bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation of the core region of HBV‐DNA and submassive hepatic necrosis in patients with anti‐HBe‐positive chronic hepatitis B
Authors: NONAKA T. , ONJI M. , HORIIKE N. , OHTA Y.
Published: March 2008

Three patients with submassive hepatic necrosis developed acute liver failure during the severe reactivation of chronic hepatitis B. The activity of hepatitis B virus (HBV) DNA polymerase increased in all three patients immediately before the onset of hepatic failure. Liver biopsy specimens obtained before and after the episode of submassive hepatic necrosis showed progression to advanced liver cirrhosis.

The nucleotide sequences of the precore and core regions of HBV‐DNA were investigated in two of the three patients and in another two patients with piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the HBV‐DNA core region changed after reactivation in the the two patients with submassive hepatic necrosis, while the sequences in the other two patients with piecemeal necrosis remained unchanged before and after reactivation. These results suggest that the antigenicity of the HBV‐DNA core region may have been changed before and after severe reactivation. Due to mutation at the core region, a different type of epitope would be expressed on the hepatocytes after submassive hepatic necrosis, which would not be a target for the cytotoxic T cell. This was evident by the continuation of the normal serum GPT for 5 and 9 years, respectively.
Three‐dimensional ultrastructure of normal rat hepatocytes by quick‐freezing and deep‐etching method
Authors: FURUTA K. , OHNO S. , GIBO Y. , KIYOSAWA K. , FURUTA S.
Published: March 2008

The three‐dimensional ultrastructure of nuclei and cell organelles including rough‐surfaced endoplasmic reticulum (RER), mitochondria, and cytoskeleton were studied in normal rat hepatocytes by the quick‐freezing and deep‐etching method. Peroxisomes and mitochondria were observed as spherical structures with granular matrices. Peroxisomes were identified by their size and matrices, which were more condensed than those of mitochondria. Ribosomes were identified as granular structures and were attached to the surface of endoplasmic reticulum. Cytoskeletal filaments were identified by their differences in diameter on the replica membranes, as well as in conventional ultrathin sections. Microfilaments were mainly localized around the bile canaliculi and adjacent to sinusoids. Intermediate filaments were observed around the bile canalicular microfilaments. Only a few filaments were observed near the lateral plasma membranes. Cross‐bridges measuring 5–7 nm in diameter were localized between the lamellae of RER and the surface of mitochondria. The quick‐freezing and deep‐etching method could be used to clarify the three‐dimensional association between the cytoskeleton and membrane‐bound organelles in hepatocytes.
Stimulation of pyloric contractions by intraduodenal triglyceride is persistent and sensitive to atropine
Authors: FRASER R. , FONE D. , HEDDLE R. , HOROWITZ M. , DENT J.
Published: March 2008

Intraduodenal lipid infusion stimulates phasic and tonic pyloric contractions and suppresses antral contractions. This study determined: (i) whether this response is sustained over 90 min; and (ii) the role of muscarinic mediation of this response. Antropyloroduodenal motility was recorded in 17 healthy volunteers with a sleeve/sidehole manometric assembly. Subjects received either a 90 min intraduodenal infusion of saline or triglyceride (20% Intralipid) at a rate of 1 mL/min; 30 min after the start of this infusion, the eight subjects who received triglyceride were given intravenous atropine 15 μg/kg over 30 s, followed by a maintenance infusion of 4 μg/kg/h until the study was completed.

Intraduodenal triglyceride infusion stimulated isolated pyloric pressure waves consistently, producing a median rate of 2.4 per min after 30 min of triglyceride infusion, compared with a median rate of 0 per min pre‐infusion. In intravenous saline studies, there was a reduction (P 0.05) in the median rate of isolated pyloric pressure waves to 1.3 per min at 90 min, when compared with pyloric pressure waves at 30 min. Atropine reduced isolated pyloric pressure waves to a median rate of 0 per min, significantly different from preatropine (P 0.01) and from intravenous saline studies (P <0.0001). These results indicate that the phasic pyloric response to intraduodenal lipid persists during 90 min stimulation, albeit with significant attenuation. In humans, muscarinic cholinergic blockade prevents the occurrence of triglyceride stimulated localized pyloric contractions.
Clinical evaluation of a newly established anti‐HCV assay for the diagnosis of hepatitis C in Japan
Authors: ISHIGURO N. , TOMIMATSU M. , NAGAHARA H. , OBATA H.
Published: March 2008

To develop a more dependable method of diagnosing hepatitis C, serum anti‐hepatitis C virus (HCV) was examined by using a new assay (anti‐HCV second generation). The results were compared with those of either the conventional assay (anti‐HCV first generation) or HCV‐RNA analysis. With the first generation assay, anti‐HCV was detected in 69% of post‐transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post‐transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1–5 weeks after onset), anti‐HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti‐HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22‐3) in this assay.

In the AH‐resolving group, anti‐HCV second generation did not disappear, but the titre tended to be lower than that in the CH‐developing group. Thus, the second generation assay for anti‐HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis.
Short and long‐term effects of interferon on serum markers of hepatitis C virus replication
Authors: YATSUHASHI H. , INOUE O. , INOKUCHI K. , KOGA M. , NAGATAKI S. , CHA T‐A. , IRVINE B. , STEMPIEN M. , KOLBERG J. , URDEA M. S. , YANO M.
Published: March 2008

Abstract Hepatitis C virus RNA (HCV‐RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non‐responders (NR). In all 11 patients in the CR group, HCV‐RNA disappeared from serum for at least 24 months and anti‐c100‐3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV‐RNA in spite of the improvement of ALT levels and decline of anti‐c100‐3. In the TR and NR groups, HCV‐RNA disappeared transiently or remained persistently positive. The results indicate that IFN‐mediated improvement of ALT and decrease of anti‐HCV (anti‐c100‐3) were not always related to the disappearance of HCV‐RNA from serum. On the other hand, sustained disappearance of HCV‐RNA from serum was demonstrated in the patients who did not have post‐treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.
Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B‐related cirrhosis
Authors: HSIA H‐C. , LIN H‐C. , LEE F‐Y. , TSAI Y‐T. , LEE S‐D. , MENG H‐C. , CHAO Y. , WANG S‐S. , LO K‐J.
Published: March 2008

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B‐related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased (P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P= 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion (P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min (P= 0.057) and 30 min (P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus‐related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.
Hypothalamic‐pituitary adrenal function in end‐stage non‐alcoholic liver disease
Authors: McDONALD J. A. , HANDELSMAN D. J. , DILWORTH P. , CONWAY A. J. , McCAUGHAN G. W.
Published: March 2008

Abstract Patients with end‐stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic‐pituitary adrenal function was evaluated in patients with end‐stage liver disease awaiting transplantation.

The study had a prospective, open comparative design with patients restricted to those having non‐alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty‐one consecutive patients with end‐stage, non‐alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n= 8) or who were unable to complete the investigations (n= 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid‐binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin‐induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 μg tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin‐induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child‐Pugh scores and peak control responses to ACTH (r= ‐0.647, P < 0.0001) and insulin‐induced hypoglycaemia (r= ‐0.597, P < 0.0001). Patients with liver disease also exhibited significantly blunted and delayed hypoglycaemic responses to insulin (0.1 U/kg), brisker growth hormone responses of reduced magnitude and decreased corticosteroid‐binding globulin levels. Baseline morning cortisol, free cortisol and dehydroepiandrosterone sulfate levels were unchanged compared with healthy controls. Patients on spironolactone had lower basal and peak cortisol responses to ACTH and hypoglycaemia, but the reductions were unrelated to spironolactone dose. Although insulin resistance and spironolactone therapy are confounding factors, it can be concluded that hypothalamic‐pituitary regulation of adrenal function is defective in end‐stage non‐alcoholic liver disease. It is therefore possible that functional central adrenal insufficiency might contribute to the mortality of patients with end‐stage liver disease and raises the question of the need for controlled studies of adrenocortical replacement therapy during acute deteriorations (sepsis and haemorrhage) in severe hepatic disease.
Fluorographic study on the oxidative stress in the process of gastric mucosal injury: Attenuating effect of Vitamin E
Authors: KUROSE I. , FUKUMURA D. , MIURA S. , SUEMATSU M. , SUZUKI M. , SEKIZUKA E. , NAGATA H. , MORISHITA T. , TSUCHIYA M.
Published: March 2008

Abstract In vivo oxidative change was visualized in the gastric mucosa of rats and the alteration was analysed by using a fluorescence microscope equipped with a digital imaging processor during the development of mucosal damage. Dichlorofluorescein (DCF)‐associated fluorescence increased after the repeated electrical stimulation on the gastric artery (irritation), suggesting the occurrence of lipid peroxidation. The increase was enhanced in the mid‐zone of two adjacent collecting venules. Allopurinol attenuated the oxidative stress in mucosa, showing the involvement of xanthine oxidase. Luminol‐dependent chemiluminescence value in the blood taken from gastric vein was elevated by the irritation, suggesting that leucocyte‐generated oxygen radicals also participate in this oxidative process. α‐Tocopherol attenuated both the DCF activation and the increase in chemiluminescence value and prevented gastric mucosal injury. The present results suggest that α‐tocopherol may be useful for the prevention of oxidative alteration in gastric mucosa.
Multiple ‘cysts’ in the entire pancreas in a case of cystic adenocarcinoma of the pancreas
Authors: SUDA K. , MATSUMOTO Y. , FUJII H. , SEKIKAWA T. , YAMAMOTO M. , EGUCHI H.
Published: March 2008

Abstract A case of multiple ‘cysts’ coexisting with cystic adenocarcinoma in the pancreas is presented. The cysts were lined by epithelium consisting of either cuboidal and flat cells or mucinous cells, which formed a papillary pattern; the former cells were more frequent and the latter were considered to be hyperplasia. The pathological findings for the diffuse multiple cysts suggested cystic disease caused by ductal stenosis, while the mucinous cells may have been related to the malignant tumour.
Measurement of intravariceal pressure by fine needle direct puncture in hepatitis B surface antigen‐positive cirrhotic patients: The effect of vasopressin
Authors: CHAO YEE , WANG SUN‐SANG , LEE FA‐YAUH , LIN HAN‐CHIEH , LO GIN‐HO , TSAI YANG‐TE , LEE SHOU‐DONG
Published: March 2008

The pressure of oesophageal varices was determined by fine needle direct puncture in 19 patients with hepatitis B surface antigen (HBsAg)‐positive cirrhosis after the first episode of variceal bleeding before endoscopic sclerotherapy. Both the stability and reliability of the measurement of intravariceal pressure by fine needle puncture were confirmed. Seven patients received intravenous 1 mL normal saline. Intravariceal pressure did not change before and after injection of normal saline (16.3 ± 4.0 vs 16.0 ± 4.0 mmHg, P > 0.05). Twelve patients received intravenous 1 units vasopressin and this caused a significant reduction in intravariceal pressure (15.6 ± 2.6 vs 10.3 ± 2.9 mmHg, P lt; 0.0001). The average basal intravariceal pressure in these patients was 15.8 ± 3.1 mmHg. After intravariceal pressure was recorded, the needle was left in situ and endoscopic sclerotherapy commenced immediately. During the investigation, no adverse reaction or complication was encountered. It was concluded that the measurement of intravariceal pressure by fine needle direct puncture followed by immediate sclerotherapy is a safe and simple method to evaluate the short‐term effect of drug prevention from oesophageal variceal bleeding and that vasopressin causes reduction of intravariceal pressure.
Extrahepatic portal vein obstruction in adults detected by ultrasound with frequent lack of portal hypertension signs
Authors: SUGIURA NOBUYUKI , MATSUTANI SHOUICHI , OHTO MASAO , EBARA MASAAKI , YOSHIKAWA MASAHARU , YAMAGUCHI TAKETO , OKUDA KUNIO , MIKI MAKOTO
Published: March 2008

Extrahepatic portal vein obstruction (EHPO) was seen in 54 adult patients at the Chiba University Hospital and affiliated hospitals from 1978 to 1991. They were classified according to the background disease (Group A, unknown aetiology; Group B, benign disease; Group C, malignant disease).

Among the initial symptoms and signs, abdominal pain was the most frequent in Group A (37%), and symptoms attributable to the primary disease in Groups B (44%) and C (75%). Definite or probable diagnosis was made in 45 of the 54 patients (81.8%) by ultrasound (US) examination carried out because of these symptoms and signs.

Signs of portal hypertension were observed in 67% of patients; oesophageal varices were seen in 60%. Extrahepatic portal vein obstruction without portal hypertension signs was characterized by thick extensive hepatopetal collaterals or patency of some intrahepatic portal veins.

Extrahepatic portal vein obstruction patients without portal hypertension remained free of its signs for more than 3 years of follow up and, in fact, EHPO without portal hypertension signs was a common occurrence. Emphasis is made on the diagnostic value of US examination which was useful in identifying the relation of clinical manifestation of EHPO to pathophysiology, and on the frequent lack of portal hypertension signs in this disease.
Regional differences in microvascular response in rat intestine during acute elevation of portal pressure
Authors: NAGATA HIROSHI , SEKIZUKA EIICHI , MORISHITA TETSUO , HOUZAWA SHIGENARI , OSHIO CHIKARA , MIURA SOHICHIRO , TSUCHIYA MASAHARU
Published: March 2008

The effect of acute elevation of portal pressure on the blood flow of rat intestinal microvessels was studied using a laser Doppler velocimeter and in vivo microscopy. The total intestinal blood flow decreased when portal pressure increased more than + 15 cmH2O above the basal value. Blood flow in villus capillaries did not change at portal pressures of + 5 to + 15 cmH2O, but did decrease at + 20 cmH2O. Blood flow in muscle capillaries decreased at all steps of portal hypertension. Red blood cell velocity was decreased by portal hypertension in large venules, but not in small venules of the submucosa. Large venules, but not small venules, dilated in acute portal hypertension. Large arterioles in the submucosa constricted, while small arterioles dilated at portal pressures of + 10 to + 15 cmH2O. In conclusion, the intestinal microvascular flow response differs according to the degree of portal hypertension and the location on the microvascular tree. Blood flow in villus capillaries and in small submucosal venules is maintained at a small degree of portal hypertension.
Whole body oxygen consumption during extracorporeal hepatic resection: Usefulness of continuous monitoring of mixed venous oxygen saturation
Authors: KAWASAKI TOSHIHIRO , IRITA KAZUO , SAKAGUCHI YOSHIRO , OKABE HIRONAO , OKAMOTO HIROTSUGU , INABA SHOICHI , INOUE HIDEFUMI , YOSHITAKE JUNICHI , TAKAHASHI SHOSUKE
Published: March 2008

Whole body oxygen consumption was measured using a thermodilution fibreoptic catheter in two patients undergoing extracorporeal hepatic resection. Each patient had virtually normal liver function before the operation. Anaesthesia was induced and maintained in a standard fashion and a venovenous bypass instituted. The anhepatic periods were 302 and 157 min. Upon removal of the liver, the oxygen consumption decreased by about 40% (50 mL/min), while the mixed venous oxygen saturation increased by about 15%. Following re‐implantation, the oxygen consumption recovered and increased transiently above control values, while the mixed venous oxygen saturation changed in a reciprocal way. Monitoring whole body oxygen consumption instead of hepatic oxygen consumption seemed helpful in estimating restoration of blood flow and functions in the liver after reperfusion. It was also suggested that changes in oxygen consumption as well as those in cardiac output and haemoglobin concentration could be predicted easily by continuous monitoring of mixed venous oxygen saturation during the peri‐anhepatic period.
Clinical evaluation of serum tissue inhibitor of metalloproteinases‐1 levels in patients with liver diseases
Authors: MUZZILLO D. A. , IMOTO M. , FUKUDA Y. , KOYAMA Y. , SAGA S. , NAGAI Y. , HAYAKAWA T.
Published: March 2008

Serum levels of the tissue inhibitor of metalloproteinases‐1 (TIMP‐1) were measured in 268 patients with liver diseases by means of a one‐step sandwich enzyme immunoassay. In the cases of acute hepatitis, chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), the levels of TIMP‐1 were higher than those of the control group. Tissue inhibitor of metalloproteinases‐1 levels correlated with type III procollagen peptide and with type IV collagen, indicating TIMP‐1 as a useful marker for hepatic fibrosis. Levels of TIMP‐1 also correlated with aspartate aminotransserase and alanine aminotransferase levels and showed the highest levels in acute hepatitis. Thus, TIMP‐1 might also reflect hepatic inflammation. Serum levels of α‐fetoprotein and TIMP‐1 had a significant positive correlation in patients with HCC. A cut‐off level of TIMP‐1 between LC and HCC was set at 440 ng/mL, having a low sensitivity and a high specificity. These results suggest the usefulness of TIMP‐1 as a tumour marker in cases of HCC where α‐fetoprotein levels are not elevated.
Elevated growth hormone levels in patients with non‐alcoholic chronic liver disease
Authors: ILAN Y. , OREN R. , TUR‐KASPA R.
Published: March 2008

High serum concentrations of growth hormone (GH) were found in five patients with chronic liver diseases, including auto‐immune chronic active hepatitis (two cases), Budd‐Chiari syndrome, primary biliary cirrhosis and hepatitis B virus associated cirrhosis. Mean levels of GH were 27.8 units (normal up to 5). In three patients elevated prolactin levels were also found (mean 37.3 units for two females, normal up to 20), and 36 units in one male (normal up to 9). No other endocrine disorders were found.

Although the association of raised GH levels in patients with alcoholic cirrhosis is well known, its occurrence in patients with non‐alcoholic chronic liver disease is not fully established. We describe the effect of the disease course, and steroid treatment on GH levels in one patient with auto‐immune chronic active hepatitis, and propose possible mechanisms for this elevation.
Role of superoxide dismutase in mechanism of diethyldithiocarbamate‐induced gastric antral ulcer in rats: Protective effect of prostaglandin, cimetidine and pirenzepine
Authors: CHEN SHENG‐HSUAN , PAN SHIANN , OKITA KIWAMU , TAKEMOTO TADAYOSHI
Published: March 2008

The role of superoxide radicals and the protective effects of superoxide dismutase (SOD), allopurinol, 16, 16‐dimethyl‐prostaglandin E2 (dmPGE2), cimetidine and pirenzepine in diethyldithiocarbamate (DDC)‐treated rats were evaluated. Pretreatment with Cu,Zn‐SOD (superoxide radical scavenger) 60 000 units/kg, allopurinol (competitive inhibitor of xanthine oxidase) 50 mg/kg, dmPGE2 (prostaglandin analogue) 10 μg/kg, cimetidine (H2‐receptor antagonist) 10 mg/kg or pirenzepine (selective antimuscarinic drug) 10 mg/kg all significantly reduced the DDC‐induced (800 mg/kg) gastric antral ulcer formation in rats. DDC treatment substantially decreases the gastric mucosal Cu, Zn‐SOD activity. In this study treatment with DDC and SOD, DDC and dmPGE2, DDC and cimetidine, and DDC and pirenzepine were demonstrated significantly to prevent the decrease of gastric mucosal Cu, Zn‐SOD activity. However, allopurinol did not have this effect. The results suggest that SOD and/or superoxide radicals may play an important role in the mechanism of DDC‐induced gastric antral ulcer. The protective property against ulcer formation of these drugs studied might be due to the action of SOD in the gastric mucosa.
Marked retention of indocyanine green and sulfobromophthalein with chronic persistent hepatitis
Authors: IKEJIMA KENICHI , ICHIKAWA SHOICHI , KITAMURA TSUNEO , WATANABE SUMIO , HIROSE MIYOKO , YOKOI YUKIO , UCHIDA SHIGEYUKI , OIDE HIROSUMI , SUZUKI HIDEO , KITAMI NORIYUKI , SATO NOBUHIRO
Published: March 2008

A hepatitis B virus (HBV) carrier with marked retention of indocyanine green (ICG) and sulfobromophthalein (BSP) was admitted to our hospital for assessment of liver function. On admission, he was asymptomatic and blood chemistry tests showed normal values for transaminases and bilirubin. Serum hepatitis B surface antigen (HBsAg) and antibody to hepatitis B e antigen (anti‐HBe) were positive. A history of drug abuse or alcoholism was denied. Dye excretion tests revealed marked retention of ICG (R15= 70%) and BSP (R45= 23%). Histopathological examination of a liver biopsy specimen obtained during laparoscopic observation showed chronic persistent hepatitis (CPH). Familial research of the patient failed to prove the existence of dye excretory defect in his siblings. Usual cases of CPH due to continuous HBV infection do not show such severe disturbance of organic anion transport.

This pattern of the dye excretory defect with CPH has not been reported. Although the relationship between this dye excretory defect and HBV infection is unclear, the existence of the constitutional dye excretory defect due to abnormal organic anion transport in the liver might be considered.
Subcortical somatosensory evoked potentials in patients with hepatic encephalopathy caused by severe acute hepatitis
Authors: YANG SIEN‐SING , CHU NAI‐HSIN , WU CHI‐HWA
Published: March 2008

We studied the median nerve stimulated somatosensory evoked potentials (SEP) of 23 patients with hepatic encephalopathy (HE) resulting from severe acute hepatitis and 22 healthy volunteers. Ten patients who improved and survived more than 60 days were classified as Group 1 and the remaining 13 patients who died shortly after the SEP studies were classified as Group 2. The mean N9‐N13 interpeak latencies (IPL) were not different among control and two patient groups. The mean N13‐N20 IPL of Group 2 was significantly prolonged when compared with normal controls (P < 0.001) and Group 1 (P < 0.001). Five of the six patients with abnormal N13‐N20 IPL died of hepatic failure within 24 h after SEP testing. The occurrence of abnormal subcortical conduction together with cortical dysfunction suggested that brain damage in terminal hepatic encephalopathy was diffuse. The presentation of abnormal prolongation of N13–N20 IPL of SEP during the course of severe acute hepatitis indicated a poor prognosis. Peripheral somatosensory conduction is unaffected even in terminal HE.
A rupture of lung metastasis of hepatocellular carcinoma causing haemothorax
Authors: AKIMARU KOHO , MIYAIRI KEN , TANAKA HIROHARU , IMAI SHIGERU , IWASE IZUMI , UCHIYAMA KIICHIRO , SHIBUYA TETSUO , SHOJI TASUKU
Published: March 2008

A 67 year old male with non‐resectable hepatocellular carcinoma (HCC) in both lobes and liver cirrhosis was treated with transcatheter arterial embolization and regional chemotherapy. He was doing well for 18 months. He was readmitted for fever, chest pain and multiple pulmonary metastases. During interleukin‐2 therapy, he suddenly developed dyspnoea and palpitation, and was in shock. Left‐sided haemothorax was confirmed by draining 3 L of fresh blood. In spite of intensive care, he died within 36 h. Autopsy showed that the haemothorax was caused by rupture of one of the metastases in the upper lobe of the left lung, and that the primary HCC was totally necrotic. Survey of the literature failed to find a report of fatal bleeding from a lung metastasis of HCC.
Regulation of core promoter of hepatitis B virus
Authors: YUH C‐H. , TING L‐P.
Published: March 2008

In order to understand the cycle and disease process of hepatitis B virus (HBV) at the molecular level, the regulation of viral gene expression was studied. This paper reports the characterization of HBV core promoter: two 3.5 kb transcripts, the precore and the pregenomic RNA are made from it. A short sequence (from nt1744 to 1851, referred to as the basic core promoter or BCP) is identified, that is sufficient to direct the correct initiations of both precore and pregenomic messages. Sequences upstream of BCP (from nucleotide, nt1636 to 1744, referred to as the core upstream regulatory sequence or CURS) have a strong stimulatory effect on BCP. Deletion analysis of CURS suggests that it contains multiple regulatory elements that control BCP in an interactive manner. The CURS stimulates BCP in a position‐ and orientation‐dependent manner. Therefore, it is unlikely that the effect is mediated through the enhancer II that has been co‐localized to the same sequence.
Hepatitis B core antigen forms oligomers and complexes with the p gene product in hepatitis B virus core particles
Authors: JENG K‐S. , HU C‐P. , CHANG C.
Published: March 2008

The nucleocapsid core of hepatitis B virus (HBV) is composed of the hepatitis B core antigen (HBcAg), a viral genome, a polymerase and a protein covalently linked to the 5'‐end of the minus DNA strand. The interactions among the constituents are still very limited. By using the in vitro phosphorylation method, it was found that the p gene product formed complexes with HBcAg in the core particles through non‐covalent linkage. After complete digestion of the HBV genome, the complexes between the HBcAg and p gene product remained intact. These results indicate that the HBcAg and p gene product are not complexed through the HBV genome. Also, it was found that the 21 kD HBcAg formed oligomers through disulfide linkages in the extracellular viral particles.
Classification of hepatitis C virus into subgroups on the basis of sequence variations in the envelope protein
Authors: HADA H. , KOIDE N. , HANAFUSA T. , TAKABATAKE H. , SAKAGUCHI K. , SHINJI T. , SASAKI S. , OKA T. , TAKAYAMA N. , YUMOTO Y. , TSUJI T.
Published: March 2008

In order to investigate the possibility that hepatitis C virus (HCV) can be classified into subgroups based on the variations in the envelope region, the nucleotide and deduced amino acid sequences were compared among the reported viral isolates including HCV1, HCJ1, HCJ4, HCVJ, HCVBK, HCVNK and HCJ6. From the homology analysis, the HCV isolates were classified into three subgroups: group I (HCV1 and HCJ1); group II (HCJ4, HCVJ, HCVBK and HCVNK); and group III (HCJ6). Furthermore, two novel regions were found in the E1 envelope region. One is located at aa246–258 (intersubtype variable region 1; ISVR‐1) where the amino acid sequences were relatively conserved within each subgroup, while the sequences were extremely different among the subgroups. Another is located at aa315–328 (intersubgroup common region‐1; ISCR‐1) where the amino acid sequences were completely identical among all seven HCV isolates despite the fact that the marked variations were distributed throughout the envelope region. The results suggest that the combination of ISVR‐1 and ISCR‐1 can be utilized as marker sequences for the classification of HCV strains and that the letter region might be one of the candidates for the vaccine.
Analysis on the status of hepatitis B virus DNA in peripheral blood mononuclear cells of chronic hepatitis B patients
Authors: WONG F‐H. , LIAW Y‐F. , HU C. , CHAO Y. , CHANG C. , PAO C. C.
Published: March 2008

Peripheral blood mononuclear cells (PBMC) from 46 hepatitis B virus (HBV) surface antigen (HBsAg)‐positive chronic active hepatitis (CAH) patients were examined for the presence and for the physical states of HBV DNA by Southern blot analysis. Twenty‐one of 46 patients (45.7%) were found to have HBV DNA in their PBMC. Further fractionation of PBMC of these patients indicated that HBV DNA can be found in both T and B lymphocytes but not in macrophages. Results also suggested that the PBMC‐associated HBV DNA was in a changing and unstable state. No HBV DNA could be detected in the long‐term culture of either Epstein‐Barr virus‐immortalized B cells or in interleukin‐2‐cultured T cells of these patients.
Immunoreactivity to M2 proteins in antimitochondrial antibody‐negative patients with primary biliary cirrhosis
Authors: KITAMI NORIYUKI , ISHII HIDEO , SHIMIZU HIDETAKE , ADACHI HIROYASU , KOMADA TOSHIYUKI , MIKAMI HIDEAKI , YOKOI YUKIO , SATO NOBUHIRO
Published: March 2008

Abstract Although antimitochondrial auto‐antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti‐M2 auto‐antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrance proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA‐negative and AMA‐positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti‐M2 auto‐antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA‐negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres ( 1: 320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 protein but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.
A Prospective study of septic complications of endoscopic retrograde cholangiopancreatography
Authors: MOLLISON LINDSAY C. , DESMOND PAUL V. , STOCKMAN KEITH A. , ANDREW JOHN H. , WATSON KATRINA , SHAW GIDEON , BREEN KERRY
Published: March 2008

Abstract Prophylactic antibiotics are used in an attempt to avoid the septic complications of endoscopic retrograde cholangiopancreatography (ERCP). We prospectively performed blood cultures and surveyed patients for complications. The aims were first, to determine the incidence of bacteraemia associated with ERCP, second, to assess the incidence of clinical sepsis following the procedure and third, to evaluate the effectiveness of our antibiotic prophylaxis.

One hundred and fifty successive patients underwent 179 ERCP. Bacteraemia related to the procedure or the underlying pathology was found in nine procedures (5.2%). Bacteraemias were more likely to complicate therapeutic procedures (P= 0.015), biliary obstruction (P= 0.045) or underlying pathology (P= 0.022).

Although 61% of ERCP received antibiotics, 22 septic events occurred. Five bacteraemic patients were septic despite antibiotics. Septic complications were associated with the same factors as bacteraemia.

It was concluded that patients with biliary obstruction and undergoing therapeutic endoscopic procedures are at greatest risk of bacteraemia. Single dose prophylactic antibiotics may not prevent sepsis in these patients and longer‐acting drugs or repeated dosing may be necessary.
A double‐blind, randomized, parallel group study of omeprazole and ranitidine in Korean patients with gastric ulcer
Authors: CHOI K. W. , SUN H. S. , YOON C. M. , PARK K. N. , MIN Y. I. , CHANG R. , LEE S. I. , CHUNG J. M. , YANG U. S. , WONG E. C. K.
Published: March 2008

Abstract The efficacy of the proton pump inhibitor omeprazole, 20 mg every morning, was compared with that of the H2‐receptor antagonist ranitidine, 150 mg every morning and at bedtime, in a double‐blind randomized parallel group study in 250 patients with gastric or prepyloric uicers. At both 4 and 8 weeks, significantly more patients had healed ulcers in the omeprazole group than the ranitidine group, whether the results were analysed on a per‐protocol or an intention‐to‐treat basis. At 4 weeks, 74% of patients in the omeprazole group were healed compared with 51% in the ranitidine group (P= 0.001), and at 8 weeks the corresponding values were 99 and 82% (P= 0.001, per‐protocol cohort). Omeprazole treatment and small ulcer size significantly increased the probability of healing, but smoking had no significant effect. Patients in the omeprazole group had significantly fewer occurrences of daytime epigastric pain during the first 4 weeks than the ranitidine group (P= 0.0037), as shown by their diary cards. Both treatments were well tolerated.
The pattern of functional and organic disorders in an Asian gastroenterological clinic
Authors: KANG J. Y. , YAP I. , GWEE K. A.
Published: March 2008

Abstract The aim of the present study was to determine the pattern of structural and functional disorders encountered in an Asian gastroenterological clinic and to compare this pattern with findings from Western centres. Consecutive new patients (totalling 2384) attending the clinics of two consultant gastroenterologists were studied. Of these, 2141 suffered from gastroenterological problems. One thousand and sixty‐three (49.6%) had structural diseases, the commoner ones being liver disease, peptic ulcer, malignancy, haemorrhoids and gallstones. The remainder who were found to have no structural disease (n= 1078; 50.4%) were deemed to have functional disorders including non‐ulcer dyspepsia, irritable bowel, simple constipation and functional diarrhoea. The proportions of functional and structural disease were similar to those in the West. Major differences included a higher frequency of hepatoma and a lower frequency of inflammatory bowel disease and gastro‐oesophgeal reflux in the present series.
Relationship between endotoxin antibody levels and portal systemic shunt evaluated by per‐rectal portal scintigraphy
Authors: SHIOMI SUSUMU , KUROKI TETSUO , UEDA TADASHI , TAKEDA TADASHI , NISHIGUCHI SHUHEI , NAKAJIMA SHINYA , KOBAYASHI KENZO , OCHI HIRONOBU , YAMAGAMI SEIJI
Published: March 2008

Abstract The reasons for the high frequency of endotoxaemia in cirrhosis, whether poor liver function or abnormal portal circulation, are not known. Accurate measurement of endotoxin itself is difficult. Instead, in this study an enzyme‐linked immunosorbent assay was used to measure levels of IgA, IgG and IgM antibodies to endotoxin in patients with chronic liver disease and underlying hepatic viral infection. The relationships between the results and clinical symptoms or the presence of a portal systemic shunt were investigated. The median level of IgA antibodies was not different in patients with chronic hepatitis and those with cirrhosis, and the same was found for IgM, but the median level of IgG antibodies was significantly higher in the patients with cirrhosis. When patients with cirrhosis were grouped by the presence or absence of ascites or hepatocellular carcinoma, no significant difference was observed in any of these antibody levels. However, in cirrhotic patients with varices, the level of IgG antibodies to endotoxin was significantly higher than in patients without varices. For evaluation of the portal systemic shunt, the per‐rectal portal shunt index was calculated. There was a significant correlation (R= 0.431, P < 0.001) between the per‐rectal portal shunt index and the level of IgG antibodies to endotoxin. That is, the degree of abnormality in the portal haemodynamics was correlated with the level of IgG antibodies to endotoxin in patients with liver disease.
Release of latent glucuronosyltransferase activity contributes to the sparing of glucuronidation in experimental liver injuries
Authors: DESMOND PAUL V , SMYTH FIONA E. , MASHFORD M. L.
Published: March 2008

Abstract In patients with parenchymal liver disease, glucuronidation of drugs is generally preserved but oxidation is impaired. This study explores the effects of liver injuries induced in rats by the administration of acute carbon tetrachloride, chronic bile duct ligation and chronic choline deficiency for 30 weeks on the glucuronidation of p ‐nitrophenol and 1‐naphthol, both before and after solubilization of the microsomes and compares this to three measures of oxidation. Cytochrome P450 content was reduced to 17% of control values after acute carbon tetrachloride and to 35% of control values after bile duct ligation. Cytochrome C reductase fell to 58 and 32% of control and aniline hydroxylase to 46 and 13%, respectively, after acute carbon tetrachloride and bile duct ligation. P‐nitrophenol glucuronidation by native microsomes was 206 and 73% of controls in the respective models, while 1‐naphthol glucuronidation was 167 and 66% of control. Latent uridine diphosphate‐glucuronosyltransferase (UDP‐GT) activity, that is, differences between solubilized and native activity, was decreased by each liver injury. Chronic choline deficiency had little effect on the oxidation and native glucurondation activity, although latent glucuronidation activity was lower. These studies suggest a preservation of glucuronidation compared to oxidation at the microsomal level in these experimental liver injuries. The data also support the hypothesis that a release of latent UDP‐GT activity may contribute to this phenomenon.
Oral contraceptive‐dependent growth of focal nodular hyperplasia
Authors: NAKAMUTA MAKOTO , OHASHI MASAO , FUKUTOMI TAKAYOSHI , TANABE YUICHI , HIROSHIGE KAICHIRO , NAKASHIMA OSAMU , NAWATA HAJIME
Published: March 2008

Abstract A 22 year old woman was incidentally found to have a hepatic small haemangioma‐like mass, measuring 1.4 cm in diameter, by an ultrasonographic examination. The mass demonstrated no change in size or appearance for 6 months until the patient began to take oral contraceptives. Eventually, the mass increased to 2.0 cm in diameter after using oral contraceptives for 6 months. A histological examination suggested the mass to be typical focal nodular hyperplasia, and not hepatic adenoma. There was no further change in either size or appearance in the ensuing 1 year after the discontinuation of oral contraceptives.
Octreotide therapy for pancreaticopleural fistula
Authors: CHAN K. L. , LAU W. Y. , SUNG J. Y.
Published: March 2008

Abstract Pancreaticopleural fistula is a rare but remediable complication of pancreatitis. Hitherto, treatment by means of total parenteral nutrition and thoracocentesis had resulted in an overall success rate of 40% only. Surgical obliteration of persistent fistulae is required in many cases, as the underlying pancreatic duct lesion often prevents spontaneous closure of the fistula. We report a patient suffering from pancreaticopleural fistula with a tightly strictured pancreatic duct. The fistula was successfully obliterated with the use of octreotide addition to thoracocentesis and total parenteral nutrition. Pancreatic bypass surgery was later performed only for pain relief. We believe that octreotide can effectively suppress pancreatic secretion and promote closure of pancreaticopleural fistula even in the presence of severe pancreatic duct lesions. Thus the risk of infection and early surgery for persistent fistula can be minimized.
Histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine
Authors: PAN S. , LIAO C. H. , LIEN G. S. , CHEN S. H.
Published: March 2008

Abstract We investigated the relationship between histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine for 4 weeks. The healing rates, 92.5 and 72.4% in omeprazole‐treated and cimetidine‐treated groups, respectively, showed no significant difference between groups (P > 0.05). Histologically, the regenerating mucosa of healed ulcer was divided into three categories: good, fair and poor patterns. Of the healed cases, 22 (59.5%) of 37 omeprazole‐treated and 12 (28.6%) of 42 cimetidine‐treated ulcers achieved a good pattern, showing significant difference between groups (P= 0.01). The recurrence rate at 3 months showed statistically significant difference (P < 0.05) between two groups: 5.4% in omeprazole‐treated and 23.8% in cimetidine‐treated patients. During the period between 3 and 6 months after healing, the difference in recurrence rate between omeprazole‐treated and cimetidine‐treated groups was statistically not significant (12.5% and 25%, respectively, P > 0.05), though the cumulative recurrence rate at 6 months showed a significant difference between groups (17.6%vs 44.7%, P= 0.027). All the recurrent cases of both groups had a fair or poor pattern of regenerating mucosa. The difference in recurrence rate was statistically significant between the healed ulcers with a good pattern and that with a fair or poor patterns both at 3 months and between 3 and 6 months after healing (P > 0.001 in each). We concluded that better histological maturity of regenerating mucosa may contribute to the lower early recurrence in omeprazole‐treated cases than in cimetidine‐treated cases.
Clinical relevance of basic research in peptic ulcer disease
Authors: GAGINELLA T. S.
Published: March 2008

Abstract Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2‐receptor antagonists. Basic research contributed again by defining the importance of H+/K+‐ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As ‘replacement’ therapy, clinicians have found that PG are protective against non‐steroidal anti‐inflammatory drug (NSAID)‐induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger‐Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori‐associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC‐15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease.
A dynamic study of viraemia in chronic hepatitis C infection
Authors: MENG ZONG‐DA , SUN YONG‐DE , SUN DE‐GUI , LIU CAI‐YUN , COPLAND JOY , GOWANS ERIC J.
Published: March 2008

The dynamics of alanine aminotransferase (ALT), anti‐hepatitis C virus and hepatitis C virus (HCV) RNA in six cases with chronic HCV infection were studied for 3‐7 years. Two of the six cases showed continued elevation of ALT, and three showed intermittent elevation. All cases were persistently positive for anti‐HCV after initial seroconversion. Five of the six cases were persistently positive for HCV RNA detected by nested polymerase chain reaction, and one was positive intermittently. Thus hepatitis C virus replicates continually in a majority of patients with chronic hepatitis C, although some cases may show intermittent replication, and replication of hepatitis C virus does not always correlate with elevated ALT.