bluuebunny/crossref_metadata_2025 huggingface dataset:
How soon can a virological sustained response be determined after withdrawal of interferon therapy in chronic hepatitis C?
Authors: Shiratori Yasushi , Kato Naoya , Yoshida Haruhiko , Imazeki Fumio , Okano Ken’ichi , Yokosuka Osamu , Omata Masao
Published: March 2003

Hepatitis C virus (HCV)‐RNA status and alanine aminotransferase (ALT) levels determined shortly after interferon (IFN) therapy in patients with chronic hepatitis C do not predict long‐term response. To determine the virological sustained response after the completion of IFN therapy, HCV‐RNA was measured at the end of treatment and at 3–4 months and 12 months after the completion of therapy in 537 patients with chronic hepatitis C. In 347 patients, HCV‐RNA was not detected by polymerase chain reaction (PCR) at the completion of therapy and 175 of these patients (50%) were still PCR negative 12 months later. In contrast, of the 180 patients who were HCV‐RNA negative at 3–4 months after completion of therapy, 99% remained negative at 12 months. Normal ALT levels were found in 80, 93 and 95% of patients who were negative for HCV‐RNA either at the end of treatment or at 3–4 months and 12 months after the completion of therapy, respectively. Of patients who were HCV‐RNA positive, 30, 15 and 20% were found to have normal ALT levels at the same respective time points. To determine a sustained virological response shortly after the completion of therapy, serum HCV‐RNA was serially examined in 66 patients negative for HCV‐RNA at the end of therapy. Of 31 patients who relapsed, HCV‐RNA reappeared in 33, 80, 97 and 100% of patients by 1, 2, 4 and 8 weeks after the completion of therapy. In conclusion, a sustained virological response could be determined with 97 and 99% certainty at 4 weeks and at 3–4 months after the completion of therapy, respectively.
Dextran sodium sulphate‐induced colitis activity varies with mouse strain but develops in lipopolysaccharide‐unresponsive mice
Authors: Stevceva Liljana , Pavli Paul , Buffinton Gary , Wozniak Andrzej , Doe William
Published: March 2003

Bacteria and their products have been implicated in the pathogenesis of chronic Inflammatory Bowel disease. The aim of this study was to investigate the potential role of lipopolysaccharides (LPS) in the development of intestinal injury by comparing the effects of the dextran sodium sulphate (DSS)‐induced model of colitis in LPS‐sensitive and ‐insensitive mice. Experimental colitis was induced in LPS‐sensitive mice (C3H/He) and their LPS‐insensitive congenic strain (C3H/HeJ). Colitis was assessed clinically using a disease activity index (derived from the three main clinical signs; diarrhoea, rectal bleeding and weight loss) and by histological scoring of the diseased colon. The clinical signs and disease activity index did not differ between the LPS‐sensitive and ‐insensitive costrains. Similarly, histological scores did not differ significantly for either C3H strain at any time point during exposure to DSS. However, there were differences in the inflammatory response when different strains were compared (C3H vs CBA): the effects of DSS in C3H mice were immediate, more severe and mainly involved the caecum and ascending colon. These findings suggest that LPS from colonic bacteria do not play a primary role in the initiation of DSS‐induced colitis and demonstrate clear differences in the responsiveness of different mouse strains to DSS.
Increased mucosal production of granulocyte colony‐stimulating factor is related to a delay in neutrophil apoptosis in Inflammatory Bowel disease
Authors: Ina Kenji , Kusugami Kazuo , Hosokawa Takehiko , Imada Akira , Shimizu Tatsuji , Yamaguchi Takeo , Ohsuga Masahiro , Kyokane Kazuhiro , Sakai Tetsu , Nishio Yuji , Yokoyama Yasuhisa , Ando Takafumi
Published: March 2003

Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony‐stimulating factor (G‐CSF) and granulocyte–macrophage CSF (GM‐CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G‐CSF and GM‐CSF in the supernatants were measured by the enzyme‐linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G‐CSF and GM‐CSF activity than controls. Notably, the levels of G‐CSF activity were approximately 1000‐fold higher than those of GM‐CSF activity. Freshly isolated PMN showed a time‐related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G‐CSF and GM‐CSF caused a concentration‐dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre‐incubation of the supernatants with anti‐G‐CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G‐CSF, in the microenvironment of IBD‐affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD.
Treatment of chronic hepatitis B virus infection: An Asia–Pacific perspective
Authors: Lau George , Carman William , Locarnini Stephen , Okuda Kunio , Lu Zhi‐Meng , Williams Roger , Lam Shiu
Published: March 2003

Chronic hepatitis B infection is a serious health threat in the Asia–Pacific area. A consensus meeting on the treatment of chronic hepatitis B infection was conducted in Hong Kong, in August 1997. It was generally agreed that treatment of chronic hepatitis B infection should be based on the understanding of the natural history of chronic hepatitis B infection. To date, interferon α is the only Food and Drug Administration (FDA)‐approved form of therapy for chronic hepatitis B infection. The overall response in Asian patients is unsatisfactory: approximately 15–20% will clear hepatitis B e antigen, but less than 5% will clear hepatitis B surface antigen. Newer immunomodulatory therapies are under trial. In contrast, nucleoside analogues, such as lamivudine (pending FDA approval) and famciclovir, have been shown to be potent suppressors of hepatitis B viral replication; however, their role as monotherapy in the treatment of chronic hepatitis B infection remains to be defined. Also, the issues of resistance to nucleoside analogues and withdrawal rebound need to be carefully studied. The future direction of therapy in chronic hepatitis B infection is probably a combination of nucleoside analogues or nucleoside analogues with immunomodulatory therapy.
CASE REPORT: Intra‐abdominal angiosarcomatosis after radiotherapy
Authors: Suzuki Fujihiko , Saito Akira , Ishi Kazuhisa , Koyatsu Junichi , Maruyama Toshihide , Suda Koichi
Published: March 2003

Background: We report a case of a 61‐year‐old Japanese woman who developed intra‐abdominal angiosarcomatosis 20 years after receiving radiotherapy for squamous cell carcinoma of the cervix.

Methods and Results: The surgically resected portion of the ileum showed diffuse proliferating angiosarcoma, with irregular channels lined by atypical vascular endothelial cells. Immunohistochemical studies showed that the tumour cells were positive for Factor VIII‐related antigen and ulex europaeus agglutinin 1. At autopsy, the tumour had disseminated to the peritoneum and invaded into the right thoracic cavity.

Conclusions: These findings were compatible with radiation‐induced angiosarcomatosis.
[14C]‐Urea breath test to confirm eradication of Helicobacter pylori
Authors: Sharma Brijesh , Bhasin Deepak , Pathak Chander , Sinha Saroj , Ray Pallab , Kim  , Singh Kartar
Published: March 2003

Background: Treatment for Helicobacter pylori reduces ulcer recurrence. Eradication rates of the organism vary with different drug regimens from 30% to 90%. There is a need to identify patients who have failed treatment. [14C]‐Urea breath test (UBT) is non‐invasive, sensitive, safe and highly reliable test for diagnosis of H. pylori infection. As there is a paucity of reports on the utility of [14C]‐UBT in confirming H. pylori eradication, this study was undertaken.

Methods: Thirty‐eight patients (age 34 ± 17 years, range 16–84 years, 27 men) with upper gastrointestinal symptoms underwent upper gastrointestinal endoscopy. Baseline H. pylori infection was diagnosed by identification of the organism on antral biopsies and positive rapid urease test (RUT). After 1 month of completion of treatment, repeat RUT and histological examination of antral endoscopic biopsies were performed. Eradication of H. pylori was defined as absence of the organism on histology, and negative RUT. The [14C]‐UBT was performed using 185 kBq [14C]‐urea dissolved in 300 mL water. Breath samples were collected once before ingestion of [14C]‐urea, and subsequently at 5 and 15 min. Results were expressed as 14CO2/mmol CO2 exhaled as per cent of administered urea.

Results: Endoscopy revealed antral gastritis (n = 14), duodenal ulcer (n = 8), duodenitis (n = 2), oesophagitis (n = 1), antral gastritis and duodenal ulcer (n = 3), antral gastritis and duodenitis (n = 7) and normal upper gastrointestinal endoscopy (n = 3). All the 20 patients who were negative for H. pylori on RUT and histology, tested negative for H. pylori on [14C]‐UBT. However, of 18 patients shown to have H. pylori infection on RUT and histology, 16 were positive for H. pylori on [14C]‐UBT. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of [14C]‐UBT were 100, 89, 91, 100 and 95% respectively.

Conclusions: The [14C]‐UBT is a reliable indicator of H. pylori eradication after treatment. It can obviate the need for antral biopsies to confirm eradication of H. pylori after completion of treatment.
High‐dose natural interferon‐α therapy for chronic hepatitis C with a high viral load: Predictors of efficacy
Authors: Komatsu Masafumi , Suto Toshiyuki , Ishikawa Kazuyoshi , Sato Shunichi ,   THE AOMORI, AKITA and IWATE AREAS VIRAL HEPATITIS RESEARCH GROUP
Published: March 2003

Background: The effectiveness of interferon against hepatitis C has been found to be greatly affected by viral factors. However, few controlled interferon trials have involved seemingly intractable cases of chronic hepatitis C.

Methods: In 44 patients with high hepatitis C virus RNA levels (≥ 105 copies/mL), we carried out a prospective, controlled study of two natural interferon‐α regimens, seeking predictors of therapeutic efficacy. Total natural interferon‐α doses over 6 months in two groups were 780 and 840 million units, respectively.

Results: High therapeutic efficacy was achieved with no significant outcome difference between the regimens. The virus eradication rate was 35% and the rate of sustained biochemical response was 45% for both regimens. Multivariate logistic regression analysis identified viral genotype as the only significant predictor of success in viral eradication.

Conclusions: Hepatitis C virus genotype 2 showed high sensitivity to interferon‐α and this therapy can be recommended even for patients with a high viral load of this genotype. In contrast, with genotype 1b, cure was extremely difficult in cases with 107 or more copies/mL with a single 6‐month course of interferon‐α.
Modelling the hepatitis C virus epidemic in Australia
Authors: Law1 Matthew G
Published: March 2003

Introduction
: In Australia, to the end of 1997, more than 110 000 people have been diagnosed with hepatitis C virus (HCV) antibodies and reported to State/Territory surveillance systems. The available data indicate that the overwhelming majority (around 80%) of people with HCV antibodies were infected through injecting drug use.

Methods
: Models of the HCV epidemic in Australia were developed based on estimates of the pattern of injecting drug use in Australia. Estimates of HCV infections due to injecting drug use thus obtained were then adjusted to allow for HCV infections resulting from other transmission routes. Projections of cirrhosis and hepatocellular carcinoma (HCC) resulting from HCV were obtained by combining modelled HCV incidence with estimates of the progression rates to these outcomes.

Results
: Based on the models, it was estimated that there were 196 000 (lower and upper limits of 149 000 and 234 000) people in Australia living with HCV antibodies at the end of 1997, with HCV incidence in 1997 estimated to be 11 000 (8500–13 500). It was estimated that 8500 (4000–13 000) people were living with HCV‐related cirrhosis in 1997 and that there were 80 (40–125) incident cases of HCV‐related HCC.

Discussion
: Model‐based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV‐related cirrhosis and the incidence of HCV‐related HCC will more than double in Australia by 2010.

© 1999 Blackwell Science Asia Pty Ltd
Genetically distinct strains of Candida albicans with elevated secretory proteinase production are associated with diarrhoea in hospitalized children
Authors: Mathaba Leslie T , Paxman Adrian E , Ward Peter B , Forbes David A , Warmington John R
Published: March 2003

Background
: Candida albicans has been implicated as the aetiological agent in a significant percentage of children with diarrhoea. The virulence properties of C. albicans strains associated with acute and chronic diarrhoea in hospitalized children were investigated.

Methods
: The genotypic relationships between the isolates were determined using restriction enzyme analysis and hybridization with a C. albicans‐specific DNA probe, 27A.

Results and Conclusion
: In patients with acute and chronic diarrhoea, there is evidence for selection of specific, genetically distinct strains of C. albicans. Higher levels of secretory Candida acid proteinase produced by isolates from patients with acute diarrhoea may account for the more severe symptoms. However, the lower adherence of these isolates may predispose to the rapid (within 2 to 4 days) resolution of the condition. In patients with chronic diarrhoea the lower levels of proteinase produced correlate with the less severe symptoms, while the increased adherence may account for the persistence of the infection.
Acute hepatic failure in India: A perspective from the East
Authors: Acharya Subrat K , Panda Subrat K , Saxena Alka , Gupta S Datta
Published: March 2003

Acute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95–100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one‐quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high‐risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non‐pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF. In our centre, approximately one‐third of AHF patients survive with aggressive conservative therapy, whereas two‐thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and Gram‐negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.
Treatment of chronic liver diseases with traditional Chinese medicine
Authors: Wang Bao‐En
Published: March 2003

Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti‐viral herbs, Phyllanthus amarus, P. niruri and P. urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN‐α. The anti‐inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6% and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV‐related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer’s and Chevallier’s criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.
Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum
Authors: Iijima Akihiro , Tanaka Eiji , Kobayashi Masanori , Yagi Shintaro , Mizokami Masashi , Kiyosawa Kendo
Published: March 2003

Background
: Hepatitis C virus (HCV) viraemia is one of the factors for histological prognosis of chronic hepatitis C.

Methods
: One hundred and thirty‐five patients who received hepatic biopsies twice at intervals of 5 years or longer were followed up for a mean of 9.7 ± 4.0 years were studied retrospectively. The amount of HCV viraemia present was measured as the concentration of HCV core protein by using the fluorescence enzyme immunoassay method.

Results
: Multiple‐regression analysis, using deterioration of the histological stage as a dependent variable, showed that greater age (P = 0.041), higher stage of hepatic histology at the start of follow up

(P = 0.029), and higher serum concentration of core protein (P < 0.001) were independent factors affecting the deterioration of the liver’s histological stage. At follow up, no significant difference in histological stage was seen between patients with serum HCV core protein ≥ 100 pg/mL (n = 60) and those with serum core protein < 100 pg/mL (n = 75). The histological grade in patients with high serum core‐protein levels tended to be significantly worse and the deterioration rate of the histological stage was significantly higher than in those with low HCV core protein levels (68 vs 35%, P < 0.001). The mutation rate of the HCV envelope‐2/non‐structural 1 (E2/NS1) nucleotide region was compared in two patients who had high serum concentrations of HCV core protein and whose histological stage had deteriorated with two patients who had low serum concentrations of the core protein and whose histological stages remained unchanged. No significant difference in E2/NS1 mutation was found.

Conclusions
: The amount of HCV viraemia was suggested to be a significant factor for determining histological outcome in patients with chronic hepatitis C. The mutation rate in the E2/NS1 region did not seem to be associated with the prognosis of chronic hepatitis C.

© 2000 Blackwell Science Asia Pty Ltd
Molecular biology of hepatitis A virus: Significance of various substitutions in the hepatitis A virus genome
Authors: Yokosuka Osamu
Published: March 2003

Hepatitis A virus (HAV) is the sole member of the hepatogenus of Picorna viridae. This virus can now be propagated in cell culture and in primates. Molecular biological studies of HAV have disclosed its genomic structure and the functional significance of the viral proteins to some extent. Hepatitis A virus has a positive‐stranded RNA of approximately 7.5 kb that encodes a large polyprotein. Translation of the protein is influenced by the function of the internal ribosomal entry site in the 5′ non‐translating region. It is generally agreed that the polyprotein is processed to four structural and seven non‐structural proteins by the proteinase encoded in the 3C region. Replication efficiency seems to be controlled by amino acid substitutions in the 2B and 2C regions. The virulence of HAV in primates may be determined by substitutions in the 2C region. Although the severity of hepatitis A was thought to be determined by immunological reactions of the host to the virus, the potential virulence of the variant viruses themselves may need further examination. Recent progress in polymerase chain reaction technology has made possible an analysis of the HAV sequence in clinical specimens; such analysis is of importance in the disclosure of differences in HAV subspecies in different clinical conditions.
Mechanism of gastric mucosal proliferation induced by gastrin
Authors: Kinoshita Yoshikazu , Ishihara Shunji
Published: March 2003

Gastrin has a potent trophic effect on gastric fundic mucosa. When serum concentrations of gastrin are elevated, proliferation of both the progenitor cells in the glandular neck zone and enterochromaffin‐like (ECL) cells in the bottom of the glands is stimulated. Because ECL cells have gastrin receptors, their proliferation is directly stimulated by gastrin. However, because the proliferation of progenitor cells cannot be directly stimulated (so far there has been no gastrin receptor demonstrated on these proliferating cells), some indirect mechanisms must be involved. Enterochromaffin‐like and parietal cells are only two types of cells that have demonstrated a strong gene expression of the gastrin receptor. Furthermore, they secrete several growth factors, such as Reg protein, heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and amphiregulin (AR). Reg protein production by ECL cells, as well as HB‐EGF and AR production by parietal cells, is stimulated by gastrin and these growth factors are potent trophic agents of progenitor cells in the neck zone of the gastric fundic mucosa. Accordingly, gastrin may stimulate the proliferation of gastric mucosal cells indirectly via these growth factors in addition to its direct trophic effect on ECL cells.
Gastrointestinal metastasis in hepatocellular carcinoma: Radiological and endoscopic studies of 11 cases
Authors: Lin Chi‐Pin , Cheng Jin‐Shiung , Lai Kwok‐Hung , Lo Gin‐Ho , Hsu Pin‐I , Chan Hoi‐Hung , Hsu Jui‐Hung , Wang Ya‐Yu , Pan Huay‐Ben , Tseng Hui‐Hwa
Published: March 2003

Background
: From October 1990 to January 1999, 11 of 2237 hepatoma patients at our hospital had gastrointestinal tract metastasis. We describe the radiological and endoscopic features, clinical course and prognoses of those patients.

Methods
: All patients were male. Six patients were hepatitis B carriers, and cirrhosis was noted in eight patients on admission. We reviewed all available radiological, endoscopic and pathological features.

Results
: The commonest clinical presentation was frank gastrointestinal bleeding. Histological proof of gastrointestinal involvement was seen in six patients. Endoscopic features included ulcerative tumours mimicking advanced gastric carcinoma (43%) and submucosal tumours (29%). The sites of organ involvement were stomach (five), duodenum (two), colon (three) and duodenum and colon (one). Direct invasion by a contiguous neoplasm was the major route of gastrointestinal tract metastasis. Portal vein thrombosis may be the key point of haematogenous spread to other sites.

Conclusions
: The prognosis in these patients was extremely poor. Almost all patients died within 5 months if no further aggressive management was performed. Surgical intervention may be the optimal choice for palliative treatment of HCC with gastrointestinal tract involvement.
Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens
Authors: Shimamura Takeshi , Saito Satoru , Morita Katsumi , Kitamura Takehiko , Morimoto Manabu , Kiba Takayoshi , Numata Kazushi , Tanaka Katsuaki , Sekihara Hisahiko
Published: March 2003

Background
: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours.

Methods
: Using nested reverse‐transcription–polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and flt‐1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens.

Results
: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non‐tumour portion of the specimens in eight patients (57%; P = 0.08). No differences were found between the tumour portion and the corresponding non‐tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and flt‐1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non‐tumour portions, respectively (χ2 test: KDR, P < 0.01; flt‐1, P = 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non‐tumour portions (Mann–Whitney U‐test: P < 0.001) but no differences were detected for flt‐1.

Conclusions
: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.
Spontaneous regression of hepatocellular carcinoma and review of literature
Authors: Takeda Yoshio , Togashi Hitoshi , Shinzawa Haruhide , Miyano Shintaro , Ishii Rika , Karasawa Tetsuru , Takeda Yumiko , Saito Takafumi , Saito Koji , Haga Hiroko , Matsuo Taku , Aoki Masanori , Mitsuhashi Hideki , Watanabe Hisayoshi , Takahashi Tsuneo
Published: March 2003

A 68‐year‐old man presented with multiple hepatocellular carcinoma, which was considered to be unresectable at the first admission in January 1994. Pathological diagnosis was made by biopsy of the one lesion among them. From January 1994 to December 1997, 10 transarterial chemoembolizations and six percutaneous ethanol injection therapies were performed on the tumours in the cirrhotic liver. In February 1998 the tumour situated in the right lobe began to increase in size. The maximum tumour diameter was 6.3 cm measured by computed tomography (CT). In the beginning of May 1998 moderate ascites was present and mild hepatic encephalopathy was noticed. The patient was in the terminal stage of hepatocellular carcinoma and no further treatment was possible at that time. However, serum α‐fetoprotein and protein induced by vitamin K absence or antagonist II dramatically decreased in June 1998. The CT scan also showed that the tumour had completely regressed without specific treatment. In February 1999 a new biopsy‐proven hepatocellular carcinoma, 2 cm in diameter, developed in the lateral segment of the liver. It was well treated by percutaneous ethanol injection therapy. The patient was alive in good condition without any symptoms or tumour recurrence in June 1999. It was concluded that a rare case of spontaneous regression of hepatocellular carcinoma had occurred.
Duodenal ulcer prevalence: Experimental evidence for the possible role of dietary lipids
Authors: Jayaraj A Paul , Tovey Frank I , Lewin Michael R , Clark Charles G
Published: March 2003

Background and Aims
: Mapping the geographical distribution of duodenal ulcer in relation to staple diets, and experiments on animal peptic ulcer models suggested that the lipid fraction in certain foodstuffs had a protective effect which was most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid obtained from stored polished rice or rice bran was ulcerogenic. Further animal experiments were designed to investigate the protective and healing effects of Horse gram lipid (HGL) against peptic ulceration.

Methods
: Three effects were investigated in rats: (i) the protective effect of HGL on peptic ulceration produced by using pyloric ligation in combination with South Indian diet or rice bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast cell degranulation in response to pyloric ligation and rice bran oil; and (iii) the healing effect of HGL on acute gastric ulceration produced by alcohol, on chronic gastric ulceration produced by topical acetic acid or on chronic duodenal ulcer following cysteamine.

Results
: Horse gram lipid was shown to be protective and to promote ulcer healing in all the models used. Mast cell degranulation was inhibited.

Conclusion
: The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.
Dendritic cell‐based cancer immunotherapy: Potential for treatment of colorectal cancer?
Authors: Chen Wangxue , Rains Natalie , Young David , Stubbs Richard S
Published: March 2003

Human tumours including those of the gastrointestinal tract express a number of specific antigens that can be recognized by T cells, thus providing potential targets for cancer immunotherapy. Dendritic cells (DC) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells, and so selectively migrate through tissues to reach lymph nodes and spleen where initiation of immune responses takes place. Studies in murine tumour models have shown clearly that DC are capable of presenting tumour antigens to initiate tumour‐specific cytotoxic T cell responses, and DC vaccination can induce anti‐tumour activity against both primary tumours and pre‐established tumour metastases. These findings together with the ability to culture sufficient numbers of DC from human bone marrow or blood progenitors have prompted the current major interest in their potential use in human tumour vaccination. Vaccine production involves harvesting autologous DC from cultured peripheral blood mononuclear cells in the presence of a cocktail of cytokines, ex vivo exposure of the DC to tumour antigens and return of pulsed DC to the patient to induce tumour immunity. Reports from Phase I/II clinical trials indicate that DC vaccines are safe with little or no side effect, and are capable of initiating antigen‐specific T cell responses. Furthermore, defined tumour antigens are not necessarily required, which may make the process more applicable to human cancers, including many gastrointestinal cancers that lack well‐characterized tumour‐specific antigens. Additional trials of DC vaccination for a variety of human cancers including colorectal cancers are under way, and refinement of vaccine protocols and methods for targeting tumour antigens to DC in vivo are also being explored. There is reason to believe that DC‐based vaccination could become an adjunct to current treatments for human cancers including colorectal cancer in the foreseeable future.
Cyclo‐oxygenase‐2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats
Authors: Sun Wei‐Hao , Tsuji Shingo , Tsujii Masahiko , Gunawan Edhi S , Sawaoka Hitoshi , Kawai Naoki , Iijima Hideki , Kimura Arata , Kakiuchi Yoshimi , Yasumaru Masakazu , Sasaki Yutaka , Kawano Sunao , Hori Masatsugu
Published: March 2003

Background and Aims
: The present study examined the effects of NS‐398, a specific cyclo‐oxygenase‐2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid‐induced injury.

Methods
: Male Sprague‐Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS‐398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo‐oxygenase (COX‐1) and mitogen‐inducible cyclo‐oxygenase (COX‐2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA).

Results
: Although there was strong expression of COX‐1, there was minimal expression of COX‐2 in the gastric mucosa. Expression of COX‐2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and NS‐398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury.

Conclusion
: The present study demonstrated that cyclo‐oxygenase‐2 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo‐oxygenase‐2 has an important role in gastric mucosal regeneration.
Reutilization of accessories in gastrointestinal endoscopic practice
Authors: Haber GB
Published: March 2003

Abstract The key issues that determine the decision between reusable versus disposable accessories are cost and functionality. In most health‐care systems the availability and dissemination of endoscopic services relates directly to the resources (i.e. budget) of that system. Given the limitations of health‐care budgets, access to endoscopic services will depend upon the cost efficiency of endoscopic practice. The onus on endoscopists and health‐care providers, therefore, is to meticulously evaluate the necessary steps for safe reutilization of accessories. This paper addresses the principles of reuse, quality assurance and particularly disinfection practices. Any change to a more costly disposable accessory policy must bear the responsibility of denied access to endoscopic services in a system with finite resources.
Portal‐systemic encephalopathy in non‐cirrhotic patients: Classification of clinical types, diagnosis and treatment
Authors: Watanabe Akiharu
Published: March 2003

Abstract Hepatic encephalopathy is suspected in non‐cirrhotic cases of encephalopathy because the symptoms are accompanied by hyperammonaemia. However, the cause of the large portal‐systemic shunt formation observed in these cases is not clear, as cirrhosis and portal hypertension are absent. The frequency of such cases reported in the literature is increasing with progress and spread of abdominal imaging diagnostic techniques. Some cases have been misdiagnosed as psychiatric diseases (dementia, depression and others) and consequently patients have been hospitalized in psychiatric institutions or geriatric facilities. Some paediatric cases have also been misdiagnosed. Therefore, the importance of accurate diagnosis of this disease should be strongly emphasized. Some paediatric cases have also been misdiagnosed. When psychoneurological symptoms are suggestive of hepatic encephalopathy but objective and subjective symptoms or abnormal values of liver function tests are not sufficiently indicative of liver cirrhosis, portal‐systemic encephalopathy should be suspected. Abnormal angiograms of the portal vein, superior mesenteric vein or splenic vein are conclusive evidence of portal‐systemic encephalopathy. Transrectal portal scintigraphy also provides information useful for detection of shunts and a quantitative estimation of shunt index. We classified the disease into five types based on whether the shunt is formed inside or outside the liver. Type I (intrahepatic type) designates cases in which shunts are located between the portal and systemic veins. Type II designates a type of intra/extrahepatic shunt that originates from the umbilical part of the portal vein and serpentines in the liver, then leaves the liver. Type III (extrahepatic type) occurs most frequently. Type IV (extrahepatic) is accompanied by shunts similar to those in type III, but hepatic pathology presents as idiopathic portal hypertension. Type V (extrahepatic) represents the congenital absence of the portal vein, where the superior mesenteric vein joins the intrahepatic inferior vena cava or the left renal vein. The prevalence of each type in our country was examined by a nationwide investigation. In addition to the conventional diet or drug treatments, obliteration by less invasive interventional radiology using a metallic coil and ethanol has recently been used more frequently than surgical occlusion of shunts. Shunt‐preserving disconnection of portal and systemic circulation and partial splenic artery embolization are also performed. International investigation of the disease status and establishment of diagnostic and therapeutic methods for the disease are awaited and investigation of long‐term prognosis after therapy is also necessary.
Effect of acute and long‐term oral tobacco use on oesophageal motility1
Authors: Bhandarkar Prashant V , Shah Saumil K , Meshram Megha , Abraham Philip , Narayanan Ts , Bhatia Shobna J
Published: March 2003

Background and Aims
: Nicotine administration is known to decrease lower oesophageal sphincter (LOS) pressure. Although a few studies have assessed the effect of tobacco on the LOS, the effect of acute and long‐term oral tobacco use on oesophageal motility is not known. The study was designed to investigate the effect of acute and long‐term oral tobacco use on LOS and distal oesophageal motility.

Methods
: Thirty‐six healthy men (aged 18–65 years, median 34 years; 18 oral tobacco users, 18 non‐tobacco users) underwent oesophageal manometry using a water‐perfusion system. After baseline manometry, tobacco users were asked to keep 0.5 g tobacco in their mouth for 10 min; non‐users of tobacco were kept in quiet surroundings for a similar period. Manometry was then repeated.

Results
: The LOS basal pressures were similar in tobacco users and non‐tobacco users (mean ± SD 15.4 ± 6.3 vs 13.4 ± 5.3 mmHg). In the distal oesophageal body, the velocity (4.4 ± 3.1 vs 4.9 ± 2.6 cm/s), amplitude (92.7 ± 38.3 vs 84.8 ± 33.2 mmHg) and duration of contraction (2.1 ± 0.7 vs 1.7 ± 0.9 s) were similar in tobacco users and non‐users. Acute tobacco use did not affect these parameters. The numbers of abnormal waves (triple peaks and non‐transmitted contractions) were also similar in the two groups.

Conclusion
: Oral tobacco use does not appear to affect LOS pressures and distal oesophageal motility acutely or in the long term.
Frequency and significance of antibodies to chromatin in autoimmune hepatitis type I
Authors: Li, Lu , Nishioka, Mikio , Huang, Dong Yang , Nishioka Mikio
Published: March 2003

Abstract Aims and Methods: To assess the frequency and clinical significance of antibodies to chromatin (ACA) in autoimmune hepatitis (AIH), 36 Japanese patients with AIH type I were studied for serum reactivity with chromatin by using an ELISA.

Results: Antibodies to chromatin were detected in 19 of 36 patients with AIH type I. There was a significantly higher frequency of ACA in patients with AIH type I than in patients with primary biliary cirrhosis, chronic hepatitis C and B (52.8 vs 13.2, 5.4 and 6.7%, respectively; P < 0.01). None of the 19 healthy subjects had positive reactions. Sixteen of 19 patients with seropositive sera (44.4%) had reactivities with other nuclear antigens (recombinant nucleoproteins U1RNP‐A, U1RNP‐70; recombinant ribonucleoprotein complexes SSA/Ro 52K, SSA/Ro 60K; recombinant centromere Cenp‐B; dsDNA and histones). Adsorption with double‐stranded DNA (dsDNA) and histones could not remove the majority of antichromatin reactivity as 81.9% of the antibody reactivity still remained. In five sera samples from AIH type I patients positive for anti‐dsDNA and antihistones, the antibody activities for dsDNA and histones were inhibited after the absorbtion of sera with chromatin. The patterns of antinuclear antibodies (ANA) detected by using indirect immunofluorescence were similar between patients with and without ACA. Patients with ACA had significantly high serum levels of gamma‐globulin and immunoglobulin G. The ACA titers dropped significantly after corticosteroid treatment (P < 0.01).

Conclusions: Antibodies to chromatin are frequently present in patients with AIH type I and they are one of the dominant autoantibodies associated with ANA reactivity in AIH type I. Antibodies to chromatin cannot be used to characterize distinct clinical subgroups of AIH type I.
A case of inability to belch
Authors: Tomizawa Michiko , Kusano Motoyasu , Aoki Takashi , Ohashi Sae , Kawamura Osamu , Sekiguchi Toshikazu , Mori Masatomo
Published: March 2003

Abstract A 22‐year‐old man was unable to belch. He could sense intraesophageal gas, but had no chest pain. An upper gastrointestinal X‐ray series and endoscopic examination showed no abnormalities. Esophageal manometry showed normal relaxation of both the upper and lower esophageal sphincters with primary peristalsis during deglutition. However, bolus injection of air into the middle esophagus failed to initiate the belch reflex.
Long‐term evaluation of extracorporeal shock‐wave lithotripsy for cholesterol gallstones
Authors: Tsumita Reiko , Sugiura Nobuyuki , Abe Asami , Ebara Masaaki , Saisho Hiromitsu , Tsuchiya Yukihiro
Published: March 2003

Background: Extracorporeal shock‐wave lithotripsy (ESWL) is a treatment that preserves the gallbladder. Problems after ESWL treatment include stone recurrence and the development of biliary symptoms.

Methods: Two hundred and sixty‐two patients with cholesterol‐type gallstones, the best indication for ESWL treatment, and 42 control patients with cholesterol‐type gallstones who received no treatment entered this study. We evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment.

Results: The 3‐, 5‐ and 7‐year cumulative probabilities of gallstone recurrence were 20.6, 27.1 and 33.1%, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, ursodeoxycholic acid (UDCA) treatment was effective. In 69 patients with residual gallstones, the 3‐, 5‐ and 7‐year cumulative risks of biliary symptoms were 17.3, 24.9 and 30.5%, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a ≤ 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL‐treated patients with residual stones who had a ≤ 3 mm fragment size after treatment compared to those of control patients.

Conclusions: Ursodeoxycholic acid was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to ≤ 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms.
Aging increases, and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia
Authors: Tsukui Taku , Kashiwagi Ryoichi , Sakane Masayoshi , Tabata Fumihira , Akamatsu Tomonori , Wada Ken , Futagami Seiji , Miyake Kazumasa , Sueoka Nobuo , Hirakawa Tsunehisa , Kobayashi Masafumi , Fujimori Takahiro , Sakamoto Choitsu
Published: March 2003

Abstract Background and Aims: The classification of gastritis by using the revised Sydney system suggests that there are two types of Helicobacter pylori‐related gastritis. The aim of the present study was to examine the risk factors that might be involved in the presence of either atrophic gastritis or intestinal metaplasia of the gastric corpus of Japanese patients.

Methods: Biopsy samples were obtained from the gastric corpus in 154 patients with dyspepsia, and the degree of atrophy or intestinal metaplasia was determined histologically. The correlation between several variables and presence of atrophy or intestinal metaplasia was evaluated by using multivariate analysis.

Results: Among the 11 variables, which included age, peptic ulcer diseases and H. pylori infection, H. pylori infection was the major risk factor associated with the presence of atrophic gastritis or intestinal metaplasia of the gastric corpus. In contrast, duodenal ulcer (DU) disease reduced the risk of contracting both conditions. Age was an independent risk factor only for intestinal metaplasia of the gastric corpus. When 128 H. pylori‐positive subjects were analyzed, DU and age were similarly associated with the presence of both conditions.

Conclusions: These results suggest that DU reduces the risk for contracting atrophic gastritis and intestinal metaplasia, and age is an independent risk factor for intestinal metaplasia of the gastric corpus in dyspeptic Japanese patients.
Small intestinal mucosal pattern of Myanmar children
Authors: Aye Win‐Myat , Htwe Than‐Than , Khin Myo , Hla S‐Kyaw , Myint Thein‐Thein , Bolin Terry D
Published: March 2003

Background:Little is known about the small intestinal mucosal pattern of Myanmar children.

Methods:Duodenal, jejunal and ileal mucosal specimens obtained from children within 6 h of death were examined under a dissecting microscope with the objective of determining villus pattern in relation to site within the small intestine and then correlated with age.

Results:Abnormalities in the small intestinal mucosa were detected at a very young age. In children under 1 year of age, the changes are more marked proximally and become less marked distally, perhaps reflecting exposure to the causative agent(s) in early life. Presumably these agents are ingested orally and inactivated progressively. The pattern in older children reflects more severe changes in the ileum.

Conclusions:It is postulated that frequent intestinal infections or small bowel bacterial contamination could lead to damage of the intestinal mucosa.