The prevalence of Centrocestus armatus metacercariae in fresh water fishes were examined in Hyogo Prefecture, western Japan for a period of one year from April 2003 to March 2004. Three species of cyprinoid fish, namely Zacco temminckii, Zacco platypus, and Pseudogobio esocinus, were found to harbor metacercariae of C. armatus. The infection rate of metacercariae in Zacco temminckii, Zacco platypus, and Pseudogobio esocinus was 99% (371⁄377), 100% (8⁄8), and 100% (2⁄2), respectively. The mean number of metacercariae recovered was 232 for Z. temminckii, 2,123 for Z. platypus, and 20 for P. esocinus. However, we focused on Z. temminckii in this study because it was found to be the most predominant fish species in the Chikusa River and to have high a metacercariae prevalence as well. In Z. temminckii, metacercariae were distributed in the brain (37%), viscera (35%), muscles (29%) and gills (0%). No metacercariae were recovered from the scales and fins. This is the first report of the occurrence of C. armatus metacercariae in the brain region of the second intermediate fish. The prevalence of C. armatus metacercariae was almost constant throughout the year, and no positive correlation was found between the prevalence and seasonal changes. However, a positive relationship was observed between prevalence of metacercariae and fish length, I.e., the intensity of infection increases with the size of the fish host (p < 0.05). People in the survey area sometimes eat fish raw, indicating enlightenment as well as the countermeasures to prevent C. armatus infection is needed.

In this summary, we reviewed Japanese large databases available as pharmacoepidemiology data sources. In addition to the National Claims Database, two commercially available insurance claims databases are widely used: Japan Medical Data Center(JMCD) and JammNet.Three large pharmacy claims databases are also reviewed.The pharmacy claims database has unique characteristics in Japan because a prescription is valid only for four days and therefore the prescription records are believed to be almost identical to the dispensing records. Two large hospital-based databases are also available.In order to properly use these databases for the pharmacoepidemiological research questions, we need to learn first the medical practice and medical systems in Japan to have a better understanding for data source and data items. Automated large databases can be a powerful tool for pharmacoepidemiology studies by learning strengths and limitations of each database. (Jpn J Pharmacoepidemiol 2012; 17(2): 135-144)

Centrocestus armatus is an intestinal parasite belonging to the family Heterophyidae. We developed an apparatus for recovering cercariae and clarified the infection dynamics of this parasite. To clarify the circadian rhythm of cercarial shedding in the summer season, we filtrated 30 l of river water every 2 h for 24 h. Cercariae were first detected between 06:00 and 08:00 h, increased over time to reach peak at 16:00 h and decreased thereafter, thus showing a single-peak pattern. In a survey of seasonal change, approximately 200 cercariae were contained in 1 l of river water during the summer season, while none were found during the winter. This cercarial shedding pattern appeared to be related to sunrise/sunset and water/atmosphere temperature. Therefore, we examined whether cercarial shedding was affected by light or temperature changes under laboratory conditions, and confirmed that both light and temperature were important factors for cercarial shedding. Light was a stronger factor than water temperature. Cercarial shedding of C. armatus occurred in response to temperature and light. The change in the number of juvenile metacercariae detected in fish brain corresponded with monthly detection rates of cercariae; however, the incidence of new infections decreased in August. This suggests that Nipponocypris temminkii contains a defense mechanism against new infections that may have hindered the increase in parasite infectivity. These results clarified the smooth infection from the first to the second intermediate host of C. armatus in the endemic river. Throughout the study period, fecal samples were collected from 19 kites, 114 herons, and three unidentified species. However, our results using C. armatus showed a low value of 1% in herons and 5% in kites. The infection dynamics of final host to first intermediate host need to be further investigated.

To clarify the recovery patterns of spontaneous activity and liver damage after different stressors, female Fischer 344 rats were treated with Propionibacterium aches (P, aches) or water immersion stress before lipopolysaccharide (LPS) injection. They were then examined for wheel running activity, serum corticosterone concentration, serum alanine aminotransferase (ALT) activity, histological appearance of liver and plasma tumor necrosis factor alpha (TNF-a) concentration.
The recovery in physical activity of P. aches-treated rats was faster than that of water immersion rats. One day after the stressors, serum corticosterone cancentration and ALT activity of P. acnes-treated rats were higher than that of water immersion rats. In addition, increases in serum ALT activity and plasma TNF- a, as well as massive necrosis of the liver in P. acnes-treated rats were observed seven days after stress treatment. The P. acnes-LPS rats also showed a reduction in survival rate after 24 hours. These results suggest that P. acnes stress causes serious inflammation when stimulated by LPS. Although rapid recovery in physical activity was not inhibited by P. acnes stress, it differed from the response of water immersion stress.

To clarify the recovery patterns of spontaneous activity and liver damage after different stressors, female Fischer 344 rats were treated with Propionibacterium aches (P, aches) or water immersion stress before lipopolysaccharide (LPS) injection. They were then examined for wheel running activity, serum corticosterone concentration, serum alanine aminotransferase (ALT) activity, histological appearance of liver and plasma tumor necrosis factor alpha (TNF-a) concentration.
The recovery in physical activity of P. aches-treated rats was faster than that of water immersion rats. One day after the stressors, serum corticosterone cancentration and ALT activity of P. acnes-treated rats were higher than that of water immersion rats. In addition, increases in serum ALT activity and plasma TNF- a, as well as massive necrosis of the liver in P. acnes-treated rats were observed seven days after stress treatment. The P. acnes-LPS rats also showed a reduction in survival rate after 24 hours. These results suggest that P. acnes stress causes serious inflammation when stimulated by LPS. Although rapid recovery in physical activity was not inhibited by P. acnes stress, it differed from the response of water immersion stress.

　　This study was conducted to clarify the benefits of using cervical cytological examinations and human papilloma virus (HPV) testing in our cervical cancer screening program, which was carried out during the period from April 2012 through March 2013 in the Yuri-Honjo district of Akita Prefecture. A total of 772 women underwent this screening. About 11.3% (87/772) of the examinees tested positive for HPV, and of these 87 women, 64 were also positive for HPV DNA in the examinations subsequently conducted in the outpatient clinic. Of the HPV DNA-positive women who showed no sign of abnormalities in cytology, 67.6% had lesions cervical intraepithelial neoplasia (CIN) 1 and above, and five women had l CIN 2/3. Compared with the conventional cytology which detected nine women with CIN 2/3, our screening method with a combination of cytology and HPV testing found 14 women with CIN 2 or 3. To upgrade the cervical cancer screening, we recommend HPV testing should be used in combination with cervical cytology.

　　This study was conducted to document a correlation between the age distribution of patients with cervical cancers and their genotype patterns of human papilloma virus (HPV). Retrospective analysis was performed on 53 patients in the clinical stage of CIN 3 and above. The patients were treated in our hospital during the period between January 2008 and May 2011. The age distribution showed that the patients in their twenties accounted for 28.0%, those in their thirties 34.0%, those in their forties 24.0%, those in their fifties 4.0%, and those in their sixties and older 10.0%, the average of the subjects was 39.5 years. This distribution pattern also indicated that the women aged 49 and younger are prone to cervical cancer. The overall detection rate of positive HPV in the high risk group was 97.1%. The detection rates varied according to the HPV genotypes, being 41.2% in HPV16, 17.6% in HPV52, 13.2% in HPV58, and 5.9% in HPV18. The average ages of patients at the stage of CIN3 and above who demonstrated the positive and negative results for HPV16/18 were 35.4 years and 44.7 years, respectively. During the follow-up period of 40 months, 27 of 179 patients with positive HPV of the high risk group showed development of grades from below CIN2 to those CIN3 and above. Of the patients positive for HPV16/18, 30.9% demonstrated a further development of the lesions, whereas there were only 8.1% in the patients negative for HPV16/18. These studies suggested a significant connection between the viral infection of HPV16/18 and the development of cervical cancer in young women.

Physical fitness of 900 volunteers over 60 years of age were analyzed using a 6-item battery test to obtain fundamental data on the fitness status of the aged Japanese. The test battery consisted of stepping, vertical jump, grip strength, breath holding, body flexion and one-leg balancing, and could be performed safely with relatively mild physical stress in the elderly after simple screening by measurement of resting blood pressure and oral check on mobility problems of the knee and the hip. Males showed significantly higher values in vertical jump, grip strength and breath holding, while females showed significantly higher values in body flexion. There were no sex differences in stepping and one-leg balancing. Lowing trend was found in the score with age in all items except breath holding, but the extent of the reduction differed among the measure elements of fitness. Most of measured items showed significant correlations each other. The values obtained with this test are considered to be useful for future analysis of the fitness of aged people and also to determine the exercise appropriate for them.

The Standardized Structured Medical record Information eXchange (SS-MIX) was started in 2006 as the project supported by the Ministry of Health, Labour and Welfare (MHLW) for promoting the exchange of the standardized medical information. Free soft wares developed in the project allow the storage of medical information to receive HL7 messages for prescription, laboratory test results, diagnoses and patient demographics in the hospital information system (HIS). We encourage the use of the SS-MIX standardized storage for postmarketing surveys and clinical studies. The recommendations consist of the following 7 parts. [1] In surveys and clinical studies, the information of drugs and laboratory test results in the SS-MIX standardized storage can be directly transferred to the electronic questionnaire and the investigators may obtain the information with high accuracy and granularity. [2] The SS-MIX standardized storage works as the backup system for the HIS because it can provide the minimum information essential in patient care even under the disastrous condition like earthquake or unexpected network failure. [3] The SS-MIX standardized storage may be useful to conduct a good pharmacoepidemiology study not only because it provides the information in the storage efficiently but also it can be used to identify “new users” who started the drug after some period of non-use.The “new user” design is often essential to have the unbiased results. [4] When the drug company conducts postmarketing surveys according to the current regulation, the use of the SS-MIX standardized storage will facilitate the fast and efficient collection of data to develop the timely measure to minimize the drug-related risk. With the SS-MIX standardized storage, it is also expected that many types of study design can be employed and the quality of data is improved in the survey. [5] The SS-MIX standardized storage maybe also useful to evaluate the risk minimization action plan by comparing the prescription pattern or incidence of the targeted adverse event between two periods before and after the implementation of the action plan. [6] In planning clinical trials, the SS-MIX standardized storage may be used to estimate the size of eligible patients. The storage may also allow conducting cross-sectional studies to know characteristics of diseases or drug treatment. In addition, cohorts of those who had coronary artery angiography, new users of a drug and those with a rare disease may be readily identified. Using such cohorts, investigators can initiate a case-control study nested within the cohort, pharmacogenomic studies and comparative effectiveness researches. [7] The SS-MIX standardized storage may be used as the formal data source in clinical trials in the future when some conditions are satisfied. For instance, the formal agreement should be reached between industry, government and academia on the use of standards of data structure in Clinical Data Interchange Standards Consortium (CDISC) and on the operation of computerized system validation (CSV) in the clinical trials.