bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features
Authors: Lee Yu Mi , Lee Ji Yun , Kim Mi Jin , Bae Han Ik , Park Jae Yong , Kim Sang Geol , Kim Dong Sun 
Published: September 2006

Protein gene product 9.5 (PGP9.5) is a neurospecific peptide that removes ubiquitin from ubiquitinated proteins and prevents them being targeted for degradation by proteosomes. Its expression is a potential marker of non‐small lung cancer, invasive colorectal cancer and esophageal squamous cell carcinoma. Gallbladder (GB) cancer is the most common malignant tumor of the biliary tract and is usually associated with gallstone disease, a late diagnosis, unsatisfactory treatment and a poor prognosis. To understand the role of PGP9.5 in GB cancer, we examined the methylation status of its promoter and its expression in surgical biopsy samples. Formalin‐fixed, paraffin‐embedded tumors and non‐neoplastic GB tissues (22 carcinomas, eight adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection. The methylation status of the promoter region of the PGP9.5 gene was determined by methylation‐specific polymerase chain reaction, and the expression of PGP9.5 was examined by immunohistochemistry using tissue microarrays. PGP9.5 promoter was methylated in 84.6% (22/26) of normal GB epithelium, 37.5% (3/8) of adenomas and 27.2% (6/22) of carcinomas. Most tumors with an unmethylated promoter exhibited positive staining for PGP9.5 in epithelial and neoplastic cells, but no PGP9.5 expression was observed in normal epithelia or in tumor tissues with a methylated promoter. No correlation was found between promoter hypomethylation of PGP9.5 and clinicopathological findings (i.e. age, sex, histological type or grade, N‐status, invasion depth or tumor stage) whereas PGP9.5 hypomethylation was found to be inversely correlated with the presence of a gallstone (P = 0.015). These results suggest that PGP9.5 promoter hypomethylation could be a reliable marker for GB cancer and that DNA hypomethylation might play an important role in re‐expression of the PGP9.5 gene in GB cancer. (Cancer Sci 2006; 97: 1205–1210)
Territorial behaviour in southern impala rams (Aepyceros melampus Lichtenstein)
Authors: Oliver C. M. , Skinner J. D. , Van der Merwe D. 
Published: September 2006

AbstractThe role of territoriality was investigated by studying 25 impala rams at a reserve in the Waterberg region of South Africa (23°45′S, 28°23′E). Mean territorial tenure was 67.25 days (range 23–99), with a mean territory size of 21.0 ± 11.27 ha, compared with home ranges of 34.1 ± 9.03 ha for territorial rams and 58.8 ± 33.35 ha for bachelor rams, using the fixed kernel method. Territory boundaries remained constant, whilst the area surrounding important features such as water holes, appears to be neutral in terms of territoriality. The rut, as evidenced from peaks in chasing and roaring, lasted for 2 months from 10 April to 10 June 2001, with intensified behaviour including matings observed from 16 May to 4 June 2001. Territorial rams chase and roar more than bachelors. Flehmen and display behaviours are performed by all rams, whilst fights and other reproductive behaviours are generally rare. Bachelors browse more than territorial rams. Only bachelors spar and allogroom, and orally groom themselves more than territorial rams.
Once daily MMX mesalazine for the treatment of mild‐to‐moderate ulcerative colitis: a phase II, dose‐ranging study
Authors: D'HAENS G. , HOMMES D. , ENGELS L. , BAERT F. , VAN DER WAAIJ L. , CONNOR P. , RAMAGE J. , DEWIT O. , PALMEN M. , STEPHENSON D. , JOSEPH R. 
Published: September 2006

SummaryBackground  SPD476 (MMX™ mesalazine), is a novel, once daily, high‐strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System™ (MMX) technology to delay and extend delivery of the active drug throughout the colon.Aim  To assess the safety and efficacy of MMX mesalazine in patients with mild‐to‐moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double‐blind, parallel‐group, dose‐ranging study (SPD476‐202).Methods  Thirty‐eight patients with mild‐to‐moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis‐disease activity index (UC‐DAI) ≤1, a score of 0 for rectal bleeding and stool frequency, and ≥1‐point reduction in sigmoidoscopy score from baseline was the primary end point.Results  Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC‐DAI and component scores from baseline, compared with the 1.2 g/day group.Conclusion  MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild‐to‐moderately active ulcerative colitis.
Systematic review: applications and future of gastric electrical stimulation
Authors: ZHANG J. , CHEN J. D. Z. 
Published: September 2006

SummaryBackground  Over the past 20 years, gastric electrical stimulation has received increasing attention among researchers and clinicians.Aim  To give a systematic review on the effects, mechanisms and applications of gastric electrical stimulation.Methods  Medline was used to identify the articles to be included in this review. Key words used for the search included gastric electrical stimulation, gastric pacing, electrical stimulation, stomach, gastrointestinal motility, central nervous system, gastroparesis, nausea and vomiting; obesity and weight loss. Combinational uses of these keywords were made to identify relevant articles. Most of the articles included in this review ranged from 1985 to 2006.Results  Based on the general search, the review was structured as follows: (i) peripheral and central effects and mechanisms of gastric electrical stimulation; (ii) clinical applications of gastric electrical stimulation for gastroparesis and obesity and (iii) future development of gastric electrical stimulation.Conclusions  Great progress has been made during the past decades. Gastric electrical stimulation has been shown to be effective in normalizing gastric dysrhythmia, accelerating gastric emptying and improving nausea and vomiting. Implantable device has been made available for treating gastroparesis as well as obesity. However, development of a new device and controlled clinical studies are required to further prove clinical efficacy of gastric electrical stimulation.
Cost‐effectiveness of growth factors during hepatitis C anti‐viral therapy
Authors: CHAPKO M. K. , DOMINITZ J. A. 
Published: September 2006

SummaryBackground Although the current standard of care for controlling anaemia and neutropenia during anti‐viral therapy for hepatitis C is to use dose reduction of ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte colony‐stimulating factor are now being advocated as alternatives to dose reduction.Aim To determine the cost‐effectiveness of erythropoietin and granulocyte colony‐stimulating factor as an alternative to anti‐viral dose reduction during antihepatitis C therapy.Methods Decision analysis was used to assess cost‐effectiveness by estimating the cost of using a growth factor per quality‐adjusted life‐year gained.Results Under baseline assumptions, the cost per quality‐adjusted life‐year of using growth factors ranged from $16 247 for genotype 1 with neutropenia to $145 468 for genotype 2/3 patients with anaemia. These findings are sensitive to the relationship between dose reduction and sustained virological response.Conclusions Based upon our findings and the varying strength of the evidence for a relationship between dose reduction and sustained virological response: granulocyte colony‐stimulating factor may be cost‐effective for genotype 1 patients; erythropoietin is probably not cost‐effective for genotype 2/3 patients; no conclusion can be reached regarding the cost‐effectiveness of erythropoietin for genotype 1 patients or granulocyte colony‐stimulating factor for genotype 2/3 patients. Randomized trials are needed to firmly establish the relationship between dose reduction and sustained virological response.
The +1059G/C polymorphism in the C‐reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease
Authors: THALMAIER D. , DAMBACHER J. , SEIDERER J. , KONRAD A. , SCHACHINGER V. , PFENNIG S. , OTTE J.‐M. , CRISPIN A. , GÖKE B. , OCHSENKÜHN T. , LOHSE P. , BRAND S. 
Published: September 2006

SummaryBackground  Serum C‐reactive protein (CRP) levels influence the response to anti‐tumour necrosis factor (TNF) therapies.Aim  To analyse the influence of the +1059G/C CRP polymorphism on CRP serum levels and disease susceptibility in patients with Crohn's disease (CD).Methods  Using restriction fragment length polymorphism (RFLP) analysis, genomic DNA from 241 CD patients and 199 unrelated controls was analysed for the +1059G/C substitution in the CRP gene and the common caspase‐activation recruitment domain 15 (CARD15) variants.Results  Homozygous C/C carriers were detected only among CD patients (P = 0.066). Patients with ileal involvement (L1 and L3 phenotype) were found in only 58.4% of patients with the wildtype G/G genotype but in 88.2% of the heterozygous G/C carriers (OR 5.26; 95% CI 1.19–23.92) and four of the five C/C homozygous carriers (80%; OR 4.55; 95% CI 1.64–16.67; P = 0.008 for hetero‐ and homozygous carriers vs. wildtype) which was independent of the presence of CARD15 variants. Increased CD activity was associated with increased CRP serum levels (P < 0.005). For Crohn's disease activity index (CDAI) < 150, C/C homozygosity for the +1059 G/C polymorphism was associated with significantly lower CRP serum levels (P < 0.01).Conclusions  The C allele of the CRP +1059G/C polymorphism is associated with decreased serum CRP levels and increased likelihood of disease involvement of the terminal ileum in CD patients.
A randomized trial of pegylated‐interferon‐α2a plus ribavirin with or without amantadine in the re‐treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin
Authors: CIANCIO A. , PICCIOTTO A. , GIORDANINO C. , SMEDILE A. , TABONE M. , MANCA A. , MARENCO G. , GARBAGNOLI P. , ANDREONI M. , CARITI G. , CALLERI G. , SARTORI M. , CUSUMANO S. , GRASSO A. , RIZZI R. , GALLO M. , BASSO M. , ANSELMO M. , PERCARIO G. , CICCONE G. , RIZZETTO M. , SARACCO G. 
Published: September 2006

SummaryBackground  There is yet no established treatment for chronic hepatitis C patients non‐responder to standard interferon and ribavirin.Aim  To evaluate efficacy and safety of pegylated‐interferon‐α2a plus ribavirin with or without amantadine in such patients.Methods  161 non‐responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg‐IFN‐α2a 180 μg plus ribavirin 1000–1200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg‐IFN‐α2a 180 μg plus ribavirin 1000–1200 mg/daily and amantadine 200 mg/daily for 12 months.Results  At the end of follow‐up, HCV‐RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi‐therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg‐interferon were associated with the treatment failure.Conclusions  The addition of amantadine does not improve the overall SVR rate in non‐responder patients retreated with Peg‐IFN and ribavirin; however, about 30% of non‐responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).
Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study
Authors: GRUDELL A. B. M. , CAMILLERI M. , BURTON D. D. , STEPHENS D. A. 
Published: September 2006

SummaryBackground  In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying.Aim  To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms.Methods  In a double‐blind, parallel‐group placebo‐controlled trial, 13 healthy participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3, fasting gastric volume was measured using intravenous 99mTc‐pertechnate and single photon emission computed tomography (SPECT). After the last dose of study medication, an 111In‐chloride egg meal (300 kcal) was ingested, and postprandial gastric volume and emptying were measured by SPECT. Symptom ratings using a visual analogue scale (fullness, nausea, bloating, abdominal pain, aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min postprandially. Group comparisons were performed using Mann–Whitney rank sum test.Results  There were no statistically significant differences in gastric volume or emptying in the two groups. However, there was a borderline increase in gastric volume with rabeprazole compared with placebo. Rabeprazole treatment reduced aggregate postprandial symptoms, particularly fullness, 30 min after the meal (P = 0.01).Conclusions  In healthy participants, rabeprazole, 20 mg b.d., did not significantly change gastric emptying, but reduced symptoms and had a borderline effect on gastric volume postprandially. The mechanism of reduced postprandial symptoms with a PPI requires further study.
Endoscopic sphincterotomy with or without cholecystectomy for choledocholithiasis in high‐risk surgical patients: a decision analysis
Authors: SIDDIQUI A. A. , MITROO P. , KOWALSKI T. , LOREN D. 
Published: September 2006

SummaryBackground Laparoscopic cholecystectomy (LC) is recommended for patients with choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction.Aim We designed a decision model to address whether ES alone versus ES followed by LC (ES + LC) is the optimal treatment in high‐risk patients with choledocholithiasis.Methods Our cohort were patients with obstructive jaundice who have undergone an ES with biliary clearance. Recurrent biliary complications over a 2‐year period stratified by gallbladder status (in/out) and age‐stratified surgical complication rates were obtained from the literature. Failure of therapy was defined as either recurrent symptoms or death attributed to biliary complications.Results For age 70–79 years, ES failed in 15% whereas ES + LC failed in 17% of cases. Mortality in the EC + LC group was 3.4 times that of the ES alone cohort. For age 80+ years, ES was dominant with an incremental success rate of 8%. Mortality in the ES + LC was 7.6 times that of ES. For age <70, ES + LC was the dominant strategy with an incremental success rate 5%. Sensitivity analysis in the groups confirmed our conclusions.Conclusions Management of choledocholithiasis by ES and stone clearance, but without cholecystectomy, should be considered for patients aged 70+. For low‐risk patients, ES + LC should be performed to prevent recurrent biliary complications.
Patient reporting of suspected adverse drug reactions: a review of published literature and international experience
Authors: Blenkinsopp A. , Wilkie P. , Wang M. , Routledge P. A. 
Published: September 2006

AimsTo synthesize data from published studies and international experience to identify evidence of potential benefits and drawbacks of direct patient reporting of suspected adverse drug reactions (ADRs) by patients.MethodsStructured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts.ResultsSeven studies (eight papers) were included in the review. None of the studies concerned spontaneous reporting by patients. Information on patient reporting systems was obtained for six countries, with summary data reported by four. Patient reports identified possible new ADRs that had not previously been reported by health professionals. The quality of patient reports appears to be similar to that of health professional reports. There is some evidence that patients report an ADR when they consider their health professional has not paid attention to their concerns. Patient reports may, at least initially, be more time consuming to process.ConclusionsOverall, the evidence indicates that patient reporting of suspected ADRs has more potential benefits than drawbacks. Evaluation of patient reporting systems is needed to provide further evidence.
Duloxetine pharmacokinetics are similar in Japanese and Caucasian subjects
Authors: Chan Clark , Yeo Kwee P. , Pan Alan X. , Lim Maggie , Knadler Mary P. , Small David S. 
Published: September 2006

What is already known about this subject• The pharmacokinetics of duloxetine have been assessed in a number of clinical studies.• Duloxetine is eliminated through oxidative metabolism via CYP1A2 and, to a lesser degree, CYP2D6.• There is strong evidence that the prevalence of CYP2D6 phenotypes and the activity of CYP1A2 enzyme activity differ between Japanese and Caucasians.• Given the characteristics of duloxetine metabolism, there is good reason to assess pharmacokinetic differences between Japanese and Caucasians.What this study adds• Duloxetine pharmacokinetics in Japanese or Caucasian subjects is not meaningfully different after single or multiple doses of duloxetine.• The magnitude of pharmacokinetic differences between groups is small relative to the pharmacokinetic variability in either group, and these small differences can be accounted for by differences in body weight.• The result of this study suggests that different dose recommendations for Caucasian or Japanese patients are not likely to be necessary.AimsTo compare single‐ and multiple‐dose duloxetine pharmacokinetics between healthy Japanese and Caucasians.MethodsTwenty‐four subjects of each race were given single oral doses of duloxetine (20, 40 and 60 mg) in a randomized, double‐blind study. Another 20 subjects of each race received 20, 40 mg or placebo (2 : 2 : 1) twice‐daily for 5 days.ResultsFollowing single doses, the mean duloxetine Cmax and AUC were approximately 20% greater in Japanese. This difference could be explained by the 15% lower average body weight in Japanese. Similar results were observed following multiple dosing.ConclusionDuloxetine pharmacokinetics are not meaningfully different between Japanese and Caucasians.
Forearm vasoconstrictor response in uncomplicated type 1 diabetes mellitus
Authors: Van Gurp P. J. , Willemsen J. J. , Lenders J. W. M. , Ross H. A. , Sweep C. G. J. , Smits P. , Tack C. J. 
Published: September 2006

AbstractBackground  According to the ‘haemodynamic hypothesis’, increased tissue perfusion predisposes to microangiopathy in diabetic patients. We hypothesized that the typical haemodynamic changes underlying the increased tissue perfusion can be explained by a decreased sympathetic nerve activity caused by chronic hyperglycaemia. In this study we investigated sympathetic activity in patients with uncomplicated type 1 diabetes mellitus (DM).Materials and methods  In 15 DM patients (DM duration 6·3 ± 3·8 year; HbA1c 7·9 ± 1·3%) and 16 age‐ and sex‐matched healthy volunteers (Control), sympathetic nervous system activity was measured at rest (baseline) and during sympathoneural stimulation (lower body negative pressure (LBNP)) by means of interstitial and plasma noradrenaline (NA) sampling and power spectral analysis. Muscle sympathetic nerve activity (MSNA) was measured before (baseline) and during a cold pressure test. Forearm blood flow was measured during forearm vascular α‐ and β‐adrenergic receptor blockade.Results  At baseline, forearm vascular resistance (FVR), plasma NA concentrations, MSNA and heart rate variability were similar in both groups. LBNP‐induced vasoconstriction was significantly attenuated in the DM group compared with the Control group (ΔFVR: 12 ± 4 vs. 19 ± 3 arbitrary units, P < 0·05). The responses of plasma NA and heart rate variability did not differ.Conclusions   Baseline FVR and sympathetic nerve activity are normal in patients with uncomplicated type 1 diabetes. However, the forearm vasoconstrictor response to sympathetic stimulation is attenuated, which cannot be attributed to an impaired sympathetic responsiveness.
Ciprofloxacin inhibits cytokine‐induced nitric oxide production in human colonic epithelium
Authors: Kolios G. , Manousou P. , Bourikas L. , Notas G. , Tsagarakis N. , Mouzas I. , Kouroumalis E. 
Published: September 2006

AbstractBackground The fluoroquinolone ciprofloxacin is a broad‐spectrum antibiotic that has been used in the treatment of inflammatory bowel diseases. There is evidence that quinolones have immunomodulating activities via the regulation of cytokine production.Materials and methods We investigated the effect of ciprofloxacin on the nitric oxide (NO) production by colonic epithelium. HT‐29 cells and colonic biopsies from patients (n = 4) with ulcerative colitis (UC) and normal controls (n = 4) were cultured with various concentrations of ciprofloxacin (10–100 µg mL−1) in the presence and absence of pro‐inflammatory cytokines. The production of NO was measured in culture supernatants with a spectrophotometric method and inducible nitric oxide synthase (iNOS) mRNA expression was examined by reverse transcription‐polymerase chain reaction (RT‐PCR).Results Ciprofloxacin did not have any effect on the basal NO production by HT‐29 cells. In contrast, ciprofloxacin significantly (P < 0·001) inhibited the pro‐inflammatory cytokines (interleukin‐1α + tumour necrosis factor‐α + interferon‐γ)‐induced NO production in HT‐29, in a concentration‐dependent manner, via the inhibition of the cytokine‐induced iNOS mRNA expression. Wortmannin produced a concentration related reversal of the inhibitory effect of ciprofloxacin at both iNOS mRNA expression and NO production in HT‐29 cells. A similar inhibitory effect of ciprofloxacin on the cytokine‐induced NO production and iNOS mRNA expression was detectedin vitroin cultures of normal colonic tissue. In addition, ciprofloxacin significantly inhibited the NO production and iNOS mRNA expression in cultures of colonic tissue from ulcerative colitis patients, in a concentration‐dependent manner.Conclusions These data suggest that ciprofloxacin, in addition to its antimicrobial role, might have an immunoregulatory effect on intestinal inflammation, via the modulation of inflammatory mediators.