Objective A treatment strategy to inhibit nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions has not yet been established. To clarify whether monotherapy with a gastromucoprotective drug, geranylgeranylacetone (GGA), inhibits NSAID-induced acute mucosal injury of the upper digestive tract and small intestine.
Methods A prospective, randomized, comparative study. All procedures were performed at Osaka Medical College. The subjects, thirty healthy adult volunteers, were randomly divided into two groups. In the NSAID-GGA group, 75 mg/day of diclofenac sodium and 150 mg/day of GGA were orally administered for two weeks. In the NSAID-FAM group, 75 mg/day of diclofenac sodium and 20 mg/day of famotidine (FAM) were orally administered for two weeks. esophagogastroduodenoscopy (EGD) and video capsule endoscopy (VCE) were performed before and two weeks after drug administration. In addition, we measured fecal occult blood reactions and the fecal calprotectin levels.
Results No significant differences were observed between the groups in the mean increase in esophageal/gastroduodenal lesions. The mean increases in the scores in the NSAID-FAM group (NSAID-GGA group) of small bowel lesions were as follows: erythema: 1.93±0.67 (0.30±0.60), erosions: 1.13±0.54 (0.38±0.35), ulcers: 0.73±0.33 (0.07±0.07) and edema: 0.53±0.44 (0.07±0.07). The scores for erythema and ulcers were significantly lower in the NSAID-GGA group than in the NSAID-FAM group (p=0.032 and 0.0165, respectively).
Conclusion We compared the prophylactic effects of a mucoprotective drug, GGA, and an H₂RA, famotidine, on mucosal injury involving the esophagus to the small intestine related to the two-week oral administration of diclofenac sodium in healthy volunteers. In the upper digestive tract, the prophylactic effects were similar between the two drugs. However, in the small intestine, GGA more markedly inhibited the development of lesions compared to famotidine.

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Objective The C825T polymorphism in the G protein β3 subunit gene (GNB3) influences the efficacy of sildenafil in patients with erectile dysfunction. The effects of this polymorphism on the therapeutic response to sildenafil in patients with pulmonary hypertension remains unknown. To investigate whether the GNB3C825T polymorphism is associated with the clinical efficacy of sildenafil in patients with pulmonary hypertension.
Methods Fifty-nine patients (age: 55.6±13.3 [SD] yrs., mean pulmonary arterial pressure (Ppa): 52±11 mmHg) with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension were treated with sildenafil. The pre- and post-treatment parameters, including pulmonary hemodynamics measured using right heart catheterization, the systolic pulmonary arterial pressure estimated on Doppler echocardiography (sPA), the six-minute walk distance (6MWD) and freedom from clinical worsening, were compared between the patients with the TT and CT/CC genotypes.
Results The pretreatment parameters were not significantly different between the two groups, with the exception of a lower mean Ppa in the TT group. The post-treatment World Health Organization (WHO) class was significantly better (p=0.03) and the 6MWD values trended toward improvement in the TT genotype patients compared with that observed in the CC/CT genotype patients (p=0.05). The time to clinical worsening was significantly longer in the TT genotype patients than in the CC/CT genotype patients (3-year freedom from clinical worsening: 83.1% vs. 46.0%, p=0.02), while the TT genotype was found to be a significant predictor of freedom from clinical worsening, even after adjusting for the baseline mean Ppa.
Conclusion The GNB3 C825T polymorphism influences the efficacy of sildenafil in patients with pulmonary hypertension.

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Objective A cluster of multiple risk factors has been noted to constitute the background of cardiovascular disease. The purpose of this study was to evaluate the relationship between the visceral fat area (VFA) or subcutaneous fat area (SFA) and a cluster of obesity-related cardiovascular risk factors, including hyperglycemia, dyslipidemia and elevated blood pressure, in middle-aged Japanese men and women.
Methods A total of 571 subjects (m=434; f=137; age: 53±9 years) who underwent health examinations with evaluations of body fat distribution using computed tomography scans and assessments of 75-g oral glucose tolerance tests were enrolled in this study.
Results The VFA and SFA were linearly correlated with the number of risk factors in both men and women. The area under the receiver-operating characteristic curve of VFA (m=0.741, f=0.763) was significantly higher than that of SFA (m=0.636, f=0.689) with respect to the clustering of risk factors (one or more). The men exhibited larger VFA values and smaller SFA values than the women in similar body mass index (BMI) categories. Men with a VFA of ≥100 cm² irrespective of BMI and women with a VFA of ≥100 cm² and a BMI of ≥25 kg/m² demonstrated a high prevalence of diabetes mellitus and impaired glucose tolerance. Men and women with a VFA of ≥100 cm² irrespective of BMI demonstrated a high prevalence of type IIb dyslipidemia.
Conclusion These results suggest that the absolute value of VFA rather than SFA is more closely associated with a cluster of risk factors irrespective of sex and is a good marker for selecting subjects to whom weight reduction should be recommended in order to prevent cardiovascular disease in the general population.

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Objective Dyslipidemia is a risk factor for not only cardiovascular diseases (CVD), but also chronic kidney disease (CKD). Ezetimibe, a cholesterol absorption inhibitor, lowers cholesterol levels by inhibiting both extrinsic and intrinsic cholesterol absorption via the gastrointestinal duct. However, very few studies have examined its efficacy and safety for patients with dyslipidemia complicated with CKD.
Methods Thirty-seven dyslipidemic patients (low density lipoprotein cholesterol (LDL-C) levels ≥120 mg/dL) complicated with CKD were given ezetimibe (10 mg/day) for twenty-four weeks. The efficacy and safety of the therapy, including the anti-atherosclerotic and renal protective effects, were then examined.
Results Significant decreases were observed in the levels of LDL-C (158.9±26.9 mg/dL→123.0±31.8 mg/dL; p<0.0001), remnant-like lipoprotein cholesterol (9.3±5.3 mg/dL→7.3±3.8 mg/dL; p<0.05) and lipoprotein (a) (22.0±16.1 mg/dL→16.4±11.0 mg/dL; p<0.01). The estimated glomerular filtration rate did not change, but the urine protein to creatinine ratio decreased significantly (1,107.3±1,454.2 mg/gCre→732.1±1,237.8 mg/gCre; p<0.05). No changes were observed in the carotid intima media thickness, but the brachial-ankle pulse wave velocity decreased significantly (1,770.4±590.3 cm/sec→1,702.5±519.9 cm/sec; p<0.05). No adverse events were observed.
Conclusion Ezetimibe can be safely administered even to patients with CKD. The results of this study indicate that ezetimibe may provide some renal protection and suppress the complications of CVD in CKD patients.

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A 40-year-old man who was referred to our hospital due to dyspnea was found to have high output cardiac failure on Swan-Ganz catheterization. An endomyocardial biopsy revealed cardiomyocyte hypertrophy with a vacuolar structure consistent with mitochondrial disease (MD). The patient was discharged, then readmitted for high output cardiac failure with hypotension and hyperlactacidemia. Treatment with cardiopulmonary support and hemodiafiltration gradually improved his general condition, although it resulted in ischemic necrosis of the right leg. The hyperlactacidemia completely resolved after amputation, and the high output cardiac failure has not recurred for two years. High output cardiac failure is rare in MD patients and is related to myocardial abnormalities and hyperlactacidemia.

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A 71-year-old man with interstitial pneumonia was hospitalized due to a pulmonary infection. He had been living in Thailand and had returned to Japan three months earlier. Antibiotic therapy initially cleared the infection; however, the patient's condition relapsed. Pseudomonas aeruginosa and Penicillium sp. were both detected in sputum and bronchial lavage fluid cultures and Penicillium sp. was identified to be P. marneffei. The infiltration observed on chest radiographs improved following treatment with itraconazole and tazobactam/piperacillin, and no relapse occurred. We herein report the first case of a non-HIV patient with P. marneffei infection in Japan.

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We herein describe the case of a 77-year-old Japanese man who presented with progressive thrombocytopenia. No lymphadenopathies, bone lesions, hepatosplenomegaly or masses within any internal organs were detectable. Bone marrow smears revealed diffuse infiltration of large atypical cells morphologically resembling mature lymphoid neoplasms. A flow cytometric analysis showed that the tumor cells strongly expressed CD56 without myeloid or lymphoid antigens, suggesting that they were non-hematologic in origin. Ultimately, amelanotic malignant melanoma of unknown primary origin was diagnosed based on positive immunostaining for S100 proteins, HMB-45 and Melan-A. This case illustrates the usefulness of flow cytometric analyses for making such diagnoses. We also review the available literature on similar cases.

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