Objective:To investigate the immune defence against acute encephalitis induced by the highly neurovirulent recombinant R404BP strain of influenza A virus.Methods:A murine model system for a lethal encephalitis due to influenza has been established by stereotaxic microinjection with the recombinant R404BP strain of influenza A virus into the olfactory bulb of the senescence-accelerated mouse(SAM) strain P1 mice. The mortality of infected mice, clearance of infected neurons and induced cellular immune responses were investigated.Results:The SAM-P1 mice showed a higher rate of mortality with prolonged virus shedding. The increased susceptibility was associated with impaired activity of both NK cells and virus-specific cytotoxic T lymphocytes.Conclusion:The decreased Th1 immune responses in the senescence-accelerated mouse might be responsible for the low defence system against neurovirulent recombinant influenza A virus.

Objective:To investigate the effect of perforin-mediated cytotoxicity in primary influenza virus infection.Methods:Perforin-deficient and wild-type C57BL/6 mice were infected intranasally with influenza virus A/PR/8/34. Pulmonary viral growth was determined at various days after infection by pfu experiment. Perforin-mediated apoptotic degeneration was observed by Immunohistochemical staining. LDH-release method was used for detection of specific CTL and NK cell activity from spleen cells.Results:Mice deficient in the perforin gene showed an increased virus growth and prolonged virus shedding. The appearance of apoptotic degeneration in virally infected lung cells was delayed in perforin-deficient mice. The cytolytic activities of natural killer cells and virus-specific cytotoxic T lymphocytes were significantly lower than that of wild-type mice.Conclusion:Perforin plays a critical role in the host defense system against primary influenza virus infection.

Objective: We aimed to develop software that could provide drug information off-line using a smart device.  Therefore, FileMaker Go® was examined and evaluated as a mobile drug information application.
Methods: A mobile drug information database (Mobile DI-DB) application was created using FileMaker Go®.  The function, search performance, and characteristics of Mobile DI-DB were evaluated.  In addition, question and answer time with Mobile DI-DB was compared with that existing drug information database (existing DI-DB) of the Soka Municipal Hospital.
Results: Mobile DI-DB can be viewed on an iPad®and iPhone®.  The software is full-text searchable, has good search performance, and is characterized by a small file size.  Furthermore, question and answer times were found to be shorter about 1/3 with Mobile DI-DB than with existing DI-DB.
Conclusion: A mobile drug information database prepared with Filemaker Go® can now be viewed on a smart device, making drug information easier to access than ever before.  Although this study focused on increasing operational efficiency of pharmacists through the use of the Mobile DI-DB application, we believe that this application can benefit other users too.

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.

Purpose：Methadone is an opioid used in Japan for the treatment of cancer pain. A thorough consideration of complex pharmacokinetics with individual differences and of serious adverse effects is necessary before switching to methadone; therefore, methadone is not yet widely used. We examined the analgesic and adverse effects of methadone through clinical cases and considered the clinical significance of methadone as an opioid analgesic for the treatment of cancer pain. Methods：The clinical course of 44 patients with cancer pain who were switched to methadone from other opioids was analyzed. Results：Out of the 44 cases investigated, 37 cases （84.1％） were successful. In the successful cases, pain intensity before and after methadone administration was reduced from an average of 7.5 to 2.8, respectively, on the numerical rating scale. Strong drowsiness （six cases） and nausea （three cases） were observed as adverse effects. However, no serious effects, such as QT prolongation and respiratory depression, were recognized. Conclusion：For patients with refractory cancer pain who require a high opioid dose, methadone is considered to be one of the alternatives in pain therapeutics.

Background: Methadone can only be administered orally in Japan. However, it is unclear how to treat pain when patients become unable to take methadone orally because of the progression of the disease. Aims: To assess retrospectively end-of-life pain control management after patients become unable to take methadone orally. Methods: Twenty-eight patients with cancer pain undergoing treatment with oral methadone died at a palliative care unit between April 2013 and September 2014. All patients died of cancer and were unable to swallow before death. We assessed pain control approaches after the patients became unable to take methadone orally. Results: Twenty-one patients survived 1 day or longer after becoming unable to swallow. Methadone was switched to another opioid because of pain. Of these 21 patients, 10 patients survived for 1 week or longer after being switched to another opioid. At this point, methadone would be mostly eliminated from the blood circulation. Among these 10 patients, seven patients were treated with subcutaneous morphine, and three patients were excluded because their pain could not be evaluated. The conversion ratio from final oral methadone dosage to oral morphine equivalent dose of opioids used on the seventh day was 6.1. Conclusion: Even when patients become unable to ingest methadone, switching to other opioids may not always be necessary because of the long half-life of methadone when pain is absent at the end of life. If necessary, pain could be managed by switching to other opioids with a conversion ratio of 6.1.

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.

Objective: The wrong dose of high-risk drugs such as oral steroids is a serious issue that needs to be addressed. This study aims to determine the appropriate upper tolerable dose threshold and to develop a multi-variable logistic regression model to detect dose-errors in oral prednisolone tablets.Methods: Data on Prednisolone prescriptions were obtained from a single center. Out of the data collected, positive cases consisted of cases where dose-related modifications were made. A univariate logistic regression model was developed with the current daily dose. In the model, the Youden Index was used to determine the upper tolerable dose threshold. The investigation was done to determine whether the performance of the multivariate model was improved by adding clinical department and previous prescription information as variables.Results: Univariate models (AUC: 0.645) with only current daily doses and estimated optimal thresholds of 6 mg/day or 11 mg/day, respectively were determined to be appropriate. Including variables improved the performance of the predictive model; the best performing model (AUC: 0.840) was derived when the following variables were entered: “current daily dose,” “current prescription days,” “clinical department,” “daily dose of the previous prescription,” and “prescription days of the previous prescription”.Conclusion: A single upper tolerance limit is insufficient to determine dose adequacy for prednisolone tablets owing to their broad clinical dose range. Itmay be possible to develop a high-performance dose audit support model by adding information.