bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of the Brisbane Liver Group to knowledge of iron metabolism
Authors: BOTHWELL TH
Published: March 2008

In celebrating this very special day, it is appropriate to look back on the achievements of the Brisbane Liver Group, in which June Halliday has played such a key and pivotal role. Over the years the group's interests have included a whole range of interwoven iron themes, but as hereditary (genetic) haemochromatosis (HH) is central to a number of these themes, it provides a good starting point.
Cellular iron processing
Authors: MORGAN EVAN H.
Published: March 2008

Iron is transported in the blood plasma, mainly bound to transferrin, but in abnormal conditions other iron containing compounds may become important. These include ferritin, haemopexin‐haem, haptoglobin‐haemoglobin and non‐specific non‐transferrin‐bound iron, all of which are taken up from the circulation by the liver. Transferrin‐bound iron can be used by all types of cells in amounts that depend on their complement of transferrin receptors. Immature erythroid cells are the most active in this function. Investigations using reticulocytes as an example of erythroid cells have demonstrated the presence of two mechanisms for the uptake of ferrous iron. One, a high affinity process disappears as reticulocytes mature. It probably represents the mechanism by which iron derived from transferrin is transported into the cytosol after receptor‐mediated endocytosis of the iron‐transferrin complex. The other mechanism has a lower affinity for iron, is retained when reticulocytes mature and is probably associated with Na+ transport across the cell membrane. The physiological characteristics of the two iron transport processes and the evidence for the above conclusions are summarized in the present paper.
Iron in an Australian population: Too little or too much?
Authors: LEGGETT BARBARA A.
Published: March 2008

In many countries in the world, iron deficiency is clearly a much greater problem than iron overload. In Australia the situation is less clear. A large population study undertaken in the Liver Unit of the University of Queensland Department of Medicine and the Queensland Institute of Medical Research under the direction of Professors June Halliday and Lawrie Powell has shed some light on this question. The study originally started out with the hypothesis that the genetic disease haemochromatosis was common in the Australian population and, therefore, significant num‐ bers of Australians had too much iron.
Review: Molecular pathogenesis of hepatic acute porphyrias
Authors: GRANDCHAMP BERNARD , PUY HERVÉ , LAMORIL JÉROME , DEYBACH JEAN CHARLES , NORDMANN YVES
Published: March 2008

The molecular cloning of cDNA and genes encoding enzymes of the haem biosynthetic pathway have permitted the genetic defects underlying acute intermittent porphyria (AIP) and hereditary coproporphyria to be unravelled. In AIP, many different gene abnormalities have been documented since 1989. The prevalence of specific defective alleles among AIP families depends on which human population is studied. Founder effects are likely to account for a high frequency of a single mutation in Finland and, to a lesser extent, in Holland, while many other mutations have only been found once, each of them in a single family. In hereditary coproporphyria several different mutations have already been identified since 1994, suggesting that a large allelic heterogeneity also exists. The search for mutations in variegate porphyria has just started since the recent publication of the human cDNA sequence. Direct detection of the mutations using DNA analysis brings a growing contribution to the detection of asymptomatic carriers among relatives of porphyric patients and will, therefore, improve the prevention of acute attacks.
Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture
Authors: TAKAHASHI MORIO , OTA SHINICHI , NISHIMURA SHUJI , OGURA KEIJI , MAEDA SHIN , TODA NOBUO , HAMADA EIJI , TERANO AKIRA , OMATA MASAO
Published: March 2008

Mesenchymal‐epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal‐epithelial interaction.
Lubrication of visceral movement and gastric motility by peritoneal surfactant
Authors: HILLS BA
Published: March 2008

Four studies are described as a means of evaluating the hypothesis that surface‐active phospholipid (SAPL) enhances the lubrication of gastric motility and visceral movement in general. In the first two studies, a lipid extract from ovine peritoneal rinsings was found to have remarkable antiwear capabilities ex vivo and to reduce friction to a remarkably low level as quantified by a coefficient of kinetic friction of 0.008 ± 0.002 (n= 10). Moreover, this lipid extract demonstrated both these features of lubrication at high load. In other studies, peritoneal lipid extract was found to be highly surfaceactive, while many lamellar bodies (LB) have been identified in omentum and, by analogy with the lung and the stomach, would therefore appear to be a source of SAPL. Lubrication by peritoneal surfactant is discussed as another example of a ubiquitous barrier to abrasion and other potential insults common to all visceral surfaces.
Cytotoxin and urease activities of Helicobacter pylori isolates from Japanese patients with atrophic gastritis or duodenal ulcer
Authors: MURAKITA HAJIME , HIRAI MASAMICHI , ITO SHIGEJI , AZUMA TAKESHI , KATO TAKUJI , KOHLI YOSHIHIRO , KURIYAMA MASARU
Published: March 2008

The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pyloripositive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin‐producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P= 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1. 6. ± 2. 3, 7. 9. ± 7. 4, 5. 8. ± 6. 0 and 9. 0 ± 9. 1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non‐ulcer patients in group 1 (P= 0.017 and 0.030, respectively). The mean of urease activity was 8. 6 ± 4. 6, 10. 0 ± 5. 9, 10. 0 ± 8. 5 and 11. 2 ± 7. 7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin‐producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease‐inducing factor.
Reduced liver function is the trigger for renal sodium retention following portal vein ligation in the rat
Authors: MURAKAMI SHIGETO , OHNO TOSHIYUKI , BERNARDO JOSÉ F. , PFEIFER CYNTHIA A. , LI TIMEO , ZHANG YONG , DUBEY RAGHVENDRA K. , BRANCH ROBERT A. , SABRA RAMZI
Published: March 2008

Sodium retention along with peripheral vasodilation are features of prehepatic portal hypertension. In several models of experimental liver damage, sodium retention occurs only when hepatic function, measured by the aminopyrine breath test (ABT‐k), falls below a critical threshold. The relationship between renal sodium handling, ABT‐k and systemic and renal haemodynamics in partial portal vein ligated (PVL) rats was examined to test the hypothesis that peripheral vasodilation was responsible for initiating sodium retention. Haemodynamic measurements were conducted early after surgery in portal hypertensive rats with and without sodium retention and in sham‐operated controls. Compared with control, both PVL groups of rats had elevated portal pressure and lower peripheral vascular resistance (P<0.05). Sodium retaining‐PVL rats had both lower ABT‐k (0.95 ± 0.05 vs 1.38 ± 0.06 times 10‐2/min; P<0.05) and higher sodium balance (1.38 ± 0.09 vs 0.43 ± 0.09 mmol/day; P< 0.05) than non‐sodium retaining PVL rats. No differences in plasma renin activity or noradrenaline concentrations were observed. In a separate group of rats, hydralazine‐induced peripheral vasodilation did not induce sodium retention. These results suggest that the presence of peripheral vasodilation alone is not sufficient to trigger a sodium‐retaining status. A factor, probably liver function‐dependent, acting directly on renal tubules may be necessary for changes in renal sodium handling in this model.
Renal and haemodynamic responses to a novel kappa opioid receptor agonist, niravoline (RU 51,599), in rats with cirrhosis
Authors: MOREAU RICHARD , CAILMAIL STEPHANE , HAMON GILLES , LEBREC DIDIER
Published: March 2008

Because renal water retention is a complication of cirrhosis, niravoline (RU 51,599), a novel kappa (κ) opioid receptor agonist which is known to cause a water diuresis under normal conditions, may be useful in the therapy of chronic liver diseases. Thus, the present study examined the effects of niravoline on renal function in rats with cirrhosis. Urine was collected during the 2 h period following the administration of vehicle (saline) in one group of animals or niravoline (3 mg/kg, i.v.) in auother group. Urinary and plasma osmolality were measured prior to and 2 h after niravoline in a third group of animals. Urine flow and natraemia were significantly higher after niravoline (147±12 μL/min and 153±2 mmol/L, respectively) than after vehicle (27 ± 7 μL/min and 146 ± 1 mmol/L, respectively). Niravoline significantly decreased urinary osmolality and significantly increased plasma osmolality and free water clearance. This substance did not significantly change urinary sodium excretion. In conclusion, this study shows that niravoline, a κ opioid receptor agonist, induced a water diuresis in rats with cirrhosis.
Career paths for clinical scientists
Authors: FARRELL GEOFFREY C.
Published: March 2008

In the 16 years since James Wyngaarden proclaimed the clinical investigator to be an endangered species, attempts to revive this fragile beast have met with limited success in North America, the UK and Australia. The situation may be more healthy in some western European countries and Japan, but in many parts of Asia clinical investigators have vanished without trace. An analysis of the Australian context during the past 16 years suggests a gradual decline in absolute numbers of clinical scientists reaching maturation, coupled with an extraordinary diminution of their research fertility relative to that of basic scientists. In the present review, it is argued that clinical scientists have a vital role to play in medical research and, particularly, in clinical research. The reason why fewer medical graduates are entering and even fewer are being retained in medical research careers cannot be attributed to restrictions at entry, according to the availability of and competition for training scholarships. Other possible explanations include the late age of entry and the negative influence of role modelling. The latter operates directly by the attitudes and pathways of peers and indirectly through the biases of peer review. There is also a perception, possibly a realistic one, that insuperable barriers exist to obtaining a stable career position at the end of training. Finally, there is real concern about whether clinical investigators will be able to compete successfully with basic researchers for research grants. If this summation is correct, the solutions include active recruitment for research training at an earlier age, simultaneous research and medical training and truncation of postgraduate clinical training in the medical specialties with earlier introduction of medical research. In addition to these strategies, the proper training of clinical scientists must afford them generic research skills and social adaptation to a team approach with basic scientists.
PEPTIC ULCER: PATHOGENESIS, HEALING AND ANTI‐ULCER DRUGS
Authors: TERASAKI TEIICHI , SHIMADA KAZUHIKO , WAKABAYASHI HIROYUKI , TANAKA MICHIO , WATANABE AKIHARU
Published: March 2008

Abstract  To investigate pathophysiological diversities in the repairing process of gastric ulcer, distribution density of basic fibroblast growth factor (bFGF)‐positive fibroblasts and myofibroblasts and vascular endothelial cells, mucosal haemoglobin content, PAS‐positive mucus amount and glandular index were compared in the peripheral region of an open ulcer (the unhealed group; n = 17), the central region of a red scar (the red scar group; n = 32) and the central region of the white scar (white scar group; n = 32). Density of bFGF‐positive fibroblasts and myofibroblasts and vascular endothelial cells was highest in the unhealed group, followed by the red scar group, while the white scar group showed a low value close to control. Mucosal haemoglobin content was high in the red scar and unhealed groups. PAS‐positive mucus amount in the unhealed and red scar groups showed lower values compared with that in the white scar group. Glandular index in the unhealed group was the lowest, followed by the red scar group, while the white scar group neared control values. Statistically significant correlations were observed between the density of bFGF‐positive ‘fibroblasts and myofibroblasts' and density of bFGF‐positive vascular endothelial cells, between the density of bFGF‐positive vascular endothelial cells and mucosal haemoglobin content and between the PAS‐positive mucus amount and glandular index. Discriminant analysis demonstrated that the unhealed group could be distinguished from the red and white scar groups, based on glandular index, density of bFGF‐positive ‘fibroblasts and myofibroblasts’, mucosal haemoglobin content and PAS‐positive mucus amount, while the red scar group could be discriminated from the white scar group based on the density of bFGF‐positive ‘fibroblasts and myofibroblasts’, density of bFGF‐positive vascular endothelial cells, glandular index, haemoglobin content and PAS‐positive mucus amount. The white scar group was difficult to discriminate from control. Our present results show that the recovery of glandular formation and mucus production continues throughout the repairing process, whereas the acceleration of angiogenesis and granulation formation is observed only in unhealed ulcers and at the red scar stage.
AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA
Authors: SATO AKIRA , KATO YUJI , NAKATA KEISUKE , NAKAO KAZUHIKO , DAIKOKU MANABU , ISHII NOBUKO , MATSUMOTO TAKEHIRO , ISEKI KEIKO , MAZUME HIROYUKI , NAGATAKI SHIGENOBU
Published: March 2008

Abstract  Most patients with hepatocellular carcinoma (HCC) in Japan have hepatitis B virus (HBV)‐or hepatitis C virus (HCV)‐associated cirrhosis. In the present study, the risk of HCC in patients with cirrhosis was analysed by the levels of serum alanine aminotransferase (ALT). One hundred and one (78%) of 129 patients with cirrhosis registered from April 1979 were followed at monthly intervals with the measurement of serum ALT. Of 101 patients, 38 tested positive for hepatitis B surface antigen (HBsAg) but negative for antibody to HCV (anti‐HCV; HBV group), 47 tested negative for HBsAg but positive for anti‐HCV (HCV group) and nine tested positive and seven tested negative for both. Mean serum ALT during follow‐up was calculated on the basis of monthly values during the observation period that started at enrolment and ended with the detection of HCC or at the end of March 1994. By the end of March 1994, 37 (37%) patients developed HCC; 12 were in the HBV group, 21 in the HCV group and four were in the group positive for both. Mean serum ALT during the observation period was similar in patients who developed HCC and those who did not develop HCC in the HBV group. In contrast, the value was significantly higher in patients who developed HCC than in patients who did not develop HCC in the HCV group (P < 0.05).
AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA
Authors: HWANG SHINN‐JANG , TONG MYRON J. , LAI PAUL PC. , KO EDISON S. , CO RUTH L. , CHIEN DAVID , KUO GEORGE
Published: March 2008

Abstract  In order to evaluate the roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) and their clinical significance in Asian‐American and Caucasian patients with hepatocellular carcinoma (HCC) in the USA, 110 HCC patients, seen in a community‐based teaching hospital in the Los Angeles area over a 10 year period, were enrolled. Seventy‐nine (72%) patients were Asian‐Americans and 31 (28%) were Caucasians. Of the 110 HCC patients, 69 (63%) were positive for serum hepatitis B surface antigen (HBsAg), 26 (24%) were positive for serum antibody to hepatitis C virus (anti‐HCV), five (all Asian‐Americans) were positive for both markers; 11 (10%) patients had a history of alcoholism. HBsAg was detected in 63 (80%) Asian‐American patients, significantly higher than in the six (19%) Caucasian HCC patients (P < 0.01). Anti‐HCV was detected in 10 (32%) Caucasian and in 16 (20%) Asian‐American HCC patients (P > 0.05). Among Asian‐American HCC patients, anti‐HCV was more prevalent in those who were HBsAg‐negative than in the HBsAg‐positive patients (69 vs 8%; P < 0.01). A history of alcoholism was obtained in nine (29%) Caucasian HCC patients, significantly higher than in the two (3%) Asian‐American HCC patients (P < 0.05). Comparing HCC patients with positive HBsAg and with anti‐HCV, HBsAg‐positive HCC patients were younger, Asian‐Americans and predominantly male; 38% had a family history of liver disease. In contrast, anti‐HCV‐positive HCC patients were older by nearly a decade and 46% had a history of blood transfusion. Using a stepwise logistic regression analysis, Asian race and patient age < 50 years were found to be independent predictors for HBsAg‐positivity, while a history of blood transfusion was the only predictor for anti‐HCV‐positivity in HCC patients. There was no significant difference in the rate of cirrhosis, serum levels of alpha‐fetoprotein and survival between HBsAg‐positive and anti‐HCV‐positive HCC patients. In conclusion, chronic HBV infection was the major aetiological factor in Asian‐American HCC patients, while chronic HCV infection and alcoholism were major aetiological factors in Caucasian HCC patients in the USA.
AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA
Authors: HIRASHIMA NOBORU , MIZOKAMI MASASHI , ORITO ETSURO , KOIDE TSUNEO , ITAZU IPPEI , KUMADA KAZUNORI , SAKAKIBARA KENJI , KANO HIDEYUKI , LAU JOHNSON YN
Published: March 2008

Abstract  A 60‐year‐old man with a chronic hepatitis C virus (HCV) infection and histological features of chronic active hepatitis was treated with interferon‐a (IFN). He successfully responded to IFN with normalization of serum ALT and disappearance of serum HCV‐RNA. His liver biochemistry profile remained normal and serum HCV‐RNA was not detected throughout the entire follow‐up period. One year later, a small hepatocellular carcinoma (HCC) was detected by routine ultrasonographic screening. Laparotomy revealed a small tumour with no metastasis and the nontumorous liver demonstrated macronodular cirrhosis. Although no space‐occupying lesions were detected by frequent radiological examinations prior to IFN therapy, the small size of the tumour suggested de novo development of HCC. Patients with chronic HCV infection, including those who have complete responses to IFN and lack clinical and histological evidence of cirrhosis, should be followed up for the potential development of HCC.
Real‐time monitoring of HCV‐RNA by single tube assay kit and potential importance for predicting virological sustained response in patients with chronic hepatitis C
Authors: SHIRATORI YASUSHI , KATO NAOYA , TAMATSUKURI SHIGERU , YOSHIDA HARUHIKO , KAWABE TAKAO , NAKATA RYO , OKANO KEN'ICHI , OMATA MASAO
Published: March 2008

In an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV‐RNA in serum was measured by a one tube RT‐PCR assay kit using the RNA corresponding to 5 μL serum (standard assay) or 300 μL serum (enhanced‐sensitivity assay). Dilution analysis revealed that sensitivity of the ‘enhanced‐sensitivity assay’ increased by 10–100‐fold when compared with a ‘standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV‐RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5–6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the ‘standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the ‘enhanced‐sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a ‘standard assay’ and in 31 (82%) by the ‘enhanced‐sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV‐RNA in serum at the end of therapy, even by the ‘enhanced‐sensitivity assay', did not show the disappearance of HCV‐RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV‐RNA becomes undetectable. That can be only feasible during treatment by real‐time monitoring of HCV‐RNA.
Relationship between the intrahepatic expression of interferon‐α receptor mRNA and the histological progress of hepatitis C virus‐associated chronic liver diseases
Authors: ISHIMURA NORIHISA , FUKUDA RYO , FUKUMOTO SHIRO
Published: March 2008

Histological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)‐associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN‐Rc) in the liver. Expression of mRNA of the IFN‐Rc for IFN‐α was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV‐associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN‐α and IFN‐β mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN‐Rc mRNA in chronic persistant hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN‐Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN‐Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN‐Rc mRNA may be partially responsible for the poor IFN response in LC.
Efficacy and side effects of intermittent recombinant interferon‐α2a in chronic aggressive hepatitis C: With or without initial daily administration
Authors: ITOH HIDEKAZU , NAKATA HIDENORI , YOKOYA YUKIHIRO , NAKASHIMA SHOICHI , YAMANISHI TETSUJI , HARA TAKESHI , KAWAI JUN , MIYAMOTO HISAO , HIGASHI KATSUHIKO , NISHIOKA SHINGO
Published: March 2008

To investigate the therapeutic effect and incidence of side effects of recombinant interferon‐α2a (IFN‐α) in chronic aggressive hepatitis C under stratification by administration mode, a study was conducted by assigning patients to either group A (daily consecutive administration of 9 million units (MU) IFN‐α for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN‐α twice weekly or 6 MU IFN‐α thrice weekly for 24 weeks). The 28 patients in group A received IFN‐α for 24 weeks up to a total dose of 324 MU and the 53 patients in group B received the same for 24 weeks up to a total dose of 432 MU. When recovery was defined as the absence of hepatitis C virus (HCV)‐RNA 6 months after the completion of treatment, the rate of recovery for group A was 32.1% and that for group B was 37.7%, the latter being higher but without significance. Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%, respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group B exhibited lower values for both side effects. No difference was detected between these groups in other side effects, including pyrexia, generalized malaise, arthralgia or psilosis. Intermittent administration from the outset permitted shortened duration of hospitalization and earlier rehabilitation. Intermittent administration of INF‐α is required when treating patients with chronic hepatitis C showing lower leucocyte or platelet counts.
Case Report: Primary splenic non‐Hodgkin's B cell lymphoma in a patient with chronic hepatitis C
Authors: FUKUTOMI TAKAYOSHI , FUKUSHIMA MARIE , TANABE YUICHI , HIROSHIGE KAICHIRO , ITASAKA HIDETOSHI , MATSUMATA TAKASHI , KASAI NORIKO , YOSHIDA KISAKU , SUZUMIYA JUNJI , KIKUCHI MASAHIRO , YUFU YUJI , SAKAI HIRONORI , NISHIMURA JUNJI , NAWATA HAJIME
Published: March 2008

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69‐year‐old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non‐enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non‐Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non‐Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.
Case Report: Delayed resolution of severe pulmonary hypertension after isolated liver transplantation in a patient with cirrhosis
Authors: LEVY MT , TORZILLO P , BOOKALLIL M , SHEIL AGR , McCAUGHAN GW
Published: March 2008

Pulmonary hypertension is now recognized to be a rare association of liver disease and portal hypertension. This report describes the slow resolution of symptomatic pulmonary hypertension in a 33‐year‐old woman with cirrhosis who underwent isolated liver transplantation. The patient survived the surgery and perioperative period without significant haemodynamic compromise. After liver transplantation, the patient was monitored with regular Doppler echocardiography. By 27 months the pulmonary hypertension had almost completely resolved. This observation is important, as it suggests that patients with severe pulmonary hypertension who survive the perioperative period may have an excellent outcome, although resolution may be slow.
Comparison of haptoglobin and apolipoprotein A‐I on biliary lipid particles involved in cholesterol crystallization
Authors: YAMASHITA GUNJI , SECKNUS ROGER , CHERNOSKY ANN , KRIVACIC KIMBERLY A , HOLZBACH R THOMAS
Published: March 2008

Several proteins are known to modulate cholesterol crystallization. We recently demonstrated that haptoglobin has cholesterol crystallization promoting activity. However, this effect is still not well understood mechanistically. The current study examined the distribution of haptoglobin compared to apolipoprotein A‐I (apo A‐I) to micelles, vesicles and crystals as an initial step in providing a focus for further studies of the mechanism of cholesterol crystallization activity. Specific protein purification was accomplished by immunoaffinity chromatography. The crystallization‐promoting activity of biliary haptoglobin, albumin and commercial apo A‐I was measured by a photometric crystal growth assay. The distribution of micelles, vesicles and proteins in model bile was determined by Sepharose CL‐6B column chromatography. Detection of the presence of test proteins in cholesterol crystals was determined using specific 125I‐radiolabelled proteins. Haptoglobin (20 μg/mL) showed a significant crystallization promoting‐activity, whereas apo A‐I (30 μg/mL) only tended to show a slight inhibitory activity. The cholesterol crystal‐bound protein in each case was found to be less than 1% of the total concentration of that protein that had been added to the model bile system. The elution profile of commercial apo A‐I from a Sepharose CL‐6B column was strikingly altered when it was added to model bile prior to elution. In contrast, the column elution profiles for both haptoglobin and albumin were unchanged when model bile was similarly added to the sample. Haptoglobin increased the amount of cholesterol found in the vesicular fraction when compared to apo A‐I. Haptoglobin does not bind tightly to either biliary lipid particles or to cholesterol crystals but does increase the amount of cholesterol in vesicles by inducing a shift from micellar cholesterol (P=0.046). This shift appears to explain in part its promoting effect on cholesterol crystallization.
A Clinicopathological study on combined hepatocellular and cholangiocarcinoma
Authors: TAGUCHI JUN , NAKASHIMA OSAMU , TANAKA MASAYA , HISAKA TOHRU , TAKAZAWA TSUTOMU , KOJIRO MASAMICHI
Published: March 2008

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC‐CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum α‐fetoprotein was positive in 70% of cases and its levels were relatively low (≤ 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC‐CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC‐CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC‐predominant type (resembles HCC 49%), and a CC‐predominant type (resembles CC 34%). The separated and HCC‐predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.
Case Report: Mucin‐producing cystic neoplasm of the pancreas with onset in childhood
Authors: KOYANAGI SHUJIRO , MIYAHARA TOSHIHIKO , MIGITA YOSIKATSU , GOTO MASAYOSHI , ITO TETSUHIDE , YAMAGUCHI HIROYA , NAKANO ITSURO , TAKANO SOICHIRO , HARA YASUHIRO , FUKUYAMA TOKIHIKO , KONOMI KOHKI , HARATAKE JYOJI , NAWATA HAJIME
Published: March 2008

Mucin‐producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle‐aged and elderly people. In the present report, a case of a 21‐year‐old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.
Abnormal gastro‐oesophageal reflux in Chinese with atypical chest pain
Authors: LAU GEORGE KK , HUI WAI MO , LAU CHU PAK , HU WAYNE HC , LAI KAM CHUEN , LAM SHIU KUM
Published: March 2008

Although atypical chest pain has been well described in the Western population, its frequency in Chinese is unknown. Over a period of 42 months, we studied 521 Chinese patients with chest pain and identified 108 patients (20.7%) whose pain was not related to cardiac causes, as determined by exercise ECG or cardiac catheterization. Using 24 h ambulatory pH monitoring and baseline oesophageal manometry, 28.7, 19.4 and 5.6% of these patients were found to have abnormal reflux parameters, abnormal manometric findings or both, respectively. There were significantly more patients complaining of chest pain during the study in the gastro‐oesophageal reflux disease (GERD) group than in the non‐GERD group (16/31 vs 20/77; P< 0.001). The lower oesophageal sphincter pressure was lower in those with abnormal reflex parameters than in those with normal reflux parameters (12.7±5.4 vs 17.8±5.8 mmHg; P< 0.05). There was no significant difference in symptoms, such as heartburn (54.8 vs 42.9%), regurgitation (38.7 vs 35.1%) and dysphagia (19.4 vs 24.7%), among the two groups. Non‐specific changes were the most frequent baseline motility pattern. In conclusion, atypical chest pain and gastro‐oesophageal reflux disease are not uncommon in Chinese and this deserves special emphasis as the continuation of anti‐anginal drugs may aggravate their condition.
Effects of endoscopic variceal sclerotherapy on azygos vein blood flow and systemic haemodynamics*
Authors: YOKOYAMA MASANORI , SHIJO HIROSHI , OTA KAZUHIRO , KUBARA KATSUHIKO , KOKAWA HIROSHI , KIM TETSUHIRO , AKIYOSHI NOBUO , TOKUMITSU HIDEO , OKUMURA MAKOTO
Published: March 2008

The present study was designed to determine the systemic haemodynamic effects of obliterating oesophageal varices by endoscopic sclerotherapy. We evaluated systemic and splanchnic haemodynamics before and after the first course of sclerotherapy in cirrhotic patients. The baseline cardiac index was significantly correlated with baseline azygos vein blood flow (r = 0.64; P< 0.01) and the azygos vein blood flow and cardiac index significantly decreased (‐33% and ‐16%, respectively; P< 0.01) following sclerotherapy. The systemic vascular resistance index was also increased significantly (+20%; P<0.01) in these patients. Moreover, the per cent change in azygos vein blood flow was directly correlated with that of the cardiac index (r=0.51; P< 0.03). We conclude from these findings that the obliteration of portosystemic collaterals by sclerotherapy significantly reverses hyperdynamic circulation in such patients via a decrease in cardiac preload. The blood flow of the portosystemic shunt per se is a leading contributor to the hyperdynamic circulation observed in patients with well‐developed portal systemic collateral vessels.
Chronic upper abdominal pain due to duodenal ulcer and other structural and functional causes: Its localization and nocturnal occurrence
Authors: KANG JY , HO KY , YEOH KG , GUAN R.
Published: March 2008

The aim of the present study was to determine the degree of pain localization and frequency of nocturnal pain in duodenal ulcer and other causes of chronic upper abdominal pain. These parameters were prospectively recorded in a consecutive series of 1615 patients with chronic upper abdominal pain presenting to one gastroenterologist. The proportion of patients who were able to localize the site of their pain using a single finger was 13% for duodenal ulcer, 5% for gastric ulcer, 17% for biliary disease, 7% for functional dyspepsia and 8% for irritable bowel syndrome. The numbers of subjects with the above diagnoses who experienced nocturnal pain were 63, 63, 51, 41 and 58%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for duodenal ulcer were 13, 92, 14 and 91%, respectively, for localized pain; 63, 50, 11 and 93%, respectively, for nocturnal pain occurrence; and 9, 96, 20 and 90%, respectively, if the pain was both localized and nocturnal. If the pain was neither localized nor nocturnal, the corresponding values for the absence of duodenal ulcer disease were 49, 68, 93 and 13%, respectively. The pain of duodenal ulcer was therefore more likely to be nocturnal and well localized compared with pain from other causes. However, while the absence of these features made duodenal ulcer unlikely, their presence was less helpful in the diagnostic process.
Case Report: Multiple Cancers: Hepatocellular carcinoma and adenocarcinomas of the common bile duct and the gall‐bladder in a woman with primary biliary cirrhosis
Authors: IMADA JUNKO , HOSHINO HIROSHI , NISHIMURA DAISAKU , MORITA KIYOSHI , YOSHIDA NORIO , KATADA NAOYUKI , SANO HIROSHI , KATO KATSUMOTO , MORI NAOYOSHI
Published: March 2008

We present a case of primary biliary cirrhosis associated with simultaneous triple cancers: a hepatocellular carcinoma and adenocarcinomas of the common bile duct and gall‐bladder. A 70 year old Japanese woman, who had been diagnosed with primary biliary cirrhosis (stage 2 by Scheuer) 15 years before, was admitted to Koseiren Kamo Hospital in a comatose state. Laboratory data were as follows: the ammonia level was high (164.0 μg/dL), the antimitochondrial antibody showed a 320‐fold increase, a high level of alpha‐fetoprotein was indicated (2677 ng/mL), hepatitis B surface antigen was negative and hepatitis C antibody by enzyme immunoassay was negative, although a test for the RNA of hepatitis C virus by polymerase chain reaction was positive (103.5 copies/50 μL). The patient's condition gradually worsened and the patient died of liver failure. Autopsy showed triple cancers in the liver (hepatocellular carcinoma; trabecular type, moderately differentiated), the common bile duct (well‐differentiated papillary adenocarcinoma) and the gall‐bladder (well‐differentiated papillary adenocarcinoma) with primary biliary cirrhosis (stage 4). Primary biliary cirrhosis has been believed to be a low risk for the development of hepatocellular carcinoma, despite the high risk of extrahepatic malignancy. The simultaneous occurrence of triple cancers with primary biliary cirrhosis, to the best of our knowledge, has never been reported. The present case may provide additional evidence for a predisposition to malignancy in primary biliary cirrhosis.
Longitudinal study of intrahepatic portal flow: A novel approach using Doppler technique
Authors: LIN ZU‐YAU , CHANG WEN‐YU , WANG LIANG‐YEN , WANG JING‐HOUNG , CHEN SHINN‐CHERNG , CHUANG WAN‐LONG , HSIEH MING‐YUH , TSAI JUNG‐FA
Published: March 2008

The present study investigates whether the application of the summation of portal blood flow (SPBF), measured from the left umbilical portion and the right anterior branch by Doppler, could be of use in the longitudinal study of intrahepatic portal flow or not. Forty‐five subjects were divided into two groups. Group I subjects included males and post‐menopausal females. Thirty‐seven subjects (19 normal volunteers, 12 subjects with chronic hepatitis, six cirrhotics) were investigated by the more experienced doctor A at 9 day intervals for an intra‐observer study. Among them, seven subjects (four normal volunteers, three with chronic hepatitis) were also investigated consecutively at 10 min apart by doctor B on days 1 and 10 for an interobserver study. Group II subjects included eight normal subjects with a regular menstrual cycle. They were investigated by doctor A during menstruation, mid‐follicular, ovulatory and mid‐luteal phases of the menstrual cycle to evaluate the possible impact of the menstrual cycle on SPBF measurement. The reproducibility of measurements was assessed by the coefficient of variation (CV) and the reproducibility coefficient. Data are expressed as mean ± s.d. The CV of the SPBF for intra‐observer and interobserver study were 4.88 ± 3.36 and 4.19 ± 2.53, respectively. All differences of SPBF were within their corresponding reproducibility limits. The results of SPBF measurements obtained from different phases of the menstrual cycle were variable. Only the comparison between the data obtained from mid‐follicular and mid‐luteal phases could demonstrate acceptable CV values (3.98 ± 3.12%) and all the differences in SPBF measurements were within the repeatability limit. In conclusion, Doppler SPBF measurement may be useful in the longitudinal evaluation of intrahepatic portal flow changes.
Distinctive portal venographic pattern in patients with sclerotherapy resistant oesophageal varices
Authors: TOYONAGA ATSUSHI , IWAO TADASHI , SUMINO MICHIHIRO , TAKAGI KOHSUKE , OHO KAZUHIKO , SHIGEMORI HIROYUKI , TANIKAWA KYUICHI
Published: March 2008

Abstract  We performed prophylactic sclerotherapy in 350 patients with ‘high risk’ oesophageal varices (F2 or F3 with a moderate or severe red colour sign). Of these patients, eight exhibited sclerotherapy resistance (i.e. no significant reduction in the size of varices after five sessions of sclerotherapy). Thus, the prevalence of sclerotherapy resistant varices was 2%. Of 350 patients, 97 underwent haemodynamic investigation before sclerotherapy. This group consisted of seven patients with sclerotherapy resistant varices and 90 patients with non‐resistant varices. Portal pressure, assessed by portal venous pressure gradient, was similar in these two groups (21.5±4.8 vs 19.8±5.0 mmHg, respectively; NS). However, the prevalence of the ‘pipe‐line’ form of variceal feeding pattern (a large dilated left gastric vein running up the oesophagus) was higher in patients with resistant varices than in those with non‐resistant varices (100 vs 3%, respectively; P<0.01) and the diameter of the left gastric vein was larger in patients with resistant varices than in those with non‐resistant varices (12.4±2.0 vs 7.8±2.3 mm, respectively; P<0.01). Moreover, the extravariceal portosystemic shunt was poorly developed in patients with resistant varices compared with non‐resistant varices (0 vs 52%, respectively; P<0.05). We conclude that the pipe‐line pattern, fed by a large left gastric vein and associated with poorly developed extravariceal portosystemic shunt, is a distinctive portal venographic feature of sclerotherapy resistant varices.
New approaches to the Budd‐Chiari syndrome
Authors: MAHMOUD AEA , ELIAS E.
Published: March 2008

Abstract  Recent research has led to an improved understanding of the aetiology of Budd‐Chiari syndrome in some patients. Fresh approaches and technical developments within methods of radiological intervention have added more effective options to its treatment. In this editorial we aim to summarize our understanding of the role of new aetiologies and new therapeutic approaches in the Budd‐Chiari syndrome.
Iron overload and liver fibrosis
Authors: ARTHUR M. J. P.
Published: March 2008

Abstract  The pathogenesis of liver fibrosis in genetic haemochromatosis and other iron overload states remains enigmatic. Recent advances in the cellular and molecular pathogenesis of liver fibrosis have determined a central role for hepatic stellate cells. These become activated to a myofibroblastic phenotype following most forms of liver injury and are the major cellular source of collagens and other matrix proteins laid down in fibrotic liver. Similar changes have now been reported in the liver in genetic haemochromatosis, with activation of stellate cells becoming more prominent with increasing hepatic iron concentration. In contrast to other liver diseases, this apparently occurs in the absence of significant necroinflammatory change. Unravelling the mechanism of liver fibrogenesis in iron overload states may, therefore, provide important general insights into the pathogenesis of liver fibrosis. The present article reviews current knowledge of this field with emphasis on the role of lipid peroxidation, sideronecrosis of hepatocytes and spillover of iron to Kupffer cells. An attempt is made to draw these observations together with previous studies of the mechanisms of stellate cell activation in other models and diseases. A unifying hypothesis emerges that helps to define some of the next research questions in the pathogenic mechanisms of liver fibrosis in iron overload.
Hepatic Proteins in Regenerating Liver
Authors: PELLIZZER AM , SMID SA , STRASSER SI , LEE CS , MASHFORD ML , DESMOND PV
Published: March 2008

Abstract  In both acute and chronic liver disease in man, elimination of drugs metabolized by the cytochrome P450 (CYP) enzymes is impaired. In contrast, those drugs metabolized by UDP‐glucuronosyltransferase (UGT) have a relatively normal elimination. Studies in rats with experimentally induced liver injury also show this relative preservation of glucuronidation. In liver disease, a number of factors, including inflammation, fibrosis and regeneration, may be associated with this differential effect on drug metabolism. Partial hepatectomy provides a model in which to isolate the effects of liver regeneration on drug metabolism. Partial hepatectomy or sham operation was performed in 24 male Sprague‐Dawley rats and three rats from each group were studied at days 1, 2, 4 and 6. Comparison between CYP and UGT was made at the protein level using immunohistochemistry and immuoblotting probed with a polyclonal antibody to UGT, identifying both family 1 and family 2 isoforms, and an antibody to the CYP isoform CYP2C11. Steady state messenger RNA levels of four isoforms of UGT were assessed by northern blot analysis. By both immunohistochemistry and immunoblotting, the level of CYP protein decreased from day 2 to 6 after hepatectomy. In contrast, the UGT protein level was not altered by partial hepatectomy. Northern blot analysis of UGT isoforms demonstrated differential regulation of isoforms from the two major families. The UGT family 1 isoforms were initially markedly depressed following partial hepatectomy and then steadily rose over 6 days to greater than the level in controls. In contrast, there was an apparent increase in UGT2B1 mRNA (not significant) on day 2, while UGT2B3 mRNA was maintained over the six days. These results demonstrate that during hepatic regeneration the protein content of total UGT is normal, while CYP2C11 protein is markedly reduced. Northern blot analysis suggests that individual isoforms of UGT are differentially regulated during the regeneration process.