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Introduction and Aim: We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients., Material and Methods: This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20])., Results: No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients., Conclusion: Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The aim of this study was to assess the effect of branched-chain amino acid (BCAA) supplements on muscle strength and muscle mass in patients with liver cirrhosis., Patients and Methods: We carried out a single-center, prospective study of adult cirrhotic patients receiving nutrition therapy at Shonan Kamakura General Hospital. A 28-day pretreatment observation period was followed by a 24-week treatment period. Patients who fulfilled the treatment criteria received one package of oral BCAA supplement powder twice a day and the response was evaluated. A responder to BCAA in muscle strength and muscle mass was defined as a patient with an increased skeletal muscle mass index and hand grip assessed 24 weeks after drug treatment commenced., Results: Eighty-two patients fulfilled our criteria and completed the treatment. In terms of muscle strength, there were 59 (72.0%) responders to BCAA supplementation with a significant increase in hand grip from before treatment (22.2±6.3 kg) to after treatment (23.9±6.4 kg) (P<0.001). In terms of muscle mass, 36 (43.9%) patients responded to BCAA with a slight decrease in skeletal muscle mass index from before treatment (7.40±1.62) to after treatment (7.30±1.49) (P=0.333)., Conclusion: BCAA supplementation improved low muscle strength in patients with chronic liver disease, but did not increase muscle mass during the treatment period.

Aim: To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients., Methods: This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics., Results: The mean body weight change from the baseline on the final dosing day was -2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768-0.9896) in the multivariate analyses., Conclusion: In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response., (© 2016 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus infection. Not all individuals develop persistent, progressive disease, but careful follow up is required with moderate-to-severe dysplasia to prevent progression to malignancy. Standard therapies include surgical treatments (trans-anal resection and trans-anal endoscopic microsurgery) and immunotherapeutic and topical methods (topical imiquimod); however, local recurrence remains a considerable problem. Here, we report a case with superficial CA of the anal canal, treated with endoscopic submucosal dissection (ESD). A 28-year-old man presented with a chief complaint of hematochezia. Digital exam did not detect a tumor. Screening colonoscopy revealed 10-mm long, whitish condyles extending from the anal canal to the lower rectum. The lesion covered almost the whole circumference, and only a small amount of normal mucosa remained. Magnifying endoscopy with narrow band imaging showed brownish hairpin-shaped, coiled capillaries. Although histopathological diagnosis by biopsy revealed CA, accurate histological differentiation between CA, papilloma, and squamous cell carcinoma can be difficult with a small specimen. Therefore, we performed diagnostic ESD, which provides a complete specimen for precise histopathological evaluation. The pathological diagnosis was CA, with moderate dysplasia (anal intraepithelial neoplasia 2). There was no recurrence at 16 mo after the initial ESD. Compared to surgical treatment, endoscopic diagnosis and resection could be performed simultaneously and the tumor margin observed clearly with a magnifying chromocolonoscopy, resulting in less recurrence. These findings suggest that endoscopic resection may be an alternative method for CA that prevents recurrence.

Objectives: Iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy provides useful diagnostic information in differentiating Parkinson's disease (PD) from other neurological diseases. Moreover, a number of studies have reported that 123I-MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients. The aim of the present study was to investigate the cardiovascular predictive value of cardiac 123I-MIBG imaging in patients with PD., Methods: Seventy-eight patients with PD were retrospectively studied. All patients underwent 123I-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated., Results: During a mean follow-up of 27 ± 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection fraction (LVEF) was normal in the HF patients. (123)I-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 ± 0.21 vs. 1.34 ± 0.08, p = 0.019; 31.9 ± 5.5 vs. 38.2 ± 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with delayed H/M (R = -0.357, p < 0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed H/M were independently associated with HF (p = 0.014, p = 0.029, respectively). Kaplan-Meier analysis revealed that patients with abnormal WR (> 37%) and delayed H/M (< 1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, respectively)., Conclusions: WR showed stronger predictive power than delayed H/M in Kaplan-Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD. Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.

Background: Contrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN., Methods and Results: Forty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704 mg orally twice daily; NAC group, n=15), hydration and aminophylline (250 mg intraveneously 30 min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00 + or - 0.36 to 0.67 + or - 0.16 mg/dl (p<0.01), and Ccr significantly increased from 62.4 + or - 15.6 to 80.4 + or - 8.39 ml/min (p<0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94 + or - 0.21 to 1.28 + or - 0.21 mg/dl (p<0.01), and Ccr significantly decreased from 63.7 + or - 16.1 to 46.1 + or - 10.6 ml/min (p<0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38 + or - 0.58 to 1.71 + or - 0.38 mg/dl (p<0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337 + or - 31.0 to 239 + or - 34 microg/ml (p<0.01)., Conclusions: These results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN., (Copyright 2009 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Skin fibrotic disorders such as systemic sclerosis (SSc) are characterized by an excessive production of extracellular matrix (ECM) and understood to develop under the influence of certain growth factors. Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-beta (TGF-beta). To better understand the mechanisms of persistent fibrosis seen in SSc, we previously established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, TGF-beta transiently induced subcutaneous fibrosis and serial injections of CTGF after TGF-beta caused persistent fibrosis. To further define the mechanisms of skin fibrosis induced by TGF-beta and CTGF in vivo, we investigated in this study, the effects of growth factors on the promoter activity of the proalpha2 (I) collagen (COL1A2) gene in skin fibrosis. For this purpose, we utilized transgenic reporter mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial beta-galactosidase gene. Serial injections of CTGF after TGF-beta resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-beta alone on day 8. We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-beta in comparison with the injection of TGF-beta alone. Furthermore, the serial injections recruited mast cells and macrophages. The number of mast cells reached a maximum on day 4 and remained relatively high up to day 8. In contrast to the kinetics of mast cells, the number of macrophages was increased on day 4 and continued to rise during the subsequent consecutive CTGF injections until day 8. These results suggested that CTGF maintains TGF-beta-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts. The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis., (Copyright 2004 Wiley-Liss, Inc.)

The role of many growth factors and cytokines in the process of wound healing has been intensively investigated in recent two decades. Among them, transforming growth factor-betas (TGF-betas) are well known to have a potent stimulatory effect on collagen synthesis as shown in various in vivo experimental systems. In the present study, we examined the effects of various growth factors on the promoter activity of the proalpha2 (I) collagen gene (COL1A2) during the wound healing process. For this purpose, we utilized transgenic mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase or a bacterial beta-galactosidase gene. These mice exhibited normal phenotypic expression and the wound healing process was not impaired. Full thickness wounds were made by punch biopsy. We examined the effects of TGF-beta1, -beta2, -beta3, basic fibroblast growth factor, platelet-derived growth factor, and connective tissue growth factor by applying them locally to the open wound every 2 days. Among the growth factors examined, all of the three isoforms of TGF- exhibited a more potent stimulatory effect on COL1A2 promoter activity than did other factors. In addition, while TGF-beta1 and -beta2 significantly increased the number of fibroblasts which were positive for X-Gal staining, TGF-beta3 treatment did not change the number of beta-galactosidase expressing cells. Accumulation of collagen fibers was observed to the same extent in the mice treated with TGF-beta1 and those with TGF-beta3. These findings suggest that TGF-beta1 and -beta3 have similar but not identical regulatory mechanisms of COL1A2 expression, and that their pathophysiological roles in wound healing might be different from each other., (Copyright 2002 Wiley‐Liss, Inc.)

The C100-3 antibodies to HCV can be examined with a Chiron kit but only the antibody to non-structure-4 can be. The antibodies in sera of pregnant women were examined by a passive hemagglutination method (PHA), which is one of the second generation kits used in detecting antibodies to the hepatitis C virus. We studied the percentage of pregnant women in our hospital with antibodies to HCV, and tried to compare the C100-3 antibodies with PHA results in pregnant women. The results are as follows. 1) In the sera of 235 pregnant women both the PHA antibody and the C100-3 antibody were examined. Two women (0.85%) had the C100-3 antibody and 4 (1.7%) had the PHA antibody. 2) Two women positive for both PHA and C100-3 antibodies were positive for PCR during pregnancy. But 2 women positive for PHA only were negative for PCR during pregnancy and positive after delivery. So 4 women positive for PHA had HCV RNA. 3) Next, the sera of 1,198 pregnant women were examined by the PHA method, and nine women were positive. Only four of the 9 were positive for C100-3. 4) It is speculated that the positive rate for anti-HCV antibodies in the sera of pregnant women in Nagoya city is 0.75%. 5) There were 3 cases that were negative for PCR during pregnancy and positive after delivery. So it is speculated that HCV can be activated after delivery.

Pharmacokinetic and clinical studies on a new cephalosporin antibiotic, cefodizime (THR-221, CDZM), were performed and the results obtained are summarized as follows: 1. At about 84 minutes after a bolus injection of 1 g dose of CDZM, the drug was transferred well into tissues of internal genital organs and remained there at therapeutic levels for 285 minutes. The drug was also transferred quickly and sufficiently into exudate from pelvic dead space and its levels were still kept at high levels at 6 hours after administration. 2. CDZM was given to 8 women affected with gynecologic infections. The outcome of CDZM therapies showed that the drug was effective in all 8 of patients (100%) clinically and bacteriologically. 3. Notable adverse effects or abnormal laboratory test results were not observed except for 2 patients with transient and slight elevation of transaminase levels. Based on these results, it may be concluded that CDZM is a highly effective and a very safe antibiotic for the treatment on infectious diseases in gynecologic field.

A patient with multiple nodules on the chin and scalp is presented. Histologically, the nodules were composed of amorphous materials which also completely filled up the whole dermis. Histochemical observation indicated that the amorphous material in the nodule was a kind of glycoprotein. Electron microscopic examination revealed that the material consists of short wavy fibrils, 60 to 100 A in diameter, and of a low electron-dense amorphous substance. Biochemical examination supported the view that the amorphous material is so-called sialomucoid. The nodules were finally diagnosed as colloid degeneration of the skin (nodular type).