bluuebunny/crossref_metadata_2025 huggingface dataset:
An Investigation of the Impact of Interest Rates and Interest Rate Volatility on Australian Financial Sector Stock Return Distributions
Authors: Faff Robert W. , Hodgson Allan , Kremmer Michael L.
Published: June 2005

Abstract:  This paper extends the existing literature by analysing the dual impact of changes in the interest rate and interest rate volatility on the distribution of Australian financial sector stock returns. In addition, a multivariate GARCH‐M model is used to analyse the impact of deregulation on the financial institutions sector. It was found that there is a consistent inter‐temporal trade off between risk and return over the different regulatory periods. Moreover, finance corporations were found to be highly sensitive to new shocks across the financial sector and deregulation increased the risk faced by finance corporations and small banks – effectively increasing the required rate of return and explaining the continued rationalisation of these sectors. Furthermore, deregulation has changed the fundamental relationship between interest rates and large bank stock excess returns from positive in the pre‐deregulation period to negative in the post‐deregulation period. This reflects the changing institutional environment from one of controlled credit rationing to a more competitive environment.
Excess Volatility and UK Investment Trusts
Authors: Agyei‐Ampomah Samuel , Davies J. R.
Published: June 2005

Abstract: The issue of whether or not asset prices are more volatile than the underlying fundamentals is an empirical question with implications for market efficiency. Recent research suggests that the volatility of closed end fund returns in the USA is significantly higher than the returns on assets held by the funds. This has been attributed to noise trading as closed‐end fund shares are predominantly held by individual investors. This study demonstrates that UK investment trust returns exhibit similar excess volatility in spite of the prevalence of institutional investors. However, big investment trusts in terms of market capitalisation show greater excess volatility than small trusts. Although most of the excess volatility appears to be idiosyncratic, investor sentiment index is the most important variable associated with residual returns.
The Effect of Decimalization on Trade Size and Adverse Selection Costs
Authors: Chakravarty Sugato , Van Ness Bonnie F. , Van Ness Robert A.
Published: June 2005

Abstract:  We examine adverse selection costs around NYSE decimalization. Further, we analyze the relation between adverse selection costs and trade size. We find a significant increase in the percentage adverse selection cost and a reduction in dollar adverse selection cost (percentage adverse selection multiplied by the spread) following complete decimalization on the NYSE. On estimating the adverse selection components by trade size classes, we find a decline in dollar adverse selection costs in trades of all sizes, with the strongest evidence coming from medium size trades, followed by small and large size trades. One implication of our findings is that there appears to be less stealth trading following complete decimalization and less institutional trading overall.
Determinants of the Accounting Change for Income Tax
Authors: Wong Norman
Published: June 2005

Abstract:  This study examines determinants of the decision of New Zealand firms to change their income tax accounting method from comprehensive to partial allocation. New Zealand provides a unique setting to investigate this issue because it allows firms the choice to use either the comprehensive or partial allocation procedures to account for income tax. I find that efficient contracting and debt‐related opportunistic factors are both important determinants that influence firms’ decisions to change to partial. Specifically, the results indicate that the change is related to the extent of investment in depreciable assets and the closeness of firms to their debt covenant restrictions.
Expression of melanoma‐associated antigens in melanoma cell cultures
Authors: Urosevic Mirjana , Braun Bettina , Willers Jörg , Burg Günter , Dummer Reinhard
Published: June 2005

Abstract:  The efficiency of melanoma immunotherapy appears to depend on both melanoma‐ and immune system‐specific factors. Melanoma‐specific factors include melanoma‐associated antigen (MAA) expression as well as HLA class I molecule expression. We investigated the expression of five MAA – Melan‐A/MART‐1, tyrosinase, gp100, MAGE‐1 and MAGE‐3 – by means of FACS analysis in 50 melanoma cell cultures and compared them to the cultures of human foreskin‐derived melanocytes and melanoma cell line UKRV‐Mel2. Melan‐A, tyrosinase and gp100 expression was frequently reduced in melanoma cell cultures, compared to that in foreskin melanocytes, whereas MAGE‐1 and MAGE‐3 expression showed variable degree of upregulation, compared to that in foreskin melanocytes. The expression of all tested MAA demonstrated high interindividual variability. We further show that cell cultures derived from the same tissue sample are oligoclonal in nature, by demonstrating the presence of up to three cell populations bearing distinct MAA profile. Analysing samples derived from the same patient but each at a different time point, we show that MAA expression profile changes over time either in positive (increase) or in negative (decrease) direction. Finally, we demonstrate that brain metastasis‐derived cell cultures significantly overexpress Melan‐A and MAGE‐3, compared to primary tumours and other metastatic sites (P‐value range: 0.05–0.001). Elucidation of the MAA expression patterns and the kinetics within the same patient as well as during the course of the disease may help improve current and develop new immunotherapeutic strategies.
Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts
Authors: Zhu Ming Ji , Kim Chang Deok , Kwon Yoo Bin , Kye Kyung‐Chae , Chen Yuan Yao , Lee Woong‐Hee , Lee Sangkeun , Lim Jong Soon , Seo Young‐Joon , Suhr Ki‐Beom , Park Jang‐Kyu , Lee Jeung‐Hoon
Published: June 2005

Abstract:  Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid metabolite that can enhance wound healing. In an effort to find downstream effectors of SPC, we performed microarray analysis and found that the expression of the gene for connective tissue growth factor (CTGF) was significantly affected in human skin fibroblasts cultured in vitro. Northern blot analysis showed that SPC markedly induced CTGF mRNA expression in a dose‐ and time‐dependent manner. Consistent with this result, Western blot analysis also showed that SPC significantly induced the CTGF production. Pretreatment with cycloheximide did not prevent the CTGF induction by SPC, indicating that SPC stimulates CTGF mRNA expression without the increased synthesis of a regulatory protein. Inhibition by pretreatment with Y27632, but not by PD98059 (a mitogen‐activated protein kinase 1/2 inhibitor) and LY294002 (a phosphatidylinositol 3‐kinase inhibitor), indicated that ρ‐kinase pathway was involved in SPC‐induced CTGF expression. Together, these results reveal the potential importance of CTGF induction as a downstream event in SPC‐induced cellular responses.
Pigmentation in basal cell carcinoma involves enhanced endothelin‐1 expression
Authors: Lan Cheng‐Che E. , Wu Ching‐Shuang , Cheng Chiu‐Min , Yu Chia‐Li , Chen Gwo‐Shing , Yu Hsin‐Su
Published: June 2005

Abstract:  Basal cell carcinoma (BCC) is the most prevalent malignant skin tumor. In Asian patients, marked pigmentation in BCC lesions is often observed. Recently, endothelins (ETs) have been implicated to participate in the pigmentation process of BCC. Therefore, we set out to investigate the involvement of ET in the pigmentation process of BCC and the potential regulators in the pigmentation pathway. We explored the effects of an established BCC cell line on melanocytes. The growth factor profiles of BCC culture supernatant and effects of supernatant on melanocytes were documented. Potential regulators involved in the pigmentation pathway were also studied. The immunohistochemical staining of pigmented and non‐pigmented BCC specimens was performed to confirm our in vitro findings. Our results showed that BCC supernatant contained significant amount of ET‐1, basic fibroblast growth factor, and nerve growth factor. Furthermore, BCC supernatant stimulated melanin formation of cultured melanocytes. Addition of ET‐receptor antagonist abrogated the melanogenic effect of BCC supernatant on melanocytes. Introduction of UVB irradiation decreased the ET‐1 secretion by BCC cells. Immunohistochemical staining of the pigmented facial BCC specimens showed prominent expression of ET‐1 on pigmented BCC, while the non‐pigmented facial BCC specimens showed little ET‐1 reactivity. Tumor necrosis factor‐alpha (TNF‐α) staining showed little expression on BCC specimens, regardless of pigmentation status. In summary, our results indicate that enhanced ET‐1 expression in pigmented BCC plays an important role in the hyperpigmentation of this tumor. Moreover, this enhanced ET‐1 cascade showed little correlation with UV irradiation and TNF‐α expression in our study.
Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin
Authors: Christensen Rikke , Alhonen Leena , Wahlfors Jarmo , Jakobsen Maria , Jensen Thomas G.
Published: June 2005

Abstract:  Phenylketonuria (PKU) is a metabolic disease causing increased levels of phenylalanine in blood and body fluids. Circulating phenylalanine is normally cleared by phenylalanine hydroxylase (PAH) expressed in the liver. The aim of this study is to exploit the skin as a ‘metabolic sink’ removing phenylalanine from the blood. We have previously showed that the overexpression of PAH and GTP cyclohydrolase I (GTP‐CH), the rate‐limiting enzyme in the synthesis of the cofactor for PAH, leads to high levels of phenylalanine clearance in primary human keratinocytes. In this study, we have investigated the ‘metabolic sink’ strategy in an in vivo model by developing three lines of transgenic mice expressing PAH and GTP‐CH in various layers of the skin. The promoters used were keratin 14 (K14), involucrin (INV) and a truncated variant of Keratin 1 (K1). The mice were crossbred to a mouse model of human PKU, the PAHenu2 mouse, in order to obtain mice that do not express PAH in the liver and the kidney. Transgenic mice containing the INV and K14 promoters expressed PAH and GTP‐CH in the epidermis. However, the K1 promoter did not lead to detectable gene expression. Analysis of the mice showed that no phenotypic effect was observed in mice expressing PAH and GTP‐CH from the INV promoter. However, low level of phenylalanine clearance was observed in mice expressing PAH and GTP‐CH from the K14 promoter, suggesting that the skin can be genetically engineered to function as a ‘metabolic sink’.
Candida albicans‐specific lymphoproliferative and cytokine (IL‐4 and IFN‐γ) responses in atopic eczema dermatitis syndrome. Evidence of CD4/CD8 and CD3/CD16+CD56 ratio elevations in vitro
Authors: Kosonen Jan , Luhtala Marko , Viander Markku , Kalimo Kirsti , Terho Erkki O. , Savolainen Johannes
Published: June 2005

Background:  Hypersensitivity to cross‐reactive mannan polysaccharide allergens of saprophytic yeasts is likely to be involved in the pathogenesis of atopic eczema dermatitis syndrome (AEDS). Mannans induce elevated specific immunoglobulin E and lymphoproliferative responses in peripheral blood mononuclear cells (PBMCs). To gain more detailed data of the involvement of different subpopulations of PBMCs in AEDS after mannan stimulation, changes in the cell‐surface marker distribution were analysed.

Methods:  The Ficoll‐isolated PBMCs of eight yeast hypersensitive AEDS patients and seven non‐AEDS controls were stimulated in vitro by mannan (CAM) or whole extract antigen [In‐House Reference (IHR)] of Candida albicans or tuberculin [purified protein derivative (PPD)] and after immunofluorescence staining analysed by flow cytometry. The expression of cytokine mRNA was measured by kinetic real‐time polymerase chain reaction (TaqMan®).

Results:  After 7‐day antigen stimulation, there were significant increases in the CD3/CD16+CD56 ratio (P = 0.028 with mannan and P = 0.006 with IHR), CD4/CD8 ratio (P = 0.049 with mannan) and interleukin‐4/interferon‐γ (IL‐4/IFN‐γ) mRNA ratio (P = 0.028 with IHR) and a decrease in the CD3/CD19 ratio (P = 0.035 with mannan) of AEDS patients' PBMCs as compared with healthy controls' cells. These changes were not seen in cultures with PPD.

Conclusions:  The observed CAM and IHR‐induced elevations in T cell/natural killer cell, CD4/CD8 and IL‐4/IFN‐γ ratios suggest that C. albicans‐induced TH2‐type responses can also play a role in AEDS.
Meta‐analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users
Authors: Vergara M. , Catalán M. , Gisbert J. P. , Calvet X.
Published: June 2005

Aim : To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer in non‐steroidal anti‐inflammatory drug users by means of a meta‐analysis.

Material and methods : A systematic search was performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register and the AGA congress. Randomized trials comparing H. pylori eradication vs. non‐eradication or eradication vs. a proton pump inhibitor in patients receiving a non‐steroidal anti‐inflammatory drug were selected.

Results : Five studies and 939 patients were included in the analysis; 34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64 of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence interval: 0.20–0.93). Sub‐analyses showed a significant reduction of risk for non‐steroidal anti‐inflammatory drug‐naive (odds ratio = 0.26; 95% confidence interval: 0.14–0.49) but not for previously treated patients (odds ratio = 0.95, 95% confidence interval: 0.53–1.72). Two studies with a total of 385 patients compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27–43.6).

Conclusion : Helicobacter pylori eradication reduces the incidence of peptic ulcer in the overall population receiving non‐steroidal anti‐inflammatory drugs. It appears to be especially effective when performed in non‐steroidal anti‐inflammatory drug‐naïve patients. Nonetheless, eradication seems less effective than treatment with a maintenance proton pump inhibitor for preventing non‐steroidal anti‐inflammatory drug‐associated ulcers.
Gastro‐oesophageal reflux is more prevalent in Western dyspeptics: a prospective comparison of British and South‐East Asian patients with dyspepsia
Authors: Mahadeva S. , Raman M. C. , Ford A. C. , Follows M. , Axon A. T. R. , Goh K.‐L. , Moayyedi P.
Published: June 2005

Background : There is a paucity of data directly comparing dyspepsia in Western and Eastern populations.

Aim : To compare clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and South‐East Asia in a cross‐sectional study.

Methods : Patients with uncomplicated dyspepsia attending endoscopy units in Leeds, UK, and Kuala Lumpur, Malaysia, were prospectively interviewed and underwent subsequent endoscopy.

Results : A total of 1003 Malaysian patients (January 2002 to August 2003) and 597 Caucasian British patients (January 2000 to October 2002) were studied. The mean age was 48.7 ± 15.8 and 47.5 ± 13.8 years for the Malaysian and British patients respectively (P = NS). There was a higher proportion of cigarette smoking (35.7% vs. 12.4%, P < 0.0001) and alcohol consumption (34.4% vs. 2.0%, P < 0.0001) amongst British patients, but no difference in non‐steroidal anti‐inflammatory drug use nor having Helicobacter pylori infection. Gastro‐oesophageal reflux disease (GERD) symptoms were more common in British compared with South‐East Asian patients [heartburn (72% vs. 41%), regurgitation (66% vs. 29.8%) and dysphagia (21.1% vs. 7.3%), P < 0.0001]. This correlated with an increased endoscopic finding of oesophagitis (26.8% vs. 5.8%) and columnar‐lined oesophagus (4.4% vs. 0.9%) amongst British patients (P < 0.001). A logistic regression model revealed that British Caucasian race (OR 9.7; 95% CI = 5.0–18.8), male gender (OR 2.0; 95% CI = 1.4–2.9) and not having H. pylori infection (OR 0.5; 95% CI = 0.3–0.7) were independent predictors for oesophagitis.

Conclusion : GERD is more common in British compared with South‐East Asian dyspeptic patients suggesting that race and/or western lifestyle are important risk factors.
Long‐term healing of Crohn's anal fistulas with fibrin glue injection
Authors: Vitton V. , Gasmi M. , Barthet M. , Desjeux A. , Orsoni P. , Grimaud J. C.
Published: June 2005

Background : Injecting fibrin glue has proved to be an effective means of treating anal fistulas (AF). There has been some debate, however, as to whether this technique should be used on the AF often involved in Crohn's disease (CD).

Aim : To assess the effectiveness of injecting heterologous fibrin glue as a means of treating AF refractory to immunosuppressive treatment in patients with CD.

Methods : Fourteen CD patients (five men and nine women, average age 42 years) presenting with refractory AFs were included in this study. Heterologous fibrin glue was injected into the fistula tract under general anaesthesia under continuous endosonographic monitoring using a 7.5‐MHz blind linear probe. The patients were followed up clinically and ultrasonographically for 3 months after the procedure, and then at regular intervals.

Results : Three months after the fibrin glue injection, the fistulas had completely dried up in 10 patients (71%), the leakage had decreased in one patient (7%), and no improvement was observed in the other three patients (21%). Endosonographic findings showed that the fistula tract had completely disappeared in two cases (14%). The fistula tract was found to be non‐permeable in eight cases (57%), and no change in the fistula was observed in four patients (29%). At the end of the follow‐up period [average 23.4 months (12–26 months)], the leakage had completely dried up in eight of the 14 patients (57%). No side effects were observed.

Conclusion : Nearly 2 years after the use of a heterologous fibrin glue to treat an AF, over half of the patients with CD showed clinical signs of remission. Because it is easy to use and harmless as well as being effective, this method provides a good alternative to classical methods of surgical treatment.
Personal view: food for thought – western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis
Authors: Gibson P. R. , Shepherd S. J.
Published: June 2005

Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking.

A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short‐chain carbohydrates and polyols (designated FODMAPs – Fermentable Oligo‐, Di‐ and Mono‐saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health‐promoting effects of FODMAPs.

One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor.
Postprandial oesophageal integrated acidity is a reliable predictor of gastro‐oesophageal reflux disease
Authors: Shih G. L. , Brensinger C. M. , Katzka D. A. , Metz D. C.
Published: June 2005

Background : Measurement of oesophageal acid exposure parameters postprandially has been shown to distinguish gastro‐oesophageal reflux disease patients from normal individuals.

Aims : To calculate the accuracy of postprandial oesophageal integrated acidity in diagnosing gastro‐oesophageal reflux disease.

Methods : Ambulatory 24‐h pH studies of 626 patients were analysed retrospectively. Gastro‐oesophageal reflux disease, defined as pH < 4 for >4.2% of time, was identified in 305 subjects. Postprandial oesophageal integrated acidity was measured for 2 and 3 h after the largest meal peak as determined from gastric pH. Postprandial symptom‐associated probability was calculated.

Results : Gastro‐oesophageal reflux disease subjects had a greater postprandial oesophageal integrated acidity than non‐gastro‐oesophageal reflux disease subjects [median (IQR): 0.57 (0.08–2.66) vs. 0.03 (0.01–0.15) mmol*h/L]. Median postprandial oesophageal integrated acidity did not differ with gender or age in gastro‐oesophageal reflux disease and non‐gastro‐oesophageal reflux disease subjects (P > 0.05 for all). A 3‐h postprandial oesophageal integrated acidity value of 0.121 mmol*h/L had a 71.1% sensitivity and 71.7% specificity in diagnosing gastro‐oesophageal reflux disease. Gastro‐oesophageal reflux disease subjects with symptoms had a higher postprandial oesophageal integrated acidity than those without (P = 0.043), whereas non‐gastro‐oesophageal reflux disease subjects with and without symptoms did not differ (P = 0.74). The correlation between symptom‐associated probability and postprandial oesophageal integrated acidity was poor (gastro‐oesophageal reflux disease: r = 0.15; non‐gastro‐oesophageal reflux disease: r = 0.25).

Conclusion : Postprandial oesophageal integrated acidity provides a robust estimation of oesophageal acid exposure and may predict symptoms in gastro‐oesophageal reflux disease patients.
Gender difference on the symptoms, health‐seeking behaviour, social impact and sleep quality in irritable bowel syndrome: a Rome II‐based survey in an apparent healthy adult Chinese population in Taiwan
Authors: Lu C.‐L. , Chang F.‐Y. , Lang H.‐C. , Chen C.‐Y. , Luo J.‐C. , Lee S.‐D.
Published: June 2005

Background : Little is known about the gender effect on irritable bowel syndrome in Asia.

Aim : To assess the gender difference in Chinese subjects with irritable bowel syndrome meeting Rome II criteria.

Methods : Irritable bowel syndrome was identified from an apparently healthy adult population receiving a routine health maintenance program (n = 2018).

Results : Female gender is not a factor associated with irritable bowel syndrome or irritable bowel syndrome‐related health care‐seeking behaviour. Female irritable bowel syndrome subjects, irrespective of consulting behaviour for irritable bowel syndrome, are likely to have <3 bowel movements/week, hard/lumpy stools and abdominal fullness/bloating (P < 0.05). Female irritable bowel syndrome subjects are prone to be absent from school/work with more days of absenteeism, irrespective of consultation status (P < 0.05). Only female irritable bowel syndrome consulters have more absenteeism for their irritable bowel syndrome‐related symptoms, reporting more sleep disturbances than their male counterparts (P < 0.001).

Conclusions : In an apparent healthy adult population in Taiwan, gender difference is present in Rome II defined Chinese subjects with irritable bowel syndrome as regards bowel symptoms, social impact and sleep quality. Female predominance was not found in irritable bowel syndrome subjects and irritable bowel syndrome‐related health care‐seeking behaviour in the current population. Both irritable bowel syndrome non‐consulters and consulters have similar gender difference profiles in presenting symptoms, suggesting that bowel symptoms per se may not be the only factor leading to health care‐seeking behaviour. The gender differences in sleep problems were observed solely in irritable bowel syndrome consulter.
Comparison of the effects of immediate‐release omeprazole powder for oral suspension and pantoprazole delayed‐release tablets on nocturnal acid breakthrough in patients with symptomatic gastro‐oesophageal reflux disease
Authors: Castell D. , Bagin R. , Goldlust B. , Major J. , Hepburn B.
Published: June 2005

Background : Many patients treated with a proton‐pump inhibitor for gastro‐oesophageal reflux disease or erosive oesophagitis still have substantial night‐time gastric acidity. A previous trial of a new immediate‐release omeprazole oral suspension suggested that nocturnal gastric acidity could be more effectively controlled with a bedtime dose of immediate‐release omeprazole than with a delayed‐release proton‐pump inhibitor administered before dinner or at bedtime.

Aim : To compare the ability of immediate‐release omeprazole with pantoprazole to control nocturnal gastric acidity, when they were dosed once daily and twice daily.

Methods : Thirty‐six patients with nocturnal gastro‐oesophageal reflux disease symptoms received immediate‐release omeprazole and pantoprazole in this open‐label, randomized‐crossover trial. Median gastric pH, the percentage of time with gastric pH > 4 and the percentage of patients with nocturnal acid breakthrough, were evaluated with 24‐h pH monitoring.

Results : Repeated once daily (bedtime) dosing with immediate‐release omeprazole suspension produced significantly better nocturnal gastric acid control than repeated once daily (predinner) or twice daily (prebreakfast and bedtime) dosing with pantoprazole delayed‐release tablets (median pH: 4.7 vs. 2.0 and 1.7; percentage of time pH > 4: 55 vs. 27 and 34; nocturnal acid breakthrough: 53 vs. 78 and 75). Twice daily dosing (prebreakfast and bedtime) with immediate‐release omeprazole 20 and 40 mg achieved the best night‐time control of gastric acidity. Repeated once daily bedtime dosing with immediate‐release omeprazole 40 mg and twice daily dosing with pantoprazole 40 mg gave similar 24‐h pH control. No safety issues were associated with either drug in this trial.

Conclusions : Dosed once daily at bedtime, immediate‐release omeprazole reduced nocturnal gastric acidity to a degree not observed with once daily dosing of delayed‐release proton‐pump inhibitors.
Variation in the use of H. pylori tests in UK general practice – a qualitative study
Authors: McNulty C. A. M. , Freeman E. , Bowen J. , Delaney B. C.
Published: June 2005

Background : Although serology is the main Helicobacter pylori test used by general practitioners in the UK, there is no information available on variation in requesting rates.

Aim : To explore the reasons for any variation in H. pylori serology testing by general practices in the UK using qualitative methods.

Methods : Serology requesting rates were determined using laboratory and population data. Staff from randomly selected practices in the lowest and highest quintiles of testing attended focus groups to discuss the management of H. pylori and dyspepsia. Transcribed data were analysed using an interpretative phenomenological approach.

Results : Serology submission varied 600‐fold (0.1–59/1000 population/year) and H. pylori positivity rate 17–100%. Low‐testing practices were less aware of the benefits of H. pylori testing and had shorter endoscopy waiting times. They preferred endoscopy diagnosis over serology test. Three high‐testing practices had a high non‐white population with high H. pylori positivity. Most staff knew little about the predictive value of serology, the availability of urea breath test on prescription or the existence of a stool test.

Conclusions : Seroprevalence of H. pylori is still high in dyspeptics, especially in non‐white populations. Laboratories and primary care trusts should audit H. pylori requests and endoscopy referrals, target education at high endoscopy referrers and low H. pylori testers and inform clinicians of the more accurate H. pylori tests and NICE dyspepsia guidance.
Gender and liver fibrosis in chronic hepatitis: the role of iron status
Authors: Rigamonti C. , Andorno S. , Maduli E. , Capelli F. , Boldorini R. , Sartori M.
Published: June 2005

Background : The role of gender in the progression of fibrosis in chronic hepatitis C is still under investigation.

Aim : To investigate whether gender affects the progression of liver disease and/or hides other risk factors.

Methods : A prospective series of 121 consecutive patients with chronic hepatitis C underwent liver biopsy. Grading and staging for chronic hepatitis were each evaluated according to Ishak's classification.

Results : In univariate and multivariate analysis on the whole group of patients, male gender was not associated either with significant liver fibrosis (Ishak's score >2) or with cirrhosis (Ishak's score >4). On the contrary, in univariate analysis on patients aged ≤50 years, male gender was nearly significantly (P = 0.06) predictive of liver fibrosis, whereas it was not in patients >50 years. Hepatic iron grading, along with age, was an independent factor associated with fibrosis. Moreover, the values of all the variables which describe iron status were significantly higher in males aged ≤50 years in comparison with females of the same age.

Conclusions : In chronic hepatitis C, male gender may be predictive of liver fibrosis only in patients aged≤50 years. Among fibrogenetic factors hidden by gender, iron status could play a major role.
High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study
Authors: Zullo A. , Gatta L. , De Francesco V. , Hassan C. , Ricci C. , Bernabucci V. , Cavina M. , Ierardi E. , Morini S. , Vaira D.
Published: June 2005

Background : Helicobacter pylori eradication rates with triple therapies are decreasing, and few data in elderly patients are available. A 10‐day sequential regimen succeeded in curing such H. pylori infection in unselected patients.

Aim : To compare this sequential regimen and the standard triple therapy for H. pylori eradication in geriatric patients with peptic ulcer.

Methods : Overall, 179 H. pylori‐infected patients with peptic ulcer were enrolled (mean age: 69.5 years; range: 65–83). Patients were randomized to 10‐day sequential therapy (rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg, all b.d., for the remaining 5 days) or standard 7‐day triple regimen (rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g, all b.d.). Helicobacter pylori status was assessed by histology and rapid urease test at baseline and 4–6 weeks after completion of treatment.

Results : The sequential regimen achieved eradication rates significantly higher in comparison with the standard regimen at both intention‐to‐treat (94% vs. 80%; P = 0.008) and per‐protocol (97% vs. 83%; P = 0.006) analyses. In both treatment groups, compliance to the therapy was high (>95%), and the rate of mild side‐effects was similarly low (<12%). At repeated upper endoscopy, peptic ulcer lesions were healed in 97% patients, without a statistically significant difference between the sequential regimen and the standard triple therapy.

Conclusions : In elderly patients with peptic ulcer disease, the 10‐day sequential treatment regimen achieved significantly higher eradication rates in comparison with standard triple therapy.
The role of evaporite mobility in modifying subsidence patterns during normal fault growth and linkage, Halten Terrace, Mid‐Norway
Authors: Richardson Nick J. , Underhill John R. , Lewis Gavin
Published: June 2005

Well‐calibrated seismic interpretation in the Halten Terrace of Mid‐Norway demonstrates the important role that structural feedback between normal fault growth and evaporite mobility has for depocentre development during syn‐rift deposition of the Jurassic–Early Cretaceous Viking and Fangst Groups. While the main rift phase reactivated pre‐existing structural trends, and initiated new extensional structures, a Triassic evaporite interval decouples the supra‐salt cover strata from the underlying basement, causing the development of two separate fault populations, one in the cover and the other confined to the pre‐salt basement.

Detailed displacement–length analyses of both cover and basement fault arrays, combined with mapping of the component parts of the syn‐rift interval, have been used to reveal the spatial and temporal evolution of normal fault segments and sediment depocentres within the Halten Terrace area. Significantly, the results highlight important differences with traditional models of normal fault‐controlled subsidence, including those from parts of the North Sea where salt is absent. It can now be shown that evaporite mobility is intimately linked to the along‐strike displacement variations of these cover and basement faults. The evaporites passively move beneath the cover in response to the extension, such that the evaporite thickness becomes greatest adjacent to regions of high fault displacement. The consequent evaporite swells can become large enough to have pronounced palaeobathymetric relief in hangingwall locations, associated with fault displacement maxima– the exact opposite situation to that predicted by traditional models of normal fault growth. Evaporite movement from previous extension also affects the displacement–length relationships of subsequently nucleated or reactivated faults. Evaporite withdrawal, on the other hand, tends to be a later‐stage feature associated with the high stress regions around the propagating tips of normal faults or their coeval hangingwall release faults. The results indicate the important effect of, and structural feedback caused by, syn‐rift evaporite mobility in heavily modifying subsidence patterns produced by normal fault array evolution. Despite their departure from published models, the results provide a new, generic framework within which to interpret extensional fault and depocentre development and evolution in areas in which mobile evaporites exist.
A three‐dimensional approach to fault seal analysis: fault‐block juxtaposition & argillaceous smear modelling
Authors: Clarke Stuart M. , Burley Stuart D. , Williams Graham D.
Published: June 2005

Three‐dimensional (3D) numerical modelling of fault displacement enables the building of geological models to represent the complex 3D geometry and geological properties of faulted sedimentary basins. Using these models, cross‐fault juxtaposition relationships are predicted in 3D space and through time, based on the geometries of strata that are cut by faults. Forward modelling of fault development allows a 3D prediction of fault‐zone argillaceous smear using a 3D application of the Shale Gouge Ratio. Numerical models of the Artemis Field, Southern North Sea, UK and the Moab Fault, Utah, USA are used to demonstrate the developed techniques and compare them to traditional one‐ and two‐dimensional solutions. These examples demonstrate that a 3D analysis leads to significant improvements in the prediction of fault seal, the analysis of the interaction of the sealing properties of multiple faults, and the interpretation of fault seal within the context of sedimentary basin geometry.
Quantifying the contribution of tectonics vs. differential compaction in the development of domes along the Mid‐Norwegian Atlantic margin
Authors: Gómez M. , Vergés J.
Published: June 2005

A sequential restoration based on combined backstripping and unfolding methods affords the opportunity to study the Cenozoic evolution of two low amplitude domes in the Mid‐Norwegian extensional margin, the Helland Hansen Arch and the Vema Dome. The integration of growth strata geometries observed in both flanks of the domes demonstrate that the structures grew by a variable combination of tectonics and differential compaction mechanisms. Sequential restoration shows that the Helland Hansen Arch grew between Early Oligocene and earliest Late Pliocene times (33–1.9 Ma). During the first phase of growth (33–9 Ma), the tectonic compression accounted for a minimum of 27% of the total dome amplitude. During Late Miocene to Pliocene times (9–1.9 Ma), differential compaction was the mechanism for dome growth. During Late Pliocene times, the Helland Hansen Arch grew with the highest rates coinciding with initial deposition of prograding wedges (3.6–1.9 Ma). In contrast, the Vema Dome started to develop in Early Eocene times and grew at a fairly constant rate up to Early Pliocene times at 3.6 Ma. The amplification of the Vema Dome took place through both differential compaction and tectonics between Early Eocene and Late Miocene times (54.8–7 Ma). The tectonic contribution accounted for a minimum of a 37% of the total dome amplitude. During Pleistocene times, the progradation of clastic wedges led to a decrease of the amplitudes of both the Helland Hansen Arch and the Vema Dome. The different timing of tectonic growth for analysed domes and arches suggest that a small and protracted phase of compression affected the Mid‐Norwegian Margin. This agrees with well‐known widespread contractional deformation affecting the Atlantic Margin of the European Plate during the Tertiary.
Changes in availability of paediatric medicines in Australia between 1998 and 2002
Authors: Chui Jocelyn , Tordoff June , Reith David
Published: June 2005

Aims

To determine changes in the availability of medicines for children in Australia and to determine the status of newly introduced chemical entities by age category.

Methods

Using the Australian Prescription Products Guide and the Schedule of Pharmaceutical Benefits, licensed medicines available in Australia in the calendar years 1998 and 2002 were examined.

Results

The total number of medicines licensed in Australia increased from 1544 to 1903, the number of licensed paediatric items increased from 579 (37.5%) to 725 (38.1%), and those both licensed for paediatric use and subsidized increased from 356 (23.1%) to 441 (23.2%). The number of medicines with formulations suitable for paediatric use increased from 861 (55.7%) to 967 (50.8%), and of these 382 (24.7%) and 466 (24.5%) were licensed for paediatric use. Of the 90 new orally available chemical entities licensed for adults only 12 (13%) were licensed for children. Three (3%) were licensed for the 0–28 days and 28 days to 23 months age groups, eight (9%) for 2–11 years and 12 (13%) for 12–18 years. An additional 14 orally available chemical entities previously only licensed for adults, were licensed for children by 2002.

Conclusions

There have been some improvements in medicines licensing for older children, but not for children under the age of two years.
Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs
Authors: Björkman Sven
Published: June 2005

Aims  To create a general physiologically based pharmacokinetic (PBPK) model for drug disposition in infants and children, covering the age range from birth to adulthood, and to evaluate it with theophylline and midazolam as model drugs.

Methods  Physiological data for neonates, 0.5‐, 1‐, 2‐, 5‐, 10‐ and 15‐year‐old children, and adults, of both sexes were compiled from the literature. The data comprised body weight and surface area, organ weights, vascular and interstitial spaces, extracellular body water, organ blood flows, cardiac output and glomerular filtration rate. Tissue: plasma partition coefficients were calculated from rat data and unbound fraction (fu) of the drug in human plasma, and age‐related changes in unbound intrinsic hepatic clearance were estimated from CYP1A2 and CYP2E1 (theophylline) and CYP3A4 (midazolam) activities in vitro. Volume of distribution (Vdss), total and renal clearance (CL and CLR) and elimination half‐life (t1/2) were estimated by PBPK modelling, as functions of age, and compared with literature data.

Results  The predicted Vdss of theophylline was 0.4‐0.6 l kg−1 and showed only a modest change with age. The median prediction error (MPE) compared with literature data was 3.4%. Predicted total CL demonstrated the time‐course generally reported in the literature. It was 20 ml h−1 kg−1 in the neonate, rising to 73 ml h−1 kg−1 at 5 years and then decreasing to 48 ml h−1 kg−1 in the adult. Overall, the MPE was − 4.0%. Predicted t1/2 was 18 h in the neonate, dropping rapidly to 4.6‐7.2 h from 6 months onwards, and the MPE was 24%. The predictions for midazolam were also in good agreement with literature data. Vdss ranged between 1.0 and 1.7 l kg−1 and showed only modest change with age. CL was 124 ml h−1 kg−1 in the neonate and peaked at 664 ml h−1 kg−1 at 5 years before decreasing to 425 ml h−1 kg−1 in the adult. Predicted t1/2 was 6.9 h in the neonate and attained ‘adult’ values of 2.5‐3.5 h from 1 year onwards.

Conclusions  A general PBPK model for the prediction of drug disposition over the age range neonate to young adult is presented. A reference source of physiological data was compiled and validated as far as possible. Since studies of pharmacokinetics in children present obvious practical and ethical difficulties, one aim of the work was to utilize maximally already available data. Prediction of the disposition of theophylline and midazolam, two model drugs with dissimilar physicochemical and pharmacokinetic characteristics, yielded results that generally tallied with literature data. Future use of the model may demonstrate further its strengths and weaknesses.
Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care
Authors: Novak Philipp H. , Ekins‐Daukes Suzie , Simpson Colin R. , Milne Robert M. , Helms Peter , McLay James S.
Published: June 2005

Aims

To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions.

Design

Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland.

Setting

One hundred and sixty‐one general practices throughout Scotland.

Results

During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non‐epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17‐year‐olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age‐adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17‐year‐old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low‐dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning.

Conclusions

In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could give rise to clinically serious drug–drug interactions.
Allometric relationships between the pharmacokinetics of propofol in rats, children and adults
Authors: Knibbe Catherijne A. J. , Zuideveld Klaas P. , Aarts Leon P. H. J. , Kuks Paul F. M. , Danhof Meindert
Published: June 2005

Aims

Allometric equations have proven useful for the extrapolation of animal data to determine pharmacokinetic parameters in man. It has been proposed that these equations are also applicable over the human size range including the paediatric population. The aim of this work was to study the relationship between various pharmacokinetic parameters for propofol and body weight using data from rats, children and adults. Furthermore, the utility of allometric scaling is evaluated by the prediction of propofol concentrations in humans based on data obtained in the rat.

Methods

The relationship between the pharmacokinetic parameters of propofol obtained in rats, children and adults was analyzed by plotting the logarithmically transformed parameters against the corresponding logarithmically transformed body weights. In addition, based on allometric equations, pharmacokinetic parameters obtained in rats were scaled to humans. These parameters were used to simulate propofol concentrations in long‐term sedated critically ill patients using NONMEM. Simulated concentrations were then compared with actually observed concentrations in humans.

Results

The relationship between pharmacokinetic parameters of propofol from rats, children and adults was in good agreement with those from the literature on allometric modelling. For clearance, intercompartmental clearance, central volume of distribution and peripheral volume of distribution, the power parameters were 0.78, 0.73, 0.98 and 1.1, respectively, and r2 values for the linear correlations were 0.990, 0.983, 0.977 and 0.994, respectively. On the basis of data obtained after a single bolus injection in the rat, adequate predictions of propofol concentrations in critically ill patients can be made using allometric equations, despite the long‐term nature of the use of the drug, the large number of infusion changes per day and/or differences in state of health and age.

Conclusions

For propofol, allometric scaling has proved to be valuable for cross species extrapolation. Furthermore, the use of the allometric equation between adults and children seems to be an adequate tool for the development of rational dosing schemes for children of varying body weights, and requires further study.