bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis induced by methylene‐blue‐mediated photodynamic therapy in melanomas and the involvement of mitochondrial dysfunction revealed by proteomics
Authors: Chen Yongjun , Zheng Wei , Li Yingqian , Zhong Jieying , Ji Jianguo , Shen Pingping
Published: October 2008

Methylene blue (MB) is a widely studied agent currently under investigation for its properties relating to photodynamic therapy (PDT). Recent studies have demonstrated that MB exhibits profound phototoxicity affecting a variety of tumor cell lines. However, the mechanistic explanation for methylene‐blue‐mediated photodynamic therapy (MB‐PDT) in the context of melanoma therapy is still obscure. In the present study, B16F1 melanoma cells were treated by MB‐PDT under different conditions, and thereafter subjected to cell viability detection assays. MB‐PDT could induce intense apoptotic cell death through a series of steps beginning with the photochemical generation of reactive oxygen species that activate the caspase‐9/caspase‐3 apoptosis pathway. Blocking activation of caspase‐3 and induction of oxidative stress by caspase inhibitor and by glutathione, respectively, markedly reduced apoptotic cell death in vitro. Importantly, proteomics study defining altered protein expression in treated cells suggests the involvement of several mitochondrial proteins playing important roles in electron transfer chain, implying mitochondrial dysfunction during the treatment. Furthermore, a transplantable mouse melanoma model was utilized to estimate the effectiveness of MB‐PDT in vivo. The treated mice displayed decreased tumor size and prolonged survival days, which was associated with enhanced apoptotic cell death. These results, offering solid evidence of the induction of mitochondria‐related apoptosis in tumor cells, reveal new aspects of MB‐PDT having potential to be a palliative treatment of melanoma. (Cancer Sci 2008; 99: 2019–2027)
Osteopontin promotes ovarian cancer progression and cell survival and increases HIF‐1α expression through the PI3‐K/Akt pathway
Authors: Song Gang , Cai Qiu‐Feng , Mao Yu‐Bin , Ming Yan‐Lin , Bao Shi‐Deng , Ouyang Gao‐Liang
Published: October 2008

Osteopontin (OPN) is a secreted, integrin‐binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. However, the functional mechanisms by which OPN contributes to the development of ovarian cancer are poorly understood. Here, we reveal that acquired expression of OPN by HO‐8910 ovarian cancer cells greatly promoted the progression of ovarian cancer. OPN expression dramatically increased the colony formation of ovarian cancer cells in vitro and tumor growth in vivo. Under the stress induced by serum depletion or curcumin treatment, OPN expression promoted the survival of ovarian cells through preventing stress‐induced apoptosis. At the molecular level, both endogenous and exogenous OPN expression activated the PI3‐K/Akt survival pathway and dramatically decreased p53 expression under serum depletion. In addition, HIF‐1α was induced in OPN‐producing cells under normoxia. Furthermore, we also found that inhibition of the PI3‐K/Akt pathway attenuated OPN‐mediated HIF‐1α up‐regulation in ovarian cancer cells. Taken together, these results indicate that OPN can increase the survival of ovarian cancer cells under stress conditions in vitro and promote the late progression of ovarian cancer in vivo, and the survival‐promoting functions of OPN are mediated through Akt activation and the induction of HIF‐1α expression. (Cancer Sci 2008; 99: 1901–1907)
Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high‐mobility group protein B1
Authors: Shiota Masaki , Izumi Hiroto , Miyamoto Naoya , Onitsuka Takamitsu , Kashiwagi Eiji , Kidani Akihiko , Hirano General , Takahashi Mayu , Ono Mayumi , Kuwano Michihiko , Naito Seiji , Sasaguri Yasuyuki , Kohno Kimitoshi
Published: October 2008

Peroxiredoxins (Prdxs) are thiol‐specific antioxidant proteins that are highly expressed in human cancer cells. Prdxs have been shown to be involved in tumor cell proliferation under conditions of microenvironmental stress such as hypoxia. We hypothesized that Prdxs could be categorized into two groups, stress‐inducible and non‐inducible ones. In this study, we analyzed the promoter activity and expression levels of five Prdx family members in human cancer cells. We found that both Prdx1 and Prdx5 are inducible after treatment with hydrogen peroxide or hypoxia, but that Prdx2, Prdx3, and Prdx4 are not or are only marginally inducible. We also found that Ets transcription factors are the key activators for stress‐inducible expression. High‐mobility group protein HMGB1 was shown to function as a coactivator through direct interactions with Ets transcription factors. The DNA binding of Ets transcription factors was significantly enhanced by HMGB1. Silencing of Ets1, Ets2, Prdx1, and Prdx5 expression sensitized cells to oxidative stress. These data indicate that transcription of Prdx genes mediated by Ets/HMG proteins might protect cells from oxidative stress. (Cancer Sci 2008; 99: 1950–1959)
Interaction between DNMT1 and DNA replication reactions in the SV40 in vitro replication system
Authors: Shimamura Shintaro , Ishikawa Fuyuki
Published: October 2008

In contrast to normal cells, cancer cells exhibit both genetic and epigenetic instability. These unique properties give rise to genetic and epigenetic heterogeneity in a given population of cancer cells and provide a means for the population to undergo phenotypic progression by clonal selection. DNA methylation at CpG dinucleotides is one of the epigenetic marks that are frequently disturbed in cancer cells. To understand how the CpG methylation pattern is changeable in cancer cells, it is necessary to know how it is faithfully maintained in normal cell proliferation. Toward this goal, we have developed a novel in vitro system that is based on the well‐established SV40 in vitro replication system and functions to reconstitute concurrent DNA replication and DNA maintenance methylation reactions. We found that DNA methylation was maintained only when exogenous DNA methyltransferase 1 (DNMT1) and S‐adenosyl methionine (SAM) were added to the reaction. We demonstrated that DNMT1 associates with replicating and/or replicated chromatin irrespective of the DNA methylation status of template DNA. Moreover, the PCNA‐binding domain (PBD) of DNMT1 is not required for the association. Taken together, we suggest that DNMT1 is recruited to replicating and/or replicated chromatin in a constitutive manner independent of the DNA methylation reaction. The in vitro system described in this report is very useful for analyzing the molecular mechanism underlying the DNA maintenance methylation reaction. (Cancer Sci 2008; 99: 1960–1966)
Factors affecting abundance and distribution of submerged and floating macrophytes in Lake Naivasha, Kenya
Authors: Ngari A. N. , Kinyamario J. I. , Ntiba M. J. , Mavuti K. M.
Published: October 2008

Macrophytes have been shown to perform important ecological roles in Lake Naivasha. Consequently, various studies regarding the impact of biotic factors on the macrophytes have been advanced but related studies on environmental parameters have lagged behind. In an attempt to address this gap, sampling on floating species and submergents was carried out in eight sampling sites in 2003 to investigate how they were influenced by a set of environmental factors. Soil texture (sandy sediments; P < 0.05, regression coefficient = −0.749) and wind were the most important environmental parameters influencing the distribution and abundance of floating macrophytes. Combination of soil texture and lake‐bed slope explained the most (86.3%) variation encountered in the submergents. Continuous translocation of the floating dominant water hyacinth to the western parts by wind has led to displacement of the submergents from those areas. In view of these findings, the maintenance and preservation of the steep Crescent Lake basin whose substratum is dominated by sand thus hosting most submergents remain important, if the whole functional purpose of the macrophytes is to be sustained.
The role of hepatitis E virus testing in drug‐induced liver injury
Authors: DALTON H. R. , FELLOWS H. J. , STABLEFORTH W. , JOSEPH M. , THURAIRAJAH P. H. , WARSHOW U. , HAZELDINE S. , REMNARACE R. , IJAZ S. , HUSSAINI S. H. , BENDALL R. P.
Published: October 2008

Background  Locally acquired hepatitis E is an emerging infection in developed countries and can be misdiagnosed as drug‐induced liver injury.

Aim  To study the role of hepatitis E virus (HEV) testing in drug‐induced liver injury.

Methods  Retrospective review of a cohort of patients with suspected drug‐induced liver injury (n = 69) and hepatitis E (n = 45). The standard criteria for drug‐induced liver injury were applied. Patients with suspected drug‐induced liver injury who met these criteria were retrospectively tested for HEV on stored sera taken at the time of presentation. The two cohorts were compared to determine variables that predicted either of the diagnoses.

Results  Forty‐seven out of 69 patients had criterion‐referenced drug‐induced liver injury. 22/47 were HEV negative and thus had confirmed drug‐induced liver injury. 19/47 were not tested for HEV, as there was no sera available from the time of presentation. 6/47 were HEV positive and thus did not have drug‐induced liver injury, but had hepatitis E infection. Compared to patients with confirmed drug‐induced liver injury, patients with hepatitis E were significantly more likely to be male (OR 3.09, CI 1.05–9.08); less likely to present in November and December (0.03, CI 0.01–0.52); have lower serum bilirubin (P = 0.015); and higher serum alanine aminotransferase (P < 0.001) and alanine aminotransferase/alkaline phosphatase ratio (P < 0.001).

Conclusion  The diagnosis of drug‐induced liver injury is not secure without testing for HEV.
Clinical trial: effects of adefovir dipivoxil therapy in Asian and Caucasian patients with chronic hepatitis B
Authors: LIM S. G. , MARCELLIN P. , TASSOPOULOS N. , HADZIYANNIS S. , CHANG T. T. , TONG M. , SIEVERT W. , HU P. , ARTERBURN S. , BROSGART C. L. ,   ON BEHALF OF THE INTERNATIONAL INVESTIGATOR GROUPS FOR STUDIES 437 AND 438
Published: October 2008

Background  Two‐thirds of the 350 million people infected with chronic hepatitis B virus live in the Asia‐Pacific region.

Aim  To compare the effects of adefovir dipivoxil therapy between Asian and Caucasian patients with chronic hepatitis B.

Methods  The safety and efficacy of 10 mg of adefovir dipivoxil was compared to placebo in 501 Asian (n = 259) or Caucasian (n = 242) HBeAg+ and HBeAg− chronic hepatitis B virus patients treated for 48 weeks in two randomized, double‐blind, placebo‐controlled studies.

Results  At week 48, histological improvement was observed in 60% and 56% of Caucasian and Asian patients, respectively. Change in serum hepatitis B virus DNA from baseline to week 48 for the adefovir dipivoxil‐treated patients was −3.89 and −3.70 log10 copies/mL in Caucasian and Asian patients, respectively, while 34 per cent of Caucasian patients and 39 per cent of Asian patients had undetectable serum hepatitis B virus DNA (<400 copies/mL) at week 48. The percentage of patients achieving alanine aminotransferase (ALT) normalization at week 48 was similar in both groups (Caucasian 64 per cent, Asian 63 per cent). No patients developed resistance through week 48. No differences in adverse events or grade 3 or 4 laboratory abnormalities were observed between groups.

Conclusions  There were no significant differences in treatment response between Asians and Caucasians. Adefovir dipivoxil was well tolerated and no resistance developed up to week 48 in both racial groups.
Resource use in patients with Crohn’s disease treated with infliximab
Authors: SARO C. , DE LA COBA C. , CASADO M. Á. , MORALES J. M. , OTERO B.
Published: October 2008

Aim  To estimate the impact of infliximab (IFX) on hospital resources for patients with Crohn’s disease.

Methods  Resource use data for at least 1 year before (B‐IFX) and after (A‐IFX) infliximab administration were retrospectively collected for all patients treated with IFX at the Hospital Cabueñes (Spain). Direct costs calculated were: hospital‐stays, surgeries, out‐patient visits, diagnostic and laboratory tests, pharmacological treatments, and day‐care hospitalization for IFX administration.

Results  Patients (n = 34; mean age at treatment: 43.6 years) with 9.8 and 4.3 years (B‐IFX and A‐IFX, respectively) had their costs estimated. Partial or complete response was achieved in 82% of patients. Total annual B‐IFX costs per patient were €4464, of which 62.4% was for hospitalization, 3.1% for surgery, 8.7% for consultation visits, 16.2% for diagnostic and laboratory tests, and 9.6% for other treatments. Total annual A‐IFX costs per patient were €10 594; of which 6.4% was for hospitalization, 0.8% for surgery, 4.2% for consultation visits, 7.6% for diagnostic and laboratory tests, 5.5% for other treatments, and 75.5% for IFX and its administration. The primary cost item was hospitalization (€2783) during the B‐IFX period as opposed to IFX itself (€7996) during the subsequent A‐IFX period.

Conclusions  In routine practice, IFX appears to be an effective treatment by reducing hospital‐stays, but increases overall budgetary cost for patients with Crohn’s disease.
Early versus late surgery for ileo‐caecal Crohn’s disease
Authors: ARATARI A. , PAPI C. , LEANDRO G. , VISCIDO A. , CAPURSO L. , CAPRILLI R.
Published: October 2008

Background  Surgical resection is almost inevitable in Crohn’s disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease.

Aim  To compare the long‐term course of Crohn’s disease following ileo‐caecal resection performed at the time of diagnosis (early surgery) or during the course of the disease (late surgery).

Patients and methods  Overall 207 patients with ileo‐caecal Crohn’s disease at their first resection were reviewed: 83 patients underwent surgery at the time of diagnosis (early surgery), while 124 underwent surgery 54.2 months (range 1–438) after diagnosis (late surgery). The mean follow‐up after surgery was 147 months (range 12–534). The primary endpoint was clinical recurrence, defined as need for corticosteroids for symptomatic disease in the presence of endoscopic and/or radiologic recurrence. Secondary endpoints were need for immunosuppressants and surgical recurrence. Statistical analysis: Kaplan–Meier survival method and Cox proportional hazards regression model.

Results  Within 10 years after surgery, the cumulative probability of clinical recurrence was significantly lower in the early surgery group (Log Rank test P = 0.01). A trend was observed regarding the need for immunosuppressants (P = 0.05). No difference was observed regarding surgical recurrence. At multivariate analysis, early surgery was the only independent variable associated with a reduced risk of clinical recurrence (Hazard ratio, HR = 0.57; 95% CI 0.35 to 0.92, P = 0.02), but not with need for immunosuppressants and surgical recurrence (HR = 0.51; 95% CI 0.20 to 1.30, P = 0.15; HR = 0.66; 95% CI 0.33 to 1.35, P = 0.25, respectively).

Conclusion  Early surgery prolongs clinical remission compared to surgery performed during the course of the disease, but the natural history of disease is not modified.
Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost‐effectiveness analysis
Authors: WINSTEAD N. S. , WILCOX C. M.
Published: October 2008

Background Erythromycin is a potent stimulator of gastrointestinal motility. Recent studies have examined the use of intravenous erythromycin to clear the stomach of blood before oesophago‐gastroduodenoscopy (EGD) for acute upper gastrointestinal haemorrhage (UGIH). These studies have shown clinical effectiveness.

Aim To evaluate the cost‐effectiveness of this intervention.

Methods We sought to determine the cost‐effectiveness of erythromycin before EGD from the payer’s perspective. We found three relevant studies of erythromycin and used these data for the analysis. We obtained costs for intravenous erythromycin and charges for peptic ulcer hospitalization, EGD, surgery, and angiographic embolization. Complication rates were also incorporated from the literature. We implemented a model of health‐related quality of life to measure the impact of the intervention. We created a decision‐analysis tree and performed a probabilistic sensitivity analysis.

Results A strategy of erythromycin prior to EGD resulted in a cost‐effective outcome in a majority of trials using willingness‐to‐pay figures of $0, $50 000 and $100 000 (US) per quality‐adjusted life‐year (QALY).

Conclusion Because of the implications for cost saving and increase in QALY, we would recommend giving erythromycin prior to EGD for UGIH.
Clinical trial: effects of tegaserod on gastric motor and sensory function in patients with functional dyspepsia
Authors: THUMSHIRN M. , FRUEHAUF H. , STUTZ B. , TOUGAS G. , SALTER J. , FRIED M.
Published: October 2008

Background  Tegaserod, a serotonin receptor type‐4 partial agonist, stimulates gastrointestinal motility and has been shown to increase gastric volumes before and after a meal in healthy volunteers. Its effect on gastric motor and sensory function in patients with functional dyspepsia is unclear.

Aim  To evaluate the effects of tegaserod on gastric compliance, accommodation and gastric sensory function in patients with functional dyspepsia and healthy volunteers.

Methods Sixteen patients with functional dyspepsia and 12 healthy volunteers were studied on two occasions, each after a 7‐day treatment with either placebo or tegaserod 6 mg b.d. using a double‐blind, randomized, crossover design. After each treatment period a gastric barostat study was performed fasting and during intraduodenal lipid infusion.

Results  Tegaserod increased postprandial gastric compliance in functional dyspepsia patients (P = 0.04). Healthy volunteers showed enhanced postprandial gastric compliance after placebo (P = 0.03). Between‐treatment analysis of gastric accommodation revealed a significant increase in intrabag volumes after tegaserod in healthy volunteer (P = 0.04); no difference could be seen in functional dyspepsia patients. Tegaserod had no effect on gastric sensation.

Conclusions  Tegaserod enhances postprandial gastric compliance in functional dyspepsia patients and gastric accommodation in healthy volunteers. The improvement of proximal gastric motor function suggests a beneficial role of tegaserod in patients with functional dyspepsia.
No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study
Authors: LEWIS N. R. , LOGAN R. F. A. , HUBBARD R. B. , WEST J.
Published: October 2008

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten‐sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.

Aims  To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population.

Methods  Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age‐, gender‐ and practice‐matched controls. We used Cox regression to estimate hazard ratios.

Results  Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77–1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73–1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67–3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44–6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03–1.39). The hazard ratio for all‐cause mortality was 0.93 (95% CI: 0.70–1.23).

Conclusions  Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.
Systematic review: tolerable amount of gluten for people with coeliac disease
Authors: AKOBENG A. K. , THOMAS A. G.
Published: October 2008

Background  The threshold amount of gluten in ‘gluten‐free’ products that can be tolerated by people with coeliac disease is unclear.

Aim  To investigate the threshold amount of gluten and the threshold concentration of gluten in food products that can be tolerated by people with coeliac disease.

Design  Systematic review of studies published between 1966 and May 2007.

Methods  The data sources used were MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and reference lists of retrieved articles. We included studies that evaluated the amount of dietary gluten or the concentrations of gluten in food products that can be tolerated by people with coeliac disease whatever their design, method or language of publication.

Results  Thirteen studies (three randomized controlled, one cohort, two crossover, and seven cross‐sectional) met the inclusion criteria. The daily amount of tolerable gluten varied widely between studies. Whilst some patients tolerated an average of 34–36 mg of gluten per day, other patients who consumed about 10 mg of gluten per day developed mucosal abnormalities. The effect of the consumption of ‘gluten‐free’ products with different degrees of gluten contamination was also inconsistent.

Conclusions  The amount of tolerable gluten varies among people with coeliac disease. Although there is no evidence to suggest a single definitive threshold, a daily gluten intake of <10 mg is unlikely to cause significant histological abnormalities.
Clinical trial: a randomized controlled cross‐over study of flupenthixol + melitracen in functional dyspepsia
Authors: HASHASH J. G. , ABDUL‐BAKI H. , AZAR C. , ELHAJJ I. I. , EL ZAHABI L. , CHAAR H. F. , SHARARA A. I.
Published: October 2008

Background  Functional dyspepsia is a prevalent condition associated with diminished quality of life (QoL) and high economic burden.

Aim  To study the efficacy of a combination of flupenthixol and melitracen (F + M) with anxiolytic and antidepressant properties in functional dyspepsia using a randomized controlled cross‐over design.

Methods  Patients met the Rome III criteria for functional dyspepsia and a validated questionnaire was used to exclude those with anxiety or depression. Moreover, patients had to have failed a trial of acid‐suppressive therapy and Helicobacter pylori eradication when positive. End points included subjective global symptom relief and QoL assessed by the Nepean Dyspepsia Index (NDI).

Results  Twenty‐five patients (14 females, 11 males; mean age = 34.3 ± 9.9 years) were enrolled and 24 completed the 8‐week study. There was a significant improvement in subjective global symptom relief with F + M vs. placebo (ITT: 73.9% vs. 26.1%, P = 0.001) and a significant drop in the NDI score vs. placebo (ITT: −9.0 ± 11.9 vs. −2.4 ± 8.9, P = 0.03). No difference was noted whether the initial treatment was F + M or placebo. No significant side effects were noted.

Conclusions  A combination of F and M is safe and effective in the short‐term treatment of functional dyspepsia. F + M is associated with significant improvement in QoL independent of the presence of anxiety or depression.
A national survey of acute hepatitis E in France
Authors: RENOU C. , MOREAU X. , PARIENTE A. , CADRANEL J.‐F. , MARINGE E. , MORIN T. , CAUSSE X. , PAYEN J.‐L. , IZOPET J. , NICAND E. , BOURLIÈRE M. , PENARANDA G. , HARDWIGSEN J. , GEROLAMI R. , PÉRON J.‐M. , PAVIO N. ,   THE ANGH, FRANCE
Published: October 2008

Background  Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries.

Aims  To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E.

Methods  This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases.

Results  A decreasing South‐to‐North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig.

Conclusions  This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non‐endemic countries.
Safety, tolerability, and efficacy of pegylated‐interferon alfa‐2a plus ribavirin in HCV‐related decompensated cirrhotics
Authors: TEKIN F. , GUNSAR F. , KARASU Z. , AKARCA U. , ERSOZ G.
Published: October 2008

Background  Pretransplantation clearance of hepatitis C virus (HCV)‐RNA reduces the risk of HCV recurrence after transplantation. Furthermore, a sustained virological response could reduce disease progression and slow clinical deterioration in nontransplanted patients.

Aim  To evaluate the safety, tolerability and efficacy of pegylated‐interferon (PEG‐IFN) alfa‐2a plus ribavirin therapy in HCV‐related decompensated cirrhotics.

Methods  Twenty HCV‐related decompensated cirrhotics (44–67 years, 12 males, six Child–Pugh score A, 14 Child–Pugh score B, all with genotype 1b) were enrolled into the study. Treatment with PEG‐IFN alfa‐2a (135 μg, once a week) plus ribavirin (1000–1200 mg/day) was commenced. A 48‐week treatment was planned in patients who had early virological response.

Results  Treatment was stopped in 8 (40%) patients. The remaining 12 (60%) patients completed 48 weeks of therapy; nine (45%) of them obtained end‐of‐therapy virological response and six (30%) of them obtained sustained virological response. Living donor liver transplantation was performed in three (15%) patients. Eight (40%) and six (30%) patients needed to reduce PEG‐IFN alfa‐2a and ribavirin dosages, respectively. No patient died during the follow‐up period.

Conclusion  PEG‐IFN alfa‐2a plus ribavirin therapy is safe, tolerable and efficacious in selected HCV‐related decompensated cirrhotics.
Review article: gastrointestinal amyloidosis – clinical features, diagnosis and therapy
Authors: PETRE S. , SHAH I. A. , GILANI N.
Published: October 2008

Background  Amyloidosis is one of the unusual diseases about which a physician may not think when it is affecting the patient. During the last three decades, there has been an enormous progress in the understanding of the chemical nature, classification, pathogenesis, clinical features, diagnostic measures and therapy of this disorder.

Aim  To provide an updated review of amyloidosis affecting the gastrointestinal tract.

Methods  Review of current medical literature.

Results  Amyloid proteins (irrespective of the type) can deposit in various parts of the gastrointestinal tract and liver resulting in symptoms of abdominal pain, dysmotility, diarrhoea, gastrointestinal bleeding, hepatomegaly and even portal hypertension with its associated complications. Definitive diagnosis can only be made by histological examination of the affected organ. Disease modifying treatment with high‐dose chemotherapy followed by autologous stem‐cell transplantation has shown promise. Liver transplantation is an option for a select group of patients.

Conclusions  Suspicion of gastrointestinal amyloidosis in patients without known history of amyloidosis is difficult, but should be considered in those older than 30 years with unexplained diarrhoea, weight loss, autonomic dysfunction, malabsorption or proteinuria. While most gastrointestinal complications are managed symptomatically, causal therapy is reserved for a select few from various subtypes of this disorder.
Systematic review: health‐related quality of life (HRQOL) questionnaires in gastro‐oesophageal reflux disease
Authors: CHASSANY O. , HOLTMANN G. , MALAGELADA J. , GEBAUER U. , DOERFLER H. , DEVAULT K.
Published: October 2008

Background  Although gastro‐oesophageal reflux disease (GERD) has a well‐established pathophysiology, the impact of GERD symptoms on the patients’ quality of life can be profound. Therefore, health‐related quality of life (HRQOL) questionnaires have become standard instruments to evaluate the effect of treatment in clinical trials.

Aim  To evaluate the reliability, validity and responsiveness of available GERD‐specific HRQOL.

Methods  A systematic literature search using the Medical Subject Headings terms: ‘Gastro‐oesophageal reflux’, ‘Heartburn’ and ‘Oesophagitis’ with ‘quality of life’ and ‘questionnaires’ was preformed to identify the available HRQOL questionnaires. To analyse the psychometric properties of the respective tools, the actual guidelines for the use of patient‐reported outcomes in clinical trials were applied.

Results  We identified five GERD‐specific HRQOL questionnaires but none of them fulfilled all quality criteria; either they did not meet the actual standards for psychometric properties (HBQOL, GERD‐HRQL, Jasani et al.Aust Fam Physician 1999; 28: 515), or were impracticable to use in clinical trials. The generic and hybrid instruments lack specificity and sensitivity and were not designed for treatment evaluation in GERD patients.

Conclusion  There is need for a new evaluative tool in the assessment of HRQOL during GERD therapy.
Review article: current management of metastatic colorectal cancer – the evolving impact of targeted drug therapies
Authors: YAU T. , CHAN P. , Ching CHAN Y. , WONG B. C. Y. , LIANG R. , EPSTEIN R. J.
Published: October 2008

Background  The field of colorectal cancer chemotherapy has been transformed by the advent of molecule‐specific drugs. Combined use of such drugs enhances tumour response rates, but controlled data quantifying the relative efficacy and cost‐effectiveness of different drug combinations on overall survival remain scarce.

Aim  To conduct an overview of published clinical trials in advanced colorectal cancer, with the objective of framing provisional approaches to current management.

Methods  An NCBI/PubMed search was performed using the strings, ‘colorectal cancer’ (‘metastatic’ or ‘advanced’ or ‘palliative’) and (‘chemotherapy’ or ‘drug therapy’ or ‘targeted’ or ‘target‐specific’ or ‘molecularly‐targeted’).

Results  Combinations of target‐specific drugs (with or without the DNA‐alkylating agent oxaliplatin) have substantially enhanced colorectal cancer time to progression over the last decade and have also expedited surgical resection of liver metastases. Disease‐free survival, overall survival and quality of life are favourably influenced.

Conclusions  Target‐specific drugs improve palliative efficacy in the setting of advanced colorectal cancer. However, key issues persist as to the cost‐effectiveness of these newer drug treatments, and further controlled trials are needed to resolve this important debate.
MMX mesalazine for the induction of remission of mild‐to‐moderately active ulcerative colitis: efficacy and tolerability in specific patient subpopulations
Authors: LICHTENSTEIN G. R. , KAMM M. A. , SANDBORN W. J. , LYNE A. , JOSEPH R. E.
Published: October 2008

Background  Two phase III studies have evaluated mesalazine (mesalamine) with MMX (Multi Matrix System) technology in patients with active mild‐to‐moderate ulcerative colitis.

Aim  To determine the efficacy of MMX mesalazine for the induction of clinical and endoscopic remission in specific subgroups of patients with active, mild‐to‐moderate ulcerative colitis.

Methods  Data from two double‐blind, placebo‐controlled trials were analysed (517 out‐patients). Patients were randomized to receive MMX mesalazine [2.4 g/day (once daily or 1.2 g twice daily) or 4.8 g/day (once daily)] or placebo for 8 weeks.

Results  The percentages of patients treated with MMX mesalazine, 2.4 or 4.8 g/day, in clinical and endoscopic remission at week 8 were similar and significantly (P < 0.05) greater than placebo in subgroups stratified by disease extent, disease severity and gender and among patients not previously receiving low‐dose 5‐aminosalicylic acid. Among patients transferring directly from prior low‐dose oral 5‐aminosalicylic acid, MMX mesalazine 4.8 g/day was significantly (P = 0.018) more effective than placebo in inducing clinical and endoscopic remission. Efficacy over placebo did not reach significance in patients transferring directly to MMX mesalazine 2.4 g/day.

Conclusion  MMX mesalazine is effective in active UC regardless of disease extent, disease severity, gender and previous, low‐dose, 5‐ASA therapy.
Watermelon stomach in systemic sclerosis: its incidence and management
Authors: MARIE I. , DUCROTTE P. , ANTONIETTI M. , HERVE S. , LEVESQUE H.
Published: October 2008

Background  To date, there are no large endoscopic studies in systemic sclerosis (SSc), and both prevalence and characteristics of watermelon stomach in SSc have not been determined.

Aims  To determine the prevalence, clinical presentation, endoscopic appearance, therapy success and long‐term outcome in SSc patients with watermelon stomach and make predictions about which SSc patients are at risk for watermelon stomach.

Patients and methods  From 1990 to 2008, 264 patients were seen for evaluation of SSc. Data were collected as regards patients’ characteristics, time of watermelon stomach onset, features, therapy and outcome of watermelon stomach.

Results  Fifteen SSc patients (5.7%) exhibited watermelon stomach. SSc onset preceded watermelon stomach manifestations in 13 patients (86.7%). Most patients (86.7%) presented with iron‐deficiency anaemia, two other patients experienced gastrointestinal haemorrhage. Gastroscopy disclosed typical ‘watermelon stomach’ characterized by prominent, erythematous stripes, radiating in a spoke‐like fashion from the antrum to the pylorus. All patients received conservative therapy; because of deterioration of watermelon stomach, eight patients (53.3%) underwent endoscopic procedures. During follow‐up, five patients (33.3%) exhibited recurrences of watermelon stomach.

Conclusions  Our series indicates that watermelon stomach should be considered when unexplained iron‐deficiency anaemia occurs in SSc patients. Moreover, because watermelon stomach may be the first manifestation of SSc, patients with unexplained watermelon stomach should systematically undergo physical examination and autoantibody testing to detect the underlying SSc.
Benefit of concomitant gastrointestinal and gynaecological evaluation in premenopausal women with iron deficiency anaemia
Authors: VANNELLA L. , ALOE SPIRITI M. A. , COZZA G. , TARDELLA L. , MONARCA B. , CUTERI A. , MOSCARINI M. , DELLE FAVE G. , ANNIBALE B.
Published: October 2008

Background  Iron‐deficiency anaemia (IDA) is common in premenopausal women and menorrhagia is often considered responsible.

Aim  To evaluate prospectively the occurrence of bleeding and iron malabsorption related gastrointestinal (GI) diseases likely responsible of IDA in premenopausal women regardless of their menstrual flow.

Methods  One hundred and eighty‐seven premenopausal women [median age 39 (20–56) years] irrespective of their menstrual flow underwent gastroscopy with gastric and duodenal biopsies and faecal occult blood test (FOBT). Patients over 50 years, positive 1st degree family history for colonic cancer and/or positive FOBT underwent colonoscopy too.

Results  Menorrhagia was present in 67.4% of premenopausal women. A possible GI cause of IDA was found in 129/187 patients; in 65.2% the cause of IDA was possibly related to iron malabsorption diseases. GI bleeding as a cause of IDA was found in seven patients. An exclusive GI cause of IDA was found in 26.7% of premenopausal women, whereas a possible GI cause was observed in 34.2% of menorrhagic premenopausal women. The main risk factor for the presence of likely GI causes was the presence of upper GI symptoms (OR 5.2: 95% CI = 1.6–16.4).

Conclusions  Most premenopausal women had a possible upper GI cause of IDA because of diseases related to iron malabsorption. Menorrhagia and a GI cause coexist in one‐third of women with iron‐deficiency anaemia.
Optimized stepwise combination algorithms of non‐invasive liver fibrosis scores including Hepascore in hepatitis C virus patients
Authors: BOURLIERE M. , PENARANDA G. , OUZAN D. , RENOU C. , BOTTA‐FRIDLUND D. , TRAN A. , ROSENTHAL E. , WARTELLE‐BLADOU C. , DELASALLE P. , OULES V. , PORTAL I. , CASTELLANI P. , LECOMTE L. , ROSENTHAL‐ALLIERI M. A. , HALFON P.
Published: October 2008

Background  Non‐invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)‐infected patients.

Aim  To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy.

Methods  The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years.

Results  Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%).

Conclusions  Hepascore is an accurate non‐invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.
Review article: the abdominal compartment syndrome
Authors: LERNER S. M.
Published: October 2008

Background  The term abdominal compartment syndrome refers to hypoperfusion and ischaemia of intra‐abdominal viscera and structures caused by raised intra‐abdominal pressure. It occurs most commonly following major trauma and complex surgical procedures, but can also occur in their absence. Definitive treatment is decompression at laparotomy. Prevention and recognition of abdominal compartment syndrome are crucial to avoid additional morbidity and mortality. Postinjury abdominal compartment syndrome continues to complicate current resuscitation methods and new strategies for resuscitating critically ill patients need to be explored in addition to more accurate monitoring of intra‐abdominal pressure.

Aim  To examine the published literature regarding the pathogenesis, diagnosis and management of the abdominal compartment syndrome.

Methods  A comprehensive review of the literature was undertaken.

Results  This syndrome is an important complication of major trauma and surgery as well as being recognized in critically‐ill medical patients. It requires prompt recognition with a view to decompression at laparotomy.

Conclusions  The abdominal compartment syndrome is an important complication of trauma, surgery and resuscitation. Key to its management are its prompt recognition and abdominal decompression.
Review article: probiotics and prebiotics in irritable bowel syndrome
Authors: SPILLER R.
Published: October 2008

Background  The human gut harbours a complex community of bacteria whose relationship with their host is normally mutually beneficial. Recent studies suggest a disturbance of this relationship in irritable bowel syndrome (IBS) and the potential to correct this using prebiotics and probiotics.

Aim  To review the mechanisms of action of probiotics and prebiotics in IBS and to assess their performance in clinical trials.

Methods  Articles relating to modes of action and randomized control trials of treatment were reviewed by searching PubMed using terms ‘probiotic’, ‘prebiotic’ and ‘irritable bowel’. Small uncontrolled studies in IBS were excluded.

Results  Probiotics can enhance gut barrier function, inhibit pathogen binding and modulate gut inflammatory response. They can also reduce visceral hypersensitivity associated with both inflammation and psychological stress. Probiotics can alter colonic fermentation and stabilize the colonic microbiota. Several large randomized, placebo‐controlled trials of adequate design have shown an improvement in flatulence and abdominal distension with a reduction in composite IBS symptoms scores.

Conclusions  Each probiotic has unique features and IBS patients are heterogeneous. Future efforts should be directed to identifying biomarkers of responsiveness to facilitate better targeting of treatment and hence improved efficacy.
Review article: diagnosis and treatment of non‐alcoholic fatty liver disease
Authors: OH M. K. , WINN J. , POORDAD F.
Published: October 2008

Background Non‐alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.

Aim To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas.

Methods An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated.

Results The diagnosis of hepatic steatosis and steatohepatitis or non‐alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression.

Conclusions There are no proven non‐invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come.
Review article: treatment algorithms to maximize remission and minimize corticosteroid dependence in patients with inflammatory bowel disease
Authors: PANACCIONE R. , RUTGEERTS P. , SANDBORN W. J. , FEAGAN B. , SCHREIBER S. , GHOSH S.
Published: October 2008

Background  Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the intestine, which frequently require surgery for complications or failure of medical therapy.

Aim  To seek evidence and provide direction for clinicians on optimal strategies to enable steroid free remission in inflammatory bowel disease.

Methods  Scientific literature was reviewed using MEDLINE with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. The results were discussed at a roundtable meeting to reach a consensus on key issues.

Results  Several therapies have demonstrated efficacy for the treatment of active, moderate‐to‐severe CD and UC. These include agents, which induce remission [corticosteroids, infliximab and adalimumab (CD only)] or maintain remission and spare corticosteroids [azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only)]. Wide variability exists in the use of these agents.

Conclusion  Treatment strategy algorithms are developed for use of these therapies that maximize remission and minimize corticosteroid dependence in patients with moderate‐to‐severe CD and UC.
The effect of functional gastrointestinal disorders on psychological comorbidity and quality of life in patients with inflammatory bowel disease
Authors: MIKOCKA‐WALUS A. A. , TURNBULL D. A. , ANDREWS J. M. , MOULDING N. T. , HOLTMANN G. J.
Published: October 2008

Background  Symptoms of functional gastrointestinal disorders (FGIDs) are common in patients with inflammatory bowel disease (IBD). Psychological comorbidities of anxiety and depression are also highly prevalent in IBD.

Aim  To quantify the burden of FGIDs in a hospital‐based cohort of patients with IBD and to determine whether there is any inter‐relationship between the presence and number of FGIDs and patients’ quality of life or psychological status.

Methods  A cross‐sectional survey of 61 out‐patients was performed. Data on psychological status, quality of life, disease activity and functional symptoms according to Rome III criteria were collected.

Results  Overall, 49 (80%) participants met Rome III criteria for a functional bowel disorder and 52% of participants met criteria for more than one FGID. Participants with no FGID had significantly better physical quality of life than those with more than two FGIDs (P = 0.025). However, there was no relationship among the number of FGIDs, mental quality of life, anxiety or depression.

Conclusions  Functional gastrointestinal disorders are highly prevalent in out‐patients with IBD. Somewhat unexpectedly, the presence of anxiety and/or depression did not appear to correlate with either the presence or the number of FGIDs.
Meta‐analysis: allopurinol in the prevention of postendoscopic retrograde cholangiopancreatography pancreatitis
Authors: BAI Y. , GAO J. , ZHANG W. , ZOU D. , LI Z.
Published: October 2008

Background  Several clinical trials evaluating the prophylactic effect of allopurinol on postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis have been published; however, there is no consensus on whether prophylactic allopurinol can reduce the incidence of post‐ERCP pancreatitis.

Aim  To compare prophylactic allopurinol with placebo on post‐ERCP pancreatitis reduction by performing a meta‐analysis in randomized controlled trials.

Methods  Databases including MEDLINE, EMBASE and the Cochrane Library, Science Citation Index were searched to find relevant trials. Two reviewers independently identified relevant randomized controlled trials assessing the effect of prophylactic allopurinol on the incidence of post‐ERCP pancreatitis. Outcome measures were the incidence of post‐ERCP pancreatitis.

Results  Four trials involving 1730 patients were included. Analysis suggested that post‐ERCP pancreatitis rates were not significantly different (allopurinol 8.9%, placebo 9.7%, P = 0.68), RR 0.86 (95% CI: 0.42, 1.77). Subsequent subgroup analysis confirmed that allopurinol was not statistically superior to placebo in reducing post‐ERCP pancreatitis.

Conclusion  Based on current best evidence, prophylactic allopurinol may not be useful for post‐ERCP pancreatitis reduction.