Objective A lower frequency for the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) Ser482 allele has been reported in elite-level endurance athletes among Caucasians, although this gene polymorphism has not been found to be associated with aerobic capacity in German, Dutch or Chinese populations. The purpose of the current study was to examine the associations between the Gly482Ser polymorphism and aerobic fitness in 112 Japanese middle-aged men.
Methods The PPARGC1AGly482Ser polymorphism was identified according to a TaqMan^® SNP genotyping assay. Habitual physical activity was objectively measured using an accelerometer. The lactate threshold (LT), an index of aerobic fitness, was measured based on a submaximal graded exercise test performed on an electric cycle ergometer. The association between the LT and the Gly482Ser polymorphism was assessed according to a multiple regression analysis and analysis of covariance, with adjustment for potential confounders (age, body mass index, cigarette smoking, physical activity level and regular exercise).
Results A significant association was observed between the PPARGC1AGly482Ser polymorphism and LT, as carriers of the Ser482 had higher LT values than the Gly482 carriers.
Conclusion The current results suggest that the PPARGC1ASer482 allele is associated with a higher aerobic capacity in Japanese middle-aged men.

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Objective Proton magnetic resonance spectroscopy (¹H-MRS) enables the clinician to noninvasively assess the amount of ectopic fat in the liver, skeletal muscle and myocardium. Recent studies have reported that the myocardial triglyceride (TG) content is associated with aging, metabolic disorders and cardiac dysfunction. However, the clinical usefulness of myocardial TG measurements in Japanese subjects has not been fully investigated.
Methods The myocardial TG content was evaluated using ¹H-MRS in 37 apparently healthy Japanese subjects, and the left ventricular function was measured on cardiac magnetic resonance imaging (MRI). Blood pressure, body composition and biochemical markers were measured in a fasting state, and cardiopulmonary exercise testing (CPX) was performed to evaluate exercise capacity.
Results The mean myocardial TG content was 0.85±0.40%. The myocardial TG content was significantly associated with the percent body fat (r=0.39), serum triglyceride level (r=0.40), estimated glomerular filtration rate (r=-0.37), anaerobic threshold (r=-0.36), maximal load of CPX (r=0.39), left ventricular end-diastolic volume (r=-0.41) and left ventricular end-systolic volume (LVESV) (r=-0.51) (all: p<0.05). In a multivariate analysis, the LVESV was found to be an independent factor of the myocardial TG content.
Conclusion ¹H-MRS may be useful for assessing the associations between the myocardial TG content and various clinical parameters, including those reflecting obesity, metabolic disorders, cardiac morphology and exercise capacity, noninvasively, even in Japanese subjects.

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Objective The impact of the clustering of metabolic factors on chronic kidney disease (CKD) in non-obese individuals remains unclear.
Methods We conducted a follow-up study of 23,894 Japanese adults (age, 18-69 years) who continuously received annual health examinations between 2000 and 2011. Obesity, high blood pressure, high triglycerides, low high-density lipoprotein (HDL) cholesterol and high fasting blood sugar were defined as metabolic factors, and CKD was defined as renal dysfunction (estimated glomerular filtration rate: <60 mL/min/1.73 m²) or proteinuria (dipstick test: ≥1+). The association between the clustering of metabolic factors and CKD was assessed based on the presence or absence of obesity using a Cox proportional hazard model.
Results Of 2,867 subjects with ≥3 metabolic factors, 650 (22.7%) were non-obese. These individuals were older and had higher metabolic risks than their obese counterparts at baseline. Among the entire cohort of 23,894 subjects, 1,764 developed renal dysfunction and 904 developed proteinuria during an average follow-up period of 7.8 years. The cumulative incidence of renal dysfunction was higher (22.1% vs. 16.1%), whereas that of proteinuria was lower (10.5% vs. 14.4%), among the non-obese subjects with ≥3 metabolic factors than the obese subjects with ≥3 metabolic factors after 11 years. The adjusted relative risk (RR) (95% confidence interval) of renal dysfunction was 1.54 (1.34-1.77) and 1.67 (1.35-2.07) for the obese and non-obese subjects with ≥3 metabolic factors, respectively.
Conclusion Non-obese subjects with ≥3 metabolic factors, who are missed based on the essential criterion of obesity for metabolic syndrome, may have an equal or slightly higher risk of renal dysfunction than obese subjects with ≥3 metabolic factors.

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Nodular regenerative hyperplasia (NRH) is associated with autoimmune and hematologic diseases and may lead to portal hypertension. We herein report a case of NRH diagnosed based on a liver biopsy. A 63-year-old woman developed esophageal varices and splenomegaly. She had undergone surgery for transverse colon cancer 24 years earlier and received systemic chemotherapy (FOLFOX4 including oxaliplatin) to treat lymph node metastasis 21 years after the operation. The present liver biopsy confirmed NRH, and, after two years, she received endoscopic injection sclerotherapy. Oxaliplatin was suspected to be the causative agent of NRH in this case. Therefore, physicians must consider the possibility of NRH in patients who receive chemotherapy.

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A 54-year-old man with decompensated alcoholic liver cirrhosis presented with acute cholangitis. Although no localized lesions were detected in the liver on contrast-enhanced computed tomography and no risky varices were noted on endoscopy, hepatic peribiliary cysts (HPBCs) developed along the intrahepatic portal vein in the course of only 40 days. Moreover, esophageal varices with the red color sign grew rapidly during the same period, and the patient ultimately died due to rupture. HPBC formation is a rare complication of liver disease, including cirrhosis. Although HPBCs are generally harmless, on rare occasions they may induce the rapid progression of esophageal varices.

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A 36-year-old Japanese woman took over-the-counter (OTC) medication for headaches for 20 days. Subsequently, five days after discontinuing the medication, a skin rash developed over the patient's upper and lower limbs and face, in addition to a fever, brown urine and serious liver dysfunction. Drug lymphocyte stimulation tests implicated ibuprofen, a main component of the OTC drugs, which has the potential to induce this pathology, and a diagnosis of drug-induced liver injury with multiform exudative erythema was made. The patient's symptoms and liver function tests returned to normal following treatment with systemic steroids.

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A 56-year-old woman with rheumatoid arthritis treated with methotrexate (MTX) was admitted to our hospital due to multiple liver tumors. Contrast-enhanced computed tomography (CT) revealed multiple hypovascular masses, and 18F-fluorodeoxyglucose positron emission tomography CT showed diffuse abnormal accumulation in the liver only. We therefore made a diagnosis of MTX-related primary hepatic lymphoma (MTX-PHL) exhibiting features of diffuse large B-cell lymphoma. Although MTX has been reported to increase the risk of lymphoproliferative disorders, MTX-PHL has not been reported previously. The present case is the first case in which MTX appears to have been involved in the development of PHL.

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A 62-year-old woman with hepatocellular carcinoma (HCC) and asthma presented with acute abdominal pain and a decreased hemoglobin level. Peritoneal fluid was detected around the lesion, and rupture was suspected based on the findings of computed tomography. Extravasation of the HCC tumor was not detected on angiography with iodine contrast agent; however, such extravasation was clearly observed on angiography with carbon dioxide (CO₂). CO₂ angiography is sometimes utilized in patients with arterial bleeding. This modality be more effective and safe than angiography with iodine contrast agent for assessing potential ruptured HCC lesions.

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We herein report the case of a 72-year-old man with endocarditis of the aortic valve who underwent urgent aortic valve replacement 36 hours after admission due to an aggravation of aortic valve regurgitation. Postoperative cultures of the blood and site of valve vegetation identified Candida parapsilosis as a pathogen. Antifungal therapy with amphotericin B and fluconazole was initiated after surgical treatment. Thereafter, the patient displayed a favorable clinical course. Candida parapsilosis endocarditis involving the native valves is extremely rare and associated with a very high mortality rate. Prompt surgical treatment and the aggressive use of antifungal agents are required to save the patient's life.

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The aldosterone-renin ratio (ARR) is considered to be the most reliable and sensitive screening parameter for primary aldosteronism (PA). However, little is known regarding how stroke influences the ARR. We herein present a case of a 35-year-old man who was ultimately found to have PA after diagnostic challenges. The patient showed an atypical ARR in the acute phase of cerebral hemorrhage. We therefore conclude that the ARR may be inappropriately decreased immediately after stroke in patients with PA, presumably due to sympathetic activation and the effects of medications. When diagnosing PA in patients with stroke, we suggest reevaluating the ARR in the stable phase.

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Two unrelated women were hospitalized for thyrotoxic crisis complicated by multiple organ failure. Both patients were treated with antithyroid drugs and hydrocortisone, as well as insulin for hyperglycemia, and underwent mechanical ventilation with sedation. Flaccid quadriplegia became apparent after each patient completely recovered their level of consciousness once sedation was discontinued on days 6 and 15, respectively. Three to six months of rehabilitation was required for the muscle strength to fully improve in both cases. Thyrotoxicosis in addition to critical illness polyneuromyopathy and the administration of glucocorticoid therapy may have contributed to the onset of quadriplegia in these two cases. Flaccid quadriplegia is one of the serious neuromuscular conditions experienced during the treatment of thyrotoxic crisis.

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A 48-year-old man experienced lateral medullary infarction resulting from spontaneous vertebral artery (VA) dissection. Minimal fusiform dilatation was noted on basi-parallel anatomic scanning-magnetic resonance imaging; therefore, the patient was treated conservatively. Eight months later, he experienced deterioration of dysphagia and the onset of gait ataxia. Repeated imaging studies showed enlargement of the VA aneurysm with bulbar compression. Parent artery occlusion on the proximal side of the VA affected by the dissection relieved the patient's symptoms. Although the majority of dissected lesions stabilize within a few months, studies with longer observation periods and more frequent neuroimaging examinations are required.

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Pulmonary arterial hypertension (PAH) is a frequent complication of connective tissue diseases, such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. However, the occurrence of PAH in a patient with ankylosing spondylitis (AS) has not been previously reported with a detailed clinical description in the English literature. We herein report the first case of AS associated PAH in a 27-year-old Taiwanese man with a chief complaint of intermittent palpitations lasting for two years. To the best of our knowledge, this is the first reported case of AS associated with PAH with a detailed clinical description and findings of right heart catheterization published in the English literature.

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