Japanese Adverse Drug Event Report database (Abbreviation; JADER) was disclosed April 2012 and will be expected to have a major role in the establishment of the adequate information for the proper usage of drugs. In this paper, we were compared using the shape parameters that were estimated by fitting the Weibull distribution, whether the adverse drug reaction of suicide- or diabetes-related onset time profiles vary depending on the type of interferon formulations. The data were used JADER of August 2013. The combined number of adverse drug reaction and drug that duplicates removed was 702,925. In diabetes-related side effects, the distribution of adverse drug reaction time was different among formulations. The shape parameters of the Weibull distribution are 1.49 (1.09-1.94), 0.84 (0.66-1.05) and 1.07 (0.92-1.23)(point estimates and two-sided 95% confidence interval) in interferon-α,-β and peginterferon, respectively. Interferon-α is categorized as the wear-out failure type adverse drug reaction onset time profile from which its 95% confidence interval exceeds 1. Peginterferon is classified as the random failures type from which its point estimates is almost 1. Since the upper 95% confidence interval is near 1, the time profile of interferon-β is close to the early failures type. We conclude that the combination of the shape parameter of the Weibull distribution and the visual inspection, like histogram and box plot, is useful in the monitoring of adverse drug reaction onset time profile.

Objective: This study aimed to confirm whether the methods for assessing the reported causal relationship between dietary supplement intake and adverse events are reliable in the clinical setting.
Design: The relationships between supplement intake and adverse events were assessed using two algorithms proposed in our previous report, and causal relationships were evaluated.
Methods: Twelve raters with a high probability of handling adverse event information examined 200 records of dialogues with supplement users.  Each rater independently assessed the causal relationship using the two algorithms.  The relationships between supplement intake and adverse events were assessed for all 200 cases.  Variability in the evaluation among raters was analyzed for each occupation and the whole group of raters.  The distributions of evaluation were analyzed, and inter-rater reliability was evaluated using the intraclass correlation coefficient (ICC) and Fleiss’ kappa coefficient.
Results: All events of 200 cases seemed to be slight and within the range of variation in daily life.  Almost all cases were classified into two categories as “Possible” and “Lack of Information” by each rater.  The ICC values for all raters, pharmacists, dieticians, and health care workers were 0.644, 0.573, 0.678, and 0.694, respectively, and the kappa coefficients using the two algorithms were 0.466, 0.426, 0.468, and 0.519 and 0.481, 0.478, 0.465, and 0.517, respectively.  There were moderate levels of agreement based on the kappa coefficients and ICC values.
Conclusion: The two algorithms proposed in our previous report may be reliable in the clinical setting.  Their reliability could be enhanced by establishing a unified method of accumulation and recording adverse events for supplement intake, which should be evaluated by more raters using more cases of adverse events.

Objective: To attain optimal blood concentration rapidly, it is needed to perform initial dose setting appropriately when vancomycin (VCM) used.  In order to design initial dose settings of VCM more currently, we compared the predictive performance of two types of VCM therapeutic drug monitoring (TDM) analysis software retrospectively.
Method: We utilized two TDM analysis software, SHIONOGI-VCM-TDM ver.2009 (VCM-TDM) and “Vancomycin MEEK TDM analysis software Ver. 2.0” (MEEK), based on patient’s background. 112 patients who received VCM and performed TDM were analyzed during the period from October 2011 through September 2012 and compared the actual trough level with the predictive trough level.  The predictive performance was evaluated by calculating ME (mean prediction error), MAE (mean absolute prediction error), and RMSE (root mean squared error).  Age, gender, and a renal function were evaluated as patient’s background.
Results: VCM-TDM gave good predictive performance for patients overall.  When classified patient’s background complexly (sex, age, and renal function), as for male patients, VCM-TDM showed good predictive performance except for the group over 65 years old and CCr over 85 mL/min.  For female patients, the difference of predictive performance was not accepted by all groups.
Conclusion: These results suggest, for male patients, we should use VCM-TDM for initial dose settings except for the group over 65 years old and over CCr 85 mL/min.  For the other patients, we consider that both of software can be used.  These new findings seem to contribute to proper dosage settings of VCM.

The remarkable increase of branched amino acid and pretty decrease of lysine venous concentration were observed in healthy nine male and female adults by the brief fast.
The increase of branched amino acid wasn't able to find by the various exercise generally. The increase of lysine venous concentration was found after the running more than 10km frequently.
Only on the subjects of 44 and 55 years of age, the increase of branched chain amino acid and lysine were observed by the running. It looks like have to take precautions that aged people run under the conditions of empty stomach.

Venous concentration of lysine and other 16 amino acids were determined in healthy 5 male 20-22 years of age subjects in the resting state, after 2 min from bigining of exercise, immediatetly after all-out exercise and 30 min after of the exercise with a bicycle ergometer at work intensities which will be fell into all-out in about 6 or 7 min.
During 2 min exercise lysine only was increased, no change of glycine and puoline were observed and other amino acids were decreased. At the point of all out increase of threonine, lysine and histidine were observed, compared with resting state
Alanine concentration at 30 min after of all out exercise was very high than that of resting state and same tendency but a little was observed on lysine. Other amino acids were decreased.
A risk connected with exercise was discussed from the data of lysine obserbed high concentration during two min exercise concerning with the variation of other amino acids by the all-out exercise.

A 76-year-old-woman, who had undergone endoscopic resection of a gastric polyp 2 years previously, had a cardiac tumor incidentaly pointed out on an abdominal ultrasonographic image. Echocardiography showed a solid round mass (34×25 mm in diameter), attached by a short stalk and which was floating on the right ventricular outflow tract and prolapsing over the pulmonary valve during systole. We suspected right ventricular myxoma. Urgent surgery was performed under cardiopulmonary bypass. After aortic clamping, the trunk of the pulmonary artery was opened near the right ventricule. The tumor was found under the pulmonary valve, attached to the anterior papillary muscle and chordae of the tricuspid valve. The tumor was completely excised with a piece of the papillary muscle and chordae. After right atriotomy, mild tricuspid regurgitation was seen on a water test. After we performed tricuspid annuloplasty and chordplasty with artificial chordae, a second water test did not show any tricuspid regurgitation. The postoperative course was uneventful, and she was discharged on the 13th postoperative day.

Objective: Anti-human cytomegalovirus (HCMV) activity of 5 compounds, especially tricin, isolated from Kumazasa extract were investigated in the human embryonic lung (HEL) fibroblast cell.
Method: This study examined the effect of tricin on HCMV replication, viral-specific major immediate early (IE) gene expression, and protein synthesis.
Results: Pretreatment of HEL cells before HCMV infection with tricin inhibited viral production in a dose-dependent manner, as well as posttreatment of HCMV-infected HEL cells with tricin. Real-time RT-PCR assay and Western blotting analysis indicated that tricin decreased expression of the HCMV IE gene in virus-infected HEL cell.
Conclusion: These date suggest that the primary mechanism of anti-HCMV activity for tricin, isolated from Kumazasa hot water extract, inhibit IE gene expression.

Aim To investigate more efficient synthetic method of the nitrogen analogue 4 of salacinol (1) for searching new antidiabetic agents. Methods The synthesis of the key intermediate 2,4-O-isopropylidene-L-erythritol 1,3-cyclic sulfate (2a) was accomplished by modification of reports from Dglucose via seven steps in much more less expensive. Using this method, an efficient synthesis of 4 was carried out. The glycosidase inhibitory activity of 4 was tested for the intestinal α-glucosidase in vitro and compared with that of salacinol. Results A nitrogen analogue 4 of salacinol (1) was synthesized by the coupling reaction between the cyclic sulfate 2a and an azasugar 3b. Conclusion Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.

A Valsalva aneurysm filled with thrombi can be difficult to diagnose, because it mimics a cardiac tumor. Both cardiac magnetic resonance imaging (MRI) and transesophageal echocardiogram (TEE) were performed on a patient who showed a low-echoic mass located between the atrial septum and the non-coronary sinus. Based on MRI findings allowing tissue characterization and the accurate location of the mass and the TEE findings of an irregular surface of the mass and a partial defect in the edge of the non-coronary sinus, we diagnosed the mass as a thrombosed Valsalva aneurysm that had perforated the inter-atrial septum. The operative findings coincided with the preoperative diagnosis. Both MRI and TEE are useful for diagnosing this condition.
Aneurysm ; Atrial Septum ; Echocardiography ; Heart Neoplasms ; Humans ; Magnetic Resonance Imaging ; Sinus of Valsalva

　The education program in all medical schools in Japan has been studied and analyzed every 2 years since 1974 by the curriculum committee of the Association of Japan Medical Colleges. Based on the most recent analysis in 2015, the marked innovation of medical education, such as an integrated curriculum, active learning, and clinical clerkship, was recognized.