bluuebunny/crossref_metadata_2025 huggingface dataset:
Sr–Nd isotope ratios of gabbroic and dioritic rocks in a Cretaceous‐Paleogene granite terrain, Southwest Japan
Authors: Iizumi Shigeru , Imaoka Teruyoshi , Kagami Hiroo
Published: March 2003

Abstract Whole‐rock chemical and Sr and Nd isotope data are presented for gabbroic and dioritic rocks from a Cretaceous‐Paleogene granitic terrain in Southwest Japan. Age data indicate that they were emplaced in the late Cretaceous during the early stages of a voluminous intermediate‐felsic magmatic episode in Southwest Japan. Although these gabbroic and dioritic rocks have similar major and trace element chemistry, they show regional variations in terms of initial Sr and Nd isotope ratios. Samples from the South Zone have high initial 87Sr/86Sr (0.7063–0.7076) and low initial Nd isotope ratios (ɛNd, −2.5 to −5.3); whereas those from the North Zone have lower initial 87Sr/86Sr (usually less than 0.7060) and higher Nd isotope ratios (ɛNd, −0.8 to + 3.3). Regional variations in Sr and Nd isotope ratios are similar to those observed in granitic rocks, although gabbroic and dioritic rocks tend to have slightly lower Sr and higher Nd isotope ratios than granitic rocks in the respective zones. Limited variations in Sr and Nd isotope ratios among samples from individual zones may be attributed partly to a combination of upper crustal contamination and heterogeneity of the magma source. Contamination of magmas by upper crustal material cannot, however, explain the observed Sr and Nd isotope variations between samples from the North and South Zones. Between‐zone variations would reflect geochemical difference in magma sources. The gabbroic and dioritic rocks are enriched in large ion lithophile elements (LILE) and depleted in high field strength elements (HFSE), showing similar normal‐type mid‐ocean ridge basalt (N‐MORB) normalized patterns to arc magmas. Geochronological and isotopic data may suggest that some gabbroic and dioritic rocks are genetically related to high magnesian andesite. Alternatively, mantle‐derived mafic or intermediate rocks which were underplated beneath the crust may be also plausible sources for gabbroic and dioritic rocks. The magma sources (the mantle wedge and lower crust) were isotopically more enriched beneath the South Zone than the North Zone during the Cretaceous‐Paleogene. Sr and Nd isotope ratios of the lower crustal source of the granitic rocks was isotopically affected by mantle‐derived magmas, resulting in similar initial Sr and Nd isotope ratios for gabbroic, dioritic and granitic rocks in each zone.
Coexistence of proguanylin (1–15) and somatostatin in the gastrointestinal tract
Authors: IEDA HIDEAKI , NARUSE SATORU , FURUYA SONOKO , OZAKI TSUYOSHI , ANDO EIJI , NOKIHARA KIYOSHI , HORI SHINICHIRO , KITAGAWA MOTOJI , HAYAKAWA TETSUO
Published: March 2003

In order to identify proguanylin‐secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1–15) and have examined the proguanylin‐positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1–15)‐immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle‐shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1–15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin‐positive cells was much larger than that of proguanylin‐positive cells in all the segments tested. The number of proguanylin‐positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin‐positive cells, most somatostatin‐positive cells were also positive for proguanylin. Thus, proguanylin (1–15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.
Low‐titre auto‐antibodies predict autoimmune disease during interferon‐α treatment of chronic hepatitis C
Authors: Bell Trudi , Bansal Amolak , Shorthouse Claudia , Sandford Neville , Powell Elizabeth
Published: March 2003

Background: In this study, we determined whether low‐titre auto‐antibodies are a risk factor for the development of autoimmune disease during interferon‐α (IFNα) therapy for chronic hepatitis C (CHC) infection.

Methods: Eighty‐three patients with circulating hepatitis C virus RNA and chronic viral hepatitis on liver biopsy, who had not received IFNα, were assessed for serum auto‐antibodies (anti‐nuclear antibodies (ANA), anti‐smooth muscle antibodies, thyroid microsomal antibodies, thyroglobulin antibodies) and thyroid function tests.

Results: Thirty‐five patients had one or more pre‐existing auto‐antibody. The majority were low titre ANA. Seven of the 35 patients had clinical autoimmune disease or immune‐mediated disorders, predominantly thyroid disease. Twenty patients with low titre auto‐antibodies received treatment with IFNα and of these 20 patients, six patients developed adverse effects with a possible auto‐immune basis. In comparison, only five of the 48 patients without auto‐antibodies had immune‐mediated disorders and no patient developed autoimmune complications during therapy with IFNα.

Conclusions: These results suggest that the presence of low‐titre auto‐antibodies may be a risk factor for the development of autoimmune dysfunction during IFNα therapy for chronic hepatitis C. Patients with no detectable auto‐antibodies have a low risk for developing autoimmune complications during treatment with IFNα.
Influence of cholesterol crystallization effector proteins on vesicle fusion in supersaturated model bile
Authors: Hattori Yoshihiro , Tazuma Susumu , Yamashita Gunji , Kajiyama Goro
Published: March 2003

Background: In lithogenic bile, cholesterol‐rich vesicles rapidly aggregate and fuse to eventually form cholesterol crystals. This process is modulated by cholesterol crystallization effector substances. In this study, we developed a method for quantitative assessment of vesicle fusion and used it to partly characterize the mechanisms of action of cholesterol crystallization effector proteins.

Methods: Cholesterol:phospholipid (1:1) liposomes were prepared and labelled with octadecyl rhodamine B chloride (R18). Fusion of these liposomes was detected by the increase of R18 fluorescence after incubation with various proteins, such as albumin, concanavalin‐A bound glycoprotein, immunoglobulins, apolipoprotein A‐I and apolipoprotein B (all at 100 μg/mL).

Results: Fusion of cholesterol/phospholipid liposomes was increased by 16 and 14% in the presence of concanavalin‐A bound glycoprotein and immunoglobulins, respectively, and decreased by 21 and 9% after addition of apolipoprotein A‐I and apolipoprotein B, respectively. The effect of each protein on vesicle fusion was correlated with its hydrophobicity.

Conclusions: These results suggest that nucleation effector proteins modulate the stability of vesicles and, thus, affect cholesterol crystallization. Such modulation is based upon protein–vesicle association, which defines the physico‐chemical metastability of vesicular cholesterol.
Is protein‐deficient diabetes mellitus a pancreatitis?
Authors: Saraya Anoop , Acharya Subrat , Vashisht Sushma , Mittal Ambrish , Tandon Rakesh
Published: March 2003

Background: Malnutrition‐related diabetes mellitus is a distinct clinical entity subdivided into protein‐deficient diabetes mellitus (PDDM) and fibrocalculus pancreatic diabetes (FCPD). Whereas FCPD has obvious pancreatitis manifested by pancreatic duct calculi, the evidence for involvement of the pancreas in PDDM is limited to the presence of ketosis‐resistant hyperglycaemia.

Methods: We studied 10 patients with PDDM biochemically and radiologically. Endoscopic retro‐ grade cholangiopancreatography was performed to determine if they had any evidence of chronic pancreatitis.

Results: Their mean faecal chymotrypsin level was low (13.2 ± 5.72 μg/g), as was their basal c‐peptide value (0.35 ± 0.15 mmol/L). Islet cell antibodies were not detected in any of these patients. Ultrasound examination revealed pancreatic atrophy. In two patients, however, the pancreas was bulky. The ERCP showed generalized thinning of the pancreatic duct, measuring 2.4 ± 0.06 mm in the head, 2.01 ± 0.08 mm in the body and 1.02 ± 0.03 mm in tail region; side branches were seen but they were too sparse and thin.

Conclusions: The significance of these changes is not clear, but they may represent an ongoing pancreatic disease and may, indeed, be the earliest changes of chronic pancreatitis.
CORRELATION OF PRESENCE OF H. PYLORI WITH HISTOLOGICAL AND SYMPTOMATIC SCORE IN PATIENTS WITH NON ULCER DYSPEPSIA (NUD)
Authors: Joshi Anoop , Ahuja Vineet , Duttagupta S. , Sharma Mp
Published: March 2003

Background

Non ulcer dyspepsia (NUD) is being postulated as one of the gastroduodenal manifestations of H. pylori infection. H. pylori infection may result in clinical symptoms as well as histological changes in (NUD).

Aim

To compare clinical symtoms score and histological changes in H. pylori (Hp) positive and negative untreated NUD patients.

Methods

Patients with dyspeptic symptoms and abnormal UGI endoscopic examination were included in the study. During endoscopy 2 biopsies each were taken from antrum and corpus. These biopsies were used for rapid urease test (RUT) and histological evaluation. There were 2 group: Hp positive and Hp negative NUD patients. Patients were diagnosed to have H. pylori infection of either of the two test (RUT, histology) were positive. Clinical scoring using glasglow dyspepsia score (max 20) and histological analysis using Sydney system (max score 11) was done and compared for both the groups. Clinical scoring RUT & histological scoring were blinded to each other.

Results

to patients (29 Hp + and 17 Hp ‐ve) were enrolled in the study. The results in both groups were:

Hp +ve
Hp ‐ve
P value

Glasgow clinical score
10.9
11.4
ns

Chr. Gastritis

Antrum
89.6%
94.1%
ns

Corpus
93.1%
76.1%
ns

Activity

Antrum
41.3%
41.1%
ns

Corpus
41.1%
29.4%
ns

Lymphoid follicles

Antrum
34.4%
11.7%
ns

Corpus
37.9%
5.8%
P < 05

Atrophy

Antrum
24.1%
11.7%
ns

Corpus
20.6%
11.7%
ns

Int. Metaplasia

Antrum
13.7%
5.8% ns

Corpus
10.3%
0% ns

Total Histological

Antrum
3.37
1.76
0.0003

Corpus
3.68
1.29
0.0001

Conclusion

Clinical scoring does not correlate with presence of H. pylori or the histological severity. In NUD patients positive for H. pylori, there is a significant increase in the severity of gastritis both in the antrum and the corpus.
HEMATEMESIS AND MELENA IN BABY WITH HELICOBACTER PYLORI INFECTION
Authors: Purnomo Budi , Soeleman Eva J. , Digdowirogo Hadjat S. , Soehardjo Hartati N.
Published: March 2003

H. pylori infection in a baby is very rare. Most Clinicians recommended treating this infection in such cases. Time of H. pylori begin to colonize human gastroduodenal is not known. We report a case: an 8‐month old baby girl who suffered from hematemesis and melena since 4‐month old.

Case report:

RK, an 8‐month baby girl was brought to children and maternity Hospital due to recurrent hematemesis and melena since 4 months ago. On physical examination, she looked pale without icterus or dyspnoe. Body weight was 6100 g. Vital signs were normal. Heart lungs, abdomen and extremities were within normal limit.

Laboratory findings:

hemoglobin 9.5 g/dl, hematrocrite 39%, leukocyte 13300 /ul, platelets 369000/ul, Prothrombin and thrombin time were normal. Radiology of the stomach with barium revealed third grade of gastroesophageal reflux. On gastroscopy, we found erosive gastritis and many nodules in duodenic bulb. Histopathological examination showed duodenitis grade I, H.pylori positive and chronic gastritis.

We gave amoxycilin, omeprazole and metronidazole for a week and sucralfate, omeprazole for 2 months. After treatment, no symptoms was found. The baby have weight gain to normal percentile.

Conclusion

The management of H.pylori infection in our case was late. We already found iron deficient anaemia due to hematemesis and melena, and malnutrition. After H. pylori eradication, all symptoms resolved.
HISTOPATHOLOGICAL PATTERN OF GASTRIC BIOPSIES OF HELICOBACTER PYLORI POSITIVE PATIENTS IN SARDJITO GENERAL HOSPITAL, YOGYAKARTA, INDONESIA
Authors: Nurdjanah Siti , Bayupurnama Putut
Published: March 2003

Objective:

To determine the gastric histopathological types distribution of H. pylori positive patients who were detected histopathologically.

Material& Methods:

Study design was prospective study. Consecutive patients who were suffering chronic dyspepsia underwent endoscopy examination between August 1998 and December 1999. The biopsy specimens were taken from gastric antrum and corpus and sent to the pathologist for histopathology type and H. pylori examinations. H. pylori were also confirmed with CLO and IgG‐Helicobacter pylori tests.

Results:

There were 92 patients (48 male (M) and 44 Female (F) who underwent gastric biopsies endoscopically between August 1998 and December 1999. Fifty‐six (60.87%) patients were chronic superficial gastritis, 11(11.96%) chronic antropic gastritis, 18 (19.56%) chronic gastritis 2 (2.17%) chronic gastritis with metaplasia, 3 (3.27%) gastric ulcer, and 2 (2.17%) gastric signet‐ring cell carcinoma. Twenty one (22.8%) patients with H. pylori positive by histopathology examination with CLO and IgG‐H.pylori tests. Those were 5 (8.90%) patients with chronic superficial gastritis, 7(63.63%) chronic atrophic gastritis, 3(100%) gastric ulcer, 2 (100%) chronic gastritis with metaplasia, 3(16.67%) chronic gastritis, 1(50%) signet‐ring cell carcinoma. The age range of the H. pylori positive patients were between 16 and 76 years old.

Conclusion:

Twenty one (22.8%) H. pylori positive patients out of 92 endoscopied patients and the high percentage tendency of H. pylori positively in chronic atrophic gastritis, gastric ulcer, and chronic gastritis with metaplasia, although most of the patients had chronic superficial gastritis. Further study is needed with larger with larger sample to get the clearer picture of H. pylori distribution based on gastric histopathological types.
ULTRASTRUCTURE OF HELICOBACTER PYLORI
Authors: Saito Nagahito , Oda Hisashi , Sato Fujio , Kato Mototsugu , Takeda Hiroshi , Sugiyama Toshiro , Asaka Masahiro
Published: March 2003

The ultrastructure of cell gives suggestions to the elucidation of the function. The study about the ultrastructure of H. pylori is important to know the nature of the organism. It is beyond doubt that Helicobacter pylori (H. pylori) is related to the pathogenesis of gastric disorders and it has been sequenced the bacterial genome. Although many morphological studies have been performed about this organism by light microscopy, few reports about theprecise ultrastructure exist. In general, H. pylori are divided into two types: spiral forms and coccoid ones. It is considered that the former is changing into the latter in an undesirable environment. It remains obscure about the nature of the letter such as the detailed ultrastructure, the transformation process or the viability. There are antithetic concepts about the coccoid H. pylori. One is that this type of the organism remains in a degenerated state. The other is that such organism is viable and non‐culturable. In addition to these opinions. I exhibit the third view. That is, the coccoid form are divided into two types; type I whose ultrastructure is generally nonspecific and type II identically intact. Moreover, type II coccoid form is also suggested to process growth viability.

In this symposium, the ultrastructure of the cultured H. pylori (ATCC43504) will suggest some hypotheses about the nature. Some other natures will be also hypothesized from our ultrastructural study.
Dilatation of benign oesophageal strictures: 10 years’ experience with Celestin dilators
Authors: Duseja Ajay , Chawla Yk , Singh Rp , Sharma Tr , Kaur U , Dilawari Jb
Published: March 2003

Background
: Endoscopic dilatation is the first line of treatment for benign oesophageal strictures. There are limited data available on the use of Celestin dilators.

Methods
: The efficacy and safety of Celestin dilators was evaluated retrospectively in 61 patients with benign oesophageal strictures. Three hundred and nintey‐three dilatations using Celestin dilators were performed over a period of 10 years on an outpatient basis in patients with corrosive, peptic and other causes of benign oesophageal strictures.

Results
: Initial success was achieved in all patients in the peptic and miscellaneous group and in 91% in the corrosive group of patients. Patients with corrosive strictures required significantly more dilatations for initial success compared with the peptic group (mean 5.82 vs 1.62 P < 0.1). At 6 months follow up after the initial success, 29% of the patients had an excellent response, 56% a good response and 15% a fair response. No patient had a poor response. During the long‐term follow up of 10 years, overall dilatation requirement decreased significantly. (72 vs 27 vs 14% of patients requiring dilatation at 1, 5 and 10 years P < 0.05). The dilatation requirement also decreased significantly within the groups (P < 0.05). Patients with corrosive stricture required more frequent dilatations on follow up compared with the other two groups. Complications in the form of oesophageal perforation occurred in only two patients. There was no mortality.

Conclusion
: Oesophageal dilatation with Celestin dilators is an effective and safe modality for managing patients with benign oesophageal strictures.
Expression of hepatic thrombopoietin mRNA in primary cultured hepatocytes and in rats with acute liver injury or bone marrow suppression with or without cirrhosis
Authors: Ishikawa Toru , Ichida Takafumi , Matsuda Yasunobu , Sugitani Soichi , Sugiyama Motoya , Kato Takashi , Miyazaki Hiroshi , Asakura Hitoshi
Published: March 2003

Background and Aims
: The main causes of thrombocytopenia in cirrhosis are thought to be platelet destruction and the reduction of thrombopoietin (TPO) expression in the liver. The mechanisms by which levels of TPO mRNA are regulated in cirrhosis have not been elucidated. In this study, we investigated some possible mechanisms.

Methods
: We used three experimental models: bone marrow suppression, acute liver injury and primary cultured hepatocytes. We used northern blots to assess the kinetics of TPO mRNA expression in the livers of irradiated rats (with and without cirrhosis) in acute liver injury and in primary cultured hepatocytes treated with hepatotoxin or cytokines.

Results
: Although the bone marrow was hypocellular, there was no apparent enhancement of TPO mRNA expression in the irradiated rats with cirrhotic livers compared with the unirradiated rats with cirrhotic livers. There were no conspicuous changes in hepatic TPO mRNA expression between the livers of the control rats and the three models of acute liver injury. There were no conspicuous changes in the levels of TPO mRNA between control hepatocytes and hepatocytes treated with hepatotoxin or cytokines.

Conclusions
: Our results suggest that bone marrow is not a regulator of hepatic TPO production in cirrhosis. The reduced TPO mRNA expression found in cirrhotic rats may not result merely from serious cellular damage; it may be associated with cirrhosis‐specific regulatory mechanisms for the expression of the TPO gene. Further studies are needed to search for other factors that may induce reduced TPO expression.
Treatment of chronic hepatitis B virus infection: who, when, what for and how
Authors: Liaw Yun‐Fan
Published: March 2003

Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its worldwide distribution and possible adverse sequelae. It is particularly important in the Asia–Pacific region where HBV infection is highly prevalent and usually acquired perinatally or in early childhood. It is now known that chronic HBV infection is a dynamic interaction between virus, hepatocyte and the host’s immune response. The natural history of chronic HBV infection can be divided into three phases: high replicative or viraemic ‘immune tolerance phase’ followed by ‘immune clearance phase’ and then the low replication ‘residual phase’. The clinical course of chronic HBV infection is characterized by a series of exacerbations and remissions during the ‘immune clearance phase’, which may lead to hepatic decompensation, progression of liver disease, development of cirrhosis and hepatocellular carcinoma (HCC). It is of paramount importance to arrest HBV replication as early as possible to reduce infectivity, improve hepatic injuries, prevent progression to cirrhosis or HCC and thereby prolong survival. There are many potentially effective agents with different mechanisms of action and there is substantial accumulated experience with these therapies, but there is also still a need for practical recommendations such as: (i) who should be treated; (ii) when to treat such patients; (iii) which drug(s) or strategy would be most cost‐effective for the patient under consideration; (iv) how the patient should be monitored; (v) what benefit the patient can expect from such treatments; (vi) what can be done for special groups of patients, such as decompensated cirrhosis immunocompromised patients or children; and (vii) what treatment of chronic HBV infection could be expected in the 21st century. The Asia–Pacific region not only has the greatest number of patients with chronic HBV infection, but also has conducted important clinical trials. It is relevant and mandatory to coordinate all current knowledge to reach a consensus and to make guidelines for the treatment of chronic HBV infection in this region.
Nucleoside analogues in the treatment of chronic hepatitis B
Authors: Leung Nancy
Published: March 2003

Many nucleoside analogues have been investigated for the treatment of chronic hepatitis B. Some were withdrawn because of significant adverse effects and some are still in the early stage of clinical assessment. Lamivudine has been demonstrated to have consistent efficacy and safety in large‐scale, phase III clinical trials. It has achieved a milestone in the treatment of chronic hepatitis B and is now commercially available in many countries. Being a potent inhibitor of hepatitis B viral replication, it achieved around 18% HBeAg seroconversion in HBeAg‐positive patients after 1 year of therapy. HBeAg seroconversion is a good endpoint for therapy and has been shown to be 80% durable. The response was better among patients with raised pretreatment alanine aminotransferase levels. Liver necro‐inflammation and fibrosis improved significantly after 1 year. Further improvement on extended therapy was observed together with an incremental increase in HBeAg seroconversion. Similar efficacy was demonstrated in HBeAg‐negative viraemic patients. The main drawback is the emergence of drug‐resistant variants starting from the sixth to ninth month of treatment. This can be associated with varying degrees of relapse of disease activity and may offset the benefit of therapy. With extended therapy, drug‐resistant variants continue to emergence at a rate of around 20% per year. Adefovir dipivoxil and entacavir are nucleoside or nucleotide analogues shown to suppress both the wild‐type and lamivudine‐resistant virus. Combination of these nucleoside/nucleotide analogues with immune modulators may be the answer to eradicate the virus in short‐term therapy and avoid the issue of drug resistance.
Molecular mechanism of the reversibility of hepatic fibrosis: With special reference to the role of matrix metalloproteinases
Authors: Okazaki Isao , Watanabe Tetsu , Hozawa Sigenari , Arai Masao , Maruyama Katsuya
Published: March 2003

The participation of matrix metalloproteinases (MMP) and their specific inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMP), in both the formation and degradative recovery processes of liver fibrosis were mainly reviewed from the molecular biological aspect. Since authors first reported increased activity of interstitial collagenase in the early stage of hepatic fibrosis in rats induced by chronic CCl4 intoxication, in baboons fed alcohol chronically and in patients with alcoholic fibrosis, other investigators have also demonstrated increased activity biologically and histochemically. However, species‐specific differences in response have been found and gene‐level research on the rat model has not demonstrated increased mRNA transcription of collagenase. It has also been clarified that activated stellate cells can also produce matrix components. Very recently, authors observed the participation of interstitial collagenase in the recovery from experimental hepatic fibrosis by using polymerase chain reaction northern blotting and in situ hybridization. The in situ hybridization findings not only demonstrated the cells responsible for interstitial collagenase, but also suggested a great deal about the mechanism of recovery from fibrosis. Hepatic stellate cells are activated via the expression of c‐myb and nuclear factor‐κB (NFκB) which is induced by oxidative stress, and inhibited by antioxidant (1‐α‐tocopherol) and butylated hydroxytoluene. The activation mechanism is now being revealed. The relationship between the activation mechanism of stellate cells and the production and secretion of MMP and TIMP in the formation and recovery process of hepatic fibrosis should be investigated from the promoter gene level. This approach might help develop a new strategy for the treatment of liver fibrosis.
Polyunsaturated fatty acids reduce non‐receptor‐mediated transcellular permeation of protein across a model of intestinal epithelium in vitro
Authors: Rosella Ourania , Sinclair Andrew , Gibson Peter R
Published: March 2003

Background
: Dietary polyunsaturated fatty acids influence the natural history of intestinal inflammatory diseases. Varying the types of long‐chain fatty acids that are exposed to cells alters the physicochemical properties of cell membranes. This study aimed to determine whether such variations alter transcellular and paracellular permeability in intestinal epithelium.

Methods
: Monolayers of Caco‐2 cells, allowed to differentiate by culturing for 7 days following confluence, were used as the model for intestinal epithelium. Paracellular permeability was assessed by measurement of transepithelial resistance, while transcellular permeability was assessed by the transepithelial flux of horseradish peroxidase.

Results
: Exposure of the cells to 100 μmol/L of palmitic acid, oleic acid, eicosapentaenoic acid, or linoleic acid, was not toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell membrane fatty acid composition (as measured by gas chromatography). Flux of horseradish peroxidase was significantly affected by 24 h fatty acid exposure (P = 0.038,
ANOVA), being decreased by 23 ± 6% (mean ± SEM) by eicosapentaenoic acid and 25 ± 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had no effect. Transepithelial resistance also varied significantly across the treatment groups (P < 0.001) due to a 28 ± 5% increase induced by butyrate. The long‐chain fatty acids had no effect.

Conclusions
: Both ω‐3 and ω‐6 polyunsaturated fatty acids reduce transcellular, non‐receptor‐mediated permeation of proteins across differentiated Caco2 cell monolayers, without altering paracellular permeability. Alteration of intestinal barrier function should be considered as a possible mechanism of action of dietary polyunsaturated fatty acids.
Pooled analysis of Helicobacter pylori eradication regimes in Asia
Authors: Wang Wei Hong , Wong Benjamin Chun Yu , Lam Shiu Kum
Published: March 2003

Background and Aims
: Differences in Helicobacter pylori strains and their resistance to antimicrobials between Asian and Western countries may affect the success in eradicating this bacterium. Our objective was to systematically review the regimens that have been tested in Asia.

Methods
: Data on anti‐H. pylori therapies reported from Asia in a large number of publications identified up to December 1998 were pooled into a few groups based on the combination of drugs used. A comparison of different groups was made by calculating the pooled eradication rates.

Results
: Seventy‐three studies with 134 treatment arms were reviewed. Pooled eradication rates of dual, triple and quadruple therapies were 61.0, 86.5 and 93.4%, respectively. Proton pump inhibitor (PPI)‐based combinations were more widely used and effective, with overall eradication rates of 90.7% in triple therapy and 93.4% in quadruple therapy. Bismuth combined with tetracycline and metronidazole also showed a high eradication rate of 92.0%.

Conclusions
: Proton pump inhibitor‐based triple therapy with either clarithromycin, amoxycillin or metronidazole was one of the most commonly used and effective anti‐H. pylori triple therapy regimens in Asia. The classical triple therapy with a bismuth, tetracycline and metronidazole combination has a similar efficacy. The results of anti‐H. pylori treatment in Asia are not different from those in Western countries.
Molecular pathogenesis of viral hepatitis
Authors: Locarnini Stephen
Published: March 2003

Abstract The global burden of chronic liver disease caused by persistent infection with hepatitis B and C viruses has meant the urgent development of therapeutic strategies designed to control active replication and therefore prevent subsequent clinical sequelae. Advances in these therapeutic strategies are now clearly happening, mainly as a consequence of a better understanding of the viral life cycle and the unique pathogenesis of each disease. Further progress should continue as further insights into the virus–cell relationship are derived, which will sharpen attention on specific viral targets as well as shift and enhance host cytokine responses.
Survey of gastrointestinal endoscope disinfection and accessory reprocessing practices in the Asia–Pacific region
Authors: Ahuja Vineet , Tandon Rakesh K
Published: March 2003

Abstract Concern has been raised about the possibility of transmission of infection by gastrointestinal endoscope. This vexation may be related to reliability of the disinfecting techniques or to the compliance with the guidelines laid down for disinfection. There have been very few recent surveys examining the disinfection practices for gastrointestinal endoscopes and their accessories. This survey was undertaken to understand such practices in the Asia–Pacific region. A questionnaire was sent by post or electronic mail to 356 randomly selected endoscopy centres in the Asia–Pacific region. Responses were received from 38.7% of the centres. The survey showed that there were significant aberrations in the application of disinfection procedures. One‐third of the respondents did not practise disinfection at the start of the day's session, 2.9% of the centres were not using a high‐level disinfectant and 34.7% of the centres used a soak time in 2% glutaraldehyde of less than 10 min. At 40% of the centres, at the end of the day's session, forced air or alcohol was not used to dry the endoscopes. Reuse of accessories meant for single use was widely practised.
Reprocessing of gastrointestinal endoscopic accessories
Authors: Ogoshi Kauzuei
Published: March 2003

Abstract In this paper, the minimal standards for the disinfection of endoscopes and endoscopic accessories, as defined by the OMED's Minimal Standards for Disinfection, are described. Given the difficulties of disinfecting reusable accessories, disposable accessories are desirable and marketed by many companies. However, they are less economical than the reusable accessories available. Presently, both disposable and reusable forceps are marketed and those that are to be reused must be disinfected according to the Minimal Standards for Disinfection. This paper will discuss the factors to consider in choosing single‐use or reusable accessories, such as economy, reliability of disinfection and durability of function. The one‐time biopsy cost of reusable and disposable accessories that can be satisfactorily disinfected will also be compared. This paper concludes that the accessories used for endoscopic retrograde cholangiopancreatography are less reliably disinfected, less expensive and less durable compared with biopsy forceps.
Mortality association of enhanced CD44v6 expression is not mediated through occult lymphatic spread in stage II colorectal cancer
Authors: Clarke Gerard , Ryan Eleanor , O'keane J Conor , Crowe John , Mathúna Padraic Mac
Published: March 2003

Background and Aims
: In the absence of other metastatic disease, the presence of lymph node metastasis remains the most important determinant of survival in colorectal cancer (CRC). Cluster designation 44 variant 6 (CD44v6) over‐expression is associated with worse outcome in all stages of CRC. The CD44v6 is believed to confer metastatic potential through its facilitation of migration, extravasation and proliferation, although the specific means by which it conveys an adverse prognosis in CRC is unknown. The aim of the present study was to determine if CD44v6 over‐expression in Stage II CRC subjects was associated with the presence of lymph node micrometastases.

Methods
: We assessed tumour CD44v6 expression in 43 randomly sampled subjects who had resections for Stage II CRC between 1984 and 1991 by using immunohistochemistry. Micrometastases were sought in corresponding lymph node (LN) sections using keratin immunohistochemistry.

Results
: There was a statistical trend between tumour CD44v6 over‐expression and mortality (P = 0.09) and a significant relationship between LN cytokeratins and mortality (P = 0.01). There was no association between the detection of LN cytokeratins and tumour CD44v6 over‐expression.

Conclusion
: We conclude that the adverse survival effect of CD44v6 over‐expression is not mediated though lymphatic spread and postulate that it may therefore facilitate haematogenous metastasis.
Detection of hepatitis A viral RNA in sera of patients with acute hepatitis A
Authors: Kwon Oh Sang , Byun Kwan Soo , Yeon Jong Eun , Park Sang Hoon , Kim Jae Seon , Kim Ju Hyun , Bak Young Tae , Kim Jin Ho , Lee Chang Hong
Published: March 2003

Background and Aims
: The Detection of hepatitis A virus (HAV) is important for diagnosis and epidemiological studies of hepatitis A. The polymerase chain reaction (PCR) technique is a sensitive test to detect HAV‐RNA in specimens. The aims of the present study were to clarify the detection rate of serum HAV‐RNA by PCR and the natural history of HAV viraemia, and to determine the correlation between viraemia and the clinical characteristics in patients with acute hepatitis A.

Methods
: Hepatitis A virus RNA was tested in 74 serum samples which were serially collected from 27 patients with acute hepatitis A. A nested reverse transcription (RT)‐PCR for HAV‐RNA was performed with primer sets located at the VP1 region of the HAV genome and the PCR products were eletrophoresed on a 1.5% agarose gel.

Results
: Hepatitis A virus RNA was found in 18 of 27 (67%) patients with hepatitis A. There were no significant differences between groups positive and negative for HAV‐RNA in clinical and laboratory data, except the time interval between clinical onset and initial serum sampling for RT‐PCR (10 ± 6 vs 19 ± 14 days) and the alanine aminotransferase (ALT) level at initial serum sampling for RT‐PCR (1436 ± 1416 vs 518 ± 432 IU/L). The mean duration of HAV viraemia was 30 ± 19 days (range, 5–59 days). The duration of HAV viraemia and duration of abnormal ALT levels from clinical onset were positively correlated (r = 0.685, P = 0.007).

Conclusion
: In conclusion, HAV‐RNA RT‐PCR is a useful tool to detect HAV viraemia and to study the molecular epidemiology of HAV infection.
Comparison of intraductal ultrasonography with percutaneous transhepatic cholangioscopy for the identification of residual bile duct stones during lithotripsy
Authors: Tamada Kiichi , Ohashi Akira , Tomiyama Takeshi , Wada Shinichi , Satoh Yukihiro , Higashizawa Toshihiko , Ido Kenichi , Sugano Kentaro
Published: March 2003

Background: An imaging modality that can be used to identity small stones after a biliary lithotripsy is required. Intraductal ultrasonography was evaluated by using percutaneous transhepatic cholangioscopy as the gold standard.

Methods: Lithotripsy, under percutaneous transhepatic cholangioscopy guidance, was performed in 20 patients. A thin‐caliber ultrasonic probe (2.0 mm in diameter and 20 MHz frequency) was inserted into the bile duct through the percutaneous tract after lithotripsy, and residual stones were identified. This was followed by percutaneous transhepatic cholangioscopy.

Results: In the extrahepatic bile ducts, intraductal ultrasonography provided images of all the stones demonstrated on cholangioscopy (n = 11). The sensitivity was superior to that of cholangiography (P < 0.005). However, in the intrahepatic bile ducts, intraductal ultrasonography only visualized the stones located in the cannulated lobe. Extrahepatic stones smaller than 5.0 mm in diameter or in a common hepatic duct larger than 15.0 mm in diameter were missed by cholangiography, but were visualized by the use of intraductal ultrasonography (P < 0.05).

Conclusions: Intraductal ultrasonography is equivalent to cholangioscopy in the extrahepatic bile ducts. Cholangiography and intraductal ultrasonography should be used in combination to image intrahepatic and extrahepatic stones.
Shift of the gastric T‐cell response in gastric carcinoma
Authors: Ren Zhigang , Pang Gerald , Clancy Robert , Li Liang Chen , Lee Cheok Soon , Batey Robert , Borody Tom , Dunkley Margaret
Published: March 2003

Background and Aims: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)‐8, IL‐4 and interferon (IFN)‐γ were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia.

Results: Interleukin‐8 levels were higher in cancer‐ and H. pylori‐infected gastritis subjects than in H. pylori‐negative subjects (12.95 ± 3.16, 10.48 ± 1.55 and 4.49 ± 1.28 ng/mL, respectively). Elevated levels of IFN‐γ were detected in both H. pylori‐infected and non‐infected subjects with uncomplicated gastritis (72.23 ± 19.0 and 34.61 ± 5.30 pg/mL) and in non‐infected dysplasia subjects (88 ± 20.5 pg/mL). Background levels of IL‐4 (≤ 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL‐4 in dysplasia subjects (25.8 ± 7.3 pg/mL) were detected. In contrast, trace amounts of IFN‐γ (16.01 ± 0.35 pg/mL) and high levels of IL‐4 (42.81 ± 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL‐4 levels (but not IL‐8 levels) correlated with infection and mucosal anti‐H. pylori immunoglobulin G antibody.

Conclusions: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN‐γ production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.
Vascularity of advanced gastric carcinoma: Evaluation by using power Doppler imaging
Authors: Kawasaki Toshihiko , Ueo Taro , Itani Toshinao , Shibatohge Mitsushige , Mimura Jun , Komori Hideshi , Todo Akio , Kudo Masatoshi
Published: March 2003

Background: We investigated the vascularity of advanced gastric adenocarcinomas by using percutaneous power Doppler imaging.

Methods: Seventeen patients with gastric cancer and 10 without a gastric tumor, but with a slightly thick gastric wall in the B‐mode ultrasound, were investigated with the use of power Doppler imaging. The color signals of the gastric lesion were graded as follows: 1, no color signals or the same as the surroundings; 2, color signals were slightly increasing; and 3, color signals were obviously increasing.

Results: The color signals of three patients were graded 1, those of eight patients were graded 2 and those of six patients were graded 3 in the gastric cancer group. The color signals of all 10 patients without a gastric tumor were grade 1. This difference was statistically significant (P = 0.0002).

Conclusions: Power Doppler imaging showed vascularity of gastric cancer increasing in the majority of patients (14 of 17: 82%). Thus, power Doppler imaging might be a good screening examination method for gastric cancer.
Clinical significance of TT virus in chronic hepatitis C
Authors: Meng Xiang Wei , Komatsu Masafumi , Goto Takashi , Nakane Kunio , Ohshima Shigetoshi , Yoneyama Kazuo , Lin Jiun Guey , Watanabe Sumio
Published: March 2003

Background and Aims: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A–G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV).

Methods: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor‐joining method.

Results: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5′ untranslated region (5′ UTR) primer. Using both sets of primers, no differences were found between TTV‐DNA‐positive and ‐negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5′ UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non‐eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV‐RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT.

Conclusion: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV.
Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3
Authors: Macdonald Graeme A , Bridle Kim R , Ward Patrick J , Walker Neal I , Houglum Karl , George D Keith , Smith Jeffery L , Powell Lawrie W , Crawford Darrell Hg , Ramm Grant A
Published: March 2003

Background and Aims:

Hepatic steatosis has been shown to be associated with lipid peroxidation and hepatic fibrosis in a variety of liver diseases including non‐alcoholic fatty liver disease. However, the lobular distribution of lipid peroxidation associated with hepatic steatosis, and the influence of hepatic iron stores on this are unknown. The aim of this study was to assess the distribution of lipid peroxidation in association with these factors, and the relationship of this to the fibrogenic cascade.

Methods:

Liver biopsies from 39 patients with varying degrees of hepatic steatosis were assessed for evidence of lipid peroxidation (malondialdehyde adducts), hepatic iron, inflammation, fibrosis, hepatic stellate cell activation (α‐smooth muscle actin and TGF‐β expression) and collagen type I synthesis (procollagen α1 (I) mRNA).

Results:

Lipid peroxidation occurred in and adjacent to fat‐laden hepatocytes and was maximal in acinar zone 3. Fibrosis was associated with steatosis (P < 0.04), lipid peroxidation (P < 0.05) and hepatic iron stores (P < 0.02). Multivariate logistic regression analysis confirmed the association between steatosis and lipid peroxidation within zone 3 hepatocytes (P < 0.05), while for hepatic iron, lipid peroxidation was seen within sinusoidal cells (P < 0.05), particularly in zone 1 (P < 0.02). Steatosis was also associated with acinar inflammation (P < 0.005). α‐Smooth muscle actin expression was present in association with both lipid peroxidation and fibrosis. Although the effects of steatosis and iron on lipid peroxidation and fibrosis were additive, there was no evidence of a specific synergistic interaction between them.

Conclusions:

These observations support a model where steatosis exerts an effect on fibrosis through lipid peroxidation, particularly in zone 3 hepatocytes.
Glucose‐6‐phosphatase gene mutations in 20 adult Japanese patients with glycogen storage disease type 1a with reference to hepatic tumors
Authors: Nakamura Toshifumi , Ozawa Takachika , Kawasaki Tsunehisa , Nakamura Hirotoshi , Sugimura Haruhiko
Published: March 2003

Background and Aims:A few cases are reported of liver neoplasms observed in patients with glycogen storage disease type 1a (GSD1a). Genetic analysis was carried out in adult Japanese patients with GSD1a and their family members, and hepatic tumors were also investigated in these patients.

Methods:DNA was extracted from the peripheral blood lymphocytes of 20 adult patients with GSD1a and 21 family members, and mutations were detected based on the differences in the polymerase chain reaction (PCR) products of the glucose‐6‐phosphatase (G6Pase) gene shown by single‐strand conformation polymorphism (SSCP) analysis. Actual mutations were confirmed by direct sequencing. The relationship between the occurrence of liver tumors and the clinical characteristics of the patients was also investigated.

Results:Nineteen of the 20 patients were homozygous for the G727T mutation and one was a compound heterozygote for G727T plus G327A mutations. All of the 19 homozygotes for G727T had hepatomegaly, three had hepatocellular carcinoma, one had cholangiocellular carcinoma, and seven had hepatic adenoma. There were no differences between the tumor and non‐tumor groups with respect to laboratory biochemical data (P> 0.05). The mean age of G727T homozygotes with hepatocellular carcinoma was 48.3 years, and that of those with hepatic adenoma was approximately 20 years younger.

Conclusion:The G727T mutation seems to be common among Japanese patients with GSD1a, and the discovery of one heterozygote with a combination of G727T and G327A mutations (the latter mutation is common among Chinese) by the use of polymerase chain reaction–single strand conformation polymorphism analysis gave further insight into Japanese ancestry. This is the first study of liver tumors in a large group of adult GSD1a patients with the G727T mutation. As most of the patients in our series are free from other chronic liver diseases such as viral hepatitis, other genetic and/or acquired factors may have influence on the sequel to this metabolic disease.