Objective The inter-individual difference in response to liver injury appears to be important in the progression of liver fibrosis. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, and several functional gene polymorphisms have been found. The aim of this study was to examine the possible association of IL-10 polymorphisms with the progression of liver fibrosis in hepatitis C virus (HCV)-related chronic liver disease patients.
Methods We examined the IL-10 -1087 A/G and -824 T/C gene polymorphisms in 184 Japanese patients with HCV-related chronic liver disease: 94 chronic hepatitis (CH) and 90 with liver cirrhosis (LC).
Results There were no significant differences in the genotype distributions or allele frequencies of IL-10 -824 T/C and -1087 A/G between the CH and LC groups. However, among the cirrhotic patients, the lower transcriptional allele, -824 T homozygotes had significantly lower serum albumin and platelet counts, and a higher Child-Pugh score than the -824 C carriers, and the lower transcriptional allele, -1087 A homozygotes had a higher ICG-R 15 compared with -1087 G carriers. Haplotype analysis of IL-10 -1087/-824 showed no significant difference between the CH and LC groups, but the combinations of AT and AC haplotypes (AT/AT, AT/AC and AC/AC) had a significantly higher ICG-R 15 than the GC carriers.
Conclusion IL-10 lower transcriptional -824 T allele, -1087 A allele, and -1087/-824 haplotypes AT and AC are risk factors for the progression of liver fibrosis in HCV-related chronic liver disease.

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Objective Gastroptosis is recognized by its characteristic appearance on barium studies. The present prospective study assessed the relationship between gastroptosis and dyspeptic symptoms.
Methods Japanese subjects underwent health screening, and gastroptosis was diagnosed by barium studies. Consecutive subjects (500 women and 167 men) with gastroptosis were identified and the same number of age-matched subjects without gastroptosis were selected as controls. Dyspepsia was classified as reflux-like (heartburn and belching), dysmotility-like (bloating and fullness), or ulcer-like dyspepsia (epigastralgia) based on the Rome II criteria.
Results Body mass index was significantly lower in women with gastroptosis than in controls [19.7±1.83 (SD) vs. 23.4±3.70, p<0.0001], and also in men (19.7±2.00 vs. 23.9±2.89, p<0.0001). The incidence of dyspepsia was significantly lower in women with gastroptosis than in controls (56/500 vs. 87/500, p<0.01) and also in men (10/167 vs. 25/167, p<0.05), especially in women with ulcer-like dyspepsia (15/500 vs. 32/500, p<0.05) and in men with reflux-like dyspepsia (2/167 vs. 12/167, p<0.05). By logistic regression analysis, gastroptosis was associated with a lower risk of dyspepsia (odds ratio: 0.62, 95% CI: 0.405-0.941, p=0.025) and ulcer-like dyspepsia (odds ratio: 0.36, 95% CI: 0.177-0.726, p=0.004) in women.
Conclusion Dyspeptic symptoms were significantly less common in subjects with gastroptosis. Accordingly, gastroptosis may protect against dyspeptic symptoms, rather than causing functional dyspepsia.

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Objectives We examined oral N-acetylcysteine effects on contrast-induced nephropathy (CIN) and clinical events in patients undergoing primary angioplasty for acute myocardial infarction.
Background Recent studies have reported that N-acetylcysteine reduces CIN and improves the clinical outcome in patients undergoing primary angioplasty. However, additional investigations are warranted to further support these findings.
Methods We randomly assigned 76 patients undergoing primary angioplasty into two groups: 38 patients were assigned to N-acetylcysteine (NAC, 705 mg orally administration before and 12, 24, 36 hours after primary angioplasty), and 38 patients to placebo. CIN was defined as an increase in the serum creatinine concentration of 25 percent or more from baseline value within the 72-hour period after primary angioplasty.
Results CIN occurred in 7 patients (9.2%). In the NAC group, the incidence of CIN tended to be lower than in the placebo group (NAC; 2/38; 5.3% vs. Placebo; 5/38; 13.2%, p=0.21). The composite endpoints such as death, acute renal failure requiring temporary renal replacement therapy, or need for mechanical ventilation did not occur in either group.
Conclusion While N-acetylcysteine might have the possibility to reduce the incidence of contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction, the in-hospital mortality and morbidity were not significantly different between the two groups.

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Objective Early studies have indicated that body fat shifts from peripheral stores to central stores with aging. The objective of this study was to investigate age-related changes in abdominal fat distribution of Japanese men and women of the general population over a wide range of body mass indices (BMI).
Methods A total of 2,220 non-diabetic, apparently healthy Japanese adults (1,240 men and 980 women; age range 40-69 years) were included in the study sample. All subjects underwent a CT scan at the level of the umbilicus, and the areas of visceral adipose tissue (AT) and subcutaneous AT were quantified.
Results When the subjects were stratified by BMI into 18.5-23.0 kg/m², 23.0-27.5 kg/m², and 27.5 kg/m² or higher, visceral AT was positively correlated with age in all of the BMI strata in both genders (p<0.01). In contrast, subcutaneous AT was negatively correlated with age in men with BMIs in excess of 23.0 kg/m² (p<0.01) and not at all in women. The mean levels of subcutaneous AT were over 2-fold greater than visceral AT in women aged 60-69 years in any BMI stratum.
Conclusion In Japanese men and women, visceral AT was increased with age in all BMI strata in both genders, whereas subcutaneous AT was decreased with age in men with BMIs in excess of 23.0 kg/m² and not at all in women. Even with these age-related changes in abdominal fat distribution, women retained the subcutaneous-dominant type of fat distribution up to 70 years.

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Objective The ergot-derived dopamine agonists, cabergoline and pergolide, are associated with valvulopathy risk. In Japan, product labels were revised in April 2007 to recommend periodic echocardiography for patients taking these dopamine agonists, however, the compliance of physicians to follow through with this recommendation is unknown. This study assessed changes in echocardiography evaluation of patients with Parkinson's disease (PD) taking cabergoline or pergolide before and after the label revision and examined the factors related with echocardiography performance.
Methods and Patients Medical claim data from January 2005 to December 2008 were used. Patients were divided into a C-P group (prescribed either cabergoline or pergolide) or reference group (prescribed other anti-PD drugs), and further classified based on whether they were prescribed these drugs "pre-revision" or "post-revision." The Cochran-Armitage trend test was used to compare the proportion of echocardiograms obtained amongst these groups before and after the revision. The frequencies of echocardiograms performed among the treatment groups for each period were compared by Fisher's exact test.
Results A total of 222 subjects (C-P, 73; reference, 149) were assessed. The proportion of C-P patients undergoing echocardiography increased from 4.8% to 27.9% after revision of product labels (p=0.001), which was higher than those in the reference group following label revisions (11.0%) (p=0.014). Prescription duration of C-P after the revision was longer in the patients with echocardiography than without echocardiography (p=0.026).
Conclusion Although echocardiography evaluations increased, more than 70% of PD patients prescribed cabergoline or pergolide did not undergo such assessment despite the product label recommendation. Adherence to drug safety recommendations should be facilitated with more feasible and effective measures.

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Objective The inhibitory response to clopidogrel considerably varies among individuals and clopidogrel resistance is a risk factor for thrombotic events in patients with cardiovascular disease. Based on the platelet aggregation evaluated by the VerifyNow P2Y12 Assay, the present study investigated clopidogrel resistance and the effect of cilostazol addition.
Methods We measured the ability of 20 μM ADP to aggregate platelets using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as % inhibition of <20% in this assay.
Patients We examined 77 patients (53 men and 24 women, aged 65.8±9.9 years) with ischemic stroke or carotid artery stenting who received clopidogrel (75 mg) for >7 days at our hospital between October 2009 and March 2010. For 62 patients (42 men and 20 women, aged 65.3±9.9 years) 75 mg clopidogrel alone was administered (clopidogrel only group); the other 15 patients (11 men and 4 women, aged 67.9±9.9 years) received 75 mg of clopidogrel plus 100 or 200 mg of cilostazol (cilostazol combination group).
Results Clopidogrel resistance was identified in 18 (29%) of the 62 patients in the clopidogrel only group. The percent inhibition was significantly higher in the cilostazol combination group than in the clopidogrel only group (41.7±28.0% vs. 64.9±22.7%, p=0.005). None of the patients in the cilostazol combination group had % inhibition of <20%.
Conclusion Clopidogrel resistance developed in 29% of patients given clopidogrel alone. The addition of cilostazol to clopidogrel may have intensified platelet inhibition.

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Background The side-effects of anti-retroviral drugs are different between Japanese and Caucasian patients. Severe central nerve system (CNS) side-effects to efavirenz and low rate of hypersensitivity against abacavir characterize the Japanese.
Objective The objective of this study was to select a once daily regimen for further non-inferior study comparing the virological efficacy and safety of the first line once daily antiretroviral treatment regimens in the current HIV/AIDS guideline.
Methods The study design was a randomized, open label, multicenter, selection study. One arm was treated with efavirenz and the other with ritonavir-boosted atazanavir. A fixed-dose lamivudine plus abacavir were used in both arms. The primary endpoint was virologic success (viral load less than 50 copies/mL) rate at 48 weeks. Patients were followed-up to 96 weeks with safety as the secondary endpoint. Clinicaltrials.Gov (NCT00280969) and the University hospital Medical Information Network (UMIN000000243).
Results A total of 71 participants were enrolled. Virologic success rates in both arms were similar at week 48 [efavirenz arm 28/36 (77.8%); atazanavir arm 27/35 (77.1%)], but were decreased at week 96 to 55.6% in the efavirenz arm and 68.8% in the atazanavir arm (p=0.33). At the 96-week follow-up, 52.8% of the EFV arm and 34.3% of the ATV/r arm reached total cholesterol more than 220 mg/dL and required treatment. None of the patients developed cardiovascular complications in this study by week 96.
Conclusion There was no significant difference in the efficacy of efavirenz and ritonavir-boosted atazanavir combined with lamivudine plus abacavir at 48 weeks. The evaluation of safety was extended to 96 weeks, which also showed no significant difference in both arms.

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Background Tobacco smoking is a major risk factor for atherosclerotic and cardiovascular disease. Studies have found evidence that smoking cessation is associated with weight gain, which is itself a leading cause of cardiovascular disease.
Aim The present study sought to determine how smoking cessation and associated weight gain affect adiponectin levels and insulin resistance.
Methods Fifty-two male habitual smokers were treated for 2 months with transdermal nicotine patches, and the 28 subjects who successfully quit smoking were analyzed. Subjects were divided into two sub-groups according to their weight change: weight maintainers and weight gainers. Serum adiponectin levels and the homeostasis model assessment ratio (HOMA-R) were evaluated at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use.
Results In weight gainers (n=18), serum adiponection levels tended to increase at 1 week after the end of treatment (mean difference 0.4±1.0 μg/mL, p=0.08). Moreover, after 9 weeks, adiponectin levels were significantly decreased in weight gainers (mean difference between 1 week and 9 weeks 0.8±0.9 μg/mL, p=0.002). In weight maintainers, adiponectin levels increased slightly after smoking cessation, but changes were not significant. In weight gainers, HOMA-R index was significantly increased (mean difference between baseline and 9 weeks 0.4±0.7, p=0.01), while in weight maintainers, HOMA-R index showed no differences throughout the study.
Conclusion Our findings suggest that the adverse effects of weight gain attenuate some of the beneficial effects of smoking cessation.

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Background Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants in the world. Recent studies, however, have raised the concern that SSRIs increase the risk of gastrointestinal dysfunction. Therefore, we conducted a case-control study on gastrointestinal symptoms and endoscopic findings in patients who were taking SSRIs in Japan.
Methods Forty-one patients who were taking SSRIs (SSRI-treated group) and 82 age- and sex-matched patients who were not taking antidepressants (control group) were selected from the population of patients who underwent endoscopic examination from January 1, 2005 to March 31, 2010 in our institution, and their subjective symptoms and endoscopic findings were analyzed. Patients who were taking proton pump inhibitors (PPIs) and/or histamine H₂-receptor antagonists (H2RAs) were excluded from this study.
Results The chief complaints at the endoscopic examination were classified into the following 4 categories: reflux symptoms, dysmotility symptoms, ulcer-like symptoms, and no upper abdominal symptoms. No significant difference was found in the complaint rate of each category between the SSRI-treated and the control groups. No significant differences were found between the groups in endoscopic findings, the LANZA score and the rate of chief complaints in patient classes stratified by the endoscopic finding.
Conclusion It was not evident that SSRIs induced mucosal damage of the upper gastrointestinal tract. And, it is considered that SSRIs do not increase the risk of upper gastrointestinal symptoms in patients treated with SSRIs for 1 month or longer. The present study suggests that SSRI medication does not have a bad influence on gastrointestinal symptoms and gastrointestinal organic diseases.

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Pericardial effusion from any cause may lead to decreased cardiac output and blood pressure, causing heart failure and reduced renal blood flow. Although pericardial effusion is not uncommon, it is usually not associated with hemodynamic compromise unless the effusion causes cardiac tamponade. Acute renal failure resulting from pericardial effusion is surprisingly rare, with only six cases described to date. We describe the first case known to us of pericardial effusion without tamponade causing acute anuric renal failure. The case was characterized initially by non-specific symptoms and signs; anuria dominated the clinical picture, and was completely reversed after pericardiocentesis.

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A 36-year-old diabetic man came to our institution presenting with constant left flank pain. Left renal embolic infarction was found by abdominal computed tomography. Silent ST segment elevation myocardial infarction was noted on 12-lead electrocardiogram. Emergent coronary angiography revealed large thrombus burdens with complete occlusion at the left anterior descending artery ostium, which may be the embolic origin. Silent ST segment elevation myocardial infarction with acute flank pain and multiple segmental renal infarction is an unusual presentation. High vigilance may prevent delay of the "golden hour" to treat acute myocardial infarction.

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Although the etiology of Takotsubo cardiomyopathy (stress-induced cardiomyopathy) is unknown, there is a wide variability in the psychological and physical triggers for Takotsubo cardiomyopathy. We report here a case of Takotsubo cardiomyopathy associated with severe hyponatremia.

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A serotype-1 hepatitis C virus (HCV) infection in a 67-year-old hemodialysis patient was treated using interferon (IFN)-beta. Although the patient had a high RNA titer (5.1 log IU/mL) and had been receiving long-term hemodialysis therapy (30 years), the initial 4-week IFN-beta administration enabled a rapid virological response without any major adverse effects. However, the final outcome after 24 weeks of IFN beta treatment was classified as unchanged based on the criteria of the Conference on Intractable Hepatitis. Here, we describe our experience treating HCV infection using IFN-beta and discuss the indications for such therapy.

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We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.

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Small molecule inhibitors targeting epidermal growth factor receptor (EGFR) are known to be active against non-small cell lung cancer (NSCLC) although the pharmacodynamics of these agents on malignant pleural effusion (MPE) remains unclear. Here we describe a case of lung adenocarcinoma with massive MPE treated successfully by gefitinib and chest drainage. Using sequential MPE samples before and during gefitinib therapy, the morphological changes and apoptosis of cancer cells were analyzed. Apoptosis of cancer cells was detected as early as 4 hours on, but not before, gefitinib therapy, suggesting that the pharmacodynamic assessment of such molecular targeting agents might be feasible for MPE.

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A 78-year-old man with an 18-year history of rheumatoid arthritis (RA) was treated with tumor necrosis factor (TNF)-α inhibitor adalimumab. Chest computed tomography showed a previously detected consolidation. The patient's arthritic symptoms substantially decreased with the initiation of adalimumab, with a simultaneous improvement of the lung lesion. However, additional interstitial pneumonia was found a month after starting adalimumab. This course suggested that adalimumab might be effective against RA-associated lung disease, but may also have caused drug-induced interstitial pneumonia. This is the first report indicating that TNF-α inhibitor shows simultaneously conflicting actions in a patient with RA-related lung disease.

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We report a 75-year-old man who was initially suggested to have acute leukemia. The hemoglobin level was 3.8 g/dL, white cell count was 7,700/μL with an absence of mature neutrophils and 69.0% leukemic cells, and platelet was 0.4×10⁴/μL. Coombs' antiglobulin test was positive. Leukemic cells were CD5^-, CD10⁺, CD20⁺, CD23^-, and IgG/λ^dim+. The bone marrow consisted of normal hematopoietic precursors, whereas fluorescence in situ hybridization detected the BCL2/IgH fusion gene. He was treated with rituximab-containing chemotherapy, resulting in the resolution of pancytopenia. The underlying disease was a leukemic B-cell tumor with t(14;18)(q32;q21), and the pancytopenia was mainly caused by autoimmune mechanisms.

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Neck dystonia is the most common cause of dropped head sign in parkinsonism. Isolated neck extensor myopathy, which is a rare condition, can also cause dropped head sign in parkinsonism, but no improvement has been achieved with immunosuppressive therapy. We report three cases of treatable neck extensor myopathy causing dropped head sign in patients with Parkinson's disease. Needle electromyography and magnetic resonance imaging suggested a restrictive active myopathy affecting neck extensor muscles. All cases responded dramatically to steroid therapy. Routine needle electromyography should be performed to explore treatable myopathy in Parkinson's disease.

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Digital ulcers (DUs) and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis. Raynaud's phenomenon (RP) is an almost universal manifestation of systemic sclerosis, with 95% of all patients being affected, and resulting in DUs in approximately 30% of the patients each year. Although RP may be present in approximately 25-50% of the patients, DUs are relatively rare in systemic lupus erythematosus (SLE) and never present as an initial manifestation of disease. In this case report DUs appear as the initial manifestation of SLE in a young woman with a capillaroscopic scleroderma pattern and elevated systolic pulmonary arterial pressure.

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Angiostrongylus cantonensis also known as the rat lungworm, is prevalent in the Pacific Islands and southeast Asia and is the most common cause of eosinophilic meningitis in humans. Although frogs and toads are known as paratenic hosts of A. cantonensis, they are rarely reported as the infectious source of human angiostrongyliasis. We report a case of encephalitis caused by Angiostrongylus cantonensis after eating raw frogs mixed with wine as a health supplement. Prednisolone at a dose of 1 mg/kg/day was prescribed for 14 days successfully. We advise that travelers and residents of endemic areas should avoid eating raw frogs and a public caution on the danger of eating raw wild animal products or the whole animal is recommended to alleviate such accidental infection.

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A 46-year-old man with no past history of underlying disease was admitted to our hospital for examination of abnormal chest shadow on chest radiograph. He had no respiratory symptoms on admission. Chest radiograph showed a solitary nodule (35×20 mm) in the left upper lung field. On chest CT, this nodule in the left upper lobe (S¹⁺²) did not demonstrate calcification, the margin was clear but irregular, and there was pleural indentation. The solitary nodule was strongly positive on PET/CT. Therefore, we suspected primary lung cancer. Because we could not establish the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery (VATS) was performed. Histological diagnosis of the solitary nodule demonstrated epitheloid granuloma with caseous necrosis. Smear test of the resected tissue was positive for acid-fast bacilli and culture was positive for mycobacteria, which was identified as Mycobacterium kansasii. There are a few case reports of solitary nodule due to M. kansasii.

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Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.

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