bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of bile duct‐ligated rats with the nitric oxide synthase transcription enhancer AVE 9488 ameliorates portal hypertension
Authors: Biecker Erwin , Trebicka Jonel , Kang Alice , Hennenberg Martin , Sauerbruch Tilman , Heller Jörg
Published: August 2010

Aim: Nitric oxide levels are decreased in the cirrhotic liver and increased in the systemic vasculature. We investigated whether the nitric oxide synthase (NOS) transcription enhancer AVE 9488 ameliorates portal hypertension in cirrhotic rats.

Methods: Rats with secondary biliary cirrhosis [bile duct ligation (BDL)] were treated with AVE 9488. BDL animals without treatment served as controls. Blood flow was determined with the microsphere technique. Intrahepatic resistance was measured by in situ perfusion. NOS‐3 mRNA and protein levels in the liver, aorta and superior mesenteric artery (SMA) were measured.

Results: Arterial pressure did not differ between treated and non‐treated animals. Portal pressure, hepatic portal‐vascular resistance and perfusion pressure of the in situ perfused liver were lower in the AVE 9488‐treated animals. Arterial splanchnic resistance, portal venous inflow and shunt volume were increased by AVE 9488. N (G)‐nitro‐l‐arginine methyl ester abolished the effect of AVE 9488. AVE 9488‐treated rats had higher liver NOS‐3 mRNA and protein levels, whereas NOS‐3 mRNA and protein in the aorta and the SMA did not vary between groups. Phosphorylation of liver vasodilator‐stimulated phosphoprotein (VASP) and NOS‐3 as well as hepatic nitrite/nitrate was increased by AVE 9488.

Conclusions: Treatment of BDL rats with the NOS transcription enhancer AVE 9488 induces an increase in NOS‐3 mRNA and protein in the liver. This is associated with an amelioration of portal hypertension.
Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta‐analysis
Authors: Değertekin Halil , Yalçιn Kendal , Yakut Mustafa , Yurdaydin Cihan
Published: August 2010

Background: Recent reports suggest a decline of delta hepatitis (DH) in the West as well as in the Far East.

Aim: To study the DH seroepidemiology in Turkey.

Methods: Statistical power analysis was utilized based on data available in a recent article using prevalence figure estimates. Binominal distribution was applied in order to assess the number of samples required to estimate the prevalence with a given precision.

Results: Out of 62 studies in the original study, 32 were eliminated because of insufficient power. A total of 6734 patients (5231 with chronic hepatitis and 1503 with cirrhosis) were analysed. Anti‐HDV seropositivity among patients with chronic hepatitis B (CHB) and hepatitis B‐induced cirrhosis was lowest in the west of the country and highest in the southeast (5 vs. 27%, P<0.0001 and 20 vs. 46%, P<0.0001) respectively. Compared with data obtained before 1995, after 1995, DH prevalence in patients with CHB and cirrhosis decreased from 29 to 12% (P<0.0001) and from 38 to 27% (P=0.03) in central and southeast Turkey and from 38 to 20% (P<0.0001) and from 66 to 46% (P<0.002) in west and southeast Turkey respectively.

Conclusion: Despite the decrease of its prevalence in Turkey, DH remains a significant health problem in parts of the country with low socio‐economic level.
Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation
Authors: Rubio‐Tapia Alberto , Abdulkarim Ahmad S. , Wiesner Russell H. , Moore S. Breanndan , Krause Patricia K. , Murray Joseph A.
Published: August 2010

Background/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end‐stage autoimmune liver disease (ESALD), (ii) the correlation among auto‐antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics.

Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non‐autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6–12 and ≥24 months post‐transplantation. Results were correlated with the HLA type of the recipient.

Results: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non‐autoimmune) of the patients (five‐fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA‐DQ2 or HLA‐DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post‐transplantation. Post‐transplantation, of the five patients with symptoms of ‘classical’ CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically ‘silent’ CD.

Conclusions: Patients with ESALD, especially those who are HLA‐DQ2 or HLA‐DQ8 positive had a high prevalence of CD‐associated antibodies. Both tTGAs and EMAs decreased post‐transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.
Nuclear factor‐κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
Authors: Liu Hongqun , Lee Samuel S.
Published: August 2010

Background/Aims:Cytokines such as tumour necrosis factor (TNF‐α) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor‐κB (NF‐κB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF‐κB involvement in cirrhotic cardiomyopathy.

Methods:Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF‐κB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11‐7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11‐7082. Myocardial NF‐κB and TNF‐α expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy.

Results:Nuclear factor‐κB and TNF‐α levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF‐κB activity and TNF‐α expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11‐7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls.

Conclusions:Inhibition of the increased NF‐κB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF‐κB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.
Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication
Authors: Ando Mie , Korenaga Masaaki , Hino Keisuke , Ikeda Masanori , Kato Nobuyuki , Nishina Sohji , Hidaka Isao , Sakaida Isao
Published: August 2010

Background/Aim:Hepatitis C virus (HCV) core protein has been shown to inhibit mitochondrial electron transport and to increase reactive oxygen species (ROS)in vitroandin vivo. The aim of this study was to investigate whether inhibiting HCV replication could restore the mitochondrial redox state and electron transport activity.

Methods:We measured ROS, mitochondrial reduced glutathione content, and mitochondrial complex I, II, III and IV activities and protein expression in full genomic HCV replicon cells and cured cells that had been prepared by eliminating HCV RNA from replicon cells by interferon (IFN)‐α treatment.

Results:Cured cells had significantly lower ROS production and greater mitochondrial glutathione content than replicon cells. Complete inhibition of HCV replication by IFN‐α restored complex I and IV activities by 20–30% (P<0.01) and complex I expression (P<0.05). Treatment with fluvastatin, one of the 3‐hydroxy‐3‐methylglutaryl co‐enzyme A reductase inhibitors, which is known to have anti‐HCV activity, partially inhibited core protein expression and restored complex I activity in full genomic HCV replicon cells to a lesser degree (P<0.05).

Conclusions:Our results show that the mitochondrial redox state and electron transport activity can be restored by reducing HCV replication.
Serological markers for monitoring disease progression in noncirrhotic primary biliary cirrhosis on ursodeoxycholic acid therapy
Authors: Färkkilä Martti , Rautiainen Henna , Kärkkäinen Päivi , Karvonen Anna‐L. , Nurmi Heimo , Niemelä Onni
Published: August 2010

Background/Aim: Liver biopsy has so far been the only method to accurately follow the progression of primary biliary cirrhosis (PBC). The stage and the severity of lymphocytic piecemeal necrosis (LPN) have been shown to be an independent factor for the development of cirrhosis. In this 3‐year prospective study, we evaluated the diagnostic value of several liver function tests, surrogate markers of fibrogenesis, hyaluronic acid (HA), procollagen III N‐terminal peptide (S‐PIIINP), cholestanol and plant sterols in noncirrhotic PBC patients treated with ursodeoxycholic acid (UDCA) or with UDCA and budesonide to assess the stage, inflammation and fibrosis.

Methods: Seventy‐seven stage I–III PBC patients were included into the study, with control biopsy at 36 months. Serum liver enzymes, bile acids (BA), HA, PIIINP, immunoglobulins, lipids and cholesterol precursors and plant sterols were measured at baseline and at 36 months.

Results: Aspartate aminotransferase (AST), HA, BA and PIINP were significantly different between stages I to III and differentiated mild (F0F1) from moderate (F2F3) fibrosis. The combination of these variables (PBC score) exhibited best sensitivity and specificity, compared with AST/platelet ratio, Forns' score and fibrosis index. Using a cut‐off value of 66 for the PBC score, the sensitivity was 81.4% and specificity was 65.2% for classifying the stage of PBC, regarding the stage the and fibrosis in noncirrhotic PBC.

Conclusions: Serum HA, BA, PIIINP and AST may serve as valuable simple tools to monitor the treatment response to UDCA in early stages of PBC. Combinations of these biomarkers into a single index further potentiate the diagnostic value of such measurements.
Association of interferon regulatory factor ‐7 gene polymorphism with liver cirrhosis in chronic hepatitis C patients
Authors: Sermasathanasawadi Radsamee , Kato Naoya , Muroyama Ryosuke , Dharel Narayan , Shao Run‐Xuan , Chang Jin‐Hai , Li Chang‐Zheng , Kawabe Takao , Omata Masao
Published: August 2010

Background and aims:Interferon (IFN) regulatory factor 7 (IRF‐7) has been shown to play an essential role in the transcriptional activation of virus‐inducible cellular genes, especially IFN genes. Polymorphisms of the IRF‐7 gene may probably affect both the quality and the quantity of IRF‐7. We investigated the role of IRF‐7 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection.

Methods:We studied a total of nine polymorphisms of the IRF‐7 gene including SNP1047A/G (Lys/Glu) and SNP2157A/G (Gln/Arg) using the Taqman allelic discrimination and sequencing techniques in 406 Japanese patients with chronic HCV infection. We further performed functional analysis of SNP1047 and SNP2157 by transcriptional activation of the IFNA promoter.

Results:We found that SNP1047AG and SNP2157AG genotypes were in complete linkage disequilibrium and were present in a significantly higher proportion in HCV‐infected patients with cirrhosis (5.6%) than in those without cirrhosis (1.7%) (P=0.03). Multivariate analysis also revealed that SNP1047 and SNP2157 were independently associated with cirrhosis at an odds ratio of 2.5. Functional analysis revealed that SNP1047G and SNP2157G alleles increased IFNA expression.

Conclusion:SNP1047AG and SNP2157AG genotypes were strongly associated with cirrhosis. SNP1047G and SNP2157G alleles might be used as markers of host factors associated with a higher risk of cirrhosis in Japanese patients with chronic HCV infection.
Outcome and prognostic factors of 391 Japanese patients with primary sclerosing cholangitis
Authors: Tanaka Atsushi , Takamori Yoriyuki , Toda Gotaro , Ohnishi Saburo , Takikawa Hajime
Published: August 2010

Objectives: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients.

Methods: Questionnaires were sent to gastroenterologists in Japan, and 391 patients with PSC were registered and enrolled in the current study. The median follow‐up was 5.3 years (range 0.1–20.8 years). The cumulative incidence for survival was analysed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox‐proportional hazards regression model for determining prognostic variables.

Results: The estimated median survival of all patients was 13.1 years, with a 5‐year survival rate of 74.5%. Thirty‐eight patients (9.7%) who underwent liver transplantation (LT) had a 5‐year survival rate of 92.0%. Both univariate and multivariate analysis demonstrated that younger age [below 49 years old; odds ratio (OR)=1.76, 1.12–2.76, P=0.0136] and lower total bilirubin (below 3.0 mg/dl; OR=2.50, 1.60–3.89, P≤0.0001) were independent prognostic factors for LT‐free survival of PSC patients in Japan. Cholangiocarcinoma (CCA) was found in 14 (3.6%) patients, and only two out of 125 PSC patients exhibited a history of inflammatory bowel diseases.

Conclusions: Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.
Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow‐up study
Authors: Catalano Daniela , Trovato Guglielmo M. , Martines Giuseppe F. , Randazzo Marianna , Tonzuso Antonia
Published: August 2010

Background: Nonalcoholic fatty liver disease (NAFLD) because of its association with obesity, diabetes and insulin resistance (IR), is the hepatic expression of metabolic syndrome. Exercise and nutritional intervention can improve and prevent these inter‐related conditions; the relationships between the degree of IR and ultrasound (US) morphological post‐interventional changes are not defined.

Aims: The aim of our study was to assess the relationship, if any, in NAFLD patients, among IR, BMI and degree of bright liver, before and after 6 months of a moderately hypocaloric/balanced dietary/lifestyle treatment. Fifty outpatients with a clinical and US diagnosis of NAFLD were studied.

Methods: Liver echogenicity [Bright Liver Score (BLS)] was scored on a four‐graded scale. IR was assessed by homoeostasis model‐insulin resistance (HOMA‐IR). Body composition was assessed by bioimpedance assessment and skinfold measurements.

Results: A significant decrease of BLS was observed, with a concurrent decrease of body weight, body mass index (BMI) and HOMA‐IR. Bright liver decrease has a trend parallel to IR, much less steep than the trend of bright liver reduction against US liver dimensions, body weight and BMI decrease. HOMA‐IR is the only baseline variable that enters significantly in the multiple regression and, alone, explains 21.4% of variance in predicting bright liver degree. After dietary interventions, both HOMA‐IR and BMI are significantly involved in the multiple regression and explain, together, 42.3% of variance in predicting bright liver degree; variation in BLS can be predicted by variation of body weight and of US longitudinal measurement of the liver.

Conclusions: Liver US BLS appears to be a useful tool, both alone and along with other US measurements and body weight changes, for the assessment of clinical‐metabolic amelioration in patients treated with dietetic interventions. The clinical‐diagnostic role, if any, of other assessed laboratory analyses, in the subset of NAFLD, does not appear to be definite.
A higher alanine aminotransferase level correlates with earlier hepatitis B e antigen seroconversion in lamivudine‐treated chronic hepatitis B patients
Authors: Tseng Tai‐Chung , Liu Chun‐Jen , Wang Chia‐Chi , Chen Pei‐Jer , Lai Ming‐Yang , Kao Jia‐Horng , Chen Ding‐Shinn
Published: August 2010

Background/Aims: A pretherapy serum alanine aminotransferase (ALT) level above five times the upper limit of normal (ULN) is known to predict hepatitis B e antigen (HBeAg) seroconversion during lamivudine therapy for chronic hepatitis B patients. However, whether an even higher pretherapy serum ALT value or other viral factors could affect treatment responses remains unclear.

Patients and methods: A total of 253 HBeAg‐positive chronic hepatitis B patients who had a pretherapy serum ALT level over five times ULN and received lamivudine for 12–18 months were retrospectively collected. Among these patients, 38% had received prior lamivudine treatment. HBeAg seroconversion was the primary endpoint of treatment. Baseline clinical and viral features were compared between responders and non‐responders at the end of treatment and 6 months post‐treatment.

Results: At the end of therapy, the overall HBeAg seroconversion rate was 33.6%. For lamivudine‐naïve patients, the HBeAg seroconversion rate was 37.8%. Subgroup analysis showed that patients with pretherapy ALT levels over 10 times ULN had a significantly higher HBeAg seroconversion rate than those with a pretherapy ALT level between five and 10 times ULN at 3 months (P=0.045) and 6 months (P=0.037) of lamivudine treatment. No significant difference was found in terms of pretherapy serum ALT values, viral load and genotypes between seroconverters and non‐seroconverters.

Conclusions: For lamivudine‐treated HBeAg‐positive patients with pretherapy ALT levels over five times ULN, an even higher ALT level could predict earlier HBeAg seroconversion; however, neither ALT levels nor viral factors correlate with higher response rates after 12–18 months of treatment.
Contribution of hepatic stellate cells and matrix metalloproteinase 9 in acute liver failure
Authors: Yan Chunli , Zhou Ling , Han Yuan‐Ping
Published: August 2010

Background/Aims: Fulminant hepatitis or acute liver failure (ALF), initiated by viral infection or hepatic toxin, is a devastating medical complication without effective therapeutic treatment. In this study, we addressed the potential roles of hepatic stellate cells (HSCs) and their produced matrix metalloproteinases (MMPs) in development of ALF.

Methods: Mice were given lipopolysaccharide (LPS) and beta‐galactosamine (GA) or carbon tetrachloride to create ALF and establish the association of IL‐1, MMP‐9, and caspase‐3 in acute liver failure.

Results: In response to the hepatic toxin, IL‐1 and MMP‐9 were promptly induced within 1 hour, followed by caspase‐3 activation at 2 hours, and dehiscence of sinusoids at 4 hours, and consequent lethality. In contrast, MMP‐9 knockout mice were resistant to lethality and absent of caspase‐3 activation, demonstrating an MMP‐9‐dependent activation of caspase in vivo. Further, IL‐1‐receptor knockout mice were resistant to lethality in MMP‐9 dependent manner, indicating a causative relationship. Although many hepatic cells are capable to produce MMP‐9 in vitro, HSCs were demonstrated here as the major hepatic cells to express MMP‐9 in liver injury. To recapitulate the sinusoidal microenvironment we cultured primary HSCs in 3‐dimensional ECM. In response to IL‐1, massive MMP‐9 was produced by the 3D culture concomitantly with degradation of type‐IV collagen.

Conclusions: Based on these evidences, we propose a novel model to highlight the initiation of acute liver failure: IL‐1‐induced MMPs by HSCs within the space of Disse and thereafter ECM degradation may provoke the collapse of sinusoids, leading parenchymal cell death and loss of liver functions.
Green tea consumption and liver disease: a systematic review
Authors: Jin Xi , Zheng Ruo‐heng , Li You‐ming
Published: August 2010

Objectives: To present the effect of green tea consumption against liver disease.

Data sources: Interventional and observational studies both in Western countries and in China and published between the years 1989 and December 2007.

Review Methods: The articles were retrieved from Medline, Embase database, Chinese biomedicine web database and Chinese scientific journal's database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics and outcomes of the chosen articles were displayed for further analysis and the quality of each study was also evaluated according to the widely acknowledged criteria. P<0.05 was defined as statistically significant in all enrolled trials.

Results: Ten qualified studies (eight from China, one from Japan and the other from the USA) with various outcomes such as liver cancer, cirrhosis and fatty liver disease were finally chosen. Among them, study designs differed in that there were four randomized‐controlled clinical trials, two cohort, one case–control and three cross‐sectional studies. The heterogeneity in the study design, outcomes, cofounders and amount of tea consumption precluded further meta‐analysis. Nevertheless, eight studies showed a significant protective role of green tea against various liver diseases as determined by relative risk/odds ratio or P‐value and among them, four studies showed a positive correlation between green tea intake and attenuation of liver disease. Moreover, the other two studies also presented the protective tendency of green tea against liver disease.

Conclusions: An increased consumption of green tea may reduce the risk of liver disease.
Aetiology and outcome of acute hepatic failure in Greece: experience of two academic hospital centres
Authors: Koskinas John , Deutsch Melanie , Kountouras Dimitris , Kostopanagiotou Georgia , Arkadopoulos Nikos , Smyrniotis Vasilis , Rapti Irene , Manesis Emmanuel , Archimandritis Athanasios
Published: August 2010

Introduction: In Western countries, the most frequent aetiology of acute liver failure (ALF) is acetaminophen overdose, while in developing countries viral infections [hepatitis A virus and hepatitis B virus (HBV)] predominate.

Aim: To evaluate the epidemiology, clinical characteristics, outcome and prognostic factors of survival of patients with ALF in Greece during the last 6 years.

Results: A total of 40 patients, 28 females (70%), with a median age of 37.4±18.6 years (range: 15–84) with ALF were studied. HBV infection was the cause in 53% of them (compared with 74% from a previous study reported in the early 1980s), drug toxicity in 15% and undetermined in 13%. The overall survival was 57.5%, including 94% with and 15% without liver transplantation. Forty‐five per cent of our patients had emergency liver transplantation in European Centers within a median time of 3.3 days (1–9) from admission. The total bilirubin level at admission and the development of infections were found to be significantly associated with poor outcome.

Conclusions: Hepatitis B virus still remains the most important cause of ALF in Greece, but shows a significant decrease as compared with studies in the early 1980s. Almost half of our patients needed emergency liver transplantation and had a very good survival rate. The other 15% of the patients presented spontaneous survival only with intensive medical support.
Ezetimibe prevents cholesterol gallstone formation in mice
Authors: Zúñiga Silvia , Molina Héctor , Azocar Lorena , Amigo Ludwig , Nervi Flavio , Pimentel Fernando , Jarufe Nicolás , Arrese Marco , Lammert Frank , Miquel Juan F.
Published: August 2010

Background:Intestinal cholesterol absorption may influence gallstone formation and its modulation could be a useful therapeutic strategy for gallstone disease (GSD). Ezetimibe (EZET) is a cholesterol‐lowering agent that specifically inhibits intestinal cholesterol absorption.

Aims:To test whether EZET can prevent gallstone formation in mice.

Methods/Results:Gallstone‐susceptible C57BL/6 inbred mice were fed control and lithogenic diets with or without simultaneous EZET administration. Lithogenic diet increased biliary cholesterol content and secretion, and induced sludge or gallstone formation in 100% of the animals. EZET administration reduced intestinal cholesterol absorption by 90% in control animals and by 35% in mice receiving the lithogenic diet. EZET prevented the appearance of cholesterol crystals and gallstones. In addition, mice fed the lithogenic diet plus EZET exhibited a 60% reduction in biliary cholesterol saturation index. Of note, EZET treatment caused a significant increase in bile flow (+50%,P<0.01) as well as bile salt, phospholipid and glutathione secretion rates (+60%, +44% and +100%, respectively,P<0.01), which was associated with a moderately increased expression of hepatic bile salt transporters. In addition, relative expression levels of Nieman–Pick C1 like 1 (NPC1L1) in the enterohepatic axis in humans were assessed. Expression levels of NPC1L1 were 15‐ to 30‐fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of EZET on intestinal cholesterol absorption in humans.

Conclusions:In a murine model of GSD, EZET prevented gallstone formation by reducing intestinal cholesterol absorption and increasing bile salt‐dependent and ‐independent bile flow. EZET could be useful in preventing GSD disease in susceptible patients.
Hepatic microwave ablation: a review of the histological changes following thermal damage
Authors: Gravante Gianpiero , Ong Seok L. , Metcalfe Matthew S. , Strickland Andrew , Dennison Ashley R. , Lloyd David M.
Published: August 2010

Microwave (MW) ablation therapy is a local treatment by which tumours are destroyed by coagulation from the passage of MWs into cells. The aim of this review is to examine histological results obtained from preclinical and clinical studies. A literature search was undertaken for all studies focusing on MW therapy and in which lesions were excised for a complete histopathological examination after treatment. Two main zones were described after ablative therapy (central and transitional). Both corresponded to specific microscopic characteristics and evolved over time in a precise manner. No viable cells even up to 6 cm in diameter were demonstrated in 93% of lesions after treatment. Microwave therapy is a reliable technique under a variety of clinical situations. Future investigations are needed to compare MW with other ablative techniques to identify factors that influence the effectiveness of the various techniques and to determine specific indications.
Preventative hepatology: minimising symptoms and optimising care
Authors: Hirschfield Gideon M. , Kumagi Teru , Heathcote E. Jenny
Published: August 2010

Most care of liver disease is in the ambulatory setting, and therefore the clinical needs of patients represent those of any other chronic illness. Emphasis must be given to preventative strategies such that liver lifetime (including pre‐emptive strategies related to potential allograft survival) is maximised through timely intervention and avoidance of side effects. This review addresses the pertinent practical clinical concerns faced by clinicians as they manage adult patients with chronic liver disease, with an emphasis on preventing and managing symptoms and complications directly and indirectly related to the underlying disease.
Hepatic granuloma: decreasing trend in a high‐incidence area
Authors: Sanai Faisal M. , Ashraf Suhail , Abdo Ayman A. , Satti Mohammed B. , Batwa Faisal , Al‐Husseini Hussa , Saleh Ahmed M. , Bzeizi Khalid I.
Published: August 2010

Background: Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology.

Methods: A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty‐six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed.

Results: Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018).

Conclusion: The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.
Pregnancy and liver transplantation
Authors: Surti Bijal , Tan Jennifer , Saab Sammy
Published: August 2010

Since the first pregnancy in a transplant recipient in 1958, pregnancy in recipients of solid organ transplants has become increasingly common. Although previously considered a hazardous event, data collected over the last 50 years demonstrate that despite an increased risk of maternal and fetal complications, pregnancy in transplant recipients can have a successful outcome. As of 2006, there were over 3000 female liver transplant recipients of childbearing age in the USA. Two hundred and two pregnancies and 205 outcomes were reported in 121 liver transplant recipients in the National Transplantation Pregnancy Registry. Children born to female liver recipients have a greater risk of prematurity and low birth weight than the general population, but no malformation patterns have been observed. Mothers are more likely to experience pregnancy‐induced hypertension, pre‐eclampsia and caesarian section, but overall mortality is not worse. Rates of acute rejection and graft loss are similar to nonpregnant liver recipients. The optimal timing of conception post‐transplant is controversial, but current recommendations suggest waiting for at least 1 year after transplantation. Choice of contraception is also debatable, although barrier methods have traditionally been preferred. Many medications used for post‐transplant immunosuppression have potential effects during pregnancy and breast‐feeding. The risks and benefits of each medication should be reviewed with patients contemplating pregnancy, and regimens should be tailored accordingly.
Ribavirin mode of action in chronic hepatitis C: from clinical use back to molecular mechanisms
Authors: Hofmann Wolf Peter , Herrmann Eva , Sarrazin Christoph , Zeuzem Stefan
Published: August 2010

Ribavirin is an old broad‐spectrum antiviral that is highly effective when used in combination with interferon‐α and also as part of triple therapies containing new inhibitors of the hepatitis C virus (HCV) non‐structural (NS)3/4 protease or HCV NS5B polymerase for the treatment of patients with chronic hepatitis C. However, the molecular mechanisms by which ribavirin enhances early and sustained virological response rates during interferon‐based antiviral HCV therapy are still unknown. Several mechanisms including (i) immunomodulatory properties, (ii) inhibition of the inosine monophosphate dehydrogenase, (iii) direct inhibition of the HCV‐encoded NS5B RNA polymerase, (iv) induction of lethal mutagenesis and (v) modulation of interferon‐stimulated gene expression are currently proposed. Here, we discuss recent advances from in vitro data and their importance for the situation in patients with chronic hepatitis C. Furthermore, theoretical aspects from mathematical modelling of ribavirin action in chronic hepatitis C are reviewed.
Standardization of intermediate goods and international trade
Authors: Lorz Oliver , Wrede Matthias
Published: August 2010

Abstract.  This paper analyzes the relationship between standardization of intermediate inputs and international trade. We employ a two‐country, general equilibrium model with differentiated manufacturing goods. Production of manufacturing goods requires specific intermediate inputs, which can be either specialized or standardized. Standardization and the pattern of trade are determined endogenously in our model. In this framework we derive the effects of trade integration, that is, a decline in trading costs for intermediate goods, on the equilibrium outcome.
Industrial targeting in free trade areas with policy independence
Authors: Grinols Earl L. , Silva Peri
Published: August 2010

Abstract. We investigate the limits of a mechanism for free trade area (FTA) formation that simultaneously satisfies internal industrialization targets. For arbitrary targets, we find necessary and sufficient conditions that guarantee that the mechanism is efficient for member countries individually, even if other members do not implement the efficient policy. When the objective is conservative – designed to protect the level of industrialization previously achieved by the target industry – member countries are guaranteed gains from the efficient policy and their FTA participation. The analysis covers cases with transportation costs and explains why minimally restrictive rules of origin support efficiency and policy independence.
Competition for exclusive customers: comparing equilibrium and welfare under one‐part and two‐part pricing
Authors: Reitzes James D. , Woroch Glenn A.
Published: August 2010

Abstract.  This paper compares one‐part and two‐part pricing in a discrete‐continuous choice model, providing more extensive welfare results than prior literature. Under two‐part pricing, firms may set fixed fees with or without ‘unit‐price commitment,’ where the lack of unit‐price commitment is consistent with ‘after‐market monopolization.’ We find that two‐part pricing with unit‐price commitment is firms’ dominant unilateral and joint pricing policy. Two‐part pricing without unit‐price commitment is the least desirable policy from a welfare standpoint. Under appropriate conditions, one‐part pricing produces the highest consumer and social welfare, but the lowest profits.
How does the marriage market clear? An empirical framework
Authors: Siow Aloysius
Published: August 2010

Abstract. The paper surveys the Choo and Siow (2006a; CS) marriage matching model and its extensions. CS derives a behavioural marriage‐matching function. The collective model of intra‐household allocations can be integrated into this framework. Spousal labour supplies respond to changing marriage market conditions. Marriage market tightness, the ratio of unmarried typeimen to unmarried typejwomen is a sufficient statistic for marriage market conditions for those types of individuals. The hypothesis that spousal labour supplies vary to equilibrate the marriage market has overidentifying restrictions. The framework extends to a dynamic marriage‐matching environment. Empirically, this paper shows how the famine caused by the great leap forward in Sichuan affected the marital behaviour of famine‐born cohorts. Marriage market tightness is shown to be a useful statistic for summarizing marriage market conditions in the United States. Marriage market conditions in the contemporary United States primarily affect spousal labour force participation rather than hours of work.
Wage distribution in Japan, 1989–2003
Authors: Kambayashi Ryo , Kawaguchi Daiji , Yokoyama Izumi
Published: August 2010

Abstract.  This study examines the recent trend of the Japanese wage distribution based on a micro‐level data set from the Basic Survey on Wage Structure (1989–2003). We perform several decomposition analyses of changes in the distribution of the hourly wage. We observe that lower returns to education and years of tenure contribute to a diminishing income disparity between groups for both sexes. A larger variance within a group contributes to the wage disparity for males, while an increased heterogeneity of workers' attributes contributes to the wage disparity for females. The Dinardo, Fortin, and Lemieux decomposition confirms the basic findings with a parametric variance decomposition.
Traffic fatalities: does income inequality create an externality?
Authors: Anbarci Nejat , Escaleras Monica , Register Charles A.
Published: August 2010

Abstract Responsible for 20 million severe injuries and/or deaths annually, few epidemics receive less attention than traffic accidents. Going beyond confirming an inverted U‐shaped relationship between mean income and fatalities, we show theoretically that income inequality can positively affect fatalities in two ways. Each operates through heterogeneity between road users, and while the direct effect can be expected to evaporate with rising income, the indirect effect may prove to be an externality in that the relationship remains regardless of the level of income. Our model is supported by evidence from 79 countries between 1970 and 2000.
Product cycles, endogenous skill acquisition, and wage inequality
Authors: Tanaka Hitoshi , Iwaisako Tatsuro
Published: August 2010

Abstract This paper presents an endogenous product cycle overlapping generations model, where the supply of skilled labour is endogenously determined. This is used to examine how production shifts through imitation by developing countries affect the domestic wage differential and supply of skilled labour in developed countries. In the model, production shifts increase the demand for researchers in developed countries and cause higher relative wages for skilled labour: this leads to more individuals acquiring the skills. As a consequence, the model helps to explain the simultaneous increase in the domestic wage gap and in the supply of skilled labour observed in developed countries.
Outsourcing, productivity, and input composition at the plant level
Authors: Paul Catherine J. Morrison , Yasar Mahmut
Published: August 2010

Abstract We evaluate the productivity and input composition effects of outsourcing (or subcontracting) for Turkish textile and apparel manufacturing plants. We analyze differences in performance indicators for plants that subcontract inputs or outputs, and find that plants that outsource internationally perform better than those that outsource domestically. We evaluate labour productivity gaps and find that more productive plants both initiate outsourcing and subsequently increase their productivity. We then estimate a flexible production function, controlling for simultaneity and selection bias, and find that higher productivity from input subcontracting involves greater skilled labour intensity but the reverse is true for output subcontracting.
Domestic rivalry and export performance: theory and evidence from international airline markets
Authors: Clougherty Joseph A. , Zhang Anming
Published: August 2010

Abstract The much studied relationship between domestic rivalry and export performance consists of those supporting a national‐champion rationale, and those supporting a rivalry rationale. While the empirical literature generally supports the positive effects of domestic rivalry, the national‐champion rationale actually rests on firmer theoretical ground. We address this inconsistency by providing a theoretical framework that illustrates three paths via which domestic rivalry translates into enhanced international exports. Furthermore, empirical tests on the world airline industry elicit the existence of one particular path – an enhanced firm performance effect – that connects domestic rivalry with improved international exports.
Fertility and the real exchange rate
Authors: Rose Andrew K. , Supaat Saktiandi , Braude Jacob
Published: August 2010

Abstract We use a quinquennial data set covering 87 countries between 1975 and 2005 to investigate empirically the relationship between fertility and the real effective exchange rate. Theoretically, a country experiencing a decline in its fertility rate can be expected to experience a real depreciation. We test and confirm this hypothesis, controlling for a number of other potential determinants. We find a statistically significant and robust link between fertility and the exchange rate. Our point‐estimate is that a decline in the fertility rate of one child per woman is associated with a depreciation of approximately 15% in the real effective exchange rate.
Union structure and firms' incentives for cooperative R&D investments
Authors: Manasakis Constantine , Petrakis Emmanuel
Published: August 2010

AbstractWe investigate the impact of alternative unionization structures on firms' incentives to invest on cost‐reducing R&D and to form Research Joint Ventures (RJVs), in the presence of R&D spillovers. We show that if firms invest non‐cooperatively and spillovers are low, R&D investments are higher under centralized rather than under decentralized wage‐setting. In contrast, investments are always higher under decentralized wage‐setting in the case of RJVs. Firms' incentives to form an RJV are stronger under centralized wage‐setting if and only if spillovers are low enough. Finally, centralized wage‐setting may hinder the formation of costly RJVs and their potential welfare benefits.
Smart fund managers? Stupid money?
Authors: Bernhardt Dan , Davies Ryan J.
Published: August 2010

Abstract We develop a model of mutual fund manager investment decisions near the end of quarters. We show that when investors reward better performing funds with higher cash flows, near quarter‐ends a mutual fund manager has an incentive to distort new investment toward stocks in which his fund holds a large existing position. The short‐term price impact of these trades increase the fund's reported returns. Higher returns are rewarded by greater subsequent fund inflows which, in turn, allow for more investment distortion the next quarter. Because the price impact of trades is short term, each subsequent quarter begins with a larger return deficit. Eventually, the deficit cannot be overcome. Thus, our model leads to the empirically observed short‐run persistence and long‐run reversal in fund performance. In doing so, our model provides a consistent explanation of many other seemingly contradictory empirical features of mutual fund performance.
Neckties in the tropics: a model of international trade and cultural diversity
Authors: Rauch James E. , Trindade Vitor
Published: August 2010

Abstract Some cultural goods are consumed socially and are characterized by the same consumption network externalities as languages. Also, producers of new cultural goods in any one country draw on the stock of ideas generated by previous cultural production in all countries. For such goods, costless trade and communication tend to lead to the dominance of one cultural style, increasing utility in the short run but reducing quality and welfare in the long run. Increasing protection while keeping communication costs low may stimulate production of cultural goods that are ‘compatible’ with the dominant style, adding little to the stock of usable ideas.
Exports, unemployment, and the welfare state
Authors: Janeba Eckhard
Published: August 2010

Abstract The paper analyzes the labour market effects of globalization when foreign market entry is costly and risky. With flexible labour markets, a fall in foreign market entry cost tends to generate more income inequality, but not necessarily so, as more firms pay foreign entry cost. By contrast, when labour markets are inflexible in the short run, globalization tends to increase unemployment. In this situation, government unemployment benefits reduce the wages that exporting firms need to pay workers as risk compensation. Thus more firms within an industry and more industries enter the foreign market, which in turn tends to increase unemployment.
Income splitting, specialization, and intra‐family distribution
Authors: Gugl Elisabeth
Published: August 2010

AbstractIncome splitting for tax purposes results in more specialization of wives, but does this in turn generate more gender inequality? In my dynamic bargaining model with a divorce threatpoint, I find that who controls the couple's labour supply plays a crucial role in establishing this link. If spouses choose their labour supply non‐cooperatively, only the husband's increase – but not her own decrease – in labour supply introduces a negative term in the wife's change in welfare. If the wife does not control her own labour supply, a decrease in her own labour supply introduces an additional negative term.
Tuition fees and equality of university enrolment
Authors: Coelli Michael B.
Published: August 2010

Abstract The relationship between tuition fee changes and the university enrolment of youth by parental income group in Canada is investigated. Comparisons between youth from Canadian provinces that increased tuition fees sharply in the 1990s and youth from provinces that instituted fee freezes were integral to identifying the relationship. Tuition fee increases coincided with reductions in the university enrolment of low‐income youth, but with significantly smaller changes in the university enrolment of other youth. The relationships between government funding of universities and cohort size and university enrolments are also analyzed.
Post‐secondary education in Canada: can ability bias explain the earnings gap between college and university graduates?
Authors: Caponi Vincenzo , Plesca Miana
Published: August 2010

Abstract Using the Canadian General Social Survey we compute returns to post‐secondary education relative to high school. Unlike previous research using Canadian data, our data set allows us to control for ability selection into higher education. We find strong evidence of positive ability selection into all levels of post‐secondary education for men and weaker positive selection for women. Since the ability selection is stronger for higher levels of education, particularly for university, the difference in returns between university and college or trades education decreases slightly after accounting for ability bias. However, a puzzling large gap persists, with university‐educated men still earning over 20% more than men with college or trades education.
Canadian city housing prices and urban market segmentation
Authors: Allen Jason , Amano Robert , Byrne David P. , Gregory Allan W.
Published: August 2010

AbstractThis paper provides a detailed empirical analysis of Canadian city housing prices. We examine the long‐run relationship between city house prices in Canada from 1985 to 2005 as well as idiosyncratic relations between city prices and city‐specific variables. The results suggest that city house prices are only weakly correlated in the long run and that there is a disconnect between house prices and interest rates. City‐specific variables such as union wage levels and the issuance of building permits tend to be positively related to existing city house prices. Surprisingly, there is mixed evidence with respect to standard measures of economic activity such as per capita GDP and interest rates.
Innis Lecture: Environmental crises: past, present, and future
Authors: Taylor M. Scott
Published: August 2010

Abstract Environmental crises are distinguished by rapid and largely unexpected changes in environmental quality that are difficult if not impossible to reverse. Examples would be major extinctions and significant degradations of an ecosystem. I argue there are three preconditions for crisis: failures in governance, an ecological system exhibiting a tipping point, and an economy/environment interaction with positive feedbacks. I develop a simple model to illustrate how a crisis may arise, and draw on our knowledge of past and present crises to highlight the mechanisms involved. I then speculate as to whether climate change is indeed a crisis in the making.