Erysipelothrix rhusiopathiae Peritonitis in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis

Erysipelothrix rhusiopathiae is known as a pathogen of occupational diseases or a zoonosis. We report a case of E. rhusiopathiae peritonitis in a 50-yr-old male undergoing continuous ambulatory peritoneal dialysis (CAPD). He was suffered from mild abdominal pain with a distinctive erysipeloid skin lesion. E. rhusiopathiae was considered to be introduced through a lacerated wound on his hand when he was exposed to contaminated materials. He was treated successfully with a first generation cephalosporin. To our knowledge, CAPD peritonitis due to E. rhusiopathiae is very rare, and this is a report of the first case in Asia.     

A retrospective analysis of re‐exploration after living donor right lobe liver transplantation: incidence,causes, outcomes,and risk factors

Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re‐exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re‐exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re‐exploration within hospital stay. Separate analyses were also performed according to cause of re‐exploration. The overall incidence of re‐exploration was 17.0% (173/1016). The most common cause of re‐exploration was bleeding (50%). Overall re‐exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re‐exploration. Risk factors of re‐exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05–2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001–1.004; P = 0.0023, respectively]. Re‐exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure.     

Lack of association between serum leptin levels and hepatic steatosis, fibrosis or response to antiviral therapy in Korean chronic hepatitis C patients

BACKGROUND/AIMS: Leptin has been recently implicated in the development of hepatic steatosis and fibrosis in chronic hepatitis C (CHC) infection. The serum levels of leptin are known to be strongly affected by anthropometric parameters such as body mass index (BMI) and total body fat, which show differences between races or ethnicities. In this study, we examined whether serum leptin levels are correlated with clinical, virological, and histological features, and with response to antiviral therapy in Korean CHC patients. METHODOLOGY: We evaluated correlations between serum leptin level and age, sex, BMI, fasting glucose, alanine aminotransferase, genotype, hepatitis C virus RNA titer, steatosis, fibrosis, and response to antiviral therapy after 24 weeks completing 24 weeks of interferon-alpha based therapy in 47 Korean CHC patients. RESULTS: Of the variables examined, only female sex and a BMI > 25kg/m2 were identified as independent variables related to a higher leptin level by multivariate analysis. Baseline leptin levels and leptin changes before/after antiviral therapy were not correlated with response to therapy. CONCLUSIONS: In Korean CHC patients, serum leptin levels were found to be correlated with anthropometric parameters, but not with virological or histological features. In addition, serum leptin levels did not predict response to antiviral therapy.     

Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat

In this study, we evaluated whether propentofylline, a methylxanthine derivative, modulates spinal glial activation and GABAergic inhibitory tone by modulation of glutamic acid decarboxylase (GAD)₆₅, the GABA synthase enzyme, in the spinal dorsal horn following spinal cord injury (SCI). Sprague–Dawley rats (225–250 g) were given a unilateral spinal transverse injury, from dorsal to ventral, at the T13 spinal segment. Unilateral spinal injured rats developed robust bilateral hindlimb mechanical allodynia and hyperexcitability of spinal wide dynamic range (WDR) neurons in the lumbar enlargement (L4–L5) compared to sham controls, which was attenuated by intrathecal (i.t.) administration of GABA, dose-dependently (0.01, 0.1, 0.5 μg). Western blotting and immunohistochemical data demonstrated that the expression level of GAD₆₅ protein significantly decreased on both sides of the lumbar dorsal horn (L4/5) after SCI (p < 0.05). In addition, astrocytes and microglia showed soma hypertrophy as determined by increased soma area and increased GFAP and CD11b on both sides of the lumbar dorsal horn compared to sham controls, respectively (p < 0.05). Intrathecal treatment with propentofylline (PPF 10 mM) significantly attenuated the astrocytic and microglial soma hypertrophy and mechanical allodynia (p < 0.05). Additionally, the Western blotting and immunohistochemistry data demonstrated that i.t. treatment of PPF significantly prevented the decrease of GAD₆₅ expression in both sides of the lumbar dorsal horn following SCI (p < 0.05). In conclusion, our present data demonstrate that propentofylline modulates glia activation and GABAergic inhibitory tone by modulation of GAD₆₅ protein expression following spinal cord injury.     

Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes

Purpose The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) implicates that a compositional alteration in bile may contribute to the genesis of this cancer. Lysophosphatidylcholine (LPC) is generated in the bile of these patients. Given the role of cyclooxygenase-2 (COX-2) in biliary tract carcinogenesis, we postulated that LPC induces COX-2 in cholangiocytes.Methods The effect of LPC on COX-2 expression in cholangiocytes was evaluated by immunoblot analysis, real-time PCR and reporter gene assay. Apoptosis was induced by TRAIL treatment, and quantified using DAPI staining.Results Lysophosphatidylcholine increased COX-2 protein expression in cholangiocytes in a concentration- and time-dependent manner. LPC-induced Raf-1 activation was responsible for this COX-2 induction. Accordingly, LPC increased COX-2 mRNA levels in a Raf-1 dependent manner by stabilizing COX-2 mRNA. Finally, LPC attenuated TRAIL-mediated apoptosis through a COX-2/PgE2 dependent mechanism.Conclusions Collectively, these results implicate that LPC inhibits cholangiocyte apoptosis by inducing COX-2 expression via a Raf-1 dependent mechanism. This anti-apoptotic signaling may participate in biliary tract carcinogenesis in APBDJ patients, and therefore, its interruption may be a viable chemopreventative strategy.This work was presented at the European Association for the Study of the Liver in Paris in 2005.     

Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients

Background and Aims: A single nucleotide polymorphism near the interleukin‐28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients. Methods: A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed. Results: The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non‐responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non‐response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non‐response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively. Conclusions: The IL28B genotype may help identify non‐responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non‐response, the IL28B polymorphism may play a smaller role in Asian patients.     

Virological response to adefovir monotherapy and the risk of adefovir resistance

AIM:To evaluate virological response to adefovir(ADV) monotherapy and emergence of ADV-resistant mutations in lamivudine(LAM)-resistant chronic hepatitis B patients.METHODS:Seventy-seven patients with documented LAM resistance who were treated with 10 mg/d ADV for>96 wk were analyzed for ADV resistance.RESULTS:At week 48 and 96,eight(10%)and 14(18%)of 77 LAM-resistant patients developed the ADV-resistant strain(rtA181V/T and/or rtN236T mutations),respectively.Hepatitis B virus(HBV)DNA levels during therapy ...     

Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas

Purpose: Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. Methods: Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. Results: Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. Conclusions: This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients. Grant Support: supported by grant No. 03-2005-024 from the Seoul National University Hospital Research Fund.