure to thrive (FTT) and dyslipidemia as main clinical manifestations is reported here. Both the weight-and length-for-age at 18 months dropped below the 3rd percentile in the corresponding WHO anthropometry percentile charts, while blood biochemical analysis revealed dramatically increased triglyceride and total cholesterol, together with reduced HDL-cholesterol. Inquiries revealed his aversion to rice and fondness for fish since the age of one year, a peculiar habit which could not be corrected. Since the age of two years, the peculiar diet became more obvious, and slightly increased citrulline and threonine levels were detected on blood amino acid analysis. At the age of two years and five months he was suspected to have CD. Since then, he has been fed in accordance with his own food preferences, and FTT improved gradually, with weight-for-age, in particular, recovering beyond the 3rd percentile at three years of age, and dyslipidemia was also ameliorated gradually. SLC25A13 gene analysis revealed a homozygote of 851del4, and CD was thus confirmed. Diet survey at four years and seven months revealed a fondness for high-protein and low-carbohydrate foods, such as seafood, meat, eggs and milk. This child presented with FTT and dyslipidemia as main clinical manifestations and this was a novel CD phenotype different from NICCD and CTLN2.
Body Weight ; Calcium-Binding Proteins ; deficiency ; Cholestasis, Intrahepatic ; etiology ; Citrulline ; blood ; Dyslipidemias ; etiology ; Failure to Thrive ; etiology ; Humans ; Infant ; Lipids ; blood ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency ; Phenotype