bluuebunny/crossref_metadata_2025 huggingface dataset:
Different processing of bile canalicular antigen in well and poorly differentiated human hepatoma cell lines
Authors: CHIU J‐H. , HU C‐P. , LUI W‐Y. , CHANG H‐M. , CHANG C.
Published: March 2008

Hepatocytes, known as polarized epithelia, are composed of sinusoid, basolateral and bile canalicular domains. Using monoclonal antibody and human hepatoma cell lines, the canalicular domain was shown to be established in well‐differentiated lines via vesicle fusion, but not in poorly differentiated lines. To understand the metabolic processing of the bile canalicular antigen in different human hepatoma cell lines, monoclonal antibody C2D4 was produced by immunizing BALB/C mice with human hepatoms cell line HA22T/VGH and fusing sensitized mouse spleen cells with mouse myeloma cells. Using two‐dimensional polyacrylamide gel electrophoresis, the monoclonal antibody C2D4 was shown to react with the same molecule recognized by monoclonal antibody 9B2, which had been known to react with the antigen on the bile canalicular domain of human hepatocytes and hepatoma cells, both in vivo and in vitro. Analysed with pulse‐chase radioimmunoprecipitation, C2D4 precipitated the 140 kD polypeptide through a 1–4 day well‐differentiated cell line, Hep G2; whereas in addition to the 140 kD polypeptide, an 80 kD protein was recognized by C2D4 in a 2 or 3 day poorly differentiated line, SK‐HEP‐1. Together with peptide mapping and subcellular fractionation analysis, the 80 kD protein was postulated to be internally degraded in the intracellular compartment, but not on the cytoplasmic membrane. It was concluded that the human hepatoma cell lines could be a good in vitro model to study the metabolic processing of bile canalicular domains of human hepatocytes. Also, the loss of the cellular polarity in poorly differentiated human hepatoma cell lines provides a good natural variant to study the differentiation and progression of human hepatoma cells.
Variations in nucleotide sequence of the 5′ untranslated region of hepatitis C viruses
Authors: LEE C‐H. , CHENG C. , WANG J. , LUMENG L.
Published: March 2008

The nucleotide sequence of the 5′ untranslated region of hepatitis C viruses (HCV) has been shown to be conserved. In contrast, this study detected in the region of several HCV isolates more sequence variation than hitherto expected. The nucleotide sequences of the 5′ untranslated region of these isolates differ significantly from that of the prototype but are very similar to each other. This study considers these isolates as belonging to the same type of HCV. Among 240 HCV RNA polymerase chain reaction positive specimens that were examined, seven of them belong to this type. The results suggest that the HCV variants detected represent a different type of HCV and that they are responsible for approximately 3% of HCV infections in this part of the United States.
Hepatitis B virus antibody escape mutant from Singapore
Authors: HARRISON T. J. , VALLIAMMAI T. , HOPES E. A. , OON C. J. , ZUCKERMAN A. J.
Published: March 2008

In order to prevent perinatal infection, the child of a hepatitis B e antigen‐positive mother was given hepatitis B immune globulin and vaccinated against hepatitis B virus (HBV) at birth. Despite circulating antibody to hepatitis B surface antigen (anti‐HBs), the child became infected and is a carrier. Recent serum samples show the co‐existence of hepatitis B surface antigen and anti‐HBs. This study tries to determine whether failure to neutralize this virus by anti‐HBs was associated with a change in the amino acid sequence of the surface protein of HBV. The polymerase chain reaction was used to amplify the region of the hepatitis B surface open reading frame encoding the major antigenic determinants from serum samples taken from the child at 2, 5 and 6 years of age. Nucleotide sequence analysis of the products revealed a point mutation which resulted in a substitution of arginine for glycine at amino acid position (145) in the second loop of the a determinant.
Acute post‐transfusion hepatitis C in Taiwan: Evaluation of two generations of hepatitis C virus diagnostic enzyme immunoassay
Authors: LEE S‐D. , HWANG S‐J. , TSAI Y‐T. , LU R‐H. , LO K‐J.
Published: March 2008

A total of 461 patients at the Veterans General Hospital, Taipei who had received blood transfusions since March 1981 were followed prospectively with serum biochemistry tests and viral hepatitis markers before and after the blood transfusions, periodically for at least 6 months. Sixty‐three (13.7%) patients developed post‐transfusion hepatitis (PTH). Of the patients with PTH, 71.4% were found to have antibody to hepatitis C virus (anti‐HCV) seroconversion during the 1 year follow‐up period by the first‐generation of the hepatitis C virus (HCV) enzyme immunoassay (EIA) antibody test, but the second‐generation EIA detected an increase to 88.9%. All sera positive by the first‐generation EIA were also positive by the second‐generation EIA. Their mean incubation of serum alanine aminotransferase (ALT) elevation was 6.5 weeks. The mean interval between the day of blood transfusion and the onset of active anti‐HCV seroconversion was 18.3 weeks if tested by the first‐generation EIA, but shortened to 9.5 weeks if tested by the second‐generation EIA. Of 49 acute PTH C patients who were followed up for more than 1 year, 32 (65.3%) still had abnormal serum ALT levels. The results of this study demonstrate that acute hepatitis C is a frequent and important complication in blood transfusions in Taiwan. The second‐generation HCV antibody EIA derived from HCV genes encoding both capsid and non‐structural proteins is more sensitive for detection of HCV infection than recombinant c100‐3 assay derived from the non‐structural region of the viral genome only.
A randomized controlled clinical trial of recombinant interferon α‐2b in the treatment of acute post‐transfusion hepatitis C: A preliminary report
Authors: HWANG S‐J. , LEE S‐D. , LEE Y‐H. W. , WU J‐C. , CHAN C‐Y. , HUANG Y‐S. , WANG Y‐J. , LO K‐J.
Published: March 2008

Twenty patients with acute post‐transfusion hepatitis C were prospectively followed after blood transfusion. All had seroconversion of serum antibody to hepatitis C virus (anti‐HCV) or hepatitis C virus (HCV) RNA. They were randomly allocated to two groups. Ten patients received a subcutaneous injection of recombinant interferon (IFN) α‐2b, 3 million units (MU) thrice weekly for 3 months; this was generally 8 weeks after the first post‐transfusional elevation of serum alanine transaminase (ALT). Ten patients without specific treatment were selected as a control group. During the 3 month period, nine (90%, 95% CI = 54–99%) patients in the IFN‐treated group normalized serum ALT level, while only three (30%, 95% CI = 8–65%) in the control group normalized the serum ALT spontaneously (P < 0.01). Two (25%) of eight patients who initially showed a complete response to IFN‐treatment had serum ALT elevated again. After a 6 month follow‐up, five (63%, 95% CI = 26–90%) of eight patients in the IFN‐treated group and four (44%, 95% CI = 15–77%) of nine patients in the control group normalized serum ALT (P= 0.40). Among the nine patients who normalized serum ALT during IFN treatment, eight had undetectable serum HCV RNA and one showed a decreased level. Two patients had detectable serum HCV RNA accompanied by elevated serum ALT again after completion of the IFN treatment. After 6 months follow‐up four (50%, 95% CI = 17–83%) of eight patients lost their serum HCV RNA in the IFN‐treated group and two (22%, 95% CI = 4–60%) of nine patients spontaneously lost their HCV RNA in the control group (P= 0.25). All patients tolerated the IFN treatment well but had minor side effects such as fever, rigor, malaise, leukopenia, myalgia, headache and hair loss. In conclusion, recombinant IFN α‐2b injections in patients with acute post‐transfusion hepatitis C can successfully suppress the viral RNA and lead to normalization of serum ALT. Whether this regimen can prevent the development of chronicity needs further evaluation.
Hepatitis B vaccine trial in neonates
Authors: LO K‐J. , LEE S‐D. , TSAI Y‐T. , WU T‐C. , YU M‐Y. , WANG Y‐J. , CHAN C‐Y.
Published: March 2008

In an attempt to interrupt perinatal and postnatal transmission of hepatitis B virus (HBV) infection, hepatitis B vaccine trials were initiated in October 1981 in Taiwan, starting in neonates of hepatitis B e antigen (HBeAg)‐positive hepatitis B surface antigen (HBsAg) carrier mothers and extending to neonates of non‐carrier mothers. All neonates had received a four‐dose schedule of Pasteur plasma‐derived hepatitis B vaccine. Among neonates of HBeAg‐positive HBsAg carrier mothers, the protective efficacy rate of vaccination was 75% in those who received vaccine alone and 90% in those who received vaccine plus hepatitis B immunoglobulin (HBIG) at birth. Among neonates of HBeAg‐negative HBsAg carrier mothers, the protective efficacy rate was 100% whether they had received vaccine alone or vaccine plus HBIG at birth. The protective efficacy rate was also 100% in neonates of non‐carrier mothers. During 6–9 years of long‐term follow‐up, 12 (6%) responsive vaccinees of HBeAg‐positive carrier mothers, one (2%) child of HBeAg‐negative carrier mothers and one child (0.4%) of non‐carrier mothers had seroconverted to antibody to hepatitis B core antigen (anti‐HBc) positivity. ‘Natural booster’ phenomenon, defined as a spontaneous sharp rise in serum antibody to HBsAg (anti‐HBs) titres in the absence of anti‐HBc and HBsAg, was observed in 7% of vaccinees whose mothers were HBeAg‐positive, 6% of vaccinees whose mothers were HBeAg‐negative HBV carriers, and 8% in vaccinees of non‐HBV carrier mothers. None of the responsive vaccinees had seroconverted to HBsAg. Thus, in the first decade of life, the protective efficacy in neonates who responded to plasma‐derived hepatitis B vaccine was 100%.
The effects of dichloroacetate on liver damage and circulating fuels in rats exposed to carbon tetrachloride
Authors: IRITA KAZUO , OKABE HIRONAO , KOGA AKITOSHI , YAMAKAWA MASAE , YOSHITAKE JUN‐ICHI , TAKAHASHI SHOSUKE
Published: March 2008

Abstract It has been known that carbon tetrachloride‐induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride‐induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non‐starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non‐starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentractions of circulating fuels. When the pyruvate‐lowering effect of dichloroacetate was diminished in carbon tetrachloride‐injected, starved rats, the alanine aminotransferase‐lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato‐protective effect.
Glutathione concentrations and glutathione S‐transferase activity in human colonic neoplasms
Authors: BUTLER R. N. , BUTLER W. J. , MORABY Z. , FETTMAN M. J. , KHOO K. K. , ROBERTS‐THOMSON I. C.
Published: March 2008

Abstract Tissue concentrations of glutathione (GSH) and the activity of glutathione S‐transferases (GST) are relevant to the inactivation of a variety of xenobiotics including carcinogens and anti‐neoplastic drugs. In this study, GSH concentrations and GST activity were determined in 25 adenomatous polyps removed at colonoscopy, and in cancer and uninvolved ‘normal’ mucosa from 58 operative specimens containing colon cancer. We also examined the relationship between GSH concentrations, GST activity and rates of cell proliferation as assessed by flow cytometry. Concentrations of GSH were significantly higher in adenomas (P= 0.001) and cancer (P= 0.001) than in uninvolved mucosa while GST activity was significantly higher in cancer (P= 0.007). There was a positive relationship between GSH concentrations and GST activity in adenomas (P= 0.001) but not in uninvolved mucosa (P= 0.06) or cancer (P= 0.4). Concentrations of GSH and GST activity were independent of results from flow cytometry. The higher concentrations of GSH in colonic neoplasms and the raised activity of GST in cancer may contribute to their resistance to anti‐neoplastic drugs.
Type C chronic hepatitis associated with thrombocytopenia in two patients
Authors: YABU KOJI , KIYOSAWA KENDO , AKO SHINJI , USUDA SEIICHI , YOSHIZAWA KANAME , TANAKA EIJI , SODEYAMA TAKESHI , FURUTA SEIICHI
Published: March 2008

Abstract Portal hypertension in the presence of chronic hepatitis is generally thought to develop during the progression of the chronic hepatitis to cirrhosis. Before the establishment of assays for diagnosing hepatitis C virus infection, such a case of portal hypertension without liver cirrhosis could be misdiagnosed as idiopathic portal hypertension. It had not fully determined whether portal hypertension might precede the onset of cirrhosis in type C chronic hepatitis. This report presents two cases of women with chronic hepatitis C who developed severe thrombocytopenia; each showed splenomegaly and hypersplenism due to portal hypertension. Angiographic study and histological analysis were conducted to determine the cause of the portal hypertension. Histological evaluation showed an intrahepatic presinusoidal block pattern and fibrotic changes in the periportal area, but no evidence of liver cirrhosis or of other incidental complications such as idiopathic portal hypertension. Both of these patients exhibited normal platelet counts after splenectomy. Thus, type C chronic hepatitis can lead to portal hypertension, as demonstrated in these two patients.
Antiviral effect of lymphoblastoid interferon‐alpha on hepatitis C virus in patients with chronic hepatitis type C
Authors: CHAYAMA KAZUAKI , ARASE YASUJI , KOIDA ISAO , TSUBOTA AKIHITO , SAITOH SATOSHI , IKEDA KENJI , MATSUMOTO TOYOMI , KANDA MASUMI , IWASAKI SATOMI , KOBAYASHI MARIKO , HASHIMOTO MICHIE , UNAKAMI MASAMITSU , MORINAGA TSUTO , KUMADA HIROMITSU
Published: March 2008

Abstract To study the antiviral effect of lymphoblastoid alpha interferon (IFN) on hepatitis C virus (HCV) we conducted a randomized, controlled trial on 80 patients with chronic hepatitis C using three different doses. Patients were randomly assigned to treatment with 1, 3 or 6 million units of lymphoblastoid IFN‐alpha daily for 2 weeks. To assess the antiviral effect of IFN, the amount of HCV present in the serum was estimated by competitive nested polymerase chain reaction (PCR) before and after 2 weeks of treatment. The multiple logistic analysis was used to evaluate factors associated with virus clearance, adjusting the imbalance in predictive factors among patients. Hepatitis C virus became negative as assessed by nested PCR after therapy in 26, 50 and 63% of patients receiving 1, 3 and 6 mega units, respectively. Hepatitis C virus was cleared more often in patients having initially low (< 105/mL) amounts of virus. No significant decrease in the amount of virus was observed in the untreated, control group. Patients without bridging fibrosis in liver histology and with HCV genotypes other than K1 (type II) tended to respond well. These results indicate that lymphoblastoid IFN‐alpha suppresses HCV in a dose dependent manner. Higher initial virus amounts, bridging fibrosis and genotype K1 were factors associated with poor response.
A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis
Authors: TURNER IAN B. , MYSZOR MARGARET , MITCHISON HARRIET C. , BENNETT MARK K. , BURT ALISTAIR D. , JAMES OLIVER F. W.
Published: March 2008

Abstract Forty‐six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo‐controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well‐matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin {MCD 5 μmol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 μmol/L (95% CI 1 to 9) at 2 years}, alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long‐term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 μmol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.

Ursodeoxycholic acid did not generally influence stage progression or histological features, although a smaller percentage of non‐cirrhotic patients were documented as having developed cirrhosis on UDCA compared to placebo (14 vs 57%) over the 2 years. There appeared to be no consistent effect on pruritus and general well‐being. The medication was well‐tolerated and safe. In conclusion, UDCA appears to have beneficial effects on some serum biochemical markers in primary biliary cirrhosis and so may have a role in retarding disease progression. It could be useful in combination with an immunosuppressive or an anti‐fibrotic agent.
Genotypes of hepatitis C virus in Guangxi Province, southern China
Authors: OKUNO HIROYASU , XIE ZHI‐CHUN , LU BONG‐YU , QIN XUE , FUKUSHIMA SHINTARO , HIROTA TOSHIYA , SHIOZAKI YASUKO , INOUE KYOICHI
Published: March 2008

Abstract Hepatitis C virus (HCV) has been subdivided into at least four genotypes, and the prevalence of each genotype has been reported to differ widely in different countries. Of 304 patients with chronic liver diseases (68 with chronic hepatitis, 50 with liver cirrhosis and 186 with hepatocellular carcinoma) from Guangxi Province in southern China, only 9 (3.0%) had antibodies to HCV as determined by a second‐generation enzyme immunoassay with a cut‐off index of 2.0 or more. The HCV genotypes of these nine cases were examined using polymerase chain reaction with type‐specific primers deduced from putative core gene. Seven of the nine cases had type II infection and the other two cases showed double infection with types II and IV. These findings indicate that the predominant HCV genotype in the Guangxi area is type II, as is the case in Japan, although the prevalence of HCV infection in patients with chronic liver diseases is much lower.
Small bowel ischaemia in Fabry's disease
Authors: JARDINE D. L. , FITZPATRICK M. A. , TROUGHTON W. D. , TIE A. B. M.
Published: March 2008

Abstract A patient with previously diagnosed Fabry's disease and a long history of post‐prandial abdominal pain died following small bowel infarction. Post‐mortem demonstrated Fabry's type deposits in the small vessels and nerves supplying the bowel but in addition, a localized atheromatous stenosis of the superior mesenteric artery. In retrospect, his terminal illness and possibly his chronic symptoms were related to the latter finding. Angioplasty to the superior mesenteric artery may have been of benefit. Mesenteric angiography should be considered in patients with chronic post‐prandial pain because large vessel disease may coexist with other a priori pathologies and is imminently treatable.
Ethanol consumption by rats is inversely related to hepatic alcohol dehydrogenase activity
Authors: KEEGAN ANDREW , BATEY ROBERT
Published: March 2008

Abstract Under normal circumstances the rate of hepatic ethanol oxidation and the rate at which ethanol is removed from the blood are dependent on the hepatic activity of alcohol dehydrogenase. It is possible that ethanol metabolism, and thus hepatic alcohol dehydrogenase, could influence ethanol consumption. In this study 11 adult female Wistar rats were provided with 20% ethanol as their sole drinking fluid and ethanol consumption was measured. After a further period of drinking tap water, the hepatic alcohol dehydrogenase activity was determined. A significant inverse relationship was found between the ethanol consumption by the rats and the hepatic activity of alcohol dehydrogenase (P < 0.05). This enzyme could therefore play a role in determining the amount of alochol an animal will consume.
Helicobacter pylori prevalence in endoscopy and medical staff
Authors: LIN SHAO K. , LAMBERT JOHN R. , SCHEMBRI MARK A. , NICHOLSON LESLEY , KORMAN MELVYN G.
Published: March 2008

Abstract The epidemiology and mode of transmission of Helicobacter pylori is currently unclear; it is postulated that the human stomach is the natural reservoir and that spread occurs by faecal‐oral or oral‐oral transmission. The aim of this study was to assess the prevalence of H. pylori in gastroenterologists and gastroenterology nurses compared with internists, general nurses and the normal population. An enzyme‐linked immunosorbent assay technique (sensitivity 96%, specificity 88%) was used to detect circulating H. pylori immunoglobulin G antibodies in 39 gastroenterologists, 107 gastroenterology nurses, 25 internists and 42 general nurses. These subjects were compared to an age‐ and sex‐matched Caucasian population obtained by random sampling of an urban population area. The overall prevalence of H. pylori in gastroenterologists was 69% compared to 40% of internists (P < 0.01), 17% of gastroenterology nurses (P < 0.001), 19% of general nurses (P < 0.01) and 32% of controls (P < 0.01). There was no significant difference in H. pylori prevalence between the gastroenterology nurses and controls, general nurses and controls. The prevalence in gastroenterologists increased with years of practice to levels greater than age‐matched controls. The prevalence in gastroenterology nurses increased with age and years of working and was similar to age‐matched control subjects. These findings of an increased prevalence of H. pylori infection in gastroenterologists performing endoscopy support human‐to‐human transmission possibly from patients to medical staff.
Genetic heterogeneity of combined gastric and duodenal ulcers detected by pepsinogen C gene polymorphism
Authors: KONISHI JUNICHI , AZUMA TAKESHI , KOHLI YOSHIHIRO , FUJIKI NORIO
Published: March 2008

Abstract It has been reported recently that there was genetic heterogeneity in gastric ulcer disease depending upon the location of the ulcer, and that there was a significant association between the restriction fragment length polymorphism (RFLP) for pepsinogen C (PGC) gene and gastric body ulcer. In the present study, the association of the RFLP for PGC gene with combined gastric and duodenal ulcers was investigated to analyse genetic factors in its aetiology. Eighty unrelated controls and 47 patients with combined gastric and duodenal ulcers were studied. The allele frequencies of the large (3.6 kilobase EcoRI fragment) and the small fragment (3.5 kilobase EcoRI fragment) were, respectively 80.6 and 19.4% in controls, 60.0 and 40.0% in patients with combined gastric body and duodenal ulcers, 69.0 and 31.0% in patients with combined gastric angular and duodenal ulcers, and 81.8 and 18.2% in patients with combined gastric antral and duodenal ulcers. The allele frequency of the small fragment was significantly higher in patients with combined gastric body and duodenal ulcers than in controls. The genotypes that possessed the small fragment were significantly more frequent in patients with combined gastric body and duodenal ulcers (66.7%) than in controls (33.8%) and combined gastric antral and duodenal ulcers (27.3%). These results suggest that there is genetic heterogeneity in combined gastric and duodenal ulcers depending upon the location of gastric ulcer, and that combined gastric body and duodenal ulcers are associated with the small fragment allele of the PGC RFLP in the same way as solitary gastric body ulcers.
Sucralfate: The Bangkok review
Authors: KORMAN M. G. , BOLIN T. D. , SZABO S. , HUNT R. H. , MARKS I. N. , GLISE H.
Published: March 2008

Abstract Sucralfate is a site‐protective ulcer healing drug with a remarkable range of mechanisms of action. Recent studies highlight the capacity of sucralfate to bind basic fibroblast growth factor (bFGF) and deliver it in high concentration to the ulcer. Basic fibroblast growth factor stimulates the production of granulation tissue, angiogenesis and re‐epithelization, thus improving the quality of ulcer healing. The effect of sucralfate in reducing parietal cell sensitivity may be another factor important in the lower relapse rate demonstrated after duodenal ulcer healing. Sucralfate has been demonstrated to be efficacious in healing both duodenal and gastric ulcers together with mild oesophagitis, and it is safe for both short‐term use and maintenance. In stress ulcer prophylaxis it is as effective as acid suppression or neutralization and has the advantage of lesser rates of nosocomial pneumonia than are demonstrated with antacids or H2 antagonists. The potential advantages of sucralfate lie in the better quality of ulcer healing associated with longer duration of remission.
Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma
Authors: OHASHI KAZUO , NAKAJIMA YOSHIYUKI , TSUTSUMI MASAHIRO , KANEHIRO HIROMICHI , FUKUOKA TOSHIYUKI , HISANAGA MICHIYOSHI , TAKI JUNICHIRO , NAKAE DAI , KONISHI YOICHI , NAKANO HIROSHIGE
Published: March 2008

Abstract To assist in the development of new approach to the palliation and treatment of intrahepatic cholangiocarcinomas, we classified tumours into mass‐forming (MF), peri‐ductal extension (PD), and spicula‐forming (SF) types in 14 subjects who underwent surgical treatment. Lymph node metastasis and microscopic lymphatic invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours the incidence of microscopic vascular and perineural invasion was high. The proliferating cell nuclear antigen labelling index, a reflection of the proliferation rate of tumour cells, was significantly higher in PD and SF types than in the MF type. The prognosis associated with the MF type tended to be better than that of the other two types.

For the MF type, liver resection with tumour free margins must be performed, whereas for the PD and SF types, aggressive treatment, that is a combination of extensive liver resection, lymph node dissection, and effective adjuvant anti‐cancer therapy should be provided to aim at life‐long cure.
Geographic variations in structure and composition of gallstones and their correlation with brittleness
Authors: CHOUDHURI G. , AGARWAL D. K. , PHADKE R. V. , RAMESH V. , HAUSER W. , KULSHRESHTHA A. K. , NEGI T. S.
Published: March 2008

Abstract Cholesterol gallstones obtained from different geographic regions have been reported to show significant differences in their minor chemical constituents. We undertook the present study with two objectives: (i) to investigate the possible physicochemical and radiological differences beween cholesterol gallstones obtained from Indian and German patients; and (ii) to compare the brittleness of the two stone groups. Forty Indian and 36 German gallstones (matched in size and shape) were subjected to assessment of physical characteristics, in vitro computed tomography (CT) and chemical analysis. German stones more often had a stone density distribution index of ≥50 Hounsfield units (HU) (26 vs 14; P <0.01), peripheral calcification (18 vs 9; P <0.02), maximum CT density ≥ 90 HU (17 vs 9; P <0.05) and significant calcium carbonate (9 vs 5; P <0.05), compared to Indian stones. The in vitro lithotripsy performed with the Siemens Lithostar Plus machine at a constant energy level showed the German stones to be more brittle (easy to fragment), more often requiring <1000 shocks for fragmentation (25/36; 69%) compared to Indian stones (18/40; 45%, P <0.05). Gallstones from different geographic regions may show significant variations in their physicochemical characteristics that may explain the differences in their brittleness to lithotripsy.
Dissolution of pancreatic stones by oral trimethadione in patients with chronic calcific pancreatitis
Authors: NODA A. , OKUYAMA M. , MURAYAMA H. , TAKEUCHI K. , YOKOTA T. , KOBAYASHI T. , TAKAYAMA T.
Published: March 2008

Abstract The effect of oral dissolution therapy for pancreatic stones was evaluated in patients with chronic calcific pancreatitis. The anti‐epileptic agent trimethadione was given orally to 30 outpatients at a dose of 0.9–1.5 g daily. On plain X‐ray films and CT scans of the abdomen, pancreatic stones began to be dissolved around 8 months of treatment, and diminished in size and number or disappeared in 21 patients (70%) during the mean follow‐up period of 32 months. The effect of trimethadione treatment on dissolution of stones was not closely related to the aetiology of the disease, distribution and size of stones, previous history of surgical interventions, or the degree of pancreatic dysfunctions. In three patients who stopped this medication of their own accord, pancreatic stones re‐increased or reappeared about 6 months later. During trimethadione treatment, impaired exocrine pancreatic function returned to normal in four of nine patients examined, and diabetes mellitus was well controlled by either diet therapy alone or oral hypoglycaemic agents in eight of 10 patients who did not need insulin before trimethadione treatment. Complete relief of pain was noted in 73% of patients during the treatment. Overall gains and no change in bodyweight were observed in 83% of patients. Mild photophobia was the most common side effect, but could be easily overcome by wearing sunglasses. No severe side effects were observed in the liver, kidney, blood or the eyeground. Pancreatic stones in 30 patients not treated with trimethadione neither disappeared nor diminished spontaneously. Trimethadione treatment may be a useful tool for chemical dissolution of pancreatic stones.
Effect of dimethadione administered intravenously on pancreatic secretion in dogs
Authors: NODA A. , TAKEUCHI K. , MURAYAMA H. , IBUKI E. , OKUMURA I. , OKUYAMA M. , OKAYAMA T. , KOBAYASHI T.
Published: March 2008

Abstract In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin‐stimulated pancreatic secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the concentration decreased exponentially as it did in plasma at the highest dose of the compound. At equilibrium of DMO between pancreatic juice and plasma, the DMO concentration in the juice depended directly on that in plasma; the juice/plasma concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pancreatic DMO caused a small but significant decrease in the water, bicarbonate and sodium secretion at non‐equilibrium, and in the bicarbonate secretion at equilibrium. A decrease in the bicarbonate secretion may result largely from the buffer action of bicarbonate on protons provided by the undissociated form of DMO. The sum of both bicarbonate and chloride concentrations in pancreatic juice decreased with the increased DMO concentration in the juice, implying that DMO may compete with the secretion of bicarbonate and/or chloride across the apical membrane of the duct cell. Pancreatic DMO can act as a non‐specific inhibitor of pancreatic water and electrolyte secretions.
Prevalence of Helicobacter pylori in southern Indian controls and patients with gastroduodenal disease
Authors: PRASAD SANDHYA , MATHAN MINNIE , CHANDY GEORGE , RAJAN D. PRASANNA , VENKATESWARAN SARADA , RAMAKRISHNA B. S. , MATHAN V. I.
Published: March 2008

Abstract The spiral organism Helicobacter pylori has been casually implicated in the genesis of various gastroduodenal diseases. Since these diseases are common in southern India, this study was undertaken to determine the prevalence of H. pylori in the gastric mucosa of asymptomatic adults and patients with various gastroduodenal diseases. H. pylori was detected in the gastric mucosa of 25 of 30 (83.3%) normal volunteers. Prevalence rates in the disease groups were also high, and included 38 of 41 patients with duodenal ulcer (92.6%), 13/16 with gastric ulcer (81.3%), and 85/119 subjects (71.4%) with non‐ulcer dyspepsia. Light microscopic examination of the gastric mucosa provided the best method of detecting H. pylori. H. pylori colonization was significantly associated with histological abnormalities, mainly chronic atrophic gastritis (147) and superficial gastritis (11), while only three of 161 H. pylori positive patients had histologically normal antral mucosa. Ultrastructural examination revealed changes in the apical complex of the gastric mucosal cells in response to bacterial adhesion, with mucus depletion and cellular damage. Bacteria were also noted disrupting the tight junctions and entering the intercellular spaces. The high prevalence of H. pylori infection may explain the high incidence of gastritis, duodenal ulceration and gastric carcinoma in this population. However, in this population, the prevalence of infection in asymptomatic individuals was nearly as high as that in duodenal ulcer, underlining the need for further study to identify the differences in host response or bacterial pathogenicity that lead to the development of ulcer in only some individuals.
Colonization by Helicobacter pylori and its relationship to histological changes in the gastric mucosa in portal hypertension
Authors: BHARGAVA N. , VENKATESWARAN S. , RAMAKRISHNA B. S. , MATHAN M.
Published: March 2008

Abstract In order to investigate the relationship between Helicobacter pylori infection of the gastric mucosa and mucosal changes in portal hypertension, gastric fundic and antral biopsies were obtained from 66 patients with portal hypertension and 49 controls with non‐ulcer dyspepsia (NUD). Gastric mucosa from portal hypertensive patients exhibited typical vascular dilatation and congestion, while mild dilatation of lamina propria blood vessels was not uncommon in NUD patients with histological evidence of gastritis. Colonization of the gastric mucosa by H. pylori infection was significantly less in portal hyptertension (51.5%) compared to controls (75.5%; P <0.01). The difference was more apparent in patients with marked vascular dilatation (18.8% colonization) compared to patients with minimal vascular dilatation (66.7%). H. pylori infection was significantly associated with active superficial gastritis (P <0.001), and with atrophic gastritis (P <0.001), in both study groups. H. pylori‐negative superficial gastritis was significantly more common in portal hypertension (25/66 patients) than in controls (7/49; P <0.05). H. pylori infection was not more common in patients who had undergone repeated sclerotherapy. The results suggest that the gastric mucosa of portal hypertension does not provide a hospitable environment for H. pylori colonization, particularly when mucosal congestion is marked. H. pylori infection does not add significantly to the gastropathy of portal hypertension.
Gastrointestinal bleeding from hepatocellular carcinoma invading the stomach
Authors: NICOLL A. J. , IRETON H. J. C. , CROTTY B.
Published: March 2008

Abstract Bleeding from hepatocellular carcinoma (HCC) invading the gastrointestinal tract is very uncommon. We report the case of a 61 year old man who had a large bleed from HCC invading the fundus of the stomach. Diagnosis was eventually made at laparotomy and he is still alive 7 months after local resection.
Central nervous system and gut interactions: Dopamine and experimental gastroduodenal lesions
Authors: GLAVIN G. B. , HALL A. M.
Published: March 2008

Abstract There is increasing evidence for brain regulation of gastroduodenal function and pathological responses. This laboratory has demonstrated a significant role for dopamine (DA) as a modulator of gastrointestinal function and disease. Using models of both acute (ethanol restraint stress; cysteamine) and chronic (iodoacetamide‐induced gastritis) gastroduodenal mucosal injury, as well as tests of gastric secretory function (conscious basal gastric acid secretion; pylorus ligation; ex vivo gastric chamber), we have shown that DA, particularly DA1/D1 receptor agonists are powerful gastroprotective agents. This action is demonstrable upon peripheral administration as well as central (particularly intramesolimbic) administration. DA1/D1 agonists such as SKF38393 and SKF75670C reduce experimental gastric mucosal injury and secretion while antagonists of these receptors, including SCH23390, worsen experimental gastroduodenal lesions and augment secretion. That there exists a significant central component to DA‐induced gastroprotection is demonstrated by data showing that rats assessed as anxiety prone, develop a greater degree of experimentally induced gastric damage, require greater amounts of DA agonists for 50% gastroprotection and respond to exogenous stress challenge with greater central DA turnover and loss, relative to rats assessed as low in anxiety. Very recently, we showed that dopamine D4 receptor blockade by clozapine and activation of dopamine D3 receptors by 7‐hydroxy‐N, N‐di‐n‐propyl‐2‐aminotetralin (7‐OHDPAT) are also associated with antisecretory and gastroprotective effects. Taken together, these data suggest that: (i) DA is a significant component of endogenous gastroprotection; (ii) central DA, particularly mesolimbic DA, is an important determinant of peripheral gastroduodenal responses to exogenous chemical and stress challenges; and (iii) the hypothesis that several DA receptor subtypes modulate gastroduodenal function and pathology is increasingly plausible.
The mechanism underlying stimulation of gastric HCO3− secretion by the nitric oxide synthase inhibitor Ng‐nitro‐l‐arginine methyl ester in rats
Authors: TAKEUCHI K. , OHUCHI T. , TACHIBANA M. , OKABE S.
Published: March 2008

Abstract We investigated the mechanism underlying stimulation of gastric HCO3− secretion by the nitric oxide (NO) synthase inhibitor Ng‐nitro‐l‐arginine methyl ester (l‐Name) in anaesthetized rats. A rat stomach was mounted in an ex vivo chamber, superfused with saline, and HCO3− secretion was measured in the absence of acid secretion (omeprazole pretreatment). Intravenous administration of l‐Name (1‐5 mg/kg) increased gastric HCO3− secretion dose dependently with concomitant rise in arterial blood pressure and decrease in heart rate, and these effects were all antagonized by simultaneous administration of l‐arginine (200 mg/kg). Vagotomy did not affect the increased blood pressure response but significantly inhibited the decrease in heart rate and increase of HCO3− secretion caused by l‐Name. The HCO3− stimulatory action of l‐Name was also inhibited by pretreatment with either yohimbine (5 mg/kg s.c.) or prazosin (0.5 mg/kg s.c.). These agents alone caused a decrease in blood pressure, and reduced the magnitude of blood pressure response caused by l‐Name, leading to inhibition of heart rate changes. When the change in HCO3− output induced by l‐Name was plotted against the change in blood pressure (from basal values) under various conditions, a significant relationship was found between these two parameters. These results suggest that l‐Name stimulates gastric HCO3− secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through vagal efferent nerves, resulting from the pressor response to l‐Name.
Dynamism of cytoprotective and antisecretory drugs in patients with unhealed gastric and duodenal ulcers
Authors: MÖZSIK G. , HUNYADY B. , GARAMSZEGI M. , NÉMETH A. , PAKODI F. , VINCZE A.
Published: March 2008

Abstract A continuous multiclinical, randomized and prospective study has been carried out in our department to compare the efficacy of different cytoprotective (sucralfate, DE‐NOL, Vitamin A) and antisecretory drugs (atropine, cimetidine, ranitidine, famotidine, pirenzepine) on ulcer healing in patients with chronic gastric ulcer (GU) and duodenal ulcer (DU).

A total of 441 patients were randomized in different groups. The patients were treated with atropine (1 mg/day), cimetidine (1000 mg/day), ranitidine (300 mg/day), famotidine (80 mg/day), pirenzepine (50 mg/day), sucralfate (1000 mg/day), Vitamin A (3 × 50 000 IU/day) alone or in combination with cyproheptadinum (3 × 4 mg/day) DE‐NOL (3 × 5 mL/day) and Tisacid® (Al‐Mg‐hydroxycarbonicum; in different doses). Endoscopy (planimetric evaluation of ulcer sizes), measurements of clinical changes in patients’ complaints, antacid consumption and laboratory tests (blood count, urine, kidney and liver functions, electrolytes, pH status) were carried out at the beginning and 2, 4 and 6 weeks after treatment with different drugs. The incidence of ulcers, changes of ulcer sizes, subjective pain score and antacid consumption were noted at the abovementioned times. There were 20 or more patients in each group. The dynamism of ulcer healing rate was studied on the unhealed GU and DU.

Our results showed that the ulcer size decreased significantly in all groups in GU and DU patients treated with cytoprotective and antisecretory drugs. Summed pain score (expressed as per cent of basic values) and antacid consumption decreased significantly in all groups. As well, some differences were found in the dynamism of ulcer healing at 2 weeks after the treatment. No significant differences were found in the dynamism of gastric and duodenal ulcers in patients treated with cytoprotective and antisecretory drugs at 4 and 6 weeks of treatment.
Gastric mucosal defensive factors: The therapeutic strategy
Authors: YEOMANS N. D. , SKELJO M. V. , GIRAUD A. S.
Published: March 2008

Abstract There are several interesting approaches to augmenting defence or repair mechanisms that can be used already or may find a place in therapy for ulcer disease. Factors such as epidermal growth factor and basic fibroblast growth factor show potential. Alternative strategies might be to stimulate mucosal blood flow with agents that release nitric oxide (NO), or to scavenge free radicals in the inflamed or ischaemic mucosa.

If such approaches are to find a role in therapy, it is likely that it will be restricted: perhaps for the treatment of refractory ulcers, or for prophylaxis of stress ulceration. This is because most ulcers in future are likely to be healed with tolerable and high efficacy acid‐inhibiting drugs then have their recurrence prevented by regimens that eradicate Helicobacter pylori.

The most important current indication for concentrating on enhancing mucosal defences is for managing non‐steroidal anti‐inflammatory drug (NSAID)‐induced ulcers. There is no clear advantage in using a defence‐enhancing agent (rather than an acid suppressant) to heal an NSAID ulcer if the NSAID can be stopped. The main value of prostaglandins is for prophylaxis of NSAID ulcers in those patients who need ongoing treatment with NSAID. For cost‐benefit reasons, prostaglandins should probably be used mainly for those at high risk of NSAID complications, and there has been progress in identifying these. Another interesting approach is aimed at clarifying mechanisms of gastric adaptation to NSAID, so that we might be able to design drugs and dosing regimens to maximize this phenomenon.
Jejunal release of prostaglandin E2 in Crohn's disease: Relation to disease activity and first‐degree relatives
Authors: AHRENSTEDT Ö , HäLLGREN† R. , KNUTSON L.
Published: March 2008

Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first‐degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first‐degree relatives. Twenty‐four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first‐degree relatives were included and compared with healthy control subjects (n= 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose‐containing solution. Luminal concentrations of PGE2 and albumin were measured and their luminal release was calculated. Luminal release of PGE2 was significantly higher in patients with Crohn's disease than in control subjects [69.7 ± 11.5 and 34.0±4.7 pg/cm per h (3.7±0.6 and 1.8±0.3 ng/L), respectively, P <0.01]. The PGE2 levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE2 in first‐degree relatives [53.6±7.0 pg/cm per h (2.9±0.4 ng/L), P <0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin. The stimulated jejunal synthesis of prostaglandins observed in patients with Crohn's disease and to some extent in their relatives may constitute a response to altered genetic mucosal characteristics.
Sulfhydryl blocker‐induced colitis in the rat: Immunological changes in thymus gland and colonic mucosa
Authors: SUZUKI HIDEKAZU , HIBI TOSHIFUMI , ODA MASAYA , HOSODA YASUO , MORI MIKIJI , MIURA SOICHIROU , TANAKA SHIN , WATANABE MAMORU , TSUCHIYA MASAHARU
Published: March 2008

The study was designed to examine the changes of thymus in sulfhydryl blocker‐induced colitis. We used N‐ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague‐Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N‐ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time‐course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities.