bluuebunny/crossref_metadata_2025 huggingface dataset:
Newly developing hiatus hernia: A survey in patients undergoing upper gastrointestinal endoscopy
Authors: LOFFELD RJLF , VAN DER PUTTEN ABMM
Published: March 2003

Abstract 
Background:
Data on the incidence of hiatus hernia are lacking. A cross‐sectional study was performed in a large population of consecutive patients undergoing endoscopy in order to assess the yearly incidence of hiatus hernia in this population.

Methods:
Consecutive patients undergoing upper gastrointestinal endoscopy in whom no macroscopic abnormalities were seen and who, in addition, underwent a second endoscopy were included in the study. The presence of newly developed hiatus hernia was noted, as well as the time elapsed between both endoscopies.

Results:
Over a period of 8 years, 12 122 endoscopies were performed in 9580 patients. Ninety patients developed a hiatus hernia; this was not the case in a control group of 353 patients. Patients who developed a hiatus hernia were significantly older than those who did not (P < 0.001). The number of women who developed hiatus hernia was higher than the number of men who developed hiatus hernia (P < 0.0001). The total time between both endoscopies in 443 patients was 897 patient years. Ninety patients (20.3%) developed a hiatus hernia. If these data are extrapolated to a yearly occurrence, then 35 of 176 patients will develop a hiatus hernia. It takes an average of 1.9 years for a hiatus hernia to develop.

Conclusions:
In the present study, it was calculated that 19.9% of the studied population would develop a hiatus hernia per year. Patients who developed a hiatus hernia were significantly older than patients who did not. The present study also shows that a hiatus hernia actually develops later in life.

© 2002 Blackwell Publishing Asia Pty Ltd
Management of refractory ascites and hepatorenal syndrome
Authors: Chutaputti Anuchit
Published: March 2003

Abstract  Refractory ascites and hepatorenal syndrome (HRS) are the late complications of the terminal stages of cirrhosis. The definitions of refractory ascites and HRS proposed by the International Ascites Club in 1996 are now widely accepted, and are useful in diagnosis, treatment and research in this field. In both conditions, the only treatment of proven value for improved survival is liver transplantation. However, because of better understanding about the pathophysiology of HRS, including the roles of portal hypertension, ascites formation and hemodynamic derangements, treatments such as transjugular intrahepatic portasystemic shunt (TIPS) and new pharmacological agents may be considered to alleviate the problem prior to transplantation. Symptomatic treatment of refractory ascites includes TIPS and repeated large volume paracentesis. Transjugular intrahepatic portasystemic shunt can improve survival while waiting for liver transplantation. Practical management guidelines for TIPS and large volume paracentesis, including the prevention and management of further complications, are considered in this review.

© 2002 Blackwell Publishing Asia Pty Ltd
Management issues in chronic viral hepatitis: Hepatitis C
Authors: Sievert William
Published: March 2003

Abstract  The natural history of chronic hepatitis C virus (HCV) infection and intervention with antiviral therapy are closely linked issues that cause the greatest controversy and concern for the person infected with HCV, as well as for the clinician involved in the assessment and treatment of people with chronic HCV infection. The outstanding challenge of natural history is to identify the person who is likely to develop serious liver disease, and to make that determination early in the course of chronic HCV infection when treatment is likely to be of the greatest benefit. Significant advances in the therapy of chronic HCV infection have occurred over the past decade. A sustained virological response (SVR), defined as undetectable HCV‐RNA in blood 6 months after completing antiviral treatment, is the best indicator of a beneficial treatment effect. Relapse, breakthrough or non‐response should all be regarded as unsuccessful outcomes of therapy. Interferons are still the mainstay of antiviral therapy for chronic HCV infection. The combination of interferon and ribavirin has improved SVR by decreasing the relapse rate. Treatment responses vary according to host factors such as age and gender, fibrotic severity and to viral factors like genotype and viral load. Patients with genotype 1 HCV and a high viral load require 12 months of treatment to achieve a SVR in approximately 30%, compared to those with genotypes 2 or 3 who achieve a SVR in approximately 65% after 6 months. Patients who relapse after an end‐of‐treatment response to interferon monotherapy have a good chance of responding to combination interferon and ribavirin given for 6 months, but a longer treatment course should be considered in less optimal cases. At present, the treatment of those with non‐response is less clear, but there is interest in more intense forms of interferon therapy, such as induction dosing or pegylated interferon in combination with ribavirin. Clinicians need to be aware of the common side‐effects of interferon and ribavirin so that appropriate counseling and testing can be instituted before and during therapy. The combination of pegylated interferon and ribavirin will be the new standard of therapy for hepatitis C and pegylated interferon monotherapy provides quite acceptable efficacy for those patients intolerant of ribavirin. Current data strongly support the concept that SVR in HCV infection (or treatment‐induced latency) provides a cure in terms of its beneficial effects on quality of life and sustained amelioration of liver injury.

© 2002 Blackwell Publishing Asia Pty Ltd
Is severe liver disease a common outcome for people with chronic hepatitisC?
Authors: Dore Gregory J , Freeman Anthony J , Law Matthew , Kaldor JohnM
Published: March 2003

Abstract  For people with chronic hepatitis C, an assessment of their riskof progression to advanced liver disease is a major priority. Earlystudies of the natural history of chronic hepatitis C suggestedthat development of cirrhosis was a relatively common outcome, evenin the first 20 years of infection. These studies wereeither cross‐sectional liver clinic series of people referred forassessment to specialist clinics, or longitudinal cohorts of peoplewith post‐transfusion hepatitis. More recent studies (particularlylong­itudinal community‐based cohorts) indicate that liverdisease progression is generally slow, and that a minority of peoplewith chronic hepatitis C will develop advanced liver disease. Basedon an extensive review of studies reporting on chronic hepatitisC natural history, we have developed a Markov model of liver diseaseprogression. This model estimates that the risk of progression tocirrhosis is 7% and 20% after 20 and 40 yearsof infection, respectively. Corresponding estimates for hepatitisC‐related mortality are 1% and 4%. However, liverdisease progression is highly variable, and certain subgroups ofpeople with chronic hepatitis C are at increased risk of advancedliver disease. Those groups include people with a heavy alcoholintake, those who have coinfection with HIV or HBV, and those whohave already progressed to moderate to severe hepatic fibrosis.

© 2002 Blackwell Publishing Asia Pty Ltd
Hepatic Kupffer cell phagocytotic function in rats with erythrocytic‐stage malaria
Authors: NOBES MICHAEL S , GHABRIAL HANY , SIMMS KATRINA M , SMALLWOOD RICHARD A , MORGAN DENIS J , SEWELL RICHARD B
Published: March 2003

Abstract
Background:
In the erythrocytic phase of malaria, Kupffer cells show marked hypertrophy and hyperplasia and are filled with malarial pigment. However, phagocytic function in this state has not been well characterized. The aim of the present study was to use mouse Plasmodium berghei to infect rats with malaria and study the phagocytic function and morphology of Kupffer cells.

Methods:
We used a recirculating isolated perfused rat liver (IPRL) to quantitate Kupffer cell phagocytic clearance of radiolabeled albumin–latex over 120 min in high parasitemia (53 ± 6%; n = 7) and low parasitemia (∼1%; n = 4) malaria‐infected rats and littermate controls (n = 7 and n = 4, respectively). In a further group of high‐parasitemic rats, perfusion was ceased after 7 min and liver radioactivity also measured. Electron microscopy was performed after perfusions.

Results:
In high‐parasitemia malaria rats, clearance of radiolabeled latex from IPRL perfusate over 120 min was significantly (P < 0.01) faster than in controls, with a lower area under the curve (0.19 ± 0.02 vs 0.43 ± 0.07 /mL per min, respectively) and shorter half‐life (t1/2k; 2.4 ± 0.6 vs 10.0 ± 2.3 min, respectively). Low‐parasitemia rats were identical to controls. After 7 min perfusion in high‐parasitemic rats (n = 4), total radioactivity in liver homogenates was higher than in controls (n = 4; 33.1 ± 6.2 vs 18.4 ± 1.9% of injected radiolabel; P < 0.05). Electron microscopy showed latex in Kupffer cells, more abundantly seen in high‐parasitemic animals.

Conclusions:
Total Kupffer cell phagocytic activity of the liver is markedly increased in rats with a high parasitemic load of malarial P. berghei infection. This is presumed to reflect an upregulation of scavenger activity phagocytosing erythrocytes and their breakdown products.

© 2002 Blackwell Publishing Asia Pty Ltd
An early cancer of the gastric cardia arising from carditis after long‐term gastroesophageal reflux disease in the absence of Helicobacter pylori infection
Authors: Yagi Kazuyoshi , Nakamura Atsuo , Sekine Atsuo , Oyamatsu Manabu , Tamiya Yoichi , Watanabe Hedenobu
Published: March 2003

Abstract  We describe an early gastric cardiac cancer in a patient who had suffered long‐term gastroesophageal reflux disease (GERD) but showed no evidence of infection with Helicobacter pylori. Proximal gastrectomy and partial resection of the lower esophagus was performed. Histological examination revealed the lesion to be a gastric cardiac adenocarcinoma, which had partially invaded the submucosal layer. Intestinal metaplasia was also found in some areas. Inflammation, however, appeared to be limited to the gastric cardia. This cancer may have arisen via a sequence of carditis and cardiac intestinal metaplasia, due primarily to the GERD and not to H. pylori infection.

© 2002 Blackwell Publishing Asia Pty Ltd
Issues of malnutrition and bone disease in patients with cirrhosis
Authors: Donaghy Anthony
Published: March 2003

Abstract  Malnutrition is a frequent complication of cirrhosis, and many studies have demonstrated the adverse influence of malnutrition on clinical outcomes in patients with cirrhosis. The coexisting complications of fluid overload and ascites may mask the severity of malnutrition, particularly in the early stages of its development. During periods of decompensation, protein and energy requirements are higher, and many patients have inadequate nutritional intake at these times. Further, protein supplementation should not be restricted ad hoc in cirrhotic patients, as for the vast majority of patients dietary protein does not precipitate hepatic encephalopathy. The impairment of hepatic glycogen storage in cirrhotic patients effects a state of accelerated starvation with catabolism of fat and protein to provide substrates for gluconeogenesis. Recent studies have demonstrated the efficacy of nocturnal nutritional supplements in improving nitrogen balance. Resistance to the actions of the anabolic growth factors insulin and growth hormone (GH) is common in cirrhosis, and recent studies have shown that GH resistance, in particular, may be overcome with exogenous GH therapy. Hypermetabolism may be observed in up to one‐third of cirrhotic patients. The recent exciting observation that beta‐blocker therapy can decrease energy expenditure and catecholamine levels in these patients indicates the need for further intervention studies of beta‐blockers as metabolic therapy in cirrhosis.

© 2002 Blackwell Publishing Asia Pty Ltd
What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?
Authors: Lee Cheng‐Chi , Wu Chun‐Ying , Chen And Gran‐Hum
Published: March 2003

Background: Hepatolithiasis is a well‐known etiology of cholangiocarcinoma. However, whether or not hepatolithiasis influences the presentation of cholangiocarcinoma is not very clear. To help clarify this, we conducted the present study to investigate the clinicopathological characteristics of cholangiocarcinoma with hepatolithiasis. As well, we made a comparison between the presence and absence of hepatolithiasis in patients with cholangiocarcinoma to determine the impact of hepatolithiasis.

Methods: Among 140 patients with histologically proven cholangiocarcinoma at the Taichung Veteran General Hospital between October 1982 and December 2000, 38 were found to have concomitant hepatolithiasis. Patients were evaluated on the basis of age, gender, presenting symptom, laboratory data, preoperative liver function (indocyanine green test), tumor markers, histological differentiation, lymph node involvement, and organ metastasis. Data were statistically analyzed using the chi‐squared test and Student's t‐test. Analysis of survival was performed using the Kaplan–Meier method, and univariate analysis and multivariate analyses for survival were performed by Cox proportional hazard model.

Results: The cholangiocarcinoma with hepatolithiasis group (CC + HL) was found to be predominantly female, with more common presentation of fever and less presentation of jaundice (P < 0.05). In addition, patients with cholangiocarcinoma without hepatolithiasis (CC − HL group) had higher serum bilirubin levels and more advanced histological differentiation (P < 0.05). As well, the percentage of resectability of the CC + HL group was higher than that of the CC − HL group, although it was not statistically significant. Univariate and multivariate analyses for overall survival showed that those patients with an age older than 65 years, hypoalbuminemia, poor histological differentiation, and a presence of hepatolithiasis were prone to a graver prognosis, albeit none of them were statistically significant. Resectability was the only independent predictor of a favorable prognosis with significant difference.

Conclusions: The clinicopathological features of cholangiocarcinoma with concomitant hepatolithiasis showed few differences from that without hepatolithiasis. Resectability was the only predictor that favored a good prognosis.

© 2002 Blackwell Publishing Asia Pty Ltd
Clinical characteristics and natural history of patients with low‐grade reflux esophagitis
Authors: Manabe Noriaki , Yoshihara Masaharu , Sasaki Atsunori , Tanaka Shinji , Haruma Ken , Chayama Kazuaki
Published: March 2003

Background and Aim: Although the incidence of reflux esophagitis (RE) has recently increased in Japan, the majority of these cases are mild (Los Angeles classification grades A and B). In order to consider therapy for these patients, it is important to understand the natural history of mild RE. There is little information concerning the natural course of RE, particularly low‐grade disease. The goal of this study is to elucidate the natural course of patients with mild RE and to identify specific prognostic indicators associated with a poor outcome.

Methods: One hundred and five patients with mild RE were followed, without medical treatment, by endoscopy in addition to a questionnaire regarding symptomatology, for a mean of 5.5 years (range, 2.0–8.8 years) after initial diagnosis. Factors associated with the development of severe esophagitis were analyzed.

Results: Endoscopically, 11 patients (10.5%) progressed to more severe forms of RE (recurrent progressive (RP) group), 60.0% of patients relapsed without disease progression (recurrent non‐progression group), and the remaining 29.5% of patients had no further episodes of RE (isolated episode group). Risk factors for progressive disease were increased age, female sex, the presence of symptoms at initial diagnosis by endoscopy, presence of a hiatal hernia, absence of atrophic gastritis, and absence of Helicobacter pylori infection. Despite having all risk factors, there were six patients who did not progress to more severe forms of RE. The primary esophageal peristaltic amplitude in these patients was significantly higher than in the RP group.

Conclusions: Among patients with mild RE, only 10.5% progressed to more severe forms of RE. The patients with risk factors are candidates for aggressive therapy in order to prevent the progression of the RE disease process.

© 2002 Blackwell Publishing Asia Pty Ltd
Detection of Chlamydia pneumoniae by polymerase chain reaction–enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls
Authors: Chen Wangxue , Li Dong , Wilson Ian , Chadwick Vinton S
Published: March 2003

Background and Aim
:

It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non‐IBD controls.

Methods
:

The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non‐IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction‐enzyme immunoassay (PCR‐EIA).

Results
:

The C. pneumoniae‐specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non‐IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non‐IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples.

Conclusion
:
The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non‐IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non‐IBD controls does not support a direct role for this organism in the pathogenesis of IBD.

© 2002 Blackwell Publishing Asia Pty Ltd
Inhibitory effects of the new anti‐inflammatory agent, IS‐741, on spontaneous colitis in HLA‐B27/β2‐microglobulin transgenic rats
Authors: Makino Jin , Andoh Akira , Hata Kazunori , Yotsuya Shuichi , Shikama Hiroshi , Imamura Masashi , Fujiyama Yoshihide , Bamba Tadao
Published: March 2003

Abstract Background: A novel anti‐inflammatory drug, IS‐741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)‐B27 and human β2‐microglobulin (HLA‐B27 rats) spontaneously develop chronic colitis, which resembles human inflammatory bowel disease. In the present study, the authors examined the efficacy of IS‐741 against spontaneous colitis in HLA‐B27 rats.

Methods: The HLA‐B 27 rats were divided in two groups after the development of colitis. IS‐741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days.

Results: The HLA‐B27 rats treated with IS‐741 remained healthy; the wet weight of the colon was significantly lower in the IS‐741‐treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA‐B27 rats, but these changes were attenuated in the IS‐741‐treated group. The mucosal damage score was also significantly reduced by treatment with IS‐741. IS‐741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine‐induced neutrophil chemoattractant‐1 levels. IS‐741 also reduced CD3‐positive T‐cell infiltration.

Conclusion: IS‐741 suppressed the spontaneous colitis that developed in HLA‐B27 rats. Some of the actions of IS‐741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS‐741 may be a useful new therapeutic agent for inflammatory bowel disease.
Three‐dimensional examination of hepatic stellate cells in rat liver and response to endothelin‐1 using confocal laser scanning microscopy
Authors: Oikawa Hiroki , Masuda Tomoyuki , Kawaguchi Junzo , Sato Ryo
Published: March 2003

Abstract Background and Aim: Hepatic stellate cells (HSC) are located in the space of Disse and are considered to participate in the regulation of sinusoidal flow. The contractility of quiescent HSC in normal liver has remained controversial, unlike activated HSC in injured liver. The aim of the present study was to examine the morphological changes in quiescent HSC in response to endothelin‐1 (ET‐1) perfusion.

Methods: Sections (50 µm thick) obtained from 15 normal rat livers with or without ET‐1 perfusion (1 or 400 nmol/L) were stained immunohistochemically with antiglial fibrillary acidic protein (GFAP) antibody and then examined using confocal laser scanning microscopy. For examination of HSC, hepatic lobules were divided into three anatomic regions from the portal areas to the central veins. The length of HSC cytoplasmic processes and area of the sinusoids relative to the section area, excluding portal tracts and central veins, were measured.

Results: The GFAP‐positive HSC were distributed relatively evenly in the hepatic lobules and those in region 2 (the area between periportal and pericentral areas) tended to have longer cytoplasmic processes. Perfusion of 1 or 400 nmol/L ET‐1 for 25 min resulted in swelling of the cell bodies of GFAP‐positive HSC and condensation of the intermediate filaments compared with those perfused with buffer only. Although narrowing of the sinusoidal lumen was observed in each region after perfusion with 400 nmol/L ET‐1, there was no apparent shortening of the cytoplasmic processes of HSC. These findings were also confirmed quantitatively.

Conclusion: In the normal rat liver, quiescent HSC are not involved in the regulation of sinusoidal blood flow in response to ET‐1.
Downregulation of the proteasome subunits, transporter, and antigen presentation in hepatocellular carcinoma, and their restoration by interferon‐γ
Authors: Matsui Masanori , Machida Sanae , Itani‐Yohda Teru , Akatsuka Toshitaka
Published: March 2003

Abstract
Background
: In our previous study, expressions of human histocompatibility leukocyte antigens class I molecules (HLA‐I) and the transporter associated with antigen processing (TAP) 1/2 genes were investigated in seven hepatocellular carcinoma (HCC) cell lines. Two cell lines, Hep‐3B and HuH‐7, showed a reduced level of TAP, which might cause the low surface expression of HLA‐I. In order to understand the downregulation mechanism of antigen presentation in tumors, the two cell lines were further investigated.

Methods
: Expressions of HLA‐I and antigen presentation‐related genes were analyzed by flow cytometry and polymerase chain reaction, respectively. Antigen presentation was tested in 51Cr‐release assays.

Results
: Flow cytometric analyses revealed low surface expression of HLA‐I on Hep‐3B and HuH‐7 cells. Introduction of HLA‐A2 gene did not result in a high surface expression of HLA‐A2. This suggested the downregulation of HLA‐I expression might be related to defects in the antigen presentation machinery. We then examined expression levels of various antigen presentation‐related genes. Hep‐3B and HuH‐7 demonstrated low expression of the low‐molecular‐weight protein (LMP) 2, LMP7, TAP1, and HLA‐I heavy‐chain transcripts. The downregulation of these genes was dissolved by treatment with γ‐interferon. Furthermore, allo‐specific cytotoxic T lymphocyte (CTL) lines failed to recognize Hep‐3B and HuH‐7 cells, while they killed IFN‐γ‐treated Hep‐3B and HuH‐7 cells.

Conclusions
: Our results suggest that defects in the antigen presentation‐related molecules might cause downregulation of HLA‐I expression, antigen presentation, and subsequently, escape from specific CTL killing. The downregulation could be restored by IFN‐γ treatment, suggesting the potential use of IFN‐γ for therapeutic purposes.
Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning†
Authors: Shinoda Masahiro , Shimazu Motohide , Wakabayashi Go , Tanabe Minoru , Hoshino Ken , Kitajima Masaki
Published: March 2003

Background:
Brief periods of hepatic ischemia produce immediate tolerance for subsequent prolonged ischemia. Although the beneficial effect of this ischemic preconditioning is recognized, the mechanism itself remains poorly understood.

Methods:
Male Wistar rats were divided into two groups: a control group that was subjected to 30 min of ischemia + following reperfusion, and an ischemic preconditioning group that was subjected to 5 min of ischemia + 5 min of reperfusion + 30 min of ischemia + following reperfusion. By using this model, hepatic damage, microcirculatory disturbances, and tumor necrosis factor‐α protein production and mRNA expression were analyzed during the course of reperfusion in both groups. For the hepatic damage evaluations, hepatic enzyme levels, histology, apoptosis analysis, and intravital microfluorography for dead cells were examined. For the microcirculatory disturbance analysis, an adhesion molecule and intravital microfluorography for endothelial‐adherent leukocytes were examined.

Results:
In the ischemic preconditioning group, ischemia/reperfusion injuries (shown by hepatic enzymes elevation, histological degeneration, and increases in the number of apoptotic cells and microfluorographic dead cells) were markedly reduced. Moreover, microcirculatory disturbances represented by intercellular adhesion molecule‐1 expression and leukocyte adhesion on the endothelium were ameliorated. Tumor necrosis factor‐α protein production and mRNA expression were also suppressed in the ischemic preconditioning group.

Conclusion:
The suppression of tumor necrosis factor‐α and the subsequent amelioration of microcirculatory disturbances were observed, suggesting that the mechanism underlying the protective effect of ischemic preconditioning in hepatic ischemia/reperfusion injuries may involve tumor necrosis factor‐α and microcirculatory regulation.

© 2002 Blackwell Publishing Asia Pty Ltd
Interferon‐γ regulates apoptosis by releasing soluble tumor necrosis factor receptors in a gastric epithelial cell line
Authors: FURUTA SHIMAKO , GOTO HIDEMI , NIWA YASUMASA , OHMIYA NAOKI , KAMIYA KENJI , OGURI AKIHIKO , HAYAKAWA TETSUO , MORI NAOYOSHI
Published: March 2003

Background and Aims
: Interferon (IFN)‐γ and tumor necrosis factor (TNF) are predominant cytokines produced in the gastric mucosa of patients with Helicobacter pylori‐infected gastritis. Several studies reported that IFN‐γ and TNF induced the synergistic effect on many cell lines. We attempted to clarify the apoptotic activity and the synergistic effect of IFN‐γ and TNF on the gastric epithelial cell, and whether IFN‐γ relates to soluble TNF receptors (sTNF‐R) release from the gastric epithelial cell.

Methods
: On the gastric epithelial cell line MKN45, cytotoxic and apoptotic effects of IFN‐γ and TNF were examined. Next, sTNF‐R released in response to IFN‐γ and the protective effect of sTNF‐R against the cytotoxic activity of TNF and IFN‐γ were examined by blocking the release of sTNF‐R with a serine protease inhibitor such as phenylmethylsulfonyl fluoride.

Results
: Interferon‐γ significantly decreased cell viability, but TNF decreased it only slightly. Interferon‐γ and TNF did not make a synergistic effect on cell viability and apoptosis. Interferon‐γ and TNF induced sTNF‐R release from gastric epithelial cells. Phenylmethylsulfonyl fluoride significantly inhibited shedding of sTNF‐R and a synergistic effect of TNF and IFN‐γ on apoptosis was observed.

Conclusion
: These results suggest that sTNF‐R released by IFN‐γ regulate the injury on the gastric epithelial cell line induced by TNF.

© 2002 Blackwell Publishing Asia Pty Ltd
Gastrointestinal dysmotility in patients with acute pancreatitis
Authors: WANG XINGPENG , GONG ZIHUA , WU KAI , WANG BINGXIAN , YUANG YAOZONG
Published: March 2003

Background and Aims: Gut‐origin bacterial translocation is one of the major causes of pancreatic necrotic tissue infection in patients with severe acute pancreatitis (SAP). The gastrointestinal dysmotility is supposed to be the fundamental event in this process. To test this hypothesis, alteration of colonic transit time (CTT) in patients with acute pancreatitis (AP) was investigated. In order to evaluate the possible mechanisms involved in gastrointestinal dysmotility, changes of serum motilin (MTL), cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in patients with AP were also measured.

Methods: Twenty‐four non‐consecutive patients with AP and 25 controls were included in this study. The diagnosis of AP was based upon clinical features, biochemical indices and radiological investigation. The severity of AP at admission was evaluated according to the APACHE‐II and Balthazar computed tomography (CT) scoring system. Total and segmental CTT in patients with AP and in controls were determined by ingestion of radiopaque markers (Sitzmarks®) according to the modified Metcalf's method. Meanwhile, serum MTL and CCK were assessed using radioimmunoassay (RIA), and serum VIP was measured by using ELISA in this study.

Results: Compared to the controls, the total CTT and segmental CTT (mainly right and left hemicolon) were prolonged significantly in 10 patients with SAP and 14 patients with MAP; P < 0.05. Moreover, the total CTT and segmental CTT were markedly more delayed in patients with SAP than in patients with MAP; P < 0.05. The concentrations of serum MTL and CCK were significantly decreased in both MAP and SAP patients compared with those in controls (P < 0.01). There was no significant differences in serum MTL and CCK levels between the SAP and MAP groups; P > 0.05. In addition, the concentration of serum VIP was increased in AP patients, and it reached statistical significance in patients with SAP (P < 0.05).

Conclusions: In conclusion, gastrointestinal dysmotility often occurred in patients with AP, especially more severely in SAP patients. One of the possible mechanisms might be related to the synergic actions of gut hormones, such as MTL, CCK and VIP.

© 2003 Blackwell Publishing Asia Pty Ltd
In vitro binding of hepatitis C virus to CD81‐positive and ‐negative human cell lines
Authors: SASAKI MINA , YAMAUCHI KATSUMI , NAKANISHI TOSHIMI , KAMOGAWA YUMIKO , HAYASHI NAOAKI
Published: March 2003

Aim: The aim of the present study is to study the mechanism of entry of hepatitis C virus (HCV) into human cells. We examined the in vitro binding of HCV to various human cell lines with or without CD81 expression.

Methods: We first used three cell lines, two hepatocyte‐derived, huH‐7 and HepG2, and one colon cancer cell line, Cw2. Among them, HepG2 did not express TAPA‐1 (CD81) on their surface but two others did. They were incubated with HCV + serum for 1 h and HCV‐RNA in extracted RNA obtained from these cells was examined by using both a quantitative test and reverse transcriptase–polymerase chain reaction (RT‐PCR).

Results: We found that a significant amount of HCV‐RNA was detected in huH‐7 and HepG2 but not in Cw2. In addition, the titer of HCV‐RNA in serum‐incubated CD81‐transfected HepG2 was similar to that of the non‐transfected titer, and the binding between HCV and huH‐7 was not inhibited by anti‐CD81. Under the same condition, HCV‐RNA tended to be detectable in serum‐pulsed hepatocyte‐derived cell lines, but not in the others.

Conclusion: These results suggest that while CD81, as reported, specifically binds to HCV‐E2 protein, the entry of HCV into human hepatocytes might be regulated by CD81‐unrelated molecule(s).

© 2003 Blackwell Publishing Asia Pty Ltd
Low‐dose ethanol attenuates gut ischemia/reperfusion‐induced liver injury in rats via nitric oxide production
Authors: HORIE YOSHINORI , YAMAGISHI YOSHIYUKI , KATO SHINZO , KAJIHARA MIKIO , KIMURA HIROYUKI , ISHII HIROMASA
Published: March 2003

Background and Aims:  The acute administration of low‐dose ethanol was demonstrated to attenuate liver injury elicited by gut ischemia/reperfusion (I/R). Nitric oxide (NO) has been found to be a modulator of adhesive interactions between leukocytes, platelets, and endothelial cells, but there has been much controversy about the effects of ethanol on NO regulation. The objective of this study was to investigate the role of NO in ethanol‐reduced hepatic microvascular dysfunction elicited by gut I/R.

Methods:  Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and non‐perfused sinusoids (NPS). Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, ethanol (10%, 1 g/kg) was administered before ischemia.

Results:  Gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma ALT activities; all of which were attenuated by pretreatment with ethanol or an NO donor. Gut I/R caused the apoptosis of hepatocytes, which was prevented by pretreatment with ethanol. Pretreatment with an NO synthase inhibitor diminished the protective effects of ethanol. The administration of ethanol increased plasma nitrite/nitrate levels.

Conclusion:  These results suggest that low‐dose ethanol attenuates the gut I/R‐induced hepatic microvascular dysfunction and sequential liver injury by increasing sinusoidal NO levels.
Anti‐Helicobacter pylori therapy in India: Differences in eradication efficiency associated with particular alleles of vacuolating cytotoxin (vacA) gene
Authors: CHAUDHURI SUJIT , CHOWDHURY ABHIJIT , DATTA SIMANTI , MUKHOPADHYAY ASISH K , CHATTOPADHYA SANTANU , SAHA DHIRA R , DHALI GOPAL , SANTRA AMAL , NAIR G BALAKRISH , BHATTACHARYA SUJIT , BERG DOUGLAS E
Published: March 2003

Background and Aims:  The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency, including bacterial genotype. The aim of the present study was to determine the efficiency of H. pylori eradication using a 10‐day proton pump inhibitor‐based triple‐therapy regimen (omeprazole, clarithromycin and amoxycillin) in an eastern Indian patient population, and to find out the relationship, if any, of the success or failure of the therapy to known features of bacterial genotype.

Methods  Helicobacter pylori infections were analyzed in 66 duodenal ulcer patients by upper gastrointestinal endoscopy, rapid urease tests, histology and culture. The cytotoxin‐associated gene (cagA) and vacuolating cytotoxin (vacA) gene status of cultured strains were studied by polymerase chain reaction. Treatment was given for 10 days and endoscopy was repeated at 4 and 12 weeks post therapy to monitor ulcer healing and H. pylori eradication.

Results:  Ulcer healing was observed in 60 patients (96.77%). Helicobacter pylori was eradicated in 41 (62.12% intention to treat, 66.13% per protocol) of the 66 duodenal ulcer patients, but not in the other 25. The bacteria from 47 patients were genotyped. The only significant disease‐associated difference in patterns observed was that the vacA m1 allele was represented more disproportionately among patients with eradication failures (68%) than in those with successful eradication (39%) (P < 0.05) No significant association of vacAs1 (signal sequence allele) or cag pathogenicity island status with persistence was detected.

Conclusions:  This study highlights the public health need for cheaper, more cost‐effective anti‐H. pylori therapies for developing countries, and suggests that subtle features of bacterial genotype can influence therapeutic efficiency. The possibility that particular vacA mid region alleles affect persistence, perhaps through toxin action on particular gastric cell types, merits further study.
Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection
Authors: DIKICI BUNYAMIN , BOSNAK MEHMET , UCMAK HASAN , DAGLI ABDULLAH , ECE AYDIN , HASPOLAT KENAN
Published: March 2003

Summary Aim:  The aim of this study was to investigate the efficacy of specific hepatitis B virus (HBV) vaccination as active immunotherapy in treating chronic hepatitis B (CHB) infection during the immune‐tolerant phase in children with normal aminotransferase levels and high viral load.

Methods:  Fifty‐one immunotolerant patients were randomly and prospectively recruited into two groups. Group 1 included 23 patients that were vaccinated with three standard injections of the GenHevac B vaccine in the deltoid or quadricep muscle, initially, and at 30 days and 60 days, for specific immunization. Group 2 contained 28 patients who did not receive any medication or vaccination and were recruited as the control group. Post‐vaccination evaluation was performed at 6 months from the first injection and at the end of the 12th month by serological and virological analyses. A response criterion to therapy was defined as loss of HBV‐DNA in serum and hepatitis B early antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg (anti‐HBe)).

Results:  The mean alanine aminotransferase (ALT) value in group 1 at the beginning of the vaccination was 33.6 ± 8.1 IU/L; this changed to 31.7 ± 9.0 IU/L at 6 months after first injection and 29.2 ± 7.1 IU/L at the end of 12 months (P > 0.05). In this group, mean HBV‐DNA load at the starting point of the vaccination was 3709 ± 1126 pg/mL; this value changed to 3569 ± 726 pg/mL at the sixth month and 3295 ± 832 pg/mL at the 12th month (P > 0.05). In group 2, the mean ALT values at the beginning of therapy, and at the 6th and 12th month were 32 ± 8 IU/L, 31.8 ± 8 IU/L, and 29.7 ± 7 IU/L, respectively (P > 0.05), and the mean viral load of HBV‐DNA values were 3827 ± 1375 pg/mL, 3498 ± 886 pg/mL, and 3059 ± 731 pg/mL, respectively (P > 0.05). The load of HBV DNA of all patients in both groups was greater than 2000 pg/mL. There was no statistically significant difference in the mean ALT values and mean viral load of HBV DNA (P > 0.05) between group 1 and group 2 at the end of the 6th and 12th months. Except for one each patient in each group, hepatitis B surface antigen (HBsAg) and HBeAg clearance or antibody to HBsAg (anti‐HBs) and anti‐HBe seroconversion were not observed during the follow‐up period (P > 0.05).

Conclusion:  In this study, comparison of vaccinated and unvaccinated groups of immunotolerant children with CHB infection showed no difference in the clearance of HBV DNA and seroconversion of HBeAg to anti‐HBe. Different immunization protocols should be considered for future investigations in the immunotolerant phase of children with CHB infection.
Evaluation of the albumin‐γ‐glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma‐complicating liver cirrhosis
Authors: POMPILI MAURIZIO , ADDOLORATO GIOVANNI , PIGNATARO GIULIA , ROSSI CRISTINA , ZUPPI CECILIA , COVINO MARCELLO , GRIECO ANTONIO , GASBARRINI GIOVANNI , RAPACCINI GIAN LUDOVICO
Published: March 2003

Aim: The present study aimed to evaluate the usefulness of albumin‐γ‐glutamyltransferase isoenzyme in the diagnosis of hepatocellular carcinoma.

Methods: Electrophoretic assays of γ‐glutamyltransferase isoenzymes were performed on sera from 190 cirrhotics with (n = 131) or without (n = 59) hepatocellular carcinoma, 36 patients with chronic active hepatitis, 17 patients with liver metastases, and 16 control subjects. In the group of cirrhotic patients, the serum level of α‐fetoprotein was also assessed.

Results: Albumin‐γ‐glutamyltransferase was found in 88 of 131 cirrhotics with hepatocellullar carcinoma, 14 of 59 cirrhotics without hepatocellular carcinoma, nine of 17 patients with liver metastases, and in none of the chronic active hepatitis or control patients. Within the cirrhotic subgroup, albumin‐γ‐glutamyltransferase was effective in detecting hepatocellular carcinoma in general (sensitivity: 67%; specificity: 76%; diagnostic accuracy: 70%), and small hepatocellular carcinoma (< 3 cm; corresponding figures: 58, 76, and 69%). The best α‐fetoprotein value discriminating between hepatocellular carcinoma and non‐hepatocellular carcinoma cirrhotics was 20 ng/mL (sensitivity: 54%; specificity 85%; accuracy: 64%). The combined use of albumin‐γ‐glutamyltransferase and α‐fetoprotein, > 20 ng/mL, was associated with greater sensitivity and accuracy (84 and 74%, respectively) than those observed with either of the two markers considered alone.

Conclusions: Albumin‐γ‐glutamyltransferase appears to be a sensitive diagnostic marker of both advanced and small hepatocellular carcinoma‐complicating liver cirrhosis.
Microbiology of choledochal bile in patients with choledocholithiasis admitted to a tertiary hospital
Authors: FLORES CRISTINA , MAGUILNIK ISMAEL , HADLICH EVERTON , GOLDANI LUCIANO Z
Published: March 2003

Aim: The present study was designed to investigate the microbiology of choledochal bile of patients with cholangitis and choledocholithiasis.

Methods: We identified and determined the antimicrobial susceptibility of bacteria isolated in the bile of patients with cholangitis and choledocholithiasis diagnosed by endoscopic retrograde cholangiopancreatography (ERCP).

Results: Nineteen (82.6%) of 23 patients with choledocholithiasis had positive bile cultures. A single agent was detected in 11 patients (57.9%), while a mixed growth, with pathogens ranging from two to three species, were seen in eight patients (42.1%). Patients with clinical manifestations of cholangitis had significantly higher counts of colonies per mL of bile (> 105 cfu/mL).The predominant Gram‐negative aerobic bacteria isolated were Escherichia coli (9, 31.0%), Klebsiella pneumoniae (5, 17.2%), Enterobacter cloacae (2, 6.9%), Pantoea agglomerans (1, 3.4%), and Pseudomonas aeruginosa (1, 3.4%). The predominant Gram‐positive bacteria were Enterococcus faecalis (5, 17.2%) and Streptococcus sp. (5, 17.2%). Bacteroides fragilis was isolated in one patient with mixed growth. All Gram‐positive bacteria isolated in bile were sensitive to ampicillin, and all Gram‐negative bacteria isolated were sensitive to gentamicin with a minimum inhibitory concentration (CIM90) ranging from 0.5 to 1.0‐µg/mL. Gram‐negative bacteria were also sensitive to imipenem, fluorquinolones, second and third generation cephalosporins. Although all five isolates of E. faecalis were sensitive to ampicillin, two of five (40%) E. faecalis isolates demonstrated high levels of resistance to gentamicin.

Conclusion: E. coli, K. pneumoniae, E. faecalis and Streptoccocus sp. were the most common bacteria isolated in the bile of patients with cholangitis and choledocholithiasis, which were sensitive to a simple therapeutic regimen, such as the combination of ampicilin and gentamicin.
A randomized controlled trial of two methods for collection of sterile urine in neonates
Authors: TOBIANSKY R , EVANS N
Published: March 2003

Objective:

To test whether urethral catheterization (UC) is better than suprapubic bladder aspiration (SPA) as a method for collection of sterile urine in neonates.

Methods:

Thirty‐three babies, requiring sterile collection of urine, were randomly assigned to either urethral catheterization (n=16), median gestation 28±3.9 weeks, median birth weight 968 g (range 650–4100) or SPA (n=17), median gestation 26±5.6 weeks, median birth weight 926 g (range 771–4070). The primary outcome was success in obtaining urine. Secondary outcomes were complications and urine culture results.

Results:

Some urine was obtained in 11 (64.7%) babies in the SPA group and in 13 (81.2%) babies in the catheter group. Sufficient urine for analysis (>0.5 ml) was obtained in 10 (58.8%) in the SPA group versus 5 (31.2%) babies in the catheter group. There were more contaminated specimens in the catheter group but this was not significant in this small study.

Conclusions:

In this small randomized controlled trial urethral catheterization offered no significant advantage over SPA.
A systematic review of clinical research addressing the prevalence, aetiology, diagnosis, prognosis and therapy of otitis media in Australian Aboriginal children
Authors: MORRIS PS
Published: March 2003

The objective of this review was to systemically identify and summarize all the clinically relevant evidence available from studies addressing the prevalence, aetiology, diagnosis, prognosis and therapy of otitis media in Australian Aboriginal children. Electronic searching of Medline, the Australian Medical Index and the Aboriginal and Torres Strait Islander Health Bibliographic Index was performed. This was supplemented by hand searching the Menzies School of Health Research otitis media collection, the Aboriginal and Torres Strait Islander Health Information Bulletin and Aboriginal Health: an annotated bibliography. Data were extracted and placed in a series of evidence tables relevant to clinical practice. There were59 studies that met the inclusion criteria. The majority were surveys, and only 19 addressed diagnosis, prognosis or therapy. Severe otitis media in rural Aboriginal children does not occur in isolation but as part of a spectrum of chronic bacterial infections of the respiratory tract. Although the aspects of poverty that result in this condition remain to be clarified, exposure to other young children with chronic nasal discharge is likely to be important. Whilst there is a considerable amount of literature on otitis media in Australian Aboriginal children, the number of studies most relevant to improving health outcomes is small. A systematic approach to disease surveillance, diagnosis, and application of medical interventions is required urgently. Future medical research should be concerned with the evaluation of interventions and the generalisabilty of studies from different populations.
Fetal defaecation: Is it a normal physiological process?
Authors: Kimble RM , Trudenger B , Cass D
Published: March 2003

Abstract: It has been long known that the late gestation human fetus passes meconium in response to hypoxia. However, there is good evidence, from amniotic fluid studies measuring bile pigment and enteric enzyme content, to suggest that passage of meconium is a normal physiological event in the second trimester. Similarly there is some indirect evidence that fetal defaecation is a normal physiological process in the third trimester. However, this evidence is less strong, and it is safer to assume that in most cases meconium staining of liquor at this time is associated with fetal hypoxia. Dilation of the rectosigmoid portion of the distal bowel found in newborn infants with anorectal malformations supports the hypothesis that fetal colonic peristalsis and defaecation is a normal physiological process.