bluuebunny/crossref_metadata_2025 huggingface dataset:
Juvenile bimodal length distribution and sea‐run migration of the lower modal group in the Pacific Ocean form of three‐spined stickleback
Authors: Kitamura T. , Kume M. , Takahashi H. , Goto A.
Published: September 2006

Juvenile three‐spined sticklebackGasterosteus aculeatusin their nursery pond had a bimodal length distribution after October in their first year of life. A sea‐run migration of all individuals belonging to the lower modal group was observed, with a peak in early November. These data suggest that partial migration based on the early status of individual juveniles occurs in the Pacific Ocean form of three‐spined stickleback.
Reconstructing habitat use of Coilia mystus and Coilia ectenes of the Yangtze River estuary, and of Coilia ectenes of Taihu Lake, based on otolith strontium and calcium
Authors: Yang J. , Arai T. , Liu H. , Miyazaki N. , Tsukamoto K.
Published: September 2006

The habitat use and migratory patterns of Osbeck’s grenadier anchovy Coilia mystus in the Yangtze estuary and the estuarine tapertail anchovy Coilia ectenes from the Yangtze estuary and Taihu Lake, China, were studied by examining the environmental signatures of strontium and calcium in their otoliths using electron probe microanalysis. The results indicated that Taihu C. ectenes utilizes only freshwater habitats, whereas the habitat use patterns of Yangtze C. ectenes and C. mystus were much more flexible, apparently varying among fresh, brackish and marine areas. The present study suggests that the spawning populations of Yangtze C. ectenes and C. mystus in the Yangtze estuary consist of individuals with different migration histories, and individuals of these two Yangtze Coilia species seem to use a variety of different habitats during the non‐spawning seasons.
Determinants of habitat use in large roach
Authors: Schulze T. , Dörner H. , Hölker F. , Mehner T.
Published: September 2006

In this study gillnet catches of large roach Rutilus rutilus and their potential predators, large perch Perca fluviatilis, pikeperch Sander lucioperca and pike Esox lucius, in combination with data on food resources and abiotic variables were used to reveal the variables influencing the habitat use of large roach in Lake Großer Vätersee. The occurrence of large roach was negatively coupled with the occurrence of potential predators. Although almost all roach studied were larger than those actually fed on by the predators, high roach catches never coincided with high predator catches. Since the overall habitat‐specific distribution of roach and its predators was nevertheless highly similar, this indicated that large roach obviously avoided the immediate vicinity of the predators without being forced to a full habitat shift. The behavioural response to predators of roach in Lake Großer Vätersee was clearly length dependent, since the patterns of diel habitat use differed between large and small roach. For lake‐wide estimates of trophic interactions, size groups of prey should be separated, since size‐dependent trait changes may impact habitat‐specific resources in a contrasting way.
Previously spawned Atlantic salmon ascend a large subarctic river earlier than their maiden counterparts
Authors: Niemelä E. , Orell P. , Erkinaro J. , Dempson J. B. , BrØrs S. , Svenning M. A. , Hassinen E.
Published: September 2006

Spawning migration timing of maiden Atlantic salmon Salmo salar and previous spawners was analysed in the catches in 1989–2004 in the large subarctic River Teno in the northernmost parts of Finland and Norway. The hypothesis was that the migration timing of previous spawners and their maiden counterparts is similar, with the migration timing similar between sexes. In most cases, however, previous spawners were observed to migrate into the River Teno and its tributaries earlier than their maiden counterparts. The difference in run timing was especially evident between maiden one‐sea‐winter (1SW) Atlantic salmon and the corresponding group of previous spawners [1S1, 1 year at sea (1) followed by first spawning (S) and reconditioning period of 1 year (1) at sea and second spawning run] for both sexes in the River Teno and in its two tributaries. The same was also evident between 2SW maiden and 2S1 previous spawning female Atlantic salmon in the River Teno. Females showed earlier spawning migration than males both in previous spawners and maiden Atlantic salmon. Different maiden sea‐age classes also showed differences in run timing as multi‐sea‐winter fish (2–4SW) ascended earlier than 1SW fish but the timing of 1S1 and 2S1 previous spawning females coincided. The results suggest that run timing of Atlantic salmon may not be strictly genetically fixed as previous spawners ascend earlier than they did on their first spawning migration as maiden fish, and indicated that the closeness of the reconditioning area of postspawners to the river of origin resulted in an early ascent. Run timing of different sea‐age groups has major management implications if the populations are heavily exploited with numerous fishing methods in different periods of the fishing season, as in the River Teno system.
Broods of attractive three‐spined stickleback males require greater paternal care
Authors: Bakker T. C. M. , Mazzi D. , Kraak S. B. M.
Published: September 2006

The relationship between egg number and survival in nests of three‐spined sticklebacksGasterosteus aculeatuswas tested in the field. Nests were deprived of paternal care during a variable period by removal of the father while preventing egg predation by protection of the nest by a net. Upon male removal, a number of male traits were quantified. Nest‐content variables and embryo survival were assessed at the end of the deprivation period. Proportional egg mortality was significantly positively correlated with the length of the deprivation period, the number of eggs present in the nest and egg size, thus suggesting that nests with more and larger eggs need more paternal care. Males with the most symmetrical ventral spines achieved the highest reproductive success as measured by the number of eggs in the nest. In addition, their nests contained relatively larger eggs. Spine length symmetry correlated with the blue intensity of the eye thus giving females several cues to assess male quality.
Ontogenetic development of electric‐organ discharges in a mormyrid fish, the bulldog Marcusenius macrolepidotus (South African form)
Authors: Werneyer M. , Kramer B.
Published: September 2006

The emergence and development of the electric‐organ discharge (EOD) in larvae and juvenile bulldog Marcusenius macrolepidotus was investigated. Larvae hatched 4–5 days after spawning, and the first EODs were recorded on days 9 and 10 at a standard length (LS) of c. 6·5 mm. The larval EOD waveform was virtually monopolar, with a strong head‐positive phase followed by a weak head‐negative phase of long duration. A small separate potential preceded the EOD by c. 1·6 ms (believed to represent postsynaptic potential from electrocyte stalks). In contrast to previous reports on Pollimyrus adspersus with its distinct larval and adult EODs, in M. macrolepidotus there was a gradual transformation of the larval into the adult EOD waveform. The transformation started at an LS of c. 17 mm (at an age of c. 40 days), first indications being a decrease in duration of the head‐negative phase, and an increase of its peak amplitude relative to that of the head‐positive phase. Still later, the weak postpotential of the adult EOD emerged on the rising edge of the head‐negative phase. The transformation was nearly completed at an LS of c. 30 mm (at an age of c. 60 days). Evolutionary and behavioural consequences of this alternative path of EOD ontogeny are discussed.
Lipid and fatty acid composition of eggs producing larvae with high survival rate in the Japanese eel
Authors: Furuita H. , Unuma T. , Nomura K. , Tanaka H. , Okuzawa K. , Sugita T. , Yamamoto T.
Published: September 2006

Eggs of Japanese eel Anguilla japonica were obtained by artificial induction of maturation. Fertilization and hatching rates, and survival rates of normal larvae were examined. The levels of total lipids and polar lipids (PL) of high quality (HQ; >80% survival rate at 8 days post‐hatch) eggs were significantly lower than low quality (LQ; hatching and survival rates were zero) eggs. The docosahexaenoic acid (DHA) level in PL of HQ eggs, however, was significantly higher than in LQ eggs. In contrast to DHA, arachidonic acid level was negatively correlated with egg quality variables and it was lower in HQ than in LQ eggs. Most of the egg lipid and fatty acid components showed larger variation in LQ than in HQ eggs.
The effect of temperature on mortality in small perch marked with coded wire tags
Authors: Dörner H. , Schulze T. , Mehner T. , Hölker F.
Published: September 2006

Mortality of small (60–100 mm total length) perch Perca fluviatilis after marking with coded wire tags in relation to water temperature (6·9, 14·2, 17·8 and 22·6° C) was experimentally tested and exclusively occurred within the first day of the experiments. Moreover, mortality rates were generally low with a maximum of 4%. No increased mortality at higher water temperatures was observed.
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)
High expression of insulin‐like growth factor binding protein‐3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma
Authors: Aishima Shinichi , Basaki Yuji , Oda Yoshinao , Kuroda Yousuke , Nishihara Yunosuke , Taguchi Kenichi , Taketomi Akinobu , Maehara Yoshihiko , Hosoi Fumihito , Maruyama Yuichiro , Fotovati Abbas , Oie Shinji , Ono Mayumi , Ueno Takato , Sata Michio , Yano Hirohisa , Kojiro Masamichi , Kuwano Michihiko , Tsuneyoshi Masazumi
Published: September 2006

Insulin‐like growth factor binding protein‐3 (IGFBP‐3) modulates cell proliferation of various cancer cell types. However, it remains unclear how IGF–IGFBP‐3‐signaling is involved in growth and progression of hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP‐3 in HCC. Type 1 receptor for IGF (IGF‐1R) was expressed at various levels in the seven lines examined, but IGF‐2R was not expressed. Of the seven lines, the growth of HAK‐1B, KIM‐1, KYN‐2 and HepG2 cells was stimulated in a dose‐dependent manner by the exogenous addition of IGF‐I or IGF‐II, but the HAK‐1A, KYN‐1 and KYN‐3 cell lines showed no growth. Exogenous addition of IGFBP‐3 markedly blocked IGF‐I and IGF‐II‐stimulated cell growth of KYN‐2 and HepG2 cells, and moderately stimulated that of KIM‐1 and HAK‐1B cells, but no growth of the KYN‐1, KYN‐3 and HAK‐1A cell lines was observed. IGF‐I enhanced the phosphorylation of IGF‐1R, Akt and Erk1/2 in KYN‐2 cells, and coadministration of IGFBP‐3 blocked all types of activation by IGF‐I investigated here. In contrast, no such activation by IGF‐I was detected in KYN‐3 cells. IGFBP‐3 also suppressed IGF‐I‐induced cell invasion by KYN‐2 cells. Moreover, we were able to observe the apparent expression of IGFBP‐3 in KYN‐3 cells, but not in the other six cell lines. Furthermore reduced expression of IGFBP‐3, but not that of IGF‐1R, was significantly correlated with tumor size, histological differentiation, capsular invasion and portal venous invasion. Low expression of IGFBP‐3 was independently associated with poor survival. IGFBP‐3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC. (Cancer Sci 2006; 97: 1182–1190)
Territorial behaviour in southern impala rams (Aepyceros melampus Lichtenstein)
Authors: Oliver C. M. , Skinner J. D. , Van der Merwe D.
Published: September 2006

The 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

Background  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

Background  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

Background 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

Background  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

Background  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

Background  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

Background 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

Aims

To 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.

Methods

Structured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts.

Results

Seven 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.

Conclusions

Overall, 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.

Aims

To compare single‐ and multiple‐dose duloxetine pharmacokinetics between healthy Japanese and Caucasians.

Methods

Twenty‐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.

Results

Following 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.

Conclusion

Duloxetine 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

Background  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

Background 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.
HFE mutations and risk of coronary heart disease in middle‐aged women
Authors: Van Der A D. L. , Peeters P. H. M. , Grobbee D. E. , Roest M. , Marx J. J. M. , Voorbij H. M. , Van Der Schouw Y. T.
Published: September 2006

Background  Although heterozygosity for the C282Y mutation in the HFE gene has been associated with an increased risk of cardiovascular events, epidemiological studies remain inconclusive. The aim of the present study was to obtain further evidence as to whether HFE mutations are associated with risk of coronary heart disease (CHD) in middle‐aged women. We used data of a cohort of 15 236 Dutch middle‐aged women to investigate whether C282Y carriers and H63D carriers are at increased risk of coronary heart disease compared with non‐carriers.

Materials and methods  Women were included in the study between 1993 and 1997 and were followed until 1 January 2000 for cardiovascular events. HFE genotyping was performed on all 211 coronary heart disease cases and a randomly selected sample from the baseline cohort (n = 1526). A weighted Cox proportional hazards model was used to estimate crude, age‐adjusted and multivariate adjusted hazard ratios for C282Y and H63D carriership in relation to coronary heart disease.

Results  Compared with non‐carriers, those that carried the C282Y allele were not at increased risk for CHD (HR = 1·25, 95% CI = 0·74–2·09). Neither did we find an association between the H63D mutation and CHD risk (HR = 0·73, 95% CI = 0·43–1·24).

Conclusions  Our results are in accordance with similar studies to date, for which we present a meta‐analysis. HFE mutations appear not to affect the risk of coronary heart disease.
Inflammatory and endothelial markers in women with polycystic ovary syndrome
Authors: Diamanti‐Kandarakis E. , Alexandraki K. , Piperi C. , Protogerou A. , Katsikis I. , Paterakis T. , Lekakis J. , Panidis D.
Published: September 2006

Background  Women with polycystic ovary syndrome (PCOS) carry a pattern of cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are early findings in the atherosclerotic process. The purpose of the study was to investigate the coexistence of active inflammation markers and endothelial dysfunction in young women with PCOS, and their relationship with metabolic and hormonal abnormalities of the syndrome.

Materials and methods  Twenty‐five young women with PCOS and 25 controls of similar age and body mass index (BMI) were studied. Endothelial function was assessed by flow‐mediated dilatation (FMD) on the brachial artery and smooth muscle cells injury was excluded by nitrate‐induced dilatation (NID). Plasma levels of endothelin‐1 (ET‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and high sensitivity C‐reactive protein (hsCRP) were measured. Hormonal and metabolic profiles were determined in both groups.

Results  Flow‐mediated dilatation (FMD) was statistically lower in PCOS (P < 0·001), whereas nitrate‐induced dilatation (NID) was similar within the two groups. Polycystic ovary syndrome (PCOS) had statistically higher levels of ET‐1 (P = 0·03), sICAM‐1 (P = 0·01), sVCAM‐1 (P = 0·02) and hsCRP (P = 0·01). Furthermore FMD was statistically higher in PCOS population with hsCRP  1 mg L−1 when compared with PCOS population with hsCRP > 1 mg L−1 (P = 0·02). Flow‐mediated dilatation (FMD) was negatively related to hsCRP (r = −0·512, P = 0·015); ET‐1 was positively related to free androgen index (r = 0·27, P = 0·05) and negatively to sex hormone‐binding globulin (r = −0·465, P = 0·022); sVCAM‐1 was positively related to total testosterone (r = 0·431, P = 0·036); hsCRP was positively related to BMI (r = 0·647, P = 0·001), and negatively related to FMD (r = −0·512, P = 0·015), quantitative insulin sensitivity check index (QUICKI) (r = −0·499, P = 0·018), and MATSUDA index (r = −0·445, P = 0·038).

Conclusions  The present study demonstrates that endothelial dysfunction coexists and is influenced by the presence of increased serum levels of inflammation and endothelial activation markers in young women with PCOS. These parameters appear to be interrelated with hyperandrogenaemia in this insulin‐resistant population.
Effect of lactose on oro‐cecal transit in lactose digesters and maldigesters
Authors: He T. , Priebe M. G. , Welling G. W. , Vonk R. J.
Published: September 2006

Background  The transit time of the small intestine, in addition to lactase activity, may influence lactose digestion and thus play a role in the occurrence of lactose intolerance. The objectives of this study were to investigate the effect of lactose on the oro‐cecal transit time (OCTT) in lactose digesters and maldigesters as well as the possible mechanisms underlying these effects.

Materials and methods  Twenty‐eight Chinese subjects and 16 Dutch subjects underwent one glucose and one lactose challenge in two single‐blinded tests. Twenty of the Chinese subjects without complaints after the challenge then underwent another lactose challenge. A 6‐h symptom score (SSC) was recorded, breath‐hydrogen concentration was measured and OCTT after consumption of glucose and lactose was determined with the lactose‐[13C] ureide breath test. The lactose digestion index (LDI) was determined in both the Dutch and 20 Chinese subjects with the 13C/2H‐glucose test.

Results  Lactose digesters (n = 13) and maldigesters (n = 20) were classified based on the results of the LDI and the breath‐hydrogen test. The OCTT after the lactose and glucose challenges did not differ in the digesters, whereas in the maldigesters the OCTT, after the lactose challenge, was shorter than that after glucose. There was no difference in OCTT after the glucose challenge between the maldigesters and the digesters. However, the OCTT after the lactose challenge in the maldigesters was shorter than that in the digesters. The LDI of the digesters was significantly higher than that of the maldigesters. The OCTT after the lactose challenge was not correlated to the LDI in the maldigesters nor in the digesters. Based on the SSC after the one glucose and two lactose challenges, a tolerant (n = 7) and an intolerant (n = 5) group were classified in the Chinese subjects. The two groups did not differ in their LDI or OCTT after the lactose challenge. The OCTT after the lactose challenge was not correlated to the SSC or the LDI.

Conclusions  Lactose triggers a faster oro‐cecal transit in lactose maldigesters, but not in digesters. However, this could not be explained by intestinal distension resulting from the osmotic load posed by maldigested lactose, and thus suggests a direct effect of lactose on intrinsic factors regulating intestinal motility.
Homocysteine, traditional risk factors and impaired renal function in coronary artery disease
Authors: Pizzolo F. , Friso S. , Olivieri O. , Martinelli N. , Bozzini C. , Guarini P. , Trabetti E. , Faccini G. , Corrocher R. , Girelli D.
Published: September 2006

Background  To establish whether the frequent finding of a moderate–intermediate increase in plasma total homocysteine (tHcy) causes coronary artery disease (CAD), the authors evaluated the number of coexisting major traditional risk factors, as well as the major tHcy determinants, in patients with the same degree of CAD but different tHcy levels.

Materials and methods  The authors studied 180 patients with CAD, who were divided into three groups according to tHcy levels: 60 patients with normal tHcy, 60 patients with moderate (15–30 µmol L−1) and 60 patients with intermediate hyperhomocysteinaemia (30–100 µmol L−1). The patient groups were matched for gender, age and number of affected coronary vessels. All patients were checked for the presence of traditional risk factors for CAD (i.e. hypertension, diabetes, hyperlipidaemia, smoking habit, familial history, obesity), as well as determinants of tHcy levels. The population was subdivided into those having, or not, a substantial burden of traditional risk factors (i.e. < 4 and ≥ 4, respectively).

Results  There was a significant trend towards a reduced number of subjects within the group with ≥ 4 risk factors across increasing tHcy levels (51·7%, 37·8%, 26%, for normal, moderate, intermediate tHcy, respectively, χ2 for linear‐trend = 0·006). Folate and vitamin B12 concentrations, estimated glomerular filtration rate (GFR), MTHFR 677C > T polymorphism were the major determinants of tHcy in this population.

Conclusions  In patients with the same degree of CAD, those with hyperhomocysteinaemia had a reduced burden of traditional risk factors as compared with those with normal tHcy levels. Hyperhomocysteinaemia was significantly associated with an emerging non‐traditional risk factor such as lower GFR.
Combined LDI/SAT test to evaluate intestinal lactose digestion and mucosa permeability
Authors: Koetse H. A. , Klaassen D. , Van Der Molen A. R. H. , Elzinga H. , Bijsterveld K. , Boverhof R. , Stellaard F.
Published: September 2006

Background  Intestinal mucosal damage causes impaired digestive capacity and increased mucosal permeability. Quantification of damage can be used to improve treatment options. Currently, the Lactose Digestion Index (LDI) and the Sugar Absorption Test (SAT) are used for evaluation. The investigation studied whether both tests could be combined to provide a useful multifunctional test and whether measurements in blood (LDI) could be replaced by measurements in urine.

Materials and methods  The LDI (25 g 13C‐lactose, 0·5 g 2H‐glucose), the SAT (5 g lactulose, 1 g L‐rhamnose) and the LDI/SAT combination test were performed in seven lactose‐digesting and eight lactose‐maldigesting adults. Plasma glucose 13C‐enrichment was determined by gas‐chromatography/combustion/isotope ratio mass‐spectrometry (GC/C/IRMS), 2H enrichment determined by gas‐chromatography/mass‐spectrometry (GC/MS) and urinary sugars by gas‐chromatography (GC).

Results  The results of the separate LDI test were not different from those of the LDI/SAT in the lactose‐digester group (0·82 ± 0·06 vs. 0·81 ± 0·09), nor in the lactose‐maldigester group (0·36 ± 0·12 vs. 0·35 ± 0·06). A significant correlation was found between the 10‐h urinary‐lactose/lactulose ratio and the LDI (R2 = 0·71, P < 0·01). There were no differences in the lactulose/L‐rhamnose ratio between lactose‐digesters and lactose‐maldigesters using both the SAT and LDI/SAT tests.

Conclusion  The LDI/SAT test is a reliable method of measuring digestion and permeability simultaneously. The 10‐h period urinary lactose/lactulose excretion ratio following lactose consumption reflects lactose digestive capacity.
Myostatin expression in ventricular myocardium in a rat model of volume‐overload heart failure
Authors: Shyu K. G. , Lu M. J. , Wang B. W. , Sun H. Y. , Chang H.
Published: September 2006

Background  Mechanical stress increases myocardial myostatin expression. However, the expression of myostatin in chronic heart failure resulting from volume‐overload and after treatment with β‐blockers is little known. The authors hypothesize that myostatin plays a role in the failing myocardium because of volume‐overload.

Materials and methods  Aorto‐caval shunt was created over a 4‐week period in adult Sprague‐Dawley rats to induce volume‐overload heart failure.

Results  Heart weight and body weight ratio significantly increased after shunting. The left ventricular end‐diastolic dimension also significantly increased. Treatment with carvedilol in the shunt group reversed the increase in heart weight and ventricular dimension to the baseline values. Myocardial and skeletal myostatin proteins were up‐regulated in the shunt group. The mRNA of myocardial myostatin also increased in the shunt group. Treatment with carvedilol reversed both protein and mRNA of myocardial myostatin to the baseline values. Treatment with N‐acetylcysteine and doxazosin partially decreased myostatin mRNA and protein expression as compared with the shunt group. Carvedilol normalized the increased immunohistochemical labelling of myocardial myostatin in the shunt group.

Conclusion  Myocardial myostatin mRNA and protein expression were up‐regulated in the rat model of volume‐overload heart failure. Treatment with carvedilol is associated with a limitation of increased myostatin expression in the failing ventricular myocardium.