bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleic acid‐based antiviral and gene therapy of chronic hepatitis B infection
Authors: WANDS JR , GEISSLER M , PUTLITZ JZU , BLUM H , VON WEIZSÄCKER F , MOHR L , YOON SK , MELEGARI M , SCAGLIONI PP
Published: March 2008

Persistent hepatitis B virus (HBV) infection often leads to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. There is a need to develop new antiviral approaches for the treatment of this disease. We have explored various nucleic acid‐based strategies designed to inhibit HBV replication including: the use of antisense RNA and DNA constructs, DNA‐based immunization techniques to stimulate broad‐based cellular immune responses with particular emphasis on the generation of cytotoxic lymphocyte (CTL) activity to viral structural proteins, hammerhead ribozymes to cleave HBV pregenomic RNA in vitro and dominant negative HBV core mutant proteins as inhibitors of nucleocapsid formation within cells. In order to optimize these antiviral effects, various novel expression vectors have been developed to deliver such DNA constructs to cells. For example, adenoviral vectors carrying genes that encode for dominant negative proteins have been employed to transfect hepatocytes in vitro and in vivo. In addition, plasmid vectors have been produced to promote expression of HBV structural genes following injection into muscle cells as a means to stimulate the host's cellular and humoral immune response in the context of histocompatibility antigen (HLA) class I and II antigen presentation. These experimental approaches may have important implications for the generation of efficient antiviral effects during chronic HBV infection.
Relationship between local immune response to Helicobacter pylori and the diversity of disease: Investigation of H. pylori‐specific IgA in gastric juice
Authors: WATANABE TAKEHITO , GOTO HIDEMI , ARISAWA TOMIYASU , HASE SATOSHI , NIWA YASUMASA , HAYAKAWA TETSUO , ASAI JUNPEI
Published: March 2008

In order to evaluate the relationship between local immune response to Helicobacter pylori and the diversity of disease, 77 asymptomatic subjects who underwent a health examination were studied. Helicobacter pylori‐specific IgG in serum and H. pylori‐specific IgA in gastric juice were measured by ELISA, and the measured IgA titre was classified into two grades, low or high. Histological classification of gastritis was performed according to the Sydney system. Cytokines in gastric juice were also measured, and the cytotoxin‐associated gene A (cagA) status of H. pylori was tested by PCR. Of the 65 subjects who were positive for H. pylori‐specific IgG in serum, 38 (58.5%) were classified as H. pylori‐specific IgA low titre in gastric juice and 27 (41.5%) had high titres. In the IgG‐positive, IgA‐low group, the rate of peptic ulcers (especially duodenal ulcers) in endoscopic findings was higher (P < 0.05); the score of activity and the density of H. pylori were higher (P < 0.001 and P < 0.05, respectively); the score of metaplasia was lower (P < 0.05); and the level of interleukin‐1β was lower (P < 0.05) than in the IgG‐positive, IgA‐high group. The positive rate of the cagA gene was 84.4% and there was no significant difference between the two groups. There were differences in endoscopic and histological findings between the IgG‐positive, IgA‐low and the IgG‐positive, IgA‐high groups. It is suggested that persons infected with H. pylori can be divided into two different states of disease according to local immune response.
Report of the 1997 Asia Pacific Consensus Conference on the management of Helicobacter pylori infection
Authors: LAM SK , TALLEY NJ
Published: March 2008

While European and United States guidelines for the management of Helicobacter pylori infection have been developed, there are no guidelines for the Asian Pacific. International experts and recognised local authorities met in Singapore in 1997 to develop appropriate guidelines, taking into account the high background prevalence of infection, high incidence rates of gastric cancer and resource limitations. Recommendations were made based on randomised controlled trials or where this was not possible, they were based on the current best available evidence or on good clinical practice. A number of acceptable diagnostic tests for infection are available throughout the region. The non‐endoscopic methods of choice are the urea breath test or a locally validated antibody test. If endoscopy was to be performed, a biopsy urease test was recommended as the test of first choice, with histology recommended only if this was negative. Post treatment testing was not recommended for all patients; a urea breath test was considered the test of choice if available. All gastric and duodenal ulcer patients who are infected with H. pylori should be treated for H. pylori whether the ulcer is active or in remission. Patients requiring long term non‐steroidal anti‐inflammatory drug therapy who have a current or recent history of dyspepsia, patients with early gastric cancer or low grade gastric mucosa associated lymphoid tissue lymphoma, and patients with a family history of gastric cancer should be treated. However, it was concluded that there wasn't sufficient evidence that cure of H. pylori infection reduces the risk or prevents the development of gastric adenocarcinoma. Many patients with dyspepsia in the region will request or require early upper endoscopy because of an inherent fear of gastric cancer. However, where endoscopy is not available or is too costly, alternative acceptable approaches were recommended in high risk cancer regions. While evidence is inconclusive to support treatment of H. pylori infection in non‐ulcer dyspepsia, it was agreed that treatment be offered to patients with documented infection on a case‐by‐case basis. Treatment regimens need to attain an eradication rate of 90% or greater by per protocol analysis and 80% or greater by intention‐to‐treat analysis. A number of 7‐day regimens were recommended based on available evidence. These regimens were considered likely to maximize the chances of successful eradication with one course of treatment, thereby reducing the risk of acquired antibiotic resistance and leading to long term cost savings.
Histological changes of concurrent hepatitis C virus infection in asymptomatic hepatitis B virus patients
Authors: LAU GEORGE KK , WU PUI CHEE , LO CHI KIN , LAU VICKY , LAM SHIU KUM
Published: March 2008

In chimpanzees and in vitro cell culture studies, hepatitis C infection has been shown to suppress hepatitis B virus expression. In addition, hepatitis C infection can cause much more severe liver disease in patients chronically infected with hepatitis B virus. The aims of the present study were to determine the prevalence of hepatitis C infection in asymptomatic chronic hepatitis B Hong Kong Chinese patients and the histological changes and hepatic expression of hepatitis B virus and hepatitis C virus. Five hundred and seventy‐one Hong Kong Chinese asymptomatic chronic hepatitis B patients were studied. Only four (0.7%) were hepatitis C virus antibody positive; they were also all positive for hepatitis C viral RNA in serum by reverse transcription‐polymerase chain reaction (RT‐PCR). Portal lymphoid aggregates and bile duct damage was noted in the liver sections of three of the four patients. Hepatic expression of hepatitis B surface antigen was detected in three patients; none had detectable hepatitis B core antigen. By branched DNA assay, serum hepatitis B DNA could not be detected in any of the four patients, but three had hepatitis C RNA. By in situ RT‐PCR, hepatitis C RNA was detected in the cytoplasm of three of the four patients. These findings suggest that hepatitis C coinfection in asymptomatic chronic hepatitis B patients is uncommon in Hong Kong Chinese and active hepatitis B viral replication is absent in these patients.
A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats
Authors: YOSHIDA MASASHI , WAKABAYASHI GO , ISHIKAWA HIDEKI , OTANI YOSHIHIDE , SHIMAZU MOTOHIDE , KUBOTA TETSURO , KUMAI KOICHIRO , KUROSE IWAO , MIURA SOICHIRO , ISHII HIROMASA , KITAJIMA MASAKI
Published: March 2008

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin‐thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol‐dependent chemiluminescence activity generated by zymosan‐stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.
Mast cells: A possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the Irritable Bowel syndrome
Authors: GUI XIAN‐YONG
Published: March 2008

Intestinal mast cell activation (degranulation), which results from previous enteric infection and/or intestinal allergy, may play a central role in the gut hypersensitivity in both motor response and visceral perception in the Irritable Bowel syndrome. This occurs through various mediators acting on enteric neurons and smooth muscle cells. Psychological stress may trigger this sensitive alarm system via the brain‐gut axis.
Role of endogenous nitric oxide in ischaemia‐reperfusion injury of rat gastric mucosa
Authors: IWATA FUMIHIRO , JOH TAKASHI , YOKOYAMA YOSHIFUMI , ITOH MAKOTO
Published: March 2008

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia‐reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG‐nitro‐L‐arginine or NG‐monomethyl‐L‐arginine. Gastric mucosal integrity was continuously monitored by measuring the blood‐to‐lumen clearance of [51chromium]‐labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]‐EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L‐arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia‐reperfusion stress in rat gastric mucosa.
The effect of minimum luminal nutrition on mucosal cellularity and immunity of the gut
Authors: HEEL KATHRYN A , KONG SUNG‐EUN , McCAULEY ROSALIE D , ERBER WENDY N , HALL JOHN C
Published: March 2008

Many catabolic patients can only consume small volumes of enteral nutrients. The aim of this study was to evaluate markers of cellularity and immunity in the small intestine of rats randomized to receive 6 days of parenteral nutrition, 25% enteral and 75% parenteral nutrition (i.e. minimum luminal nutrition) or enteral nutrition. The same glutamine‐enriched solution was used for both parenteral and enteral nutrition. Enteral nutrition was associated with the least amount of jejunal atrophy (P < 0.01), with the results from the minimum luminal nutrition group approximating those of the parenteral nutrition group. Parenteral nutrition was associated with the greatest number of CD2+ cells ( P < 0.05) and the lowest CD4/CD8 cell ratio ( P < 0.01) in the jejunal mucosa. In essence, we failed to demonstrate that there are any appreciable benefits associated with the enteral consumption of 25% of a nutrient load.
Symptomatic gastro‐oesophageal reflux in pregnancy: A prospective study among Singaporean women
Authors: HO KHEK YO , KANG JIN YONG , VIEGAS OSBORNE AC
Published: March 2008

The present study was undertaken to estimate the prevalence and time course of reflux‐type symptoms in Singaporean women and to determine if these symptoms were associated with nausea and vomiting of pregnancy. Consecutive pregnant women in the first trimester of pregnancy were recruited during attendance at an antenatal clinic in a Singapore teaching hospital. Each was interviewed, using a reliable questionnaire detailing demographic characteristics and symptoms, at four time points during the first, second and third trimesters of pregnancy and postpartum period. A total of 35 of 47 women originally enrolled (response rate 74%) completed the study. Heartburn alone, acid regur‐gitation alone and both heartburn and acid regurgitation were reported by 5.7, 17.1 and 17.1% of the subjects, respectively. Subjects who had these symptoms were more likely to suffer daily nausea and/or vomiting (78.6%) than those who did not (33.3%, P < 0.05). In the majority of subjects, heartburn and/or acid regurgitation began in the first trimester (78.6%) and disappeared during the second trimester (71.4%). Nausea alone and in combination with vomiting similarly came on in the first trimester (100%) and subsided by the second trimester (85.7%) in the majority of the subjects studied. The reported prevalence of heartburn and/or acid regurgitation among Western pregnant women were 48–96% and 62%, respectively. Our data, therefore, showed that reflux‐type symptoms were less common in Singaporean pregnant women. Reflux‐type symptoms were related to nausea and vomiting, both in frequency and time pattern of onset and disappearance of symptoms. The association suggested either a common mechanism or a cause and effect relationship.
Oesophageal motility and gastro‐oesophageal reflux: Effect of variceal eradication by endoscopic sclerotherapy*
Authors: GHOSHAL UDAY C , SARASWAT VIVEK A , AGGARWAL RAKESH , MISRA ASHA , DHIMAN RADHA K , NAIK SUBHASH R
Published: March 2008

Endoscopic injection sclerotherapy (EIS) is known to produce oesophageal structural and motility changes; however, alterations in frequency and severity of gastro‐oesophageal reflux (GER) following EIS have not been investigated in detail. We studied 22 patients with cirrhosis and oesophageal varices before EIS and 26 after variceal eradication with intravariceal EIS using manometry and 24 h pH monitoring. The post‐EIS group had reduced oesophageal sphincter pressure (19.2 ± 11.4 vs 26.1 ± 16.4 mmHg, P < 0.05) and slower velocity of oesophageal peristalsis (2.47 ± 0.71 vs 3.06 ± 0.77 cm/s, P < 0.01) than the pre‐EIS patients. There was no difference in the amplitude or duration of the contraction. Abnormal contraction wave‐forms were observed more frequently in post‐EIS than in the pre‐EIS patients (3/22 vs 12/26, P < 0.05). Various quantitative parameters for GER were not increased in post‐EIS compared with pre‐EIS patients. Abnormal GER was present in nine of 21 pre‐EIS and eight of 17 post‐EIS patients (no significant difference). These results suggest that although persistent oesophageal motility changes are frequent after intravariceal EIS, these do not lead to a significant increase in GER.
Differential north to south gastric cancer‐duodenal ulcer gradient in China
Authors: WONG BCY , CHING CK , LAM SK , LI ZL , CHEN BW , LI YN , LIU HJ , LIU JB , WANG BE , YUAN SZ , XU CP , HOU XH , ZHANG AT , ZHENG ZT
Published: March 2008

There are suggestions that duodenal ulcer protects individuals from gastric cancer and that rice is ulcerogenic while wheat is gastro‐protective. We aimed to examine the relationship of gastric cancer, duodenal and gastric ulcers in different geographical regions in China and identified dietary risk factors for duodenal ulcer and gastric cancer. The prevalence of peptic ulcer and gastric cancer among symptomatic patients in eight major cities, four each from the north and the south representing all the six defined regions of China were studied. Endoscopy and case records over a 10 year period were reviewed and cases of confirmed duodenal and gastric ulcer and gastric cancer, together with the total number of endoscopies performed per year, were recorded. Rates were expressed as cases/1000 endoscopies. Results were compared to another epidemiological study on diet and mortality in the same regions in China conducted at the same time. Duodenal ulcer rates were 2.4‐fold higher in southern China than northern China, whereas gastric cancer rates were 1.6‐fold higher in the north than in the south. Correlation studies showed for the first time an inverse linear relationship between the gastric cancer rates and the duodenal ulcer rates (r=‐0.8076, P=0.015), as well as the duodenal ulcer: gastric ulcer ratios (r=‐0.9133, P=0.002). Gastric ulcer rates were higher in southern China but did not correlate with the gastric cancer rates (r=0.1455, P=0.731). Duodenal ulcer rates were found to be related to daily rice intake (r=0.8554, P=0.029) and inversely related to daily wheat flour intake (r=‐0.8472, P=0.033). Gastric cancer rates were not related to any dietary risk factors tested. We concluded there was an inverse relationship between gastric cancer rates and duodenal ulcer rates. Although duodenal ulceration and gastric cancer are both linked to Helicobacter pylori infection, the findings of this study indicate independent additional aetiological factors for the pathogenesis of these conditions. Dietary factors such as rice or wheat intake may play a role.
CASE REPORT: A patient who developed an amoebic liver abscess during treatment with interferon
Authors: MATSUO TAKU , SHINZAWA HARUHIDE , SUGAHARA KAZUHIKO , MITSUHASHI HIDEKI , WATANABE HISAYOSHI , ABE TAKASHI , OHNO SHIGERU , TERASHITA MASAKI , SAITO KOUJI , SAITO TAKAFUMI , MISAWA HIROYUKI , TOGASHI HITOSHI , TAKAHASHI TSUNEO
Published: March 2008

A 65‐year‐old female received recombinant interferon (IFN) α‐2b daily for the treatment of chronic hepatitis C. Fever (39°C or higher) developed 14 days after the start of administration. Abdominal computed tomography suggested multiple liver abscesses, which had not been detected before IFN administration. An autopsy revealed an amoebic liver abscess. A subclinical infection of Entamoeba histolytica in this case developed into amoebic liver abscess during IFN administration.
CASE REPORT: Intrahepatic portal‐hepatic venous shunts associated with a huge pelvic leiomyoma
Authors: AIBA NOBUYASU , MORIOKA JUNICHIRO , MIYAZONO TAKAYOSHI , OKITA HIDEAKI , YATA YUTAKA , OKADA KAZUHIKO , NAMBU SHUJI , WATANABE AKIHARU , SHIMIZU MASASHI , FUJIMURA MASAKI , IZUMI RIKUICHI
Published: March 2008

We present a case of portal‐systemic encephalopathy due to intrahepatic multiple portalhepatic venous shunts. A 71‐year‐old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 μg/dL. Portal venography revealed dilatation of the portal vein and multiple portal‐hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow‐up portal venogram demonstrated decreased portal vein dilatation and minor portalhepatic venous shunts, considered to be congenital in origin. It is concluded that liepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre‐existent (probably congenital) intrahepatic anastomoses.
Use of fructose 1,6‐diphosphate aldolase to detect tumour necrosis after transcatheter arterial embolization of hepatocellular carcinoma
Authors: KHAN KHALEQUE NEWAZ , NAKATA KEISUKE , KUSUMOTO YUKIO , NAKAO KAZUHIKO , KATO YUJI , NAGATAKI SHIGENOBU
Published: March 2008

Transcatheter arterial embolization (TAE) is a popular and well‐established devascularization treatment modality for hepatocellular carcinoma (HCC). The persistent retention of lipiodol on follow‐up computed tomography (CT) scan and time‐dependent decrease in size of the lipiodol‐stained area of tumour after TAE does not reveal the biological death of tumour cells. Moreover, it is difficult to clinically evaluate the effective necrosis of tumour cells by TAE in cases of HCC that do not produce α‐fetoprotein (AFP). We therefore studied the release of a relatively tumour‐specific protein by the necrotic hepatoma cells to evaluate the effectiveness of TAE. Transcatheter arterial embolization was performed in 17 patients with the imaging diagnosis of HCC; either superselective (n= 6) or non‐superselective (n= 11) techniques were used. We measured serum levels of relatively tumour‐specific fructose 1,6‐diphosphate (FDP) aldolase and non‐tumour‐specific fructose 1‐phosphate (F1P) aldolase by substrate‐specific enzymatic methods. Enzyme activities were performed before and after TAE. The time‐dependent decrease in size of the lipiodol‐stained areas was studied on follow‐up CT scans after TAE. Pre‐ and post‐treatment serum AFP levels were determined by radio‐immunoassay. The six cases of superselective TAE underwent marked tumour regression by CT compared with the 11 cases of non‐superselective TAE. Fructase 1,6‐diphosphate aldolase output correlated well with post‐necrotic tumour regression after TAE (r= 0.87, P= 0.001). The elevation of serum FDP aldolase was also significantly associated with a decrease in serum AFP (r= 0.72, P < 0.01). In contrast, serum F1P aldolase output was inversely correlated with either tumour regression or serum AFP concentrations after TAE. The serum levels of the tumour‐specific enzyme FDP aidolase correlated significantly with effective tumour necrosis and consequent tumour regression after TAE. We suggest that measurement of FDP aldolase activity in serum after TAE can be used clinically to detect the degree of tumour necrosis by TAE.
Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer healing
Authors: KOBAYASHI ICHIZO , KAWANO SUNAO , TSUJI SHINGO , NAKAMA AKIHIRO , SAWAOKA HITOSHI , MASUDA EIJI , NAGANO KOICHI , FUSAMOTO HIDEYUKI , KAMADA TAKENOBU
Published: March 2008

Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H2 blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA‐synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 ± 1.3), peaked during the healing stage (15.4 ± 2.8) and returned to the same level at the scarring stage (10.9 ± 2.0) as normal controls (10.3 ± 1.7). However, the index was not elevated in intractable ulcers (10.3 ± 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.
A study of laboratory based faecal occult blood testing in Melbourne, Australia
Authors: SINATRA MARC A , YOUNG GRAEME P , ST JOHN D JAMES B , BLAKE DENNIS , RATNAIKE SUJIVA
Published: March 2008

Faecal occult blood tests (FOBT) are widely used in clinical practice and are under increasing scrutiny as a tool for colorectal cancer screening. However, there is little information regarding the quality of testing performed in pathology laboratories. Therefore, we asked 13 pathology laboratories in Melbourne, Australia, to test coded contrived faecal samples prepared from a composite stool specimen which had been spiked to various concentrations of haemoglobin. The samples were provided to the laboratories in two forms: (i) on/in the sample collection device appropriate for the faecal occult blood test they normally used; and (ii) as a moist faecal sample. Some variation in threshold analytical sensitivity between laboratories for the same FOBT was observed for Hemoccult® SENSA®, Colo‐Rectal®, Hematest®, MonoHaem® and Hemolex® suggesting that, at least for those tests, technician training could be improved. Two tests, Hematest® and an in‐house FOBT did not perform as well as the other FOBT. When samples were sent in moist form, Hemoccult® SENSA® (P= 0.0002), Colo‐Rectal (P=0.02) and MonoHaem® (P=0.04) had significantly lower overall positivity rates; for Hemolex® the decrease was not significant (P= 0.3). The lower positivity rate with moist samples is important, given that 11 of the 13 laboratories in the study stated that they receive at least some samples in moist form. Thus, technician training and laboratory procedure need to be reviewed to maximize the benefits of faecal occult blood testing in clinical practice, especially with its expanding role in colorectal cancer screening.
How much does alcohol contribute to the variability of hepatic fibrosis in chronic hepatitis C?
Authors: KHAN MAHBUB H , THOMAS LIZA , BYTH KAREN , KENCH JAMES , WELTMAN MARTIN , GEORGE JACOB , LIDDLE CHRISTOPHER , FARRELL GEOFFREY C
Published: March 2008

In order to determine the contribution of alcohol intake to the severity of hepatic fibrosis in patients with chronic hepatitis C, we studied associations between various levels of alcohol intake, other demographic variables and semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical, demographic and disease‐related data were entered into a relational database. Liver histology was scored according to Scheuer. The average daily alcohol intake for the year preceding liver biopsy (recent exposure) and for earlier periods (past exposure) was categorized into five levels of intake. One‐third of patients gave a history of alcohol intake that had exceeded 40g/day for at least 5 years. By univariate analysis, age, but not recent or past alcohol intake or other baseline variables, was associated with portal score (r=0.14, P= 0.004), fibrosis score (r= 0.46, P < 0.001), total Scheuer score (r= 0.35, P < 0.001), However, by multivariate analysis, age (P < 0.001), past (but not present) alcohol intake (P < 0.001) and birth in Egypt (P= 0.006) were independently associated with fibrosis score. Age, past alcohol and birth place in Egypt contributed 27% to total variance of the hepatic fibrosis score, while age alone accounted for 23%. Age also independently predicted portal activity (P=0.02) and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with total Scheuer score (P= 0.002) but not with other histological indices. A separate multivariate analysis was performed on a more homogeneous subgroup of 196 patients who acquired hepatitis C by injection drug use. In this subgroup, age (P < 0.05) and past alcohol (P < 0.05) were independently associated with fibrosis score. In both the overall and subgroup analyses, there was a threshold level of past alcohol intake (>80g/day) beyond which the risk of fibrosis increased significantly. It is concluded that toxic levels of alcohol exposure for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence of alcohol appears to be minor compared with age and other variables and is exerted only at toxic levels of intake.
Antipyrine clearance in chronic and neoplastic liver diseases: A study of 518 patients
Authors: GRIECO ANTONIO , CASTELLANO ROSARIO , MATERA ANNA , MARCOCCIA STEFANIA , DI ROCCO PAOLA , RAGAZZONI ENZO , VECCHIO FABIO MARIA , GASBARRINI GIOVANNI
Published: March 2008

Antipyrine metabolism is widely used as an index of the drug‐metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver‐function parameters and antipyrine metabolism (antipyrine per o.s. 18mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety‐two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 ± 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 ± 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 ± 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 ± 0.174 mL/min per kg) was similar to that of the healthy group (0.489 ± 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2= 0.10, P= 0.01) and prothrombin time (r2= 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.
CASE REPORT: A hepatocellular carcinoma metastasis in the distal pancreas
Authors: TEXLER MICHAEL L , PIERIDES JOHN , MADDERN GUY J
Published: March 2008

Hepatocellular carcinoma is a highly malignant neoplasm. Extrahepatic metastases are found in 64% of patients with hepatocellular carcinoma. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of metastases. Pancreatic metastases are not common (<5%). A case report of a hepatocellular carcinoma with a metastasis in the distal pancreas is presented. A resection of the primary tumour and metastasis was carried out with the patient still alive 16 months after resection. This case illustrates that hepatic resection for hepatocellular carcinoma with a single local metastasis can be reasonably considered although a cure has not been established.
CASE REPORT: Steatonecrosis in the upper abdomen following transcatheter arterial embolization for hepatocellular carcinoma
Authors: UMEMURA TAKEJI , YAMAMURA NOBUYOSHI , NAGATA ATSUO , SHIBATA ATSUSHI , YAMASHITA KUNIHIKO , OHATA TAKEO , YAMADA TAKEO , KATSUYAMA TSUTOMU , KIYOSAWA KENDO
Published: March 2008

A 66‐year‐old female with liver cirrhosis was treated by transcatheter arterial embolization (TAE) for a small hepatocellular carcinoma. She developed steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The hepatic falciform artery from the middle hepatic artery was detected by arteriography. Necrosis in the upper abdomen was considered to be due to ischaemic changes caused by micromaterials for embolization of this artery, injuries of hepatic arterial endothelia slowly caused by carcinostatics, and chemotoxicity. It was considered that such complication as observed in this patient should be taken into consideration when performing TAE.
Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis
Authors: NAKAMURA KIMIHIDE , YONEDA MASASHI , YOKOHAMA SHIRO , TAMORI KEISUKE , SATO YOICHI , ASO KAZUNOBU , AOSHIMA MASARU , HASEGAWA TAKENAO , MAKING ISAO
Published: March 2008

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti‐nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 ± 24 IU/L and 170 ± 17 IU/L before UDCA therapy to 31 ± 3 IU/L and 25 ± 5 IU/L (P < 0.001) after 1 year of treatment and 28 ± 2 IU/L and 23 ± 4 IU/L (P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5. patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.
CASE REPORT: Pneumatosis cystoides intestinalis associated with post‐surgical bowel anastomosis: A report of three cases and review of the Japanese literature
Authors: HORIUCHI A , AKAMATSU T , MUKAWA K , OCHI Y , ARAKURA N , KIYOSAWA K
Published: March 2008

We report three cases of pneumatosis cystoides intestinalis (PCI) occurring in association with post‐surgical bowel anastomosis. A 74‐year‐old man, a 58‐year‐old woman, and a 62‐year‐old woman were found to have PCI at the colonic side of a bowel anastomosis at 4 years, 3 years and 1 year after operation, respectively, for right colon carcinoma, although all were asymptomatic. They all had a positive anti‐nuclear antibody test and had received postoperative cancer chemotherapy. The clinical features of 123 cases of PCI reported in Japan between 1981 and 1995 were also reviewed. On the basis of the present and previous cases, we propose that post‐surgical anastomosis, cancer chemotherapy, and predisposition to collagen vascular disease might be responsible for the damage to intestinal mucosa that leads to the development of PCI.
Follow up after successful eradication of Helicobacter pylori: Symptoms and reinfection
Authors: FRASER ALAN G , SCHREUDER VANYA , CHUA LING‐ERN , MOORE LILIAN
Published: March 2008

The important long‐term outcomes after Helicobacter pylori eradication are the proportion of patients with continuing symptoms, and the rate of recrudescence of the infection. Patients with proven H. pylori infection prior to treatment and a negative urea breath test at least 4 weeks after completing treatment were invited to return for a further urea breath test and a questionnaire. There were 167 patients and the mean interval since the post‐treatment urea breath test was 16 months. The endoscopic diagnoses were duodenal ulcer 72, duodenitis 17, gastric ulcer 26, normal or oesophagitis 52. The ethnic groups were European 86, Maori 25, Pacific Island 28 and other ethnic groups 28. Ten patients (6%) had a positive urea breath test at follow up. The proportion of patients showing recrudescence of H. pylori was related to the delta value (δ) of the post‐treatment urea breath test: δ 0–2. five of 146 (3.4%); δ 2–3, two of 18 (11%); and δ 3–4, three of five (60%). A symptom questionnaire was given to 147/157 patients with a persistently negative breath test; 60 had no symptoms, 31 had heartburn, 30 had epigastric pain, 15 had both heartburn and epigastric pain, and 11 had nausea or other symptoms. There were fewer symptoms in patients with gastric ulcer (GU) compared with patients with duodenal ulcer (DU) and non‐ulcer patients. Twenty‐four patients (16%) were taking H2‐antagonists (including seven DU and five GU), 15 were taking antacids and four were taking omeprazole. There was no difference in medication use between diagnostic groups. Eighteen of the 46 patients (39%) with heartburn stated that this was a new symptom. Heartburn was a common symptom for duodenal ulcer patients after eradication (24/74, 32%). A second urea breath test 6–12 months after eradication is required to definitely prove eradication. Patients with a breath test † value of 2–4 should have a repeat urea breath test.
Intestinal metaplasia subtypes and Helicobacter pylori infection: A comparison of ethnic groups in New Zealand
Authors: FRASER ALAN G , PENG SZE‐LIN , JASS JEREMY R
Published: March 2008

Gastric cancer is two to four‐fold more common in Maori and Pacific Island ethnic groups compared with Europeans. This study aimed to determine if intestinal metaplasia was more common in these ethnic groups. Patients attending for endoscopy for dyspepsia had six biopsies to determine the presence of Helicobacter pylori by at least two of the following tests: rapid urease test, 13C urea breath test, culture or histology and the presence, extent and subtypes of intestinal metaplasia. Biopsies were taken from 158 patients: Europeans (42%), Maori (23%), Pacific Islanders (35%). Helicobacter pylori and intestinal metaplasia were detected in 88 and 60% of Maori/Pacific Island patients, respectively, and 47 and 29% of Europeans, respectively. Type I intestinal metaplasia was detected in 43% of all patients, type II (26%) and type III (7.0%). The mean age of Maori/Pacific Island patients with intestinal metaplasia and type III intestinal metaplasia was 53 and 51 years respectively, compared with Europeans aged 65 and 72 years. Univariate analysis showed that intestinal metaplasia was associated with ethnicity and H. pylori (P < 0.001) but not age, smoking, endoscopic diagnosis or gender. Intestinal metaplasia is more common and occurs at an earlier age in Maori and Pacific Island patients.
Effect of Helicobacter pylori infection on gastric mucosal phospholipid contents and their fatty acid composition
Authors: WAKABAYASHI HIROYUKI , ORIHARA TADAHIRO , NAKAYA ATSUKO , MIYAMOTO AYUMU , WATANABE AKIHARU
Published: March 2008

To investigate the effect of Helicobacter pylori infection on the ‘gastric mucosal barrier’, phospholipid contents and the fatty acid composition of endoscopic biopsy specimens of the gastric mucosa were analysed in healthy volunteers with and without H. pylori infection. The gastric corporeal phos‐phatidylcholine (PC) content of H. pylori‐positive healthy volunteers was less than that of H. pylori‐negative healthy volunteers (P < 0.05). Moreover, H. pylori‐positive healthy volunteers had a decrease in linoleic acid composition (P < 0.0001) and an increase in arachidonic acid composition (P < 0.0001) and in the arachidonic acid/linoleic acid ratio (P < 0.0001) of antral and corporeal PC compared with H. pylori‐negative healthy volunteers. These findings suggest that H. pylori infection enhances production of various eicosanoids, resulting in changes in the gastric mucosal phospholipid contents and their fatty acid composition, that may consequently cause the gastric mucosal barrier to be weakened.
Biliary stenting for management of common bile duct stones
Authors: CHOUDHURI G , SHARMA BC , SARASWAT VA , AGARWAL DK , BAIJAL SS
Published: March 2008

Large and multiple common bile duct stones may defy extraction despite an adequate endoscopic papillotomy. We treated 65 patients with symptomatic bile duct stones with endoscopic stents after failed attempts at stone extraction. Of the 65 patients, bile duct stones were extracted in eight at a second attempt, 29 underwent elective surgery and 28 patients were followed with the stent in situ for 21–52 months (median 42 months). During follow up, two patients had recurrent pain and two required surgery. The remaining 24 patients remained asymptomatic. Biliary stenting is a safe and effective mode of treatment for common bile duct stones in patients who have failed stone extraction after endoscopic papillotomy.
Endoscopic retrograde cholangiopancreatography in paediatric patients with biliary disorders
Authors: ASHIDA KIYOSHI , NAGITA AKIRA , SAKAGUCHI MASAHIRO , AMEMOTO KANJI , TADA HIDEKI
Published: March 2008

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty‐two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.
Prospective follow‐up study of hepatitis C virus infection in patients undergoing maintenance haemodialysis: Comparison among haemodialysis units
Authors: KOBAYASHI MAMORU , TANAKA EIJI , OGUCHI HISAO , HORA KAZUHIKO , KIYOSAWA KENDO
Published: March 2008

A prospective follow‐up study on hepatitis C virus (HCV) infection was conducted in seven haemodialysis units from April 1990 to March 1995. A total of 634 patients were undergoing maintenance haemodialysis in the seven units. Of those, 302 patients participated in the follow‐up study; 179 were initially HCV antibody negative and 123 were initially positive. Nine of the 179 initially negative patients became positive for HCV antibody during the follow‐up period. In accordance with the appearance of HCV antibody, indicating new infection of HCV, all nine of these patients were diagnosed with HCV viraemia. As no other routes were apparent, HCV infection in all nine patients was likely due to nosocomial transmission. Prevalence of HCV antibody at the start of follow up was significantly higher (P < 0.001) in haemodialysis units A‐C (37.9%) than in haemodialysis units D‐G (17.0%). Incidence of new HCV infection was significantly higher (P= 0.005) in the former units (2.2% per year) than in the latter (0.2% per year). Ten of the 123 patients who were initially positive for the HCV antibody exhibited a loss of reactivity during the follow‐up period; of these 10 patients, nine were negative for HCV‐RNA from the start of the study. In conclusion, the incidence of new HCV infection seen in patients undergoing haemodialysis suggests that their risk of acquiring HCV infection is directly related to the prevalence of HCV antibody positive patients being treated in the units.
Cellular expression and regulation of iron transport and storage proteins in genetic haemochromatosis
Authors: BASCLAIN KERRIE A , SHILKIN KEITH B , WITHERS GEOFFREY , REED WILLIAM D , JEFFREY GARY P
Published: March 2008

: Genetic haemochromatosis is a common iron overload disorder of unknown aetiology. To characterize the defect of iron metabolism responsible for this disease, this study localized and semiquantified the mRNA and protein expression of transferrin, transferrin receptor and ferritin in the liver and duodenum of patients with genetic haemochromatosis. Biopsies were obtained from iron‐loaded non‐cirrhotic patients with genetic haemochromatotic and control patients with normal iron stores. Additional duodenal biopsies were obtained from patients with iron deficiency. Immunohistochemical and in situ hybridization analysis for transferrin, transferrin receptor and ferritin was performed. Hepatic transferrin, transferrin receptor and ferritin protein expression was localized predominantly to hepatocytes and was increased in patients with genetic haemochromatosis when compared with normal controls. Interestingly, hepatic ferritin mRNA expression was not increased in these same patients. In the genetic haemochromatotic duodenum, ferritin mRNA and protein was localized mainly to crypt and villus epithelial cells and the level of expression was decreased compared with normal controls, but similar to iron deficiency. Duodenal transferrin receptor mRNA and protein levels colocalized to epithelial cells of the crypt and villus were similar to normal controls. Early in the course of genetic haemochromatosis and before the onset of hepatic fibrosis, transferrin receptor‐mediated iron uptake by hepatocytes contributes to hepatic iron overload. Increased hepatic ferritin expression suggests this is the major iron storage protein. While persisting duodenal transferrin receptor expression may be a normal response to increased body iron stores in patients with genetic haemochromatosis, decreased duodenal ferritin levels suggest that duodenal mucosa is regulated as if the patient were iron deficient.
Effect of transient cyclic AMP elevation on DNA synthesis in rat hepatocytes at G1 phase
Authors: KIKUKAWA MASAJI , OKAMOTO YASUYUKI , NAKANO HIROSHI
Published: March 2008

: Maintaining high levels of intracellular cyclic AMP (cAMP) is known to inhibit the growth of various proliferating cells including hepatocytes. We show here that transient (30 min) elevations of cAMP induced by addition of 8‐bromo‐cAMP (1 mmol/L) to rat hepatocytes in primary culture at three time points (12h, 16h and 20h) after seeding stimulated DNA synthesis. Sustained levels of cAMP stimulated DNA synthesis to a lesser degree at a lower concentration (1 μmol/L), but inhibited it at concentrations higher than 100μmol/L. We also determined cyclin‐dependent kinase 2 (cdk2) activity in the hepatocytes during this incubation period. The transient addition of 8‐bromo‐cAMP at the late G1 phase increased cdk2 activity. This suggests that transient cAMP elevation in hepatocytes at the late G1 phase has a growth stimulation effect. Up‐regulation of cdk2 activity may have a role in this process.