bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐talk between pro‐inflammatory transcription factors and glucocorticoids
Authors: Adcock Ian M , Caramori Gaetano
Published: March 2003

Asthma is a chronic inflammatory disease of the airway that is characterized by cellular infiltration and activation. These processes are induced by overexpression of chemokines and cytokines, such as eotaxin, IL‐1β and GM‐CSF. These mediators are downstream targets for the transcription factors activator protein‐1 (AP‐1) and nuclear factor‐κB (NF‐κB), which control the expression of most immunomodulatory genes and whose activity and expression are elevated in asthma. Glucocorticoids are the most effective anti‐inflammatory drugs used in the treatment of chronic inflammatory diseases such as asthma. They act by binding to a specific glucocorticoid receptor (GR) that on activation translocates to the nucleus and either increases (transactivates) or decreases (transrepresses) the expression of responsive genes. Transrepression is the major mechanism of glucocorticoid action in inhibiting inflammatory gene expression. Thus, the ability of the transciption factors AP‐1 and NF‐κB to induce gene transcription is attenuated by GR. Although only 5–10% of asthmatic subjects are glucocorticoid‐insensitive, these subjects account for over 50% of the health‐care costs for asthma (> $6 billion per annum). Examining these patients also gives an insight into important aspects of glucocorticoid action in controlling inflammation and into the development of potential new drugs. Biochemical and genomic studies have indicated abnormal induction of the c‐Jun N‐terminal kinase (JNK) pathway in some of these patients. The ability of most patients to respond to dexamethasone with induction of histone acetylation correlated with nuclear translocation of GR. However, a subgroup of these patients had an inability to correctly interact with the basal transcription complex in spite of high levels of nuclear GR. This suggests that cross‐talk between pro‐ and anti‐inflammatory transcription factors may modulate activation of the transcriptional complex and thereby reduce steroid actions.
Older women, medication use and nursing care
Authors: Watson Jennifer , Mitchell Trish , DeCrespigny Charlotte , Grbich Carol , Biggins Annie
Published: March 2003

Watson J, Mitchell T, deCrespigny C, Grbich C, Biggins A. International Journal of Nursing Practice 1998; 4: 189–196

Older women, medication use and nursing care

The purpose of this study is to listen to and interpret the experiences of independent older women in the community regarding their medication use. Their experiences were examined regarding medication information, sources of information, types of medication used, relationships with health care professionals and social support systems. The techniques used for data collection included guided qualitative semistructured interviews based on the principle of empowerment and notions of ideal and nonhierarchical communication. The emergent themes show that for these older women general practitioners were important in their medication experiences. Whilst trusted as carers in the acute care setting, registered nurses did not play a role in the medication experiences of these older women. Registered nurses are perceived as ‘traditional carers’ associated with medical and acute care settings. Although medication issues emerged that ideally required attention, the older women in this study generally perceived themselves to be capable of actively managing their health and medication use.
Tackling inequalities in health and social wellbeing: Evidence of ‘good practice’ by nurses, midwives and health visitors
Authors: Lazenbatt Anne , Orr Jean , Bradley Martin , McWhirter Liz , Chambers Mary
Published: March 2003

This paper details a project which assessed the contribution made by nurses, midwives and health visitors to Targeting Health and Social Need (THSN). Targeting Health and Social Need is an important theme within the Northern Ireland Regional Strategy entitled Health and Wellbeing into the Next Millennium: A Regional Strategy for Health and Social Wellbeing 1997–2002 which is concerned with addressing inequalities in health status and social wellbeing. While there is a considerable body of research and information on variations in health and social wellbeing there is a paucity of corresponding research on those interventions which may improve the health of disadvantaged groups. Health professionals are addressing such inequalities so it is appropriate that their efforts should be recorded and assessed. The project was conducted jointly by the departments of nursing at The Queen's University of Belfast and the University of Ulster, funded by the Department of Health and Social Services and had a timetable that covered three phases. Phase 1 entailed the distribution of a survey questionnaire to all nurses, including those professionals working with community and voluntary groups, to assess their contribution to THSN. The paper describes the results from the 392 questionnaires identified (a response rate of almost 40%) and the work in phase 2 of analysing the responses by selection criteria devised by the Project Advisory Board to allow further investigation. The resulting interventions were reduced to 22 and in an overview of each of these a number of characteristics kept recurring that could serve to define aspects of ‘good practice’. These 22 case studies demonstrate the efforts made by nurses and health professionals to change behaviour, practice, the community and the environment. Also highlighted are the nursing competencies gained through working, the lessons learnt and the problems and difficulties encountered. The paper concludes that the use of qualitative research opens the door to measures of social position that reflect the ways in which people define themselves and the relationships that sustain them. Although there is still some way to go in understanding the different approaches to evaluation, an environment that fosters the monitoring and assessment of practice might be created in the future within the nursing community.
Coping with radiation therapy: Effects of a nursing intervention on coping ability for women with breast cancer
Authors: Wengström Yvonne , Häggmark Caroline , Forsberg Christina
Published: March 2003

A randomized study was carried out to investigate whether a nursing intervention, using Orem's self‐care theory as a framework, would affect the coping ability of women with breast cancer during and following radiation therapy. The intervention consisted of promoting of behaviours to support the patient to restore, maintain or increase their abilities to interact with the situation and adapt to the demands of radiation treatment. The control and experimental groups both consisted of 67 patients. The Wheel Questionnaire was used to evaluate the effect of the intervention. Our results showed that the intervention provided patients older than 59 years the ability to cope with the treatment (df = 2,F= 3.463,P= > 0.05). The present study supports the idea that individual interventions aimed at improving well‐being helps patients. It also highlights the fact that individual approaches to improving well‐being are needed. Such interventions should be directed to patients at risk for poor adjustment, such as those older than 50 years of age.
The morning tea break ritual: A case study
Authors: Lee David S
Published: March 2003

Many nursing scholars have examined the negative effects of rituals in nursing practice, and have argued for nurses to abolish these ritual practices; however, rituals remain resilient. There must be reasons that nurses are keeping these rituals alive. This study aimed to explore the meanings of the ‘morning tea break ritual’ to a group of nurses in a medical ward. The study employed an ethnographic methodology and found that the morning tea break ritual provided time, space and an environment where nurses can ventilate their feelings and gain each other's support. Thus, the morning tea break ritual has positive contribution to nurses' work and both nurses and patients are the beneficiaries of this ritual act.
A failed fall prevention study in an acute care setting: Lessons from the swamp
Authors: O'Connell Bev , Myers Helen
Published: March 2003

Designing and implementing fall intervention studies in acute care settings presents researchers with a number of challenges. To date, there are no fall prevention interventions that have unequivocal empirical support in these settings. Based on the best available evidence a multistrategy fall prevention program was implemented using a pretest–post‐test design over a 12‐month period. The results indicated no reduction in the fall rate. Contrary to the expected result, the fall rate increased post the implementation of the multistrategy fall prevention program. To assist other researchers understand the contextual and methodological barriers to conducting fall prevention research in acute care settings, this paper discusses the difficulties experienced in this study.
Nurses' perceptions of care and caring
Authors: Bassett Chris
Published: March 2003

Care and caring have been identified as inherently difficult concepts to define, but many authors believe that care is the central and unifying core of nursing. It is vital that nurses understand what care is, with the current issues about measuring and justifying exactly what they do for patients in order to be clear about what good care is. If nurses are to constantly improve the care they give, they need to be clearer about how to care for patients. Nurses need to make sure that they are giving the patients what they want and not what the nurses want. This review of the literature explores nurses' perceptions of care and compares it with what patients want in terms of care. It also highlights some important and interesting differences between what patients and nurses perceive as good care.
Element transport by dehydration of subducted sediments: Implication for arc and ocean island magmatism
Authors: Aizawa Yoshitaka , Tatsumi Yoshiyuki , Yamada Hirohisa
Published: March 2003

High‐pressure experiments on a natural pelite have been conducted at 2–11‐GPa pressures in order to evaluate contributions of subducted sediments to arc and ocean island magmatism. Obtained phase relations suggest that, at least in modern subduction zones, subsolidus dehydration of chlorite and phengitic muscovite in the subducted sediments, rather than partial melting, is a predominant process in overprinting sediment components onto the magma source region. Trace element compositions of sediment‐derived fluids are estimated based on dehydration experiments at 5.5 GPa and 900/1300°C. Pb is effectively transported by fluids relative to other elements. This results in the Pb enrichment for arc basalts by fluids, generated by the dehydration of subducted sediments, together with altered mid‐ocean ridge basalt (MORB), and complementary depletion of Pb in subducted sediments. Inferred arc magma compositions obtained by model calculations based on the present experimental results agree well with a natural primitive arc basalt composition. A large increase in the U/Pb ratio in the subducted sediments at deeper levels than major dehydration depths results in a high Pb isotopic ratio through radioactive decay after long periods of isolation. Combined with other isotopic ratios such as Sr and Nd, it is possible to produce the EM II source, one of the enriched geochemical reservoirs for ocean island basalt magmas, by mixing of a small amount of subducted sediments with depleted or primitive mantle.
Debris flow and slide deposits at the top of the Internal Liguride ophiolitic sequence, Northern Apennines, Italy: A record of frontal tectonic erosion in a fossil accretionary wedge
Authors: Marroni Michele , Pandolfi Luca
Published: March 2003

Abstract In the Northern Apennines, the Internal Liguride units are characterized by an ophiolite sequence that represents the stratigraphic base of a late Jurassic–early Paleocene sedimentary cover. The Bocco Shale represents the youngest deposit recognized in the sedimentary cover of the ophiolite and can be subdivided into two different groups of deep sea sediments. The first group is represented by slide, debris flow and high density turbidity current‐derived deposits, whereas the second group consists of thin‐bedded turbidites. Facies analysis and provenance studies indicate, for the former group, small and scarcely evoluted flows that rework an oceanic lithosphere and its sedimentary cover. We interpret the Bocco Shale as an ancient example of a deposit related to the frontal tectonic erosion of the accretionary wedge slope. The frontal tectonic erosion resulted in a large removal of materials, from the accretionary wedge front, that was reworked as debris flows and slide deposits sedimented on the lower plate above the trench deposits. The frontal tectonic erosion was probably connected with subduction of oceanic crust characterized by positive topographic relief. This interpretation can be also applied for the origin of analogous deposits of Western Alps and Corsica.
Late Paleozoic brachiopod faunas of the South Kitakami Belt, northeast Japan, and their paleobiogeographic and tectonic implications
Authors: TAZAWA JUN‐ICHI
Published: March 2003

Abstract  Late Paleozoic (Middle Devonian, Early Carboniferous and Middle Permian) brachiopod faunas of the South Kitakami Belt, northeast Japan, are closely related paleobiogeographically to those of the Xinjiang–Inner Mongolia–Jilin region, northwest–northeast China. This relationship suggests that the South Kitakami Belt was part of the trench or continental shelf bordering the northern and eastern margins of North China (Sino‐Korea) during the Middle Devonian to Middle Permian times. Among the three models on the origin and tectonic development of the South Kitakami Belt, the strike–slip model is most consistent, but both the microcontinent model and the nappe model have considerable inconsistencies with the above paleobiogeographic and paleogeographic evidence.
Pathogenesis of hepatic encephalopathy
Authors: HÄUSSINGER DIETER , SCHLIESS FREIMUT , KIRCHEIS GERALD
Published: March 2003

Abstract  Hepatic encephalopathy (HE) is a neuropsychiatric syndrome during the course of acute or chronic liver disease. It is functional in nature, potentially reversible and precipitated by rather heterogeneous factors. At the neurophysiological level HE is characterized by a low frequent cortico‐cortical electrical coupling, which may explain the cognitive deficits and a low frequent corticomuscular coupling, which may explain the fine motor deficits. Current evidence suggests that HE is the consequence of a low grade chronic glial edema with subsequent alterations of glioneuronal communication. Different factors, such as ammonia, benzodiazepines, inflammatory cytokines can induce or aggravate astrocyte swelling, which results in the activation of osmosignaling cascades, protein modifications, alterations in gene expression and neurotransmission. Among the protein modifications nitration of critical tyrosine residues in glial proteins may play an important role. Several proteins, which are nitrated in response to ammonia, benzodiazepines, hypoosmotic astrocyte swelling or inflammatory cytokines have been identified, inluding glutamine synthetase and the peripheral type benzodiazepine receptor.

© 2002 Blackwell Publishing Asia Pty Ltd
Animal models for the study of HBV infection and the evaluation of new anti‐HBV strategies
Authors: ZOULIM F , BERTHILLON P , GUERHIER F LE , SEIGNÈRES B , GERMON S , PICHOUD C , CHENG YC , TRÉPO C
Published: March 2003

Backgroud
: Our aim was to evaluate the anti‐HBV activity of a novel L‐nucleoside analog, 2′,3′‐dideoxy‐2′,3′‐didehydro‐β‐L‐5‐fluorocytidine (β‐L‐Fd4C), in study models of HBV infection.

Method
: Its mechanism of action was evaluated on the in vitro expressed duck HBV (DHBV) reverse transcriptase and in primary hepatocyte cultures of duck and human origin. The capacity of antiviral therapy to clear viral infection was analyzed in vivo in the duck and woodchuck models.

Results
: β‐L‐Fd4C‐TP exhibited a more potent inhibitory effect on the RT activity of the DHBV polymerase than other cytidine analogs (lamivudine‐TP, ddC‐TP, β‐L‐FddC‐TP). In primary duck hepatocyte cultures, β‐L‐Fd4C exhibited a long‐lasting inhibitory effect on viral DNA synthesis but could not clear viral cccDNA. In vivo treatment with β‐L‐Fd4C in infected ducklings and woodchucks, induced a greater suppression of viremia and intrahepatic viral DNA synthesis than with lamivudine. However, covalently closed circular DNA persistence explained the relapse of viral replication after treatment withdrawal. Viral spread was strongly reduced in the case of early therapeutical intervention, but the number of infected cells did not decline when therapy was started during chronic infection. Liver histology analysis showed a decrease in the inflammatory activity of chronic hepatitis while no ultrastructural modification of liver cells was observed in electron microscopy studies. Furthermore, in human primary hepatocyte cultures, β‐L‐Fd4C induced a significant inhibition of HBV DNA synthesis.

Conclusion
: β‐L‐Fd4C is a potent inhibitor of hepadnavirus RT and inhibits viral DNA synthesis in hepatocytes both in vitro and in vivo. These experimental studies allowed as to show that β‐L‐Fd4C is a promising anti‐HBV agent. Combination therapy should be evaluated to eradicate viral infection.

© 2002 Blackwell Publishing Asia Pty Ltd
CASE REPORT: Isolated gastric tuberculosis of the cardia
Authors: Lin Otto , Wu Shun‐Sheng , Yeh Kun‐Tu , Soon Maw‐Soan
Published: March 2003

Background: Isolated gastric tuberculosis is extremely rare, especially in the subcardiac region, where the low pH, high motility and absence of lymphoid tissue result in an unfavourable environment for the development of tuberculous lesions.

Methods and Results: Here we present a case of isolated gastric tuberculosis in the gastric cardia with no evidence of pulmonary involvement. Our patient was a young man with vague gastrointestinal symptoms and no previous history of tuberculosis. His condition was first detected on upper endoscopy as a raised subcardiac ulcer similar in appearance to a submucosal tumour. An endoscopic forceps biopsy showed the presence of caseating granulomata and acid‐fast bacilli. The lesion resolved completely with 12 months of oral anti‐tuberculosis therapy.

Conclusions: This case illustrates the need for a high index of suspicion in order to diagnose this rare condition, as it can present in patients with no particular risk factors or symptoms. Once diagnosed, a complete cure can often be achieved with a course of oral anti‐tuberculosis medication, with surgery being reserved for severely symptomatic or refractory lesions.
Role of anti‐Helicobacter pylori treatment in H. pylori‐positive and cytoprotective drugs in H. pylori‐negative, non‐ulcer dyspepsia: Results of a randomized, double‐blind, controlled trial in Asian Indians
Authors: Dhali Gopal Krishan , Garg Pramod Kumar , Sharma Mahesh Prakash
Published: March 2003

Background
: The efficacy of anti‐Helicobacter pylori treatment and cytoprotective drugs in H. pylori‐positive and ‐negative non‐ulcer dyspepsia (NUD), respectively, is debatable.

Methods
: In a randomized study, the efficacy of anti‐H. pylori treatment versus sucralphate was tested in patients with NUD. One hundred and twelve patients with NUD, 62 positive and 50 negative for H. pylori were studied. Of 62 patients positive for H. pylori, 32 were treated with triple therapy (colloidal bismuth subcitrate, tetracycline and metronidazole) for 2 weeks and the remaining 30 were treated with sucralphate (1 g, q.i.d.) for 4 weeks. Of 50 patients negative for H. pylori, 25 each were treated with either sucralphate (1 g, q.i.d.) or ranitidine (150 mg, b.d.) for 4 weeks.

Results
: In patients with NUD and H. pylori infection, triple therapy eradicated H. pylori in 88% and was superior to sucralphate in producing symptom relief (81 vs 33%, P = 0.0003) and histological improvement in gastritis (73 vs 30%, P = 0.003). In the H. pylori‐negative group, sucralphate was superior to ranitidine with regard to symptom relief (68 vs 36%, P = 0.04) and improvement in gastritis (44 vs 12%, P = 0.09). The symptomatic improvement persisted until 12 weeks after the start of treatment in triple therapy group only.

Conclusions
: In patients with NUD associated with H. pylori, triple therapy was better than sucralphate in terms of symptomatic and histological improvement. However, sucralphate was superior to ranitidine in providing symptom relief in patients with H. pylori‐negative NUD.

© 1999 Blackwell Science Asia Pty Ltd
Long‐term survival among patients operated upon for peptic ulcer disease
Authors: Duggan John M , Zinsmeister Alan R , Kelly Keith A , Melton L Joseph Melton
Published: March 2003

Background: Although surgery has been used widely for treating peptic ulcer disease, there is conflicting evidence with respect to subsequent life expectancy and the determinants of mortality. Our aim was to compare long‐term survival in a large, population‐based cohort of operated patients with that expected in the general population.

Methods: We followed 471 Rochester, Minnesota residents who had surgery for peptic ulcer at the Mayo Clinic during 1956–85 for a total of 6174 person‐years. Patients were followed through their complete (inpatient and outpatient) medical records in the community until death or last clinical contact and death certificates were obtained for all who succumbed. We compared observed survival and cause‐specific death rates in this cohort with expected values and identified the determinants of short (30 day) and long‐term mortality.

Results and Conclusions: Survival was worse than expected, but excess deaths were confined to those with perforated ulcers (42 deaths observed; 18.8 expected). Independent predictors of death included age, male gender, emergency operation, gastric ulcer and cigarette smoking. Most deaths were due to heart disease and cancer, but only those due to digestive diseases (standardized mortality ratio (SMR) 3.8, 95% CI 2.4–5.7) and respiratory diseases (SMR 1.9, 95% CI 1.3–2.7) were increased compared to expected figures. Overall survival was reduced in this cohort but was normal among those whose ulcers were not perforated. However, the data suggest an adverse role for alcohol and smoking in these patients.

© 1999 Blackwell Science Asia Pty Ltd
Projections of nitric oxide synthase and vasoactive intestinal polypeptide‐reactive submucosal neurons in the human colon
Authors: Porter Anthony J , Wattchow David A , Brookes Simon Jh , Costa Marcello
Published: March 2003

Background
: The submucosal plexus is important in the control of secretomotor and motor function of the intestine. Our aim was to describe the projections of submucosal neurons to the mucosa within the submucosal plexus and to the circular muscle of human colon and to determine whether submucosal neurons that projected to different layers were located at different levels of the submucosa.

Methods
: A retrogradely transported fluorescent dye was applied to the mucosa, submucosa or circular muscle layer of human colon which was then maintained in organotypic culture for 5 days. The submucosa was then dissected into two preparations, one containing the inner layer of the submucosal plexus and the other containing both the intermediate and outer layers. The dissected preparations were labelled with antibodies to nitric oxide synthase (NOS) or vasoactive intestinal peptide (VIP).

Results
: Submucosal neurons projected to the mucosa, submucosa and circular muscle layers for mean distances of 3.7, 3.0 and 4.3 mm, respectively. Ninety‐seven per cent of submucosal neurons labelled from the circular muscle were located in the outer or the intermediate layers, while 51% of those projecting to the mucosa were in inner layer and 49% in the intermediate/outer layers of the submucosal plexus. Eleven per cent of submucosal neurons projecting to the circular muscle were immunoreactive for NOS and 12% were immunoreactive for VIP. Forty‐five per cent of those projecting within the submucosa were immunoreactive for VIP and 38% of those projecting to the mucosa were immunoreactive for VIP.

Conclusions
: Submucosal neurons in the human colon innervate the mucosa, circular muscle and submucosa and different functional classes of neurons are located in different layers of the submucosal plexus.

© 1999 Blackwell Science Asia Pty Ltd
Augmentative effects of L‐cysteine and methylmethionine sulfonium chloride on mucin secretion in rabbit gastric mucous cells
Authors: Watanabe Tomoe , Ohara Susumu , Miyazawa Shitirou , Saigenji Katunori , Hotta Kyoko
Published: March 2003

Background
: Our previous study showed that
L‐cysteine (Cys) and methylmethionine sulfonium chloride (MMSC) inhibited ethanol‐induced gastric mucosal damage and increased the amount of surface mucin in rats. This study examined whether Cys and MMSC augmented mucin secretion and changed distribution of mucin vesicles ultrastructurally in mucous cells by using primary cultured mucous cells from rabbit glandular stomach. Changes in intracellular cyclic adenosine 3′,5′‐monophosphate (cAMP) and in levels of cytosolic free Ca2+ were investigated by treatment with Cys and MMSC.

Methods
: Mucin content was measured by an enzyme‐linked lectin assay. Transmission electron micrography was used to examine ultrastructural distribution of mucin granules. The amount of cAMP or levels of free Ca2+ were measured by enzyme immunoassay or by fura‐2. 16,16‐Dimethyl prostaglandin E2 (dmPGE2) or ATP was used as the positive control.

Results
:
L‐Cysteine and MMSC increased mucin secretion and decreased cellular mucin content. The same was noted for dmPGE2. Accelerated mucin granule movements toward the plasma membrane were shown by these agents. Intracellular cAMP increased with exposure to dmPGE2 for 20 min, while neither Cys nor MMSC increased cAMP. No increase in cytosolic free Ca2+ levels occurred after treatment with Cys or MMSC, but an increase was induced 10 s after the addition of ATP.

Conclusions
: The present findings indicate that the increase in mucin secretion by Cys and MMSC was not mediated through the cAMP or Ca2+ signal transduction pathway, but might occur through non‐receptor‐mediated mechanisms.
Cavographic study of an early stage of obstruction of the hepatic portion of the inferior vena cava
Authors: Shrestha Santosh M , Joshi Bishnu L , Shrestha Shobhana , Maharajan Krishna G
Published: March 2003

Background
: Liver disease caused by a chronic lesion of the hepatic portion of the inferior vena cava (IVC) is clinically characterized by dilated superficial veins in the body trunk with cephalad flow, hepatomegaly and splenomegaly. Cavography shows stenosis or complete obstruction near the cava‐atrial junction.

Methods
: Early (acute and subacute) forms of the disease were recognized. The early stage of the disease manifested as jaundice, hepatomegaly or ascites and fever. Patients with acute and subacute onset of the illness with no past history of liver disease were studied with inferior vena cavography. Some of the patients had repeat cavography at 6 months and at 1 year after the initial investigations.

Results
: Three types of cavographic lesions were observed in the early stages of the disease: type 1, linear lucent area in the IVC close to cava‐atrial junction; type 2, a smooth or irregular narrowing of almost the whole segment of the hepatic portion of the IVC; and type 3, a constriction or narrowing of a segment of the IVC near the cava‐atrial junction. The first two types were associated with the acute stage of the disease and type 3 with the subacute stage. Type 2 and 3 lesions were associated with post‐stenotic dilatation (PSD) close to the atrium. Lucent areas resulting from thrombosis are common in PSD. The acute and subacute hepatic IVC diseases in Nepal are commonly associated with bacterial infection.

Conclusions
: It is postulated that the early cavographic lesions are consistent with thrombosis and thrombophlebitis of the hepatic portion of the IVC, and that resolution of the lesions leads to the development of stenosis and to complete obstruction.
Putative role of hepatitis B virus X protein in hepatocarcinogenesis: Effects on apoptosis, DNA repair, mitogen‐activated protein kinase and JAK/STAT pathways
Authors: Arbuthnot Patrick , Capovilla Alexio , Kew Michael
Published: March 2003

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV‐induced malignant transformation is, however, incompletely understood. HBx, the protein encoded by the X open reading frame, is a transcriptional activator that has been implicated in hepatocarcinogenesis. HBx inhibits the function of the tumour suppressor protein p53 in what is thought to be an early event in hepatocyte transformation before the later accumulation of inactivating p53 point mutations. HBx inhibits apoptosis but also exerts pro‐apoptotic effects. The effects of HBx on apoptosis may be important not only for the development of HCC but also for the establishment of HBV infection. Further implication of HBx in hepatocyte transformation has been the demonstration that it inhibits the repair of damaged hepatocyte DNA. This effect may be mediated by interaction with p53 or through binding to the damaged DNA binding protein (DDB), which plays an accessory role in nucleotide excision repair. In addition, HBx activates cell signalling cascades involving mitogen‐activated protein kinase (MAPK) and Janus family tyrosine kinases (JAK)/signal transducer and activators of transcription (STAT) pathways. The implications of these modulating effects of HBx are not fully understood, but they are likely to have wide‐ranging effects on hepatocyte proliferation, apoptosis and the regulation of cell growth checkpoints. The cellular functions ascribed to HBx are unusually diverse, and defining the biologically important role of HBx during HBV replication will go some way to understanding the sequelae of chronic HBV infection.
Extracorporeal shock wave lithotripsy of gallstones revisited: Current status and future promises
Authors: Mulagha Eneya , Fromm Hans
Published: March 2003

The improvement and refinement of extracorporeal shock wave lithotripsy (ESWL) has made this non‐invasive treatment modality not only more effective, but also applicable to a larger population of gallstone patients. It can be performed safely on an outpatient basis. Advances in lithotripsy technology have made it possible to fragment stones into very small, sand‐like particles (pulverization), which clear the gall‐bladder faster than large fragments. Recent studies provide evidence that adjuvant bile acids may not be necessary in most cases in which pulverization is achieved. Good gall‐bladder emptying appears both to promote the clearance of gallstones after ESWL and to decrease their recurrence. Although generally found to be more expensive than surgery if bile acids are used, ESWL should be cost‐effective, as bile acids may not be necessary in all patients. Elderly patients with radiolucent, solitary and less than 30 mm gallstones can particularly benefit from lithotripsy.

© 2000 Blackwell Science Asia Pty Ltd
Firstline treatment for hepatitis C: combination interferon/ribavirin versus interferon monotherapy
Authors: Lai Ming‐Yang
Published: March 2003

In the initial treatment of chronic hepatitis C, interferon‐alfa (IFN‐α) monotherapy for 24–48 weeks induces sustained response rates of only 10–20%. Combination therapy with IFN‐α plus ribavirin induces a sustained response in 40–50% of patients, and can be now recommended as the firstline therapy for chronic hepatitis C. Stopping therapy at week 12 because of persistent viraemia is unnecessary with the combination therapy because later clearance of HCV RNA can still occur with a sustained response. Patients with HCV genotype 1 should receive 48 weeks of combination therapy, in contrast to 24 weeks for patients with genotypes 2 or 3. For patients who cannot tolerate the side effects of ribavirin, such as anaemia, IFN‐α at 3 MU three times weekly for 48 weeks is preferred as the initial therapy. The long‐acting pegylated IFN can be expected to enhance the efficacy of combination therapy in the treatment of chronic hepatitis C and appears to be much more potent as monotherapy. Further studies are needed to improve the current ‘half‐full’ status of chronic hepatitis C treatment.
Role of Kupffer cells and gut‐derived endotoxins in alcoholic liver injury1
Authors: Enomoto Nobuyuki , Ikejima Kenichi , Bradford Blair U , Rivera Chantal A , Kono Hiroshi , Goto Moritaka , Yamashina Shunhei , Schemmer Peter , Kitamura Tsuneo , Oide Hirosumi , Takei Yoshiyuki , Hirose Miyoko , Shimizu Hidetake , Miyazaki Akihisa , Brenner David A , Sato Nobuhiro , Thurman Ronald G
Published: March 2003

The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut‐derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol‐induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.
Effect of branched‐chain amino acids on the composition and cytolytic activity of liver‐associated lymphocytes in rats
Authors: Tsukishiro Takashi , Shimizu Yukihiro , Higuchi Kiyohiro , Watanabe Akiharu
Published: March 2003

Background
: Although branched‐chain aminoacids (BCAA) are reported to be effective in prolongation of the mean survival time of patients with liver cirrhosis, it is not clear whether BCAA could influence the immune function in those patients.

Methods
: Branched‐chain amino acids were given as a supplement to carbon tetrachloride‐induced cirrhotic rats, and an aminogram of the liver and kinetics of liver‐associated lymphocytes (LAL) were then analysed.

Results
: Liver cirrhosis was established at the 12th week, and glutathione S‐transferase placental form (GST‐P)‐positive lesions, which are known to be pre‐neoplastic lesions, occupied 1.72 ± 0.84% of the liver at the 16th week in the controls. At this time the LAL showed an increase in the number of CD5‐, CD8‐ and CD18‐positive cells and augmentation of lectin‐dependent cellular cytotoxicity (LDCC) activity. Furthermore, supplementation of BCAA increased the number of LAL, especially CD8‐positive cells and natural killer cells, and augmented LDCC activity of LAL at the 16th week. The number of LAL was positively correlated with the valine concentration in the plasma and liver, and the area of GST‐P‐positive lesions tended to be decreased in the BCAA group.

Conclusion
: These findings suggest that BCAA administration has stimulatory effects on the local immune systems of the liver, which may have a potential to inhibit hepatocarcinogenesis. Moreover, among all amino acids valine might be an important amino acid for enhancing the immune function of LAL.
Biliary excretory function is regulated by canalicular membrane fluidity associated with phospholipid fatty acyl chains in the bilayer: Implications for the pathophysiology of cholestasis
Authors: Hyogo Hideyuki , Tazuma Susumu , Kajiyama Goro
Published: March 2003

Background and Aims
: Bile canalicular membrane fluidity is modulated by phospholipid molecular species within membrane lipid bilayers. Thus, organellar membrane lipid composition is a determinant of canalicular function. In this study, the effect of phalloidin‐induced cholestasis on bile lipid composition and liver subcellular membrane fraction composition in rats was examined to clarify the relationship between cholestasis and hepatic lipid metabolism.

Methods and Results
: Each rat received one phalloidin dose (400 μg/kg, i.v.). After the bile was collected, liver microsomes and canalicular membranes were analysed. The bile flow rate decreased by 50% 3.5 h after phalloidin administration. Although the bile acid output remained almost the same, the phospholipid and cholesterol output were significantly decreased (by 40.3 ± 5.97% and 76.9 ± 5.56%, respectively). Thus, the cholesterol : phospholipid (C : P) ratio in bile was significantly decreased by 80.4 ± 10.1%. Phalloidin administration also increased the saturated : unsaturated fatty acid ratio (S : U) in bile for phosphatidylcholine by 25.5 ± 3.2%. In the canalicular membrane, the C : P and S : U ratios for phosphatidylcholine were increased (24.8 ± 4.2% and 34.4 ± 6.9%, respectively), while the S : U for sphingomyelin was decreased by 61.0 ± 6.2%. In microsomes, the C : P was decreased by 41.0 ± 6.0%, but the S : U for both phosphatidylcholine and sphingomyelin were unaffected. Canalicular membrane fluidity, assayed by 1,6‐diphenyl‐1,3,5‐hexatriene fluorescence depolarization, decreased significantly. Therefore, increased secretion of hydrophobic phosphatidylcholine into bile was associated with more hydrophobic canalicular membrane phosphatidylcholine, while sphingomyelin in the canalicular membrane was less hydrophobic.

Conclusions
: These results indicate that phalloidin uncouples secretion of cholesterol and phospholipids, which causes a redistribution of fatty acyl chain species among canalicular membrane phospholipids that alters membrane fluidity. These changes may be a homeostatic response mediated by the phospholipid translocator in the canalicular membrane, although direct evidence for this is unavailable.
Effect of a calcium channel blocker and antispasmodic in diarrhoea‐predominant irritable bowel syndrome
Authors: Lu Ching‐Liang , Chen Chih‐Yen , Chang Full‐Young , Chang Shen‐Shong , Kang Lih‐Jiun , Lu Rei‐Hwa , Lee Shou‐Dong
Published: March 2003

Background
: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long‐term (12–16 weeks) treatment of IBS patients. Their efficacy in the short‐term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown.

Methods and Results
: A clinical trial was conducted with 91 patients with diarrhoea‐predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuro‐peptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9 ± 1.2 vs 2.0 ± 1.0, P < 0.05; mebeverine, 2.7 ± 1.1 vs 2.1 ± 1.0, P < 0.05). The stool consistency became well formed after both treatments (P < 0.05). Both drugs similarly improved the global well‐being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P > 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4 ± 15.5 vs 30.8 ± 14.8 h, P < 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments.

Conclusion
: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoeapredominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptide Y appear less important in the pathogenesis of diarrhoea‐predominant IBS.

© 2000 Blackwell Science Asia Pty Ltd
Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology
Authors: McHutchison John G , Blatt Larry M , De Medina Maria , Craig John R , Conrad Andrew , Schiff Eugene R , Tong Myron J , Group The Consensus Interferon Study
Published: March 2003

Background and Aims
: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including pro‐collogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients.

Methods and Results
: Patients were anti‐HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non‐cirrhotic patients (382 ± 31 vs 110 ± 9 μg/L respectively, P < 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179 ± 11 μg/L) compared with patients without fibrosis (62 ± 20 μg/L; P < 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R = 0.5421, P < 0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 μg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively.

Conclusions
: Serum HA measurement may be clinically useful to non‐invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non‐invasive marker of liver fibrosis.
Use of tamoxifen in hepatocellular carcinoma: A review and paradigm shift
Authors: Tan Chee Kiat , Chow Pierce Kh , Findlay Michael , Wong Camilla , Machin David
Published: March 2003

Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. The oral anti‐oestrogen drug, tamoxifen, has been used in such patients, based on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor‐mediated process. In this review, we examine the trials reported in the literature using tamoxifen in hepatocellular carcinoma. Randomized controlled trials with tamoxifen have so far revealed mixed results. We propose that this may be due to the fact that the mechanism of action of tamoxifen in hepatocellular carcinoma is via an oestrogen‐receptor independent pathway that requires much higher doses of tamoxifen for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that future trials with tamoxifen in hepatocellular carcinoma should use higher doses of tamoxifen, at least four to eight‐fold that of the dose that is efficacious in an oestrogen‐receptor dependent mechanism.
Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions
Authors: Suzuki Kaori , Kashimura Hiromasa , Ohkawa Jun , Itabashi Masayuki , Watanabe Teruo , Sawahata Tatuo , Nakahara Akira , Muto Hiroshi , Tanaka Naomi
Published: March 2003

Background and Aims
: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia.

Methods
: Using reverse transcription‐polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol.

Results
: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P = 0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA.

Conclusions
: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.