If mother use drugs during pregnancy, the risk to the fetus is concerned. So the management of the drug is important. Previously, we have experienced The Thalidomide Disaster, the drug has not been used for many years since then. However, since thalidomide is found to have an effect on multiple myeloma, its management method is problematic. In the patients who use thalidomide, there are few women with the possibility of pregnancy. And by strict management, it has been concerned about the problem of the things that is difficult to use in patients not related to pregnancy. Isotretinoin is currently being used in the United States as the drug for acne therapy. Although there is no adaptation in Japan, the physician personally import the drug and administer to the patients. Because a lot of childbearing women are included in the patient who use the drug, strict management is necessary. Because the drug is not marketed in Japan, the offer of the information is not enough. Valproic acid has both adaptation the prevention of the migraine headache other than epilepsy. The control of epilepsy is very important, there are patients that use the drug after consideration of risk benefit balance. On the other hand, benefit was relatively small when use it for the prevention of the migraine headache. FDA prohibited the use during pregnancy for this purpose. In Japan, it is the same regulation regardless of adaptation, and balance of the risk benefit is not clear. It was thought that different attention awakening should be carried out by adaptation in future.

We report a successfully treated case of infectious endocarditis with ventricular septal defect (VSD) and double-chambered right ventricle. A 41-year-old man complained of dyspnea. Echocardiography showed his tricuspid valve, aortic valve, and pulmonary valve had vegetation and severe regurgitation. He received treatment with antibiotics but it was not effective. He underwent TVR, AVR, pulmonary valve resection, VSD patch closure and RV abnormal muscle resection. Pathological findings of resected valves showed infectious endocarditis. He recovered uneventfully and resumed his original social activities.

If mother use drugs during pregnancy, the risk to the fetus is concerned. So the management of the drug is important. Previously, we have experienced The Thalidomide Disaster, the drug has not been used for many years since then. However, since thalidomide is found to have an effect on multiple myeloma, its management method is problematic. In the patients who use thalidomide, there are few women with the possibility of pregnancy. And by strict management, it has been concerned about the problem of the things that is difficult to use in patients not related to pregnancy. Isotretinoin is currently being used in the United States as the drug for acne therapy. Although there is no adaptation in Japan, the physician personally import the drug and administer to the patients. Because a lot of childbearing women are included in the patient who use the drug, strict management is necessary. Because the drug is not marketed in Japan, the offer of the information is not enough. Valproic acid has both adaptation the prevention of the migraine headache other than epilepsy. The control of epilepsy is very important, there are patients that use the drug after consideration of risk benefit balance. On the other hand, benefit was relatively small when use it for the prevention of the migraine headache. FDA prohibited the use during pregnancy for this purpose. In Japan, it is the same regulation regardless of adaptation, and balance of the risk benefit is not clear. It was thought that different attention awakening should be carried out by adaptation in future.

Studies have shown that postoperative disseminated intravascular coagulopathy (DIC) occurs in some patients with cardiac disease, acute aortic dissection, and ruptured abdominal aortic aneurysm. The specific pathophysiology of DIC in these settings are related to low cardiac function, shock, infection and sepsis as well as activation of coagulation cascade in the aneurysm sac or dissected aorta. A soluble form of recombinant human thrombomodulin (rhsTM) was approved in 2008 for the treatment of DIC. This report describes the safety and efficacy of rhsTM for the treatment of DIC in patients with cardiovascular disease operated in our department. Between October 2010 and March 2012, 35 patients with postoperative DIC were treated with rhsTM. Diagnosis of DIC was based on the diagnostic criteria for DIC of the Japanese Association for Acute Medicine (JAAM). During the first 6 months of the study period, after a diagnosis of DIC was made, the patients were treated with gabexate mesilate and antithrombin III, and if patients showed no improvement with conventional treatment, they received rhsTM for 6 days. During the last 10 months of the study period, patients received rhsTM soon after a diagnosis of DIC was made. Twenty seven patients survived for 28 days after rhsTM treatment, and the mortality rate was 22.9% (8/35). Patients who survived showed improvement in acute phase DIC scores, FDP levels, D-Dimer, fibrinogen and platelet counts during rhsTM treatment, but no improvement was observed in patients who died. No serious adverse events were found up to 28 days after the start of rhsTM administration. In conclusion, this study showed no adverse events of rhsTM, and further studies are needed to confirm that rhsTM administration is an effective therapeutic modality in the management of DIC after cardiovascular surgery.

A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.
1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities
2．How to select Safety Specification (SS) and describe its characteristics
・Selection of SS
・Characterization of SS
・Association with Research Questions (RQ)
3．How to define and describe RQ
・What is RQ ?
・RQ interpretation in other relevant guidelines
・Methodology to develop RQ for PVP with examples
・Best approach to integrating PVP for whole aspects of safety concern
4．How to optimize PVP for specific RQ
・Routine PVP or additional PVP ?
・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)
・Checklist to help develop PVP
5．Epilogue:
・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.
・Significance of background incidence rate and needs for comparator group
・Infrastructure for the future PVP activities
6．Appendix: Checklist to help develop PVP activities in RMP
The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.

Objective: In 2000, the Ministry of Health and Welfare issued an advisory that recommended intake of 0.4mg of folic acid in dietary supplements to reduce the risk of development of neural tube defects.  Since subsequent reports of questionnaire surveys by various investigators showed a low in the intake rate, we surveyed and evaluated the folic acid intake rate among the pregnant women consulting the Japan Drug Information Institute in Pregnancy.
Methods: We evaluated differences in folic acid intake rate according to the consulting women’s background factors. i.e., age, pregnancy planning, pregnancy history, and taking of anticonvulsant drugs in the 1053 women capable of participating in the survey among the 1061 pregnant women who requested a consultation with the Japan Drug Information Institute in Pregnancy between April 2006 and August 2008.
Results: According to the result of our survey, the intake rate of folic acid was 29% of the 1053 pregnant women.  The only 3 women of the 42 pregnant women taking anticonvulsant drugs took folic acid before they got pregnant.
Conclusion: Even now, 8 years after the Ministry of Health and Welfare advisory, the folic acid intake rate is low.  Drawing upon successful measures promoting intake in the U.S. and Canada,we play a vital role in delivering this critical health information to pregnant women.

In Mongolian gerbils, bilateral common carotid artery occlusion (BCCAO) for several minutes induces ischemia, due to an incomplete circle of Willis, resulting in delayed neuronal cell death in the Cornet d'Ammon 1 (CA1) region of the hippocampus. Neuronal cell death in the hippocampus and changes in behavior were examined after BCCAO was performed for 5 min in the gerbils. One day after BCCAO, the pyramidal neurons of the CA1 region of the hippocampus showed degenerative changes (clumped chromatin in nuclei). At 5 and 10 days after BCCAO, extensive neuronal cell death was observed in the hippocampal CA1 region. Cognitive performance was evaluated by using the radial maze and passive avoidance tests. In the radial maze test, which examines win-stay performance, the number of errors was significantly higher in ischemic gerbils than in sham-operated gerbils on days 1 and 2 post-operation. In the passive avoidance test, the latency and freezing times were significantly shorter in ischemic gerbils than in sham-operated gerbils on the days 1, 2, and 4–6 post-operation. These results indicate that transient forebrain ischemia impairs cognitive performance, even immediately after the ischemic insult when there are only subtle signs of neuronal cell death.
CA1 Region, Hippocampal ; Carotid Artery, Common ; Cell Death ; Chromatin ; Circle of Willis ; Freezing ; Gerbillinae ; Hippocampus ; Ischemia ; Neurons ; Prosencephalon ; Pyramidal Cells

Purpose: Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP. Materials and Methods: A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes. Results: Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs.Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014). Conclusions Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.