A platelet is a discoid and anucleate microcytic cell of diameter 2-4μm. It contains various substances such as platelet-derived growth factor, β-thromboglobulin, and von Willbrand factor（vWF）in its α-granule, as well as ADP, ATP, and serotonin in its dense granule. Platelet membrane has some unique glycoprotein（GP）such as GP Ib/IX/V complex：the receptor for vWF, and GPVI：the receptor for collagen. These play an important role in body’s hemostatic mechanism. However, platelet is difficult to operate as an object of a clinical investigation, because it is easily-activated, makes form change, adheres, clumps, and eventually, it becomes micro particles（MP）after activations.Activated-platelet-derived MP has been produced from activated-platelet, which has strong procoagulant actions and important roles for a formation of thrombus after bleeding. On the other hand, MPs can also be produced by various cells such as monocytes, vascular endothelial cells, and cancers et al., and methods to identify sources of their MPs are not developed yet. We focus on developing highly-sensitive ELISA which enables to specifically measure aPLT-MP and engage in improving its diagnosis and prediction to patients with thrombosis. The progress of our research for various roles of platelets is reported here.

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Secondary formation of retinal proliferative fibrous tissue in refractory vitreoretinal diseases such as age-related macular degeneration proliferative vitreoretinopathy, and diabetic retinopathy sometimes causes visual loss. It is important, therefore, to control the formation of proliferative fibrous tissue in retina or contraction. Retinal pigment epithelial cells play a central role in this proliferative fibrous tissue formation mediated by epithelial-mesenchymal transition（EMT）and remodeling of the extracellular matrix. Sexual difference has been reported to have effects on the development of some vitreoretinal diseases. Sex hormones are also involved in maintaining homeostasis of retina. We have examined the action of sex hormones to contraction by RPE cells and extracellular matrix remodeling. As a result, the female hormones suppressed cell contraction of RPE cells, MMPs expression and EMT. Female sex hormones might thus prove effective for the treatment of the development and contraction of fibrous tissue in refractory vitreoretinal diseases.

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It is well-known that the majority of hypertensive patients will require several antihypertensive drugs to reach the target blood pressure. The Combination Therapy of Hypertension to Prevent Cardiovascular Events trial was an investigator-initiated multi-center study with PROBE design, and compared the dihydropyridine T/L-type calcium channel blocker benidipine based therapies with an angiotensin receptor blocker（ARB），a β-blocker（BB），or a thiazide diuretic（TD），and the results suggested that benidipine combined with a BB appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-TD combination. We further evaluated the treatment effects on different stroke subtypes among the three benidipine-based regimens. All stroke events were sub-classified with the TOAST criteria. Although few differences in stroke subtypes were observed among the three treatment groups, multi-adjusted hazard ratios of the incidence of all types of stroke, hemorrhagic stroke and ischemic stroke were significantly higher with the benidipine-BB regimen than with the benidipine-TD regimen. The incidence of both hemorrhagic and ischemic stroke in the benidipine-ARB regimen was not different compared to the other two treatment regimens. This sub-analysis demonstrated that blood pressure-lowering therapy with a benidipine-TD regimen might be beneficial for hypertensive patients to prevent both hemorrhagic and ischemic stroke.

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Greater use of regional health care clerkships for medical students is needed to address the lack of physicians in rural areas and the increased importance of general medicine and comprehensive community health care. Yamaguchi University has introduced a comprehensive health care clerkship, in which third-year students study community health at small hospitals and clinics over a two-day period in depopulated and remote areas of Yamaguchi prefecture. The clerkships were introduced as a selective program in 2010 and became a compulsory subject in 2012. To make the program more effective, we set the purpose and objectives and asked students to write self-introductory letters and to interview patients and staff in the institutes. We also provided some related lectures and orientation to improve the students’ motivation and attitude. A survey of students who undertook the clerkship in 2014 demonstrated that almost all the students were better motivated to learn at university and to practice as physicians, and that they had found role models during the clerkship. The clerkship generated the expected outcomes by providing students with actual experience of community health care. However, it was not clear whether the clerkships were effective in increasing the numbers of physicians in Yamaguchi prefecture. Further research is needed to evaluate longer-term outcomes and to improve the content of the clerkships.

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Spontaneous rupture of hepatocellular carcinoma（HCC）is well known. However, rupture of HCC after transcatheter arterial chemoembolization（TACE）is a rare but potentially fatal complication. Herein, we report a case of ruptured HCC after TACE in a 73-year-old man with chronic liver injury（non-B and non-C）．He had previously undergone subsegmental resection of S7 of the liver for HCC. One year later, multiple HCCs were detected. TACE was performed for the recurrent HCCs located on the surface of S2 of the liver. Epigastric pain and decreased blood pressure were observed after the treatment. Although his symptoms improved immediately, the patient gradually became anemic. Radiological examination after TACE revealed a hematoma around the S2 lesion. Therefore, we diagnosed rupture of HCC. We performed TAE and could control the bleeding. Few possible mechanisms of ruptured HCC after TACE include increasing pressure inside the tumor and capsular injury due to TACE. Consequently, HCC which has a high risk of rupture after TACE should be assured embolization and careful observation.

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The patient was a 70-year-old man undergoing medical treatment in our hospital hematology department for cyclic thrombocytopenia whose platelet count had hovered between 5?30×10４/μl for about 1 month. Because he was found to have black stools during the same period as the thrombocytopenia in 2008, he underwent upper and lower gastrointestinal endoscopy, but the source of bleeding could not be identified. Capsule endoscopy showed findings suspicious of ulcer or erosion with bleeding, and drug-related damage to the small intestinal mucosa caused by aspirin was suspected. Administration of irsogladine maleate 4 mg/day and rebamipide 300 mg/day was begun, and then by changing to a low-residue diet to match the cyclic phase of the thrombocytopenia of about once per month, no progression of the anemia was seen for about 1 year. However, since he was admitted to our hospital immediately after he experienced a large amount of bloody bowel discharge, administration of packed red blood cell preparation and platelet concentrates was required, and in consultation with the Department of Cardiology, we stopped the aspirin and continued to administer only sarpogrelate hydrochloride. There has been no further progression of the anemia. Cyclic thrombocytopenia is a very rare disease, and a curative treatment is unclear. Therefore, it was difficult to respond to gastrointestinal bleeding associated with drug-related damage of the small intestinal mucosa.

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The patient was a 34-year-old female who visited our hospital in May 2008 for a chief complaint of nausea and lower abdominal pain upon fasting. Esophagogastroduodenoscopy（EGD）revealed nodular gastritis in the gastric antrum. Blood test showed positive for anti-Helicobacter pylori IgG antibody. We performed eradiation therapy for Helicobacter pylori. After eradiation therapy, urea breath test showed successful eradiation.6 years after the successful eradiation, the patient visited our hospital again due to nausea/vomiting and diarrhea in January 2014. EGD indicated early gastric cancer on the anterior wall of the gastric middle body, and biopsy detected undifferentiated cancer. Distal gastrectomy, D2 dissection, and Billroth-I reconstruction were performed. Histopathological analysis revealed signet ring cell cancer with an invasion depth of SM2 and multiple regional lymph nodes metastases. Atrophy, inflammatory cell infiltrate, and intestinal metaplasia were not detected in the non-cancer mucosa.Nodular gastritis is observed in young patients with Helicobacter pylori infection, and can induce gastric cancer. However, the clinical course after eradication therapy is still unclear. We reported an example of early gastric cancer that developed after a long-term period（6 years）after eradication therapy in this report.

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A 36-year-old man diagnosed with Charcot-Marie-Tooth（CMT）disease type 1B was treated in the department of neurology of this hospital. Due to a liver injury（AST 237IU/ml, ALT 496IU/ml）which occurred in November 200X, he was introduced to our department. As a result of scrutiny, we diagnosed him with chronic hepatitis C genotype 2a（HCV-RNA 5.4logIU/ml）．He will be admitted to the hospital for Interferon（IFN）therapy in April next year. Although the mechanism is unknown, there are a few reports of peripheral neuropathy related to IFN therapy. Therefore, IFN therapy is generally unfavorable for patients with neuromuscular disorders. There are several IFN preparations used in Japan. IFN alfa associated peripheral neuropathy appears less than 0.1-5% of the time. While there is no report of peripheral neuropathy related to IFN beta, we performed IFN beta and Rivabirin combination therapy with a severe follow-up by a neurologist. We could accomplish treatment without the exacerbation of neurologic symptoms. He achieved sustained viral response. When IFN therapy was provided for chronic hepatitis B or chronic hepatitis C complicated with peripheral neuropathy, there is some possibility of performing antiviral therapy safely by using IFN beta.

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