bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease
Authors: MULDER T. P. J. , VEER A. VAN DER SLUYS , VERSPAGET H. W. , GRIFFIOEN G. , PEÑA A. S. , JANSSENS A. R. , LAMERS C. B. H. W.
Published: March 2008

AbstractOxygen‐derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals, were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease.

Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo‐controlled double‐blind cross‐over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 ± 1.7 μmol/L,P<0.05), when compared to that of 22 healthy controls (13.6 ± 2.3 μmol/L), but increased (P<0.05) towards the levels of controls during the supplementation period (13.3 ± 2.5 μmol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non‐inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study. Thus, although zinc supplementation therapy increased plasma zinc concentrations, there was no effect on the plasma, erythrocyte and mucosal metalloprotein levels in inactive to moderately active patients with inflammatory bowel disease.
Validity of kissing gastric ulcers induced in rats for screening of antiulcer drugs
Authors: TSUKIMI Y. , OKABE S.
Published: March 2008

Abstract We examined the validity of kissing gastric ulcers induced in rats by determining the effects of conventional antiulcer drugs. Gastric ulcers were produced by luminal application of 60% acetic acid (0.2 mL, 45 s) to an area clamped with a pair of forceps. The ulcers were evaluated as to either the ulcerated area (mm2) or ulcer index (ulcerated area x depth). The healing of kissing ulcers was significantly enhanced by 2 week treatment with oral omeprazole (10, 30 mg/kg per day), leminoprazole (30, 60 mg/kg per day) or cimetidine (300, 450 mg/kg per day). The rate of healing was > 50% to both the ulcerated area and ulcer index. Aluminium hydroxide (up to 1800 mg/kg per day) had no effect on ulcer healing on the ulcerated area, but it caused a significant reduction in the ulcer index. Gastric acid secretion was significantly inhibited by repeated administration of omeprazole, leminoprazole and cimetidine in a dose‐dependent manner. Aluminium hydroxide significantly increased the pH of the gastric contents. The mechanism of action of these drugs appears to involve partly the inhibition of gastric acid secretion and neutralization of secreted acid. We conclude that kissing gastric ulcers are a sensitive ulcer model for the screening of antiulcer drugs.
Stereospecific effects of tryptophan on gastric emptying and hunger in humans
Authors: CARNEY BERNARD I. , JONES KAREN L. , HOROWITZ MICHAEL , SUN WEI MING , HEBBARD GEOFFREY , EDELBROEK MICHELA A. L.
Published: March 2008

The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L‐enantiomer. The effects of D‐ and L‐tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L‐tryp (50 mmol/L), D‐tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at ‐2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L‐tryp and D‐tryp (P <0.05) and D‐tryp emptied faster than L‐tryp (P <0.005). Emptying from the proximal stomach was fastest for saline (P <0.05) and faster for D‐tryp than L‐tryp (P <0.005). Emptying from the distal stomach was faster for saline than both D‐ and L‐tryp (P <0.05). A reduction in hunger (P <0.05) and a non‐significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L‐tryp than after ingestion of D‐tryp (P <0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.
Serum α2‐macroglobulin–trypsin complex and early recognition of severe acute pancreatitis after endoscopic retrograde pancreatography
Authors: NAKAE YASUYUKI , HAYAKAWA TETSUO , KONDO TAKAHARU , SHIBATA TOKIMUNE , KITAGAWA MOTOJI , SAKAI YUZO , SOBAJIMA HIROSHI , ISHIGURO HIROSHI , TANIKAWA MAKOTO
Published: March 2008

Serum α2‐macroglobulin‐trypsin complex (α2M‐T) was measured to differentiate the elevation of serum pancreatic enzymes caused by severe acute pancreatitis from simple elevation after endoscopic retrograde pancreatography (ERP). A patient with severe acute pancreatitis demonstrated marked elevation of serum α2M‐T. In patients without severe acute pancreatitis, serum αM‐T did not rise in spite of elevated serum pancreatic enzymes. In conclusion, abdominal pain with elevated serum α2M‐T can be an early diagnostic clue to severe acute pancreatitis after ERP.
Don't forget prostatic carcinoma in abdominal carcinomatosis
Authors: HOUGHTON A. , MARSH J. , SOPHER M. , STOKER A. , VANDAL M.
Published: March 2008

An incarcerated hernia containing peritoneal secondaries from carcinoma of the prostate is presented. Abdominal carcinomatosis may be due to a prostatic primary and will benefit from hormonal treatment.
Liver disease complicating bone marrow transplantation: A clinical audit
Authors: FORBES GEOFFREY M. , DAVIES JOHN M. , HERRMANN RICHARD P. , COLLINS BRENDAN J.
Published: March 2008

Abstract Hepatic dysfunction following bone marrow transplantation (BMT) may present complex management issues. The incidence and aetiology of abnormal liver function following allogeneic and autologous BMT was reviewed over a 2 year period in Royal Perth Hospital and these findings were related to management decisions and patient outcome. Abnormal serum liver biochemistry during the first 12 post‐transplant months occurred in all allogeneic (n= 31) and 14 of 23 (61%) autologous transplant patients; 13 (41%) allogeneic and three (13%) autologous patients developed severe hepatic dysfunction. In allogeneic transplants, the most common causes of liver disease were graft‐versus‐host disease (33%), drug hepatotoxicity (19%) and post‐transplant viral hepatitis (15%); in autologous patients, disease recurrence (28%) and sepsis (17%) were the most frequent identifiable cause of abnormal liver function. The aetiology of abnormal liver biochemistry was not determined in 13 instances, but this did not adversely affect patient outcome. Percutaneous liver biopsy or endoscopic cholangiography were only required in three patients. Liver disease contributed to death in two allogeneic patients with multiple causes for liver dysfunction, and in one patient with refractory severe hepatic graft‐versus‐host disease. It was concluded that hepatic dysfunction is common after BMT, the cause of which can be determined in many cases with simple non‐invasive tests used in conjunction with the clinical setting. Specific treatment, where necessary, is then able to be commenced in a majority of patients without the need for invasive investigation.
Effect of α‐interferon on hepatitis B virus‐specific cytotoxic T cells
Authors: ISONO ETSUKO , YAMAUCHI KATSUMI , HARUTA IKUKO , KAMOGAWA YUMIKO , HAYASHI NAOAKI
Published: March 2008

Abstract To study the mechanism of the effects of α‐interferon (α‐IFN) on chronic hepatitis B, we examined its effect on hepatitis B virus (HBV)‐specific cytotoxic T cells (CTL). Using two different HBV‐DNA transfected human myeloma cell lines, one expressing hepatitis B core antigen (HBcAg; C4) and the other expressing hepatitis B surface antigen (HBsAg; S6) as targets in cytotoxic tests in vitro, peripheral blood mononuclear cells obtained from chronic hepatitis B patients who were treated with α‐IFN were examined for their cytotoxic activity against these transfectants. During the treatment with α‐IFN, in association with a decline of serum alanine amino transferase levels, CTL activities were significantly reduced. An inhibition study in vitro revealed that α‐IFN did not directly inhibit these CTL activities, indicating that α‐IFN may inhibit the induction of CTL, and thereby may be related to the reduction of hepatocyte injury.
Point mutations in the c‐K‐ras 2 gene in multiple colorectal carcinomas
Authors: HAYAKUMO TAKANOBU , CHO EISAI , NAKAJIMA MASATSUGU , KATO GENICHI , KAWAI KEIICHI , AZUMA TAKESHI
Published: March 2008

Abstract The c‐K‐ras 2 gene mutations were examined in colorectal tumours from patients with synchronous or metachronous tumours in order to investigate tumorigenesis. Sixty‐seven colorectal carcinomas from patients with a single lesion, 50 from patients with synchronous lesions, and 12 from patients with metachronous lesions were analysed for the presence of point mutations in codons 12 and 13 of c‐K‐ras proto‐oncogene. In the patients with metachronous or synchronous lesions, the finding of the mutation in one tumour was not associated with a greater frequency of the mutation in other carcinomas from the same patient. In the patients with tumours that each contained the mutation, the mutations were not always the same. In tumours from the patients with original and synchronous lesions, the mutation frequency was significantly lower in advanced carcinomas invading through the entire muscularis propria (10.5%) than in early carcinomas confined to the mucosa (47.8%), and the mutation frequency in carcinomas invading through the entire muscularis propria was significantly lower in patients with synchronous lesions (10.5%) than in patients with a single lesion (37.7%). These results suggest that the tumorigenesis of colorectal carcinomas from patients with synchronous lesions is different from that in patients with a single lesion.
Ras oncogene and p53 gene hotspot mutations in colorectal cancers
Authors: LIN SHYR‐YI , CHEN PAO‐HUEI , YANG MING‐JUI , CHEN TE‐CHUAN , CHANG CHIH‐PENG , CHANG JAN‐GOWTH
Published: March 2008

Abstract Ras oncogene and p53 gene mutations are frequently observed in colorectal cancers. The role of co‐operation between these two genes in the tumorigenesis of colorectal cancer was evaluated. Point mutations in K‐ras oncogene and hotspot codons of p53 gene of colorectal cancers were evaluated by naturally created or amplified created restriction site method. Nine of 42 cases (21.4%) of colorectal cancer showed K‐ras oncogene mutations. Six of 42 cases (14.3%) of colorectal cancer showed p53 gene hotspot point mutations. The low frequency of p53 gene mutation in this series may be due to racial difference or different hotspot codons. When six cases with mutated p53 gene were examined, only one (16.7%) showed concurrent K‐ras oncogene codon 12 and p53 gene codon 248 mutations. We concluded that the co‐operation between ras oncogene and p53 gene hotspot point mutations in the tumorigenesis of colorectal cancer in Chinese was not common. Other factors such as adenomatous polyposis coli gene mutations, oncogene activation or tumour suppression gene inactivation may be involved.
Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma
Authors: YUMOTO YASUHIRO , HANAFUSA TADASHI , HADA HAJIME , MORITA TAKECHIYO , OOGUCHI SOUHEI , SHINJI NORIYUKI , MITANI TSUYOSHI , HAMAYA KAZUO , KOIDE NORIO , TSUJI TAKAO
Published: March 2008

Abstract Thirty‐six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well‐differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non‐tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty‐nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma).

The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC.

LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade. These findings suggest that the accumulation of genetic changes in multiple tumour suppressor genes is involved in the progression of HCC.
Hepatitis B vaccination alone is not adequate for the categorizing of adult subjects with isolated anti‐HBc
Authors: CHAN CHO‐YU , LEE SHOU‐DONG , TSAI YANG‐TE , LO KWANG‐JUEI
Published: March 2008

Abstract To evaluate the meaning of isolated antibody to hepatitis B core antigen (anti‐HBc), 88 Chinese subjects with isolated anti‐HBc received rescreening of hepatitis B virus (HBV) markers. Eighty (90.9%) of them were still positive for this antibody and 29 were also found to be positive for antibody to hepatitis B surface antigen (anti‐HBs). The remaining 51 subjects (58.0%) were positive for anti‐HBc alone; 50 of them received a four‐dose schedule of hepatitis B (HB) vaccine. After the initial dose, only one vaccinee disclosed an amnestic anti‐HBs response, that is, anti‐HBs titre > 1000 miu/mL. Forty‐five vaccinees completed the vaccination schedule and 44 (97.8%) had anti‐HBs response. The anti‐HBs responses in 25 of these vaccinees were compared with 25 age‐ and sex‐matched normal susceptible vaccinees. The anti‐HBs response rates in both groups were the same (96 vs 96%). However, the geometric mean titre was significantly lower in the vaccinees with isolated anti‐HBc (512 mIU/mL vs 4688 mIU/mL, P < 0.001). Prevaccinated sera were available in 49 vaccinees with isolated anti‐HBc for detection of antibody to hepatitis B e antigen (anti‐HBe) and HBV DNA; 37 (75.5%) of them had one or two of these markers. As we regarded the rescreening of HBV markers, response to hepatitis B vaccination and presence or absence of anti‐HBe and/or HBV DNA together for categorizing the 88 subjects with isolated anti‐HBc, at least three‐quarters of them had past infection of HBV. The subjects with false positive anti‐HBc test were a minor group. We concluded that the presence or absence of amnestic anti‐HBs response to HB vaccination is not a reliable indicator for categorizing subjects with isolated anti‐HBc. Rescreening of HBV markers, with addition of anti‐HBe and HBV DNA, may be helpful in determining the necessity of HB vaccination.
Interferon therapy for patients more than 60 years of age with chronic hepatitis C
Authors: HORIIKE NORIO , MASUMOTO TOSHIKAZU , NAKANISHI KIMIO , MICHITAKA KOJIRO , KUROSE KIYOTAKA , OHKURA IZUMI , ONJI MORIKAZU
Published: March 2008

Abstract Nineteen patients aged > 60 years with chronic hepatitis C (CHC) received interferon (IFN) therapy and a complete response (CR) was achieved by five of them (26%). The incidence of CH with severe fibrosis in this elderly group was significantly higher than in another 52 patients with CHC who were < 60 years of age (the younger group; P < 0.05). There was no significant difference in the hepatitis C virus (HCV) genotype distribution between the elderly group and the younger group. However, the HCV‐RNA titre was significantly higher in the elderly group than in the younger group (P < 0.05). There was no significant difference in the efficacy rate of IFN in the elderly and younger groups after standardization of the background factors. In the elderly group, the HCV‐RNA titre was significantly lower in the patients achieving CR than in those with no response (P < 0.05). These data suggest that elderly patients with a low HCV‐RNA titre can still respond well to IFN therapy.
Hepatoprotection in ethinylestradiol‐treated rats is provided by tauroursodeoxycholic acid, but not by ursodeoxycholic acid*
Authors: AZER SAMY A. , CANFIELD PAUL J. , STACEY NEILL H.
Published: March 2008

Abstract Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) have been suggested as potential treatments for drug‐induced cholestasis. It was therefore decided to study the effects of administration of UDCA or TUDCA on individual serum bile acid concentrations, conventional liver tests and associated hepatic ultrastructural changes in ethinylestradiol‐treated (EE) rats (5 mg/kg per day). Control rats were treated s.c. with propylene glycol. EE‐treated rats were randomly assigned to receive daily i.p. injections of placebo, TUDCA or UDCA. Four rats in each group were treated for 4 consecutive days, and a second four for 14 days. After 4 days of treatment, the serum levels of cholic acid and taurocholic acid were significantly increased in EE‐treated rats. None of the conventional liver tests were significantly different among the four groups. After 14 days of treatment the serum levels of cholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, bilirubin, alkaline phosphatase and gamma glutamyltransferase were significantly raised in EE and EE plus UDCA treated rats. EE plus TUDCA treated rats, however, had no significant changes in these individual serum bile acids or conventional liver tests. The ultrastructure of livers from EE plus TUDCA treated rats was similar to those of controls. On the other hand, EE and EE plus UDCA rats both showed a significant reduction in sinusoidal microvilli. These results show that treatment of rats for 4 days with EE induces significant rises in the serum concentrations of two individual bile acids and that TUDCA protects against this. On treatment over 14 days TUDCA provides protection against changes in several biochemical liver tests as well as ultrastructural hepatoprotection. Treatment with UDCA, however, afforded no such protection.
How safe is endoscopic sphincter of Oddi manometry?
Authors: SCICCHITANO JANICE , SACCONE GINO T. P. , BAKER ROBERT A. , ROBERTS‐THOMSON IAN C. , TOOULI JAMES
Published: March 2008

Abstract The safety of endoscopic manometry of the sphincter of Oddi was evaluated in a prospective survey of 158 consecutive procedures in 126 patients with either unexplained pain after cholecystectomy or idiopathic recurrent pancreatitis. The only complication was that of pancreatitis which was defined as the development of abdominal pain in association with a plasma amylase above the reference range. This occurred in 13 patients (8%) and was more frequent (P= 0.001) when the indication for the procedure was idiopathic recurrent pancreatitis (29%) than unexplained pain (6%). Pancreatitis was also more frequent (P= 0.02) in patients with abnormal manometry (14%) than in those with normal manometry (3%) and occurred at highest frequency (50%) in a subgroup of patients with idiopathic recurrent pancreatitis and sphincter stenosis (high sphincter basal pressure). All episodes of pancreatitis were mild with a median increase in hospital stay of 2 days; no patients died. The risk of pancreatitis after endoscopic manometry is relatively low but increases in patients with abnormal sphincter manometry, particularly those with idiopathic recurrent pancreatitis.
National survey of alcoholic liver disease in Japan (1968–91)
Authors: TAKADA AKIRA , TSUTSUMI MIKIHIRO ,   THE JAPANESE STUDY GROUP FOR ALCOHOLIC LIVER DISEASE
Published: March 2008

National surveys of alcoholic liver disease (ALD) in Japan were performed in 1978 and 1985 by a previous Japanese study group for ALD (the Takeuchi group). In the present study, a subsequent nationwide survey of ALD in Japan was conducted from 1986 to 1991 and the results compared with the previous studies. In order to clarify the aetiological relationship between hepatitis C virus (HCV) infection and ALD, results were also analysed according to new diagnostic criteria for ALD proposed by the current ALD study group (the Takada group).

According to the diagnostic criteria of the Takeuchi group, the incidence of ALD did not differ significantly from 1986 to 1991. However, the incidence of hepatocellular carcinoma (HCC) in alcoholic cirrhosis (AL‐LC) clearly increased during this period. The analysis, which included analysis of results from the previous studies, indicated that the incidence of ALD reached a plateau in 1980 and then stablized. However, HCC in AL‐LC continued to show a linear increase from 1976 to 1991.

The new diagnostic criteria of the Takada group were used to analyse cases from 1990 and 1991. Approximately two out of every three cases of ALD were caused by alcohol alone, and the remainder were caused by a combination of alcohol and HCV. Cases caused only by HCV were very rare. The main aetiology in patients with alcoholic hepatitis and fibrosis was alcohol alone, and in the case of chronic hepatitis, in heavy drinkers, it was a combination of alcohol and HCV. In half the patients with AL‐LC the aetiology was alcohol alone, and in the other half it was a combination of both alcohol and HCV. In the majority of patients with HCC, the aetiology was a combination of alcohol and HCV, indicating that HCV infection may be important in the development of HCC in alcoholics.
Influence of pregnancy and uterine weight on rat gastrointestinal transit
Authors: CHANG F‐Y , LEE SD , YEH GH , WANG PS
Published: March 2008

Orogastric feeding of a charcoal meal to rats was employed to measure whether the various stages of pregnancy could influence gastrointestinal transit. The oestrous cycle of female Sprague‐Dawley rats was checked daily. If pro‐oestrus occurred, the first day of pregnancy was defined to be on the next day after the copulation. Gastrointestinal transit studies were conducted on day 7 (first trimester), day 14 (second) and day 21 (third), respectively. The rats were killed 15 min after the successful feeding of a calorie‐free, charcoal‐containing test meal via a transiently placed orogastric catheter. Gastrointestinal transit was defined as the per cent of charcoal transit divided by the total length of the small intestine. These results were compared with the data obtained from non‐pregnant female rats. Mean percentages of transit for the first, second and third trimester, and for controls were 42.8 ± 1.9, 45.3 ± 4.1, 35.7 ± 1.7 and 42.6 ± 1.4%, respectively (mean ± s.e.). Late pregnancy elicited a marked inhibition of transit (P < 0.01). A significant negative correlation between transit and uterine weight of all pregnant rats was seen (r= ‐0.50, P < 0.05). The present study indicates that inhibited gastrointestinal transit occurs in the late pregnant rat.
Emphysematous gastritis secondary to acute gastric dilatation
Authors: LIN CHUN‐YEN , LEE CHING‐SONG , LIN DENG‐YN , HONG CHIEN‐FU , JAN YI‐YIN , LIN PAUL‐Y , CHEN PANG‐CHI , WU CHENG‐SHYONG
Published: March 2008

Emphysematous gastritis is a life‐threatening disease. Although rare in incidence, it has a fulminating course with a high mortality rate. A case of a 58 year old male with emphysematous gastritis is reported. Initially, he presented with acute gastric dilatation secondary to anorexia/bulimia‐like behaviour. Later, emphysematous gastritis developed. The abdominal sonographic findings, which have not been previously described in the literature, showed intramural gas and gastric wall thickening. After receiving a total gastrectomy, he had a satisfactory outcome. The present report discusses the possible aetiologic relationship between acute gastric dilatation and emphysematous gastritis, and suggests abdominal sonography to be the first choice of diagnostic measure for patients with the intramural gas in the gastric wall. This is the first case of emphysematous gastritis diagnosed by abdominal sonography.
CD34 expression in endothelial cells of small hepatocellular carcinoma: Its correlation with tumour progression and angiographic findings
Authors: MAEDA TAKASHI , ADACHI EISUKE , KAJIYAMA KIYOSHI , TAKENAKA KENJI , HONDA HIROSHI , SUGIMACHI KEIZO , TSUNEYOSHI MASAZUMI
Published: March 2008

The angiogenic process plays an important role in tumour growth and metastasis during hepatocarcinogenesis, but it is still uncertain when the process begins during tumour formation. Forty‐two small hepatocellular carcinomas (HCC) that measured either less than or equal to 2 cm in diameter were studied by comparing the histologic findings with the angiographic findings, and with immunohistochemical expression of endothelial marker QB‐end/10 (QB), a new monoclonal antibody raised against CD34, in the sinusoidal wall. Twenty (91%) of 22 moderately or poorly differentiated HCC revealed a positive reaction for QB, while only eight (40%) of 20 well differentiated HCC demonstrated a positive reaction (P < 0.01). In the tumours showing a ‘nodule in nodule’ appearance, the less differentiated areas were more reactive for QB. Twenty‐three (82%) of 28 QB positive tumours were hypervascular, while only three of 14 (21%) QB negative tumours were hypervascular (P < 0.01) by angiography. All six of the poorly differentiated and 13 (81%) of the 16 moderately differentiated tumours were hypervascular, while only seven (35%) of 20 well differentiated HCC were hypervascular (P < 0.01). These results indicate that as the tumour becomes less differentiated, the QB positive areas become wider and angiography demonstrates hypervascularity. We therefore speculate that the HCC sinusoids acquire the characteristics of capillary and precapillary blood vessels during de‐differentiation from well to moderate, and thus the tumour begins to reveal hypervascularity on angiography. The above process may be correlated with the stepwise progression of HCC.
Primary prevention of hepatocellular carcinoma
Authors: YU SHUN‐ZHANG
Published: March 2008

Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly, the mortality rates in 1990 (per 100 000) were 20.10 in certain cities and 24.32 in certain counties. More than 90% of HCC cases and 70% of controls were infected with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10–50). In the same group of patients, 8–27% of those with HCC and 0–11% of the healthy controls were also infected with hepatitis C (HCV) (OR = 2.11–17.29). There appears to be some correlation between HBV markers and the OR. The government requires that 85% of infants be immunized with HBV vaccine. In 1992, there were 3 million infants inoculated with HB vaccines. Aflatoxins have been found as contaminants in food, particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake of aflatoxin B1, (AFB1) by people of ten different villages correlated with HCC mortality rates (r =0.55; P < 0.05). The concentration of AFB1‐albumin adducts is an indicator of individual exposure to aflatoxins. These adducts are higher in hyperendemic HCC areas and cases. Most people have now changed their staple food and eat rice instead of corn. Six large epidemiological studies have confirmed that people who drink pond‐ditch water experience higher HCC mortality rates than people who drink deep‐well water. Recent research has found that the blue‐green algal toxin microcystin (MCYST) was a contaminant of pond‐ditch water. MCYST is a strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver necrosis. More than 30% of people in Qidong County have already changed their sources of water from pond‐ditches to deep wells. Therefore, a combined strategy of the prevention of hepatitis, control of crops and control of drinking water is advocated for the primary prevention of HCC in China.
Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double‐blind controlled multicentre study in Singapore
Authors: FOCK KM , KANG JY , NG HS , NG TM , GWEE KA , LIM CC
Published: March 2008

Roxatidine acetate, a new H2 receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double‐blind multicentre study. Eighty‐four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.
Immunolocalization of pS2, a putative growth factor, in pancreatic carcinoma
Authors: COLLIER JD , BENNETT MK , BASSENDINE MF , LENDRUM R.
Published: March 2008

pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described family of trefoil‐shaped growth factors. It is widely distributed throughout the gastrointestinal tract, particularly adjacent to damaged mucosa, and is also expressed by some epithelial tumours such as breast carcinoma. The aim of this study was to examine the expression of pS2 in pancreatic cancer. The presence of pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR‐2) and a monoclonal (pS2TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of ampullary carcinoma. The findings were compared with chronic pancreatitis and normal pancreas.

No immunostaining was seen in normal pancreas, with the exception of one area of ductular proliferation, and although 8/10 cases of chronic pancreatitis expressed pS2, it was focal and confined to the occasional duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed immunoreactive pS2.

The finding of pS2 expression in more than 50% of pancreatic and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis and normal pancreas suggests that pS2 may play an important role in the growth of these highly malignant tumours.
Efficacy of ursodeoxycholic acid in the treatment of patients with chronic hepatitis C
Authors: LU CHING‐LIANG , CHAN CHO‐YU , HWANG SHINN‐JANG , LU RUEY‐HWA , LEE SHOU‐DONG
Published: March 2008

A case‐control study was conducted to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with chronic hepatitis C. Patients who failed to have sustained responses to interferon (IFN) therapy, refused to take IFN or were unsuitable for IFN treatment were enrolled into this study. The treatment group had 15 patients and they received UDCA 600 mg orally per day for 6 months. Another 15 patients with matched sex, age and initial serum alanine aminotransferase (ALT) levels were chosen as the control group. Three parameters (i.e. serum ALT levels, serum hepatitis C virus (HCV) RNA and serum cytokines) were measured before and after UDCA treatment. After the treatment period, the mean serum ALT levels in both groups were not significantly different (153.8 ± 111.0 U/L vs 112.1 ± 53.8 U/L, P > 0.05) and mean serum ALT level in the UDCA‐treated group did not decrease after the treatment (pre‐treatment vs post‐treatment value: 139.1 ± 73.1 U/L vs 153.8 ± 111.0 U/L, P > 0.05). In addition, all of the patients with positive HCV RNA before treatment still had active HCV viraemia after the UDCA treatment. Also, the serum levels of interleukin‐6 (IL‐6) and the tumour necrosis factor‐α (TNF‐α) were not significantly different between the two groups before and after the treatment period. In conclusion, a regimen of UDCA as prescribed in the present study did not show obvious benefits in the treatment of Chinese patients with chronic hepatitis C.
High prevalence of antibodies to recombinant CENP‐B in primary biliary cirrhosis: Nuclear immunofluorescence patterns and ELISA reactivities
Authors: PARVEEN SALINA , MORSHED SYED AHMED , NISHIOKA MIKIO
Published: March 2008

The purpose of the present study is to evaluate the centromeric pattern on human laryngeal tumour (HEp‐2) cells by indirect immunofluorescent (IIF) test and to compare their reactivities with a newly developed recombinant centromere protein B enzyme linked immunosorbent assay (CENP‐B ELISA) test using sera of antinuclear antibody (ANA)‐reactive primary biliary cirrhosis (PBC) patients. Antimitochondrial antibody (AMA) subtypes (PDC‐E2, BCOADC‐E2, OGDC, protein X, and PDC‐E1α) by Western blot were also investigated to see whether they have any effect on the expression of CENP‐B reactivities. A centromeric pattern (anticentromere antibody [ACA]) was detected in 11 of 25 (44%) PBC patients whereas CENP‐B reactivity was found in 15 (60%) of them. There were some differences in IIF patterns and CENP‐B reactivities. One PBC serum with indistinguishable ANA pattern reacted with CENP‐B. Eight of 15 (53%) CENP‐B reactive patients had other autoimmune‐like disorders. Of 181 healthy sera, none was reactive for ACA either by IIF or by ELISA test. There was a correlation between ACA IIF and CENP‐B ELISA titres (r= 0.824, P < 0.001). However, no correlation was observed between either CENP‐B or AMA reactivities and/or between either autoantibodies or laboratory and histologic indices of PBC. These findings suggest that recombinant CENP‐B ELISA appears to be more sensitive in identifying ACA than IIF, underlying its potential value as a screening test for the diagnosis of PBC complicated with other autoimmune‐like disorders. The presence of multiple autoantibodies in PBC sera may reflect heterogeneous antigens recognition, and requires further study to identify target antigens at cellular and molecular levels.
Chemosensitivity test for repeated arterial infusion chemotherapy by reservoir for unresectable hepatocellular carcinoma
Authors: DENDA TADAMICHI , SAISHO HIROMITSU , YOSHIKAWA MASAHARU , EBARA MASAAKI , OHTO MASAO , FUJIMOTO SHUICHI , TOKITA HISASHI
Published: March 2008

The experimental and clinical usefulness of a chemosensitivity test (Nuclear Damage Assay) was studied. Karyologic degenerative changes were observed as an indicator of drug sensitivity, in repeated arterial infusion chemotherapy (RAIC) using a reservoir for advanced hepatocellular carcinoma (HCC). In the experimental study, this sensitivity test was performed using five liver cell lines against 15 drugs. At the same time, the succinate dehydrogenase inhibition (SDI) test was also performed. Comparison of the results between these two tests gave a high consistency rate of 81%. Clinically, the karyologic sensitivity test was carried out in 135 patients with unresectable HCC. Drug sensitivity could be evaluated in as many as 89% of the total 135 patients. Of the patients, 43 received RAIC on an outpatient basis via a subcutaneously implanted reservoir. The objective response of RAIC on tumours of the 43 patients was evaluated as complete response, partial response, in 3 (9%) and 8 (23%) in 35 patients treated with positive drugs (positive group), and as 0 (0%) and 0 (0%) of 8 patients treated with negative drugs (negative group), respectively. As regards the prognosis, 1 year and 1.5 year survival rates were 70 and 45% in the positive group, and 42 and 0% in the negative group, respectively. As objective response in the positive group tended to be better than that in the negative group, and prognosis in the positive group was significantly better than that in the negative group, this sensitivity test appears to contribute to the improvement of therapeutic results if used to select drugs suitable for RAIC for advanced HCC.
Endoscopic injection sclerotherapy of bleeding duodenal varices
Authors: WU CHEN‐SHYONG , CHEN CHIN MING , CHANG KENG YUNG
Published: March 2008

Bleeding from duodenal varices is a rare finding in patients with liver cirrhosis. We report a 43 year old male with alcoholic liver cirrhosis who presented with upper gastrointestinal bleeding. Panendoscopy identified prominent tortuous varices over the second portion of duodenum with spurting of blood. At first, the varices were treated successfully with sodium tetradecyl sulfate and bleeding stopped. Consequent endoscopic sclerotherapy was done 1 week later. The varices almost disappeared 2 weeks after the second endoscopic sclerotherapy and the patient was in good condition following this.
Role of Kupffer cells in failure of fatty livers following liver transplantation and alcoholic liver injury
Authors: THURMAN RONALD G , GAO WENSHI , CONNOR HENRY D , ADACHI YUKITO , STACHLEWITZ ROBERT F , ZHONG ZHI , KNECHT KATHRYN T , BRADFORD BLAIR U , MASON RONALD P , LEMASTERS JOHN J
Published: March 2008

Kupffer cells have been implicated in mechanisms of pathophysiology following liver transplantation. Recently, postoperative injury in ethanol‐induced fatty liver has been evaluated because fatty livers often fail following transplantation. The low‐flow, reflow liver perfusion model was used to study the role of Kupffer cells (KC) in reperfusion injury to fatty livers from rats fed a diet containing ethanol for 4–5 weeks. Treatment with GdCl3, which selectively destroys KC, decreased cell death significantly. Thus, destruction of KC minimized hepatic reperfusion injury, most likely by inhibiting free radical formation and improving microcirculation.

Since it was demonstrated recently that destruction of KC prevented the hypermetabolic state observed with acute alcohol exposure, their involvement in events leading to alcohol‐induced liver disease was investigated. In rats exposed to ethanol continuously via intragastric feeding for up to 4 weeks, GdCl3 treatment prevented elevation of aspartate aminotransferase (AST) and dramatically reduced the average hepatic pathological score. These results indicate that KC participate in the early phases of alcohol‐induced liver injury.

Endotoxaemia occurs in alcoholics and activates KC; therefore, we evaluated the effect of minimizing bacterial endotoxin by intestinal sterilization with the antibiotics polymyxin B and neomycin. Antibiotics diminished plasma endotoxin levels significantly and prevented ethanol‐induced increases in AST values. These results indicate that endotoxin is involved in the mechanism of ethanol‐induced liver injury.

A six‐line radical spectrum was detected with electron paramagnetic resonance spectroscopy in bile from alcohol‐treated rats which was blocked by GdCl3. The free radical adducts had hyperfine coupling constants characteristic of lipid‐derived free radical products. In conclusion, these studies demonstrate that KC are involved in reperfusion injury to ethanol‐induced fatty livers and hepatic injury due to long‐term treatment with ethanol.
Human liver‐associated lymphocytes: An overview
Authors: WINNOCK M , BARCINA M GARCIA , LUKOMSKA B , HUET S , SARIC J , BALABAUD C , BIOULAC‐SAGE P
Published: March 2008

Morphological and phenotypical data indicate that liver sinusoids contain a heterogeneous population of lymphocytes of which large granular lymphocytes are only one element. It is suggested that the term of liver‐associated lymphocytes (LAL), which encompasses all sinusoidal lymphocytes, be used for this fourth sinusoidal cell type.

Studies realized by flow cytometry on isolated cells have shown that human LAL differ phenotypically from peripheral blood lymphocytes (PBL). LAL are characterized by a three‐fold increase in the percentage of cells presenting the CD56 antigen, a natural killer (NK) marker, but also an increase in the percentage of CD8 cells and a decrease in the percentage of CD4. Furthermore, within the CD56+ LAL population, 95% of cells are CD3+/‐ CD16‐, whereas the majority of CD56+ cells in PBL are CD3‐/CD16+. These differences do not seem to depend on liver pathology since no differences were found in the LAL phenotype, for all markers analysed, between patients with liver metastasis or with benign liver tumours. Liver sinusoids also harbour T cells bearing the γ/δ chains with a repertoire of V gene arrangements which differs from that found in PBL from the same patients, confirming a site‐specificity.

Functionally, LAL were shown to possess a higher level of NK cell activity against K‐562 cells than PBL. LAL also expressed a lymphokine activated killer (LAK) activity against NK‐resistant cell lines (Raji cells), whereas no such activity was detected in PBL from the same patients. Interestingly, LAK‐activity from LAL isolated from patients with liver metastases was dramatically decreased compared to that from LAL isolated from patients with benign liver disease. The level of LAK activity of LAL situated distant to the malignant tumour was higher than that obtained from LAL close to the tumour, thus suggesting that cytotoxic lymphocyte capabilities could be inhibited by tumoral celis. LAL differ, both quantitatively and qualitatively, from PBL in the expression of cellular adhesion molecules. Precise mechanisms of their homing or in situ differentiation must still be elucidated.
Hepatitis C transmission between spouses
Authors: KODA TETSUZO , YONAHA MARI , HAYASHI AKIO , ISHIKAWA KATSUNORI
Published: March 2008

To examine inter‐spouse transmission as one of the potential routes of infection for hepatitis C virus (HCV), 121 patients with HCV‐related chronic liver disease who tested positive for antibodies to HCV (anti‐HCV) and their spouses were studied. Of these, 21 (17.4%) patients had spouses with anti‐HCV. In 12 couples, the HCV genotype matched (type II: 10 couples, type III: two couples). The genotype differed in six couples. One patient was positive for anti‐HCV, but negative for HCV‐RNA, while the spouse was positive for both. The remaining two couples were only positive for anti‐HCV. Genetic heterogeneity in the hypervariable region 1 of HCV was analysed in 11 couples with matched genotypes. In two couples, no mutation was recognized in the putative E2/NS1 genes using the heteroduplex method. The present study provides evidence to verify household transmission of HCV between patients and their spouses. These results suggest that inter‐spouse transmission may be a potential route of transmission of HCV infection. However, other environmental factors (e.g. the duration of the marriage) cannot be ignored.
Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: Markers of fibrosis in primary biliary cirrhosis
Authors: REMMEL TRIIN , REMMEL HELE , SALUPERE VELLO
Published: March 2008

The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have previously been studied in different liver diseases. The results of these studies are controversial. The aim of the present study was to examine the relationship between PIIINP and hyaluronan levels and the clinical, biochemical and histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty‐five PBC patients were studied at the time of diagnosis of PBC and were followed up for a mean of 58 months. During the follow‐up period 21 patients died. In addition, 30 healthy subjects were examined in the present study. Hyaluronan and PIIINP were measured by radioimmunoassay and the levels of both PIIINP and hyaluronan were higher in PBC patients than in healthy volunteers (P< 1.8 times 10‐6 and 1.6 times 10‐9, respectively). Hyaluronan and PIIINP levels were above normal values in 82 and 84% of PBC patients, respectively. There were correlations between PIIINP and hyaluronan and the histological stage of PBC (r=0.44, P< 0.004 and r=0.56, P< 0.00001, respectively). The correlation between PIIINP and hyaluronan was 0.46 (P< 0.0035). In symptomatic patients, both PIIINP and hyaluronan values were higher than in controls (P< 0.002 and P< 0.006, respectively). The levels of PIIINP correlated significantly with bilirubin (r=0.43, P< 0.006), while hyaluronan was correlated with age (r=0.33, P< 0.015), pruritus (r=0.32, P< 0.02), fatigue (r=0.41, P< 0.003), hepatomegaly (r=‐0.46, P< 0.0008), the presence of oesophageal varices (r=0.34, P< 0.002), weight loss (r=0.29, P< 0.05), bilirubin (r=0.54, P< 0.0001), albumin (r=‐0.30, P< 0.04), extent of fat excretion (r=0.53, P< 0.009) and length of symptomatic period before diagnosis of PBC (r=0.43, P< 0.002). Using Cox's logistic regression analysis, survival was found to be influenced by bilirubin concentration but not by hyaluronan, PIIINP, age, albumin or histological stage. Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of prognostic outcome.
Determinants of disease expression in Australian haemochromatosis patients
Authors: CRAWFORD DARRELL HG
Published: March 2008

Many of the clinical manifestations of haemochromatosis are determined by the hepatic iron concentration which, in turn, may be influenced by environmental and genetic factors. The environmental factors that influence iron stores include age, gender and blood loss (pathological and physiological). There is evidence that genetic factors also influence hepatic iron accumulation, as patients with two copies of the ancestral haplotype accumulate more iron than subjects with one or no copies of the ancestral haplotype. Concordance of iron storage between siblings also suggests genetic factors play an important role in determining disease expression. However, clarification of the exact role of genetic factors awaits the conduct of further studies following the cloning of the haemochromatosis gene.