bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of endothelin‐1 in congestive gastropathy in portal hypertensive rats
Authors: Migoh Shinichiro , Hashizume Makoto , Tsugawa Kouji , Tanoue Kazuo , Sugimachi Keizo
Published: March 2003

Background
: The aim of this study was to determine the role of endothelin (ET)‐1 in portal hypertensive gastropathy (PHG) under portal hypertension, in order to investigate whether the ETA/B receptor inhibitor improves the permeability of gastric mucosal microvessels in PHG.

Methods and Results
: Portal hypertensive rats (PVL) and sham‐operated rats (CTR) were prepared and then the concentration of plasma ET‐1 was measured and the vasopressor response to ET‐1 was compared between the two groups. The plasma ET‐1 levels in PVL increased significantly compared with CTR; however, the vasopressor response to ET‐1 in PVL decreased more than in CTR. Next, the portal venous pressure was measured in both CTR and PVL pretreated with or without a nitric oxide (NO) synthase inhibitor, NG‐nitro‐
L‐arginine methyl ester (
L‐NAME), before the injection of ET‐1. The portal venous pressure of PVL after receiving ET‐1 and being pretreated with
L‐NAME significantly increased in comparison to the pressure of PVL treated with ET‐1 alone (without
L‐NAME). Moreover, Evans‐Blue was injected into each rat and the absorbancy of the gastric contents was measured. The absorbancy of Evans‐Blue in PVL increased significantly compared with CTR; however, the absorbancy in PVL + ETA/B receptor inhibitor (Ro47–0203) decreased significantly more than in PVL.

Conclusions
: This study showed that ET‐1 is a potent vasoconstrictive substance that also has a transitory vasodilative response through NO induced by ET‐1 in portal hypertension. In addition, it was found that the vascular permeability of the gastric mucosa increased in portal hypertension and that Ro47‐0203 inhibited the hyper‐permeability. Accordingly, ET‐1 may, thus, play an important role in the development of PHG through NO induced by ET‐1. Ro47‐0203 may, therefore, be a useful substance for improving PHG in portal hypertension.
Relationship between Helicobacter pylori infection and smoking and drinking habits
Authors: Ogihara Atsushi , Kikuchi Shogo , Hasegawa Ayako , Kurosawa Michiko , Miki Kazumasa , Kaneko Eizo , Mizukoshi Hiroshi
Published: March 2003

Background
: Helicobacter pylori is a major cause of various gastroduodenal diseases. Some risk factors related to H. pylori infection have been reported; however, studies on the relationship between H. pylori infection and smoking or drinking habits have given conflicting results. In the present study, these relationships were investigated by collecting sera and information from 8837 subjects.

Methods
: Serum H. pylori immunoglobulin G antibody was measured by an enzyme‐linked immunoassay. In addition to sex and age, information on smoking and drinking habits was collected by questionnaire. Age‐ and sex‐adjusted odds ratios (95% confidence interval) of smoking and alcohol consumption were calculated for H. pylori seropositivity using logistic regression models.

Results
: Current smokers had a 0.82 (0.74–0.91)‐fold greater risk of H. pylori seropositivity than those who had never smoked. Current cigarette consumption showed a dose‐dependently negative association with H. pylori seropositivity, and the association between smoking and H. pylori infection was strong in younger subjects. Current drinkers had a 0.88 (0.79–0.98)‐fold greater risk of H. pylori seropositivity than those who had never drunk alcohol. The volume of alcohol consumed showed a negative association with H. pylori seropositivity.

Conclusions
: In the current study, smoking was negatively associated with H. pylori infection. The risk of H. pylori seropositivity decreased linearly with cigarette consumption per day. Increased gastric acidity in the stomach through smoking may be a cause of the dose‐dependently negative association between H. pylori and smoking. Drinking was negatively and dose‐dependently associated with H. pylori positivity, although the effect of drinking was weaker than that of smoking.

© 2000 Blackwell Science Asia Pty Ltd
Use of a dry latex agglutination test to measure eradication of Helicobacter pylori infection
Authors: Midolo Peter D , Dakic Bilijana , Nicholson Lesley , Lambert John R , Lin Shaokai , Russell Edward G
Published: March 2003

Background and Methods
: A total antibody latex serology test was compared with enzyme immunoassay serology after treatment for Helicobacter pylori infection in 22 patients.

Results
: Nineteen patients were cured of infection, but only nine (47%) were negative by the latex test after 6 months. However a significant decline in immunoglobulin (Ig)G was seen in 90% of the cured patients.

Conclusions
: Although the latex test is suitable for initial diagnosis of H. pylori infection, it is not suitable for monitoring treatment success. A decline in IgG of more than 40% correlates well with successful eradication of H. pylori.

© 2000 Blackwell Science Asia Pty Ltd
Treatment of hepatitis C with interferon and ribavirin
Authors: Pianko Stephen , McHutchison John G
Published: March 2003

Hepatitis C is a worldwide problem that frequently results in end‐stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment‐naive patients, relapsers and non‐responders. In naive patients the combination results in improved end‐of‐treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high viral load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first‐line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient’s HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV‐RNA at 24 weeks and monitoring for the additional ribavirin side‐effects.
Natural history of hepatitis B virus infection in children
Authors: Chang Mei‐Hwei
Published: March 2003

Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant or chronic hepatitis, liver cirrhosis, and liver cancer. Approximately 90% of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2–7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by an elevation of aminotransferases. In a long‐term follow‐up study, the annual HBeAg seroconversion rate was 4–5% in children older than 3 years of age and less than 2% in children under 3 years. The annual seroconversion rate of HBsAg was very low (0.56%). Age at infection, maternal HBsAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children.
Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease
Authors: Bautista Abraham P
Published: March 2003

Chemokines are implicated in the pathogenesis of alcoholic liver disease in humans and in experimental models of alcohol intoxication. The major sources of these chemokines are Kupffer cells which represent more than 80% of tissue macrophages in the body. Kupffer cells are highly responsive to the effects of ethanol, endotoxin and human immunodeficiency virus (HIV)‐1 glycoprotein120. These agents, either independently or in combination, may exacerbate the production of chemokines. Chemokines are agents that are highly chemotactic to mononuclear cells and granulocytes. The levels of these chemokines in sera and tissue are elevated in patients with alcoholic hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in experimental models of chronic alcohol intoxication. Alcohol‐induced influx of endotoxin from the gut into the portal circulation is suggested to play an important role in the activation of Kupffer cells which leads to enhanced chemokine release. The up‐regulation of chemokines during alcohol consumption is selective. During the early phase of alcoholic liver disease, C‐X‐C or α‐ chemokines predominate. This is also associated with neutrophilic infiltration of the liver. In the later stage, up‐regulation of C‐C or β‐chemokine production and migration of mononuclear cells into the liver are observed, and this may lead to liver cirrhosis. Selective up‐regulation of chemokine synthesis and release may involve differential modulation of the transcription factors required for chemokine gene expression. Increased cytokine release following alcohol consumption may also regulate chemokine secretion in Kupffer cells via paracrine and autocrine mechanisms and vice versa. In addition, infection with HIV‐1 may further compromise the liver to more damage. During HIV‐1 infection, a pre‐existing liver disease superimposed on chronic alcohol consumption may also exacerbate HIV‐1 replication and lymphocytic infiltration in the liver, because of the ability of HIV‐1 gp120 to stimulate chemokine production by Kupffer cells and stimulate migration of inflammatory leucocytes in the liver.
Haemorrhagic cerebral sinus thrombosis associated with ulcerative colitis: A case report of successful treatment by anticoagulant therapy
Authors: Tsujikawa Tomoyuki , Urabe Mitsuyo , Bamba Hiromichi , Andoh Akira , Sasaki Masaya , Koyama Shigeki , Fujiyama Yoshihide , Bamba Tadao
Published: March 2003

A 29‐year‐old man with ulcerative colitis was admitted to our hospital because of convulsions and a headache. Before admission, oral prednisolone had been administered due to his ulcerative colitis relapse. Computed tomography revealed a low‐density area in the right frontal pole suggestive of a venous infarction. Once his headache and convulsions improved after the administration of an anti‐epileptic drug, he began to complain of right arm numbness and right hemianopsia again. An urgent magnetic resonance imaging angiograph showed extensive thrombosis in the superior sagittal sinus. We finally used the anticoagulant agents, heparin and urokinase, which eased his complaints and prevented the development of bloody stools. He was discharged with no neurological symptoms 25 days after admission. This is a rare case of sinus thrombosis complicated by ulcerative colitis, in which anticoagulant therapy was successful. Magnetic resonance imaging angiography was useful for the diagnosis and for evaluating the therapeutic effect.
Transjugular intrahepatic portosystemic shunt for intractable colonic bleeding in a patient with cirrhosis
Authors: Malki Sina , Allen Robert , Pavli Paul
Published: March 2003

A patient with portal hypertension due to alcoholic liver disease developed colonic bleeding that responded to transjugular intrahepatic portosystemic shunt (TIPS) after the failure of other measures. This case illustrates that TIPS should be considered in the treatment of colonic, as well as upper gastrointestinal, bleeding associated with portal hypertension.
Reactive oxygen and mechanisms of inflammatory liver injury
Authors: Jaeschke Hartmut
Published: March 2003

Reactive oxygen species (ROS) are important cytotoxic and signalling mediators in the pathophysiology of inflammatory liver diseases. They can be generated by resident and infiltrating phagocytes and/or intracellularly in every liver cell type after stimulation with cytokines. Although ROS are able to cause cell destruction by massive lipid peroxidation, in most cases, ROS are more likely to modulate signal transduction pathways by affecting redox‐sensitive enzymes, organelles (e.g. mitochondria) and transcription factors. Thus, ROS can directly induce and/or regulate apoptotic and necrotic cell death. In addition, ROS can have indirect effects on the pathophysiology by supporting protease activity through inactivation of antiproteases and by modulating the formation of inflammatory mediators and adhesion molecules. Many of the effects of ROS may occur simultaneously or sequentially in the pathophysiology. Although mainly described in this review as detrimental, ROS are essential for host‐defence functions of phagocytes and can modulate the formation of mediators involved in regulating sinusoidal blood flow and liver regeneration. Thus, continuous efforts are necessary to improve our understanding of the role of ROS in the pathophysiology of inflammatory liver diseases and to discover therapeutic interventions that selectively target the negative effects of reactive oxygen formation.
Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of α‐interferon and oral tegafur/uracil
Authors: Miyamoto Atsushi , Umeshita Koji , Sakon Masato , Nagano Hiroaki , Eguchi Hidetoshi , Kishimoto Shin‐Ichi , Dono Keizo , Nakamori Shoji , Gotoh Mitsukazu , Monden Morito
Published: March 2003

We report a case of advanced hepatocellular carcinoma (HCC), successfully treated by a combination therapy of α‐interferon (IFN‐α) and tegafur/uracil (UFT). A 44‐year‐old Japanese man who underwent a partial hepatectomy for HCC developed tumor recurrence in the liver 10 months after surgery. Transcatheter arterial chemoembolization (TAE) was performed twice within 7 months, but was ineffective. Later, multiple metastatic lesions appeared in the liver, lung and spine. Following the third TAE, a combination therapy of IFN‐α (10 × 10 6 units, i.m., t.i.w.) and UFT (300 mg, p.o.d.) was started. The treatment resulted in a fall in serum PIVKA‐II (protein induced by vitamin K antagonism) levels from 906 mAU to normal levels and a complete resolution of all lung nodules within 6 months. At the latest follow up 24 months after the initiation of combination treatment, the patient was working full‐time and showed no evidence of tumor relapse. A combination therapy of IFN‐α and UFT may be promising for the treatment of advanced HCC.
A multicenter, randomized, controlled trial of interferon alfacon‐1 compared with α‐2a‐interferon in Chinese patients with chronic hepatitis C virus infection
Authors: Yao Guang‐Bi , Fu Xi‐Xian , Tian Geng‐Shan , Xu Dao‐Zhen , Hao Lian‐Jie , Huangfu Yu‐Shan , Su Chun‐Xin
Published: March 2003

Abstract Background: α −Interferons are the accepted therapy for patients infected with chronic hepatitis C virus (HCV) in China. However, consensus interferon (CIFN) for HCV treatment is effective in patients with chronic hepatitis C from Western countries.

Methods: This randomized, controlled trial was conducted to determine the safety and efficacy of CIFN at two doses, and to compare it with α‐2a‐interferon (IFN‐α‐2a) in Chinese patients with chronic HCV. Interferon‐naive patients with chronic HCV infection (n = 187) were randomly chosen to receive 15 μg CIFN or 9 μg or 3 MU IFN‐α‐2a subcutaneously, three times a week for 24 weeks, followed by a 24 week observation period. Efficacy was evaluated by the normalization of serum alanine aminotransferase (ALT) and the non‐detectability disappearance of serum HCV‐RNA by using reverse‐transcription–polymerase chain reaction. The safety of CIFN was evaluated by recording the type and severity of adverse effects.

Results: The combined ALT and HCV‐RNA end‐of‐treatment and sustained responses were observed to be greater for treatment with 15 μg CIFN (59.0% and 55.7%, respectively) compared to IFN α‐2a (36.1% and 39.3%, respectively; P = 0.01 for the end‐of‐treatment, P = 0.07 for the sustained response). The combined ALT and HCV‐RNA end‐of‐treatment and sustained responses for treatment with 9 μg CIFN (both 49.2%) were higher than those for IFN‐α‐2a (not statistically significant). Data were analyzed by using a logistic‐multiple‐variate regression model, which indicated that the higher IFN dose (15 μg or 9 μg CIFN vs 3 MU IFN‐α‐2a; P < 0.01) appeared to be associated with a better sustained response. The type, frequency and severity of adverse effects were comparable across treatment groups.

Conclusions: Consensus interferon appears to be safe and effective at concentrations of 9 and 15 μg, but 15 μg CIFN may be more effective than 3 MU IFN‐α‐2a, without increased toxicity.
Status and natural course of GB virus C/hepatitis G virus infection among high‐risk groups and volunteer blood donors in Taiwan
Authors: Yu Ming‐Lung , Chuang Wan‐Long , Wang Liang‐Yen , Dai Chia‐Yen , Chiou Shyh‐Shin , Sung Ming‐Hsing , Chang Chao‐Sung , Chen Shinn‐Cherng , Wang Ching‐Shan , Chang Tai‐Tsung , Chang Wen‐Yu
Published: March 2003

Background

Hemophilia, thalassemia and uremia patients are at risk of parenterally transmitted infectious agents. The status and nature of the course of GB virus C/hepatitis G virus (GBV‐C/HGV) infection among these groups and blood donors in Taiwan was investigated.

Methods

Serum GBV‐C HGV‐RNA and antibodies to GBV‐C/HGV envelope‐2‐protein (anti‐E2) were determined in 500 blood donors and in 44 hemophilia, 37 thalassemia and 85 uremia patients. Phylogenetic analysis was performed.

Results

The prevalence of GBV‐C/HGV‐RNA and anti‐E2, respectively, was 38.6 and 27.3% in hemophilia patients, 27.0 and 27.3% in thalassemia patients, 14.1 and 10.6% in uremia patients and 3.4 and 7.2% in blood donors. The prevalence of GBV‐C HGV exposure was 59.1 and 51.4% in hemophilia and thalassemia patients, respectively, which was significantly higher than that for uremia patients (22.4%; P < 0.01) and blood donors (10.2%; P < 0.001). The anti‐E2 seroconversion rate was 66.7% in blood donors and 47.4, 36.8 and 34.6% in thalassemia, uremia (P < 0.05 compared with blood donors) and hemophilia (P < 0.01 compared with blood donors) patients, respectively. Discrepancies in the prevalence of GBV‐C HGV and hepatitis C virus infection were found among the three risk groups. Phylogenetic analysis showed that 51 of 56 GBV‐C HGV isolates clustered in group 3; the remaining five were of group 2a. Twelve of 39 viremic patients in the risk groups cleared the virus during the 4 year follow‐up period; seven developed concomitant anti‐E2 reactivity.

Conclusions

GB virus C hepatitis G virus infection is epidemic among risk groups and GBV‐C HGV group 3 is the major strain in Taiwan. In the risk groups, approximately 18% of infections resolve with concomitant anti‐E2 seroconversion within 4 years.
Wilson’s disease presenting with rapidly progressive visual loss: Another neurologic manifestation of Wilson’s disease?
Authors: Gow Paul J , Peacock Sophie E , Chapman Roger W
Published: March 2003

Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism resulting in copper‐induced tissue damage that primarily involves the liver and central nervous system. The neurologic manifestations of WD almost universally involve a derangement of basal ganglia function or psychiatric disturbance. We report the case of a 46‐year‐old man presenting with end‐stage liver disease caused by WD who had associated rapidly progressive optic neuropathy. We also discuss the possible association between the two conditions.
Auditory P300 event‐related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: A follow‐up study
Authors: Saxena Nandini , Bhatia Manvir , Joshi Yogendra K , Garg Pramod K , Tandon Rakesh K
Published: March 2003

Background and Aims: The P300 event‐related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow‐up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy.

Methods: P300 event‐related potential latencies were measured and the NCT time was recorded in 81 non‐encephalopathic cirrhotic patients (Aged 43.8 ± 11 years, 23 alcoholic and 58 non‐alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut‐off values for abnormality in the tests were developed from age‐, sex‐ and education‐matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 ± 34 msec vs 349 ± 23 msec), as well as NCT time (54.6 ± 30.6 s vs 39.5 ± 15.8 s) were significantly prolonged (P < 0.01) in patients with liver cirrhosis when compared with the non‐cirrhotic controls.

Results: The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non‐SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT.

Conclusions: The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.
A randomized controlled comparison of three quadruple therapy regimens in a population with low Helicobacter pylori eradication rates
Authors: Sotudehmanesh Rasool , Malekzadeh Reza , Fazel Ali , Massarrat Sadegh , Ziad‐Alizadeh Behrooz , Eshraghian Mohammed Reza
Published: March 2003

Background and Aim: We sought to compare the efficacy and tolerability of an omeprazole/clarithromycin/bismuth/tetracycline‐based quadruple therapy to that of a ranitidine/metronidazole/bismuth/tetracycline‐based quadruple therapy of 2 or 3 weeks duration in a population with a high prevalence of metronidazole‐resistant Helicobacter pylori and low triple therapy eradication rates.

Methods: Two hundred and twenty‐one patients who presented endoscopically proven duodenal ulcers and a positive rapid urease test were randomized to receive either: (i) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d (OCBT) for 2 weeks; (ii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT2) for 2 weeks; or (iii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT3) for 3 weeks. Patients were interviewed 2 weeks after the completion of therapy to review compliance and side‐effects. Eradication of H. pylori was assessed 8 weeks after the completion of therapy with the use of a 14C‐urea breath test.

Results: The per‐protocol eradication rate was significantly higher with OCBT (88%) than RMBT2 (73%) or RMBT3 (71%) (P < 0.05). The intent‐to‐treat eradication rate was numerically higher with OCBT (80%) than RMBT2 (68%) or RMBT3 (68%), although this difference did not reach statistical significance (P = 0.09). Per‐protocol or intent‐to‐treat eradication rates were similar with RMBT2 and RMBT3. There were significantly greater side‐effects with the RMBT2 regimen.

Conclusions: The omeprazole/clarithromycin/bismuth/tetracycline‐based quadruple therapy provides higher H. pylori eradication rates than the ranitidine/metronidazole/bismuth/tetracycline‐based quadruple therapy when administered per protocol. The prolongation of the latter regimen from 2 to 3 weeks did not increase eradication rates.
Difference in quasispecies of the hypervariable region 1 of hepatitis C virus between alcoholic and non‐alcoholic patients
Authors: Takahashi Kou , Takahashi Toru , Takahashi Sumio , Watanabe Koji , Boku Saihiro , Matsui Shigeru , Arai Futoshi , Asakura Hitoshi
Published: March 2003

Background: Habitual alcohol intake is known to aggravate the clinical outcome of hepatitis C virus (HCV)‐related chronic liver diseases and to increase the risk of hepatocellular carcinoma.

Methods: To investigate the possible mechanism of these effects by alcohol, we examined 31 cases of HCV‐related chronic liver diseases of which 17 cases were drinking just before admission and the remaining 14 cases were non‐drinkers. The studied cases included 18 patients with chronic hepatitis, six with liver cirrhosis and seven with hepatocellular carcinoma. The quasispecies of the hypervariable region 1 of the HCV genome were analyzed by using polymerase chain reaction–single strand conformation polymorphism (PCR‐SSCP). Hepatitis C virus viral load was quantitated by using multicyclic PCR after reverse transcription of the 5′ non‐coding region of the genome.

Results: The mean PCR‐SSCP band number that reflected the quasispecies complexity in hypervariable region 1 was more significantly increased in alcoholics than in non‐alcoholics (5.5 ± 1.4 vs 3.9 ± 1.1, P < 0.01). The significant increase in alcoholics remained, even if the cases were restricted to males (P < 0.01), to HCV genotype 1b (P < 0.05) or to chronic hepatitis (P < 0.05). The HCV viral load was not statistically different between alcoholic and non‐alcoholic HCV‐related chronic liver diseases (5.02 × 106± 5.16 × 106 copies/mL vs 9.00 × 107± 2.75 × 108 copies/mL, P = 0.28). Mutation events seemed to occur randomly when amino acid sequences of hypervariable region 1 were compared between four drinkers and four non‐drinkers.

Conclusions: The enhanced quasispecies complexity in hypervariable region 1 of HCV in alcoholics may be the main cause of more progressive HCV‐related chronic liver diseases, and may provide the disease the resistance against any therapeutic modalities including interferon.
Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma
Authors: Demir Kadir , Kaymakoglu Sabahattin , Besisik Fatih , Durakoglu Ziya , Ozdil Sadakat , Kaplan Yersu , Boztas Güngör , Cakaloglu Yilmaz , Okten Atilla
Published: March 2003

Abstract In this study, two cases of biopsy‐proven pancreatic tuberculosis are reported. The patients presented with fever, anorexia, fatigue, abdominal pain and weight loss. A differential diagnosis of fever of unknown origin was conducted. Computed tomography (CT) revealed a cystic mass image in the pancreatic head in one patient, and a hypodense lesion in the pancreatic head in the other. The first patient was diagnosed by a wedge biopsy specimen obtained in the exploratory laparotomy. The other patient was diagnosed by percutaneous fine‐needle aspiration biopsy. Both patients were successfully treated with quadruple antituberculous therapy for 12 months. We concluded that especially in young patients who present with a mass in the pancreas, pancreatic tuberculosis should be considered among the differential diagnoses, particularly in developing countries and immunosuppressed individuals.
Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement
Authors: Tazawa Junichi , Maeda Manabu , Sakai Yoshinori , Yamane Michio , Ohbayashi Hideo , Kakinuma Sei , Miyasaka Yuka , Nagayama Kazuyoshi , Enomoto Nobuyuki , Sato Chifumi
Published: March 2003

Aim:

The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT).

Methods:

The combined therapy was performed in 24 HCC patients with extensive PVTT. External radiation targeted for PVTT (50 Gy in 2 Gy fractions) was performed in combination with repetitive TACE for intralobar lesions using 30–60 mg epirubicin every 3 months, and associations of the following variables with the survival rate were evaluated: gender, age, viral etiology, Child’s class, performance status, extrahepatic metastasis, size and number of HCC, and location of PVTT.

Results:

The local response confined to PVTT was complete response (CR) in four patients, partial response (PR) in eight patients, no change (NC) in eight patients, and progressive disease (PD) in four patients. By using the stepwise Cox’s regression analysis, only Child’s class was associated with the survival rate. The survival rates after 1 and 2 years were 73 and 21% in Child’s A, 10 and 0% in Child B or C, and 61 and 21% in patients in whom the local response was CR or PR, and 19 and 9% in those in whom the local response was NC or PD, respectively. By using the multiple logistic regression analysis, Child’s class was the only factor associated with the local response (P = 0.006).

Conclusions:

The combined therapy is feasible and may be useful to reverse PVTT in patients with good hepatic function reserve.
A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism
Authors: Miyoshi Masatsugu , Mizuno Motowo , Ishiki Kuniharu , Nagahara Yasuhiro , Maga Toshirou , Torigoe Tomomi , Nasu Junichirou , Okada Hiroyuki , Yokota Kenji , Oguma Keiji , Tsuji Takao
Published: March 2003

Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so‐called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2‐week dual therapy in relation to CYP2C19 polymorphism.

Methods: One hundred and ninety‐nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]‐urea breath test at 1–2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction–restriction fragment length polymorphism.

Results: Intention‐to‐treat‐based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56–75) and 62.4% (95% CI, 52–71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure.

Conclusion Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.
Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography by the 4‐h post procedure amylase level
Authors: Thomas Peter R , Sengupta Shomik
Published: March 2003

Background: Pancreatitis is the commonest and most significant complication of endoscopic retrograde cholangiopancreatography (ERCP). Early detection of post‐ERCP pancreatitis would allow the safe discharge of day‐case patients and targeted use of preventive therapies. Clinical diagnosis is inaccurate, and the aim of this study was to evaluate the 4‐h post‐ERCP hyperamylasemia as a predictor of pancreatitis.

Methods: Two hundred and sixty‐three consecutive ERCPs performed at one center were prospectively analyzed, examining patient and procedure characteristics, as well as the amylase level as predictors of pancreatitis.

Results: Younger age (< 25 years), Sphincter of Oddi dysfunction, pancreatogram and failed cannulation were risk factors for pancreatitis; sphincterotomy conferred an increased risk, which was not statistically significant. Hyperamylasemia was a highly sensitive and moderately specific predictor of pancreatitis. A cut‐off level of 1.5‐fold higher than normal was useful for the exclusion of pancreatitis, while a cut‐off level of threefold higher than normal was more specific, so as to target potential preventive therapies.

Conclusions: The 4‐h post‐ERCP amylase level is a useful test to base management decisions on. It needs to be interpreted in conjunction with clinical assessment as well as identifiable risk factors related to the patient or the procedure.
Antibiotic susceptibility of Helicobacter pylori in the Chinese population
Authors: Yakoob Javed , Fan Xuegong , Hu Guoling , Liu Li , Zhang Zheng
Published: March 2003

Aim: To assess antibiotic susceptibility of Helicobacter pylori (H. pylori) strains to metronidazole, clarithromycin and tetracycline in the Chinese population, and to test the stability of antibiotic resistance in H. pylori 1 year after storage at −80°C.

Methods: Fifty H. pylori strains isolated from patients with peptic ulcer disease were recovered from storage at −80°C. Susceptibility of these strains to metronidazole, clarithromycin and tetracycline was determined by using validated disk diffusion tests, which was repeated 1 year after storage at −80°C. The DNA profiles of each strain were determined by using the polymerase chain reaction‐based–random amplified polymorphic DNA fingerprinting technique (PCR‐RAPD). This was repeated if any change in antibiotic susceptibility pattern was noticed.

Results: The resistance rate was 50% to metronidazole and 8% to clarithromycin. None of the strains was resistant to tetracycline. A dual resistance to metronidazole and clarithromycin was demonstrated in three H. pylori strains. The antibiotic susceptibility test reproduced itself in 92% (36 of 39) of the strains 1 year later; the three strains with dual resistance exhibited susceptibility to both antibiotics. Variation in antibiotic susceptibility pattern in the three H. pylori strains was associated with change in the RAPD fingerprint.

Conclusion: The prevalence of resistance in H. pylori is high to metronidazole but low to clarithromycin in the Chinese population. The disk diffusion test appears to be a simple and reliable test, while antibiotic resistance in some H. pylori strains may disappear after long‐term storage at −80°C.
Extensive mesenteric vein and portal vein thrombosis successfully treated by thrombolysis and anticoagulation
Authors: Tateishi Ayako , Mitsui Hiroshi , Oki Toshihiko , Morishita Jo , Maekawa Hisato , Yahagi Naohisa , Maruyama Toshiyuki , Ichinose Masao , Ohnishi Shin , Shiratori Yasushi , Minami Manabu , Koutetsu Shinichiro , Hori Nobukazu , Watanabe Toshiaki , Nagawa Hirokazu , Omata Masao
Published: March 2003

Abstract Mesenteric vein thrombosis is generally difficult to diagnose and can be fatal. A case of extensive thrombosis of the mesenteric and portal veins was diagnosed early and successfully treated in a 26‐year‐old man with Down syndrome who was admitted to hospital because of abdominal pain, severe nausea and high fever. Ultrasonography revealed moderate ascites, and there was minimal flow in the portal vein (PV) on the Doppler examination. Computed tomography (CT) showed remarkable thickening of the walls of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, combined thrombolysis and anticoagulation therapy without surgical treatment was chosen. Urokinase was administered intravenously and later through a catheter in the superior mesenteric artery. Heparin and antibiotics were given concomitantly. The patient's symptoms and clinical data improved gradually. After 10 days, CT revealed that collateral veins had developed and the thrombi in the distal portions of the mesenteric veins had dissolved, although the main trunk of the PV had not recanalized. The only risk factor of thrombosis that was detected was decreased protein S activity.
Safety of an ofloxacin‐based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: A preliminary report
Authors: Saigal Sanjiv , Agarwal Shri Ram , Nandeesh Hosur Prabhuswamy , Sarin Shiv K
Published: March 2003

Background and Aims: Hepatotoxicity is a major side‐effect of antitubercular drugs (ATD). As these drugs are metabolized in the liver, there is a theoretical risk of increased hepatotoxicity in patients with underlying chronic liver disease (CLD). Ofloxacin has antitubercular activity and has exclusive renal clearance. The aim was to study the efficacy and safety of an ofloxacin‐based antitubercular regimen for treating tuberculosis in patients with underlying CLD.

Methods: Thirty‐one cases were randomly assigned to two drug regimens using WHO dosage schedules: (i) regimen A (n = 15): isoniazid, rifampicin and ethambutol for 2 months, followed by isoniazid and rifampicin for a further 7 months; and (ii) regimen B (n = 16): isoniazid, pyrazinamide, ethambutol and ofloxacin for 2 months, followed by isoniazid, ethambutol and ofloxacin for a further 10 months. Hepatotoxicity was diagnosed if alanine aminotransferase/aspartate aminotransferase increased > fivefold from the baseline or to > 400 IU/L, or if bilirubin increased by > 2.5 mg/dL from the baseline.

Results: The response to ATD was achieved in all the patients who completed the therapy. Four (26.6%) patients on regimen A developed hepatotoxicity as compared to none on regimen B (P = 0.043). None of these patients could be restarted on ATD using the same regimen A because of the persistently deranged liver functions.

Conclusions: In patients with tuberculosis who have underlying CLD: (i) an ofloxacin‐based antitubercular regimen without rifampicin is as effective as a rifampicin‐based regimen; and (ii) a combination of isoniazid with rifampicin is more hepatotoxic than a combination with ofloxacin and pyrazinamide.
Upright versus supine reflux in gastroesophageal reflux disease
Authors: Ouatu‐Lascar Rodica , Lin Otto S , Fitzgerald Rebecca C , Triadafilopoulos George
Published: March 2003

Background:

Postural measures are early recommendations in the management of heartburn, and are aimed at preventing acid reflux through an incompetent lower esophageal sphincter (LES). However, LES incompetence is found in only a minority of patients, and transient LES relaxations, primarily in the upright position, are currently recognized as the main pathophysiological abnormality in gastroesophageal reflux disease (GERD). We investigated the importance of supine acid reflux in patients with GERD.

Methods:

Upon review of their clinical, manometric, pH monitoring and endoscopic characteristics, 85 patients with reflux symptoms were classified into three groups: Group A (n = 22), consisting of symptomatic patients without esophagitis or pathological reflux; group B (n = 38), symptomatic patients with reflux but no endoscopic esophagitis; and group C (n = 25), symptomatic patients with both ulcerative or complicated esophagitis and pathological reflux.

Results:

All groups were similar in age distribution. Groups B and C had a higher prevalence of hiatal hernia and reflux symptoms. Manometry revealed similar LES pressures in groups A and B, but lower LES pressure in group C (P < 0.005). In groups A and B, supine reflux, in terms of percentage of time with pH < 4, was less pronounced than upright reflux (P < 0.0001). In contrast, group C supine reflux was as pronounced as the upright reflux.

Conclusions:

The majority of patients reflux in the upright position. Only patients with complicated esophagitis have significant bipositional acid reflux. These findings suggest that unless the patient has severe reflux disease, postural measures may not be indicated.
Interleukin‐1β induces cyclo‐oxygenase‐2 expression in gastric cancer cells by the p38 and p44/42 mitogen‐activated protein kinase signaling pathways
Authors: Fan Xiao Ming , Wong Benjamin Chun Yu , Lin Marie Chia Mi , Cho Chi Hin , Wang Wei Ping , Kung Hsiang Fu , Lam Shiu Kum
Published: March 2003

Background and Aims: Cyclo‐oxygenase‐2 (COX‐2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX‐2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)‐1β on COX‐2 expression in the human gastric cancer cell, and explored the signaling pathways involved.

Methods: Gastric cancer cell line AGS was treated with IL‐1β or the inhibitors of mitogen‐activated protein‐Erk kinase (MEK) and p38 mitogen‐activated protein (MAP) kinase prior to the addition of IL‐1β. The COX‐2 mRNA or protein levels were measured by using RT‐PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho‐specific antibodies.

Results: Interleukin‐1β treatment dose‐ and time‐dependently increased COX‐2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL‐1β had no effect on the level of the constitutively expressed COX‐1. In parallel to the increase of COX‐2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL‐1β treatment. To demonstrate the cause–effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL‐1β‐mediated increases in COX‐2 mRNA and protein levels, and the PGE2 production.

Conclusions: Our results demonstrated that in human gastric cancer cells, IL‐1β upregulates the COX‐2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.
N‐Acetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma
Authors: Yanagi Masahiko , Aoyagi Yutaka , Suda Takeshi , Mita Yuhsaku , Asakura Hitoshi
Published: March 2003

Background:

A close relationship has been shown to exist between the metastatic potential and β1–6 branched oligosaccharides in human and rodent cells. N‐acetylglucosaminyltransferase V (GnT‐V) catalyzes this process. Although this phenomenon has been reported, little is known about the clinical usefulness of the determination of GnT‐V in the evaluations of tumor invasiveness in hepatocellular carcinoma (HCC). In this study, we measured the GnT‐V activity in serum of patients with HCC, together with its activity and gene expression in HCC tissues, and elucidated the clinical usefulness of the GnT‐V level in evaluating tumor invasiveness.

Methods:

Seventy‐three serum samples from 38 patients with HCC, 11 with chronic hepatitis, eight with hepatic cirrhosis and 16 healthy controls were used. Twenty‐one liver tissues were obtained by surgical resection from 17 patients with HCC, three with colorectal cancers and one with gallbladder cancer metastatic to the liver. The GnT‐V activity was determined by using high performance liquid chromatography. The GnT‐V mRNA was quantified by using competitive RT‐PCR.

Results:

There were statistically significant correlations between GnT‐V activity in sera of HCC, and GnT‐V activity and GnT‐V mRNA expression in tumor tissue. The mean GnT‐V activity in the sera of patients with HCC increased in accordance with the degree of tumor invasion. The HCC group with intrahepatic and extrahepatic metastases showed the highest serum GnT‐V‐value.

Conclusions:

The present study demonstrated that there was a close association between tumor invasiveness and GnT‐V activity in sera, and that the measurement of GnT‐V may improve prognostic estimates and therapeutic outcomes for patients with HCC.
Reinfection rate following effective therapy against Helicobacter pylori infection in Japan
Authors: ADACHI MASAYASU , MIZUNO MOTOWO , YOKOTA KENJI , MIYOSHI MASATSUGU , NAGAHARA YASUHIRO , MAGA TOSHIROU , ISHIKI KUNIHARU , INABA TOMOKI , OKADA HIROYUKI , OGUMA KEIJI , TSUJI TAKAO
Published: March 2003

Background and Aim: In developed countries, reinfection of Helicobacter pylori (H. pylori) after
eradication of the bacterium is unusual, while the reinfection rate in developing
countries is variable. In this study, we determined the reinfection rate after successful
H. pylori eradication in Japan, a country with a high prevalence of H.
pylori infection.

Methods: After successful eradication, 377 patients were followed up by endoscopy and urea breath test annually. In reinfected patients, H. pylori strains isolated initially and after reinfection were compared by using random amplification of polymorphic DNA fingerprinting.

Results: H. pylori became positive in four of 337 patients (1.2%) 1 year after eradication and in two of 133 patients (1.5%) 2 years after eradication. One patient experienced an ulcer relapse 2 years after eradication therapy. Random amplification of polymorphic DNA fingerprinting of the isolated strains from four of the six patients showed two had identical strains (at 1 year) while the other two had different strains (one at 1 year and one at 2 years). When infection in the two patients reinfected with identical strains is considered a recrudescence, the true reinfection rate is < 0.8% per patient year.

Conclusions: The reinfection rate after eradication of H. pylori is low in Japan despite
the country’s high prevalence of H. pylori infection.