bluuebunny/crossref_metadata_2025 huggingface dataset:
Are indirect genetic benefits associated with polyandry? Testing predictions in a natural population of lemon sharks
Authors: DiBATTISTA JOSEPH D. , FELDHEIM KEVIN A. , GRUBER SAMUEL H. , HENDRY ANDREW P.
Published: June 2010

Multiple mating has clear fitness benefits for males, but uncertain benefits and costs for females. We tested for indirect genetic benefits of polyandry in a natural population, by using data from a long‐term genetic and demographic study of lemon sharks (Negaprion brevirostris) at Bimini, Bahamas. To do so, we followed the fates of individuals from six cohorts (450 age‐0 and 254 age‐1 fish) in relation to their individual level of genetic variation, and whether they were from polyandrous or monoandrous litters. We find that offspring from polyandrous litters did not have a greater genetic diversity or greater survival than did the offspring of monoandrous litters. We also find no evidence of positive associations between individual offspring genetic diversity metrics and our surrogate measure of fitness (i.e. survival). In fact, age‐1 individuals with fewer heterozygous microsatellite loci and more genetically similar parents were more likely to survive to age‐2. Thus, polyandry in female lemon sharks does not appear to be adaptive from the perspective of indirect genetic benefits to offspring. It may instead be the result of convenience polyandry, whereby females mate multiply to avoid harassment by males. Our inability to find indirect genetic benefits of polyandry despite detailed pedigree and survival information suggests the need for similar assessments in other natural populations.
Microbiological risk of anaesthetic breathing circuits after extended use
Authors: HARTMANN D. , JUNG M. , NEUBERT T. R. , SUSIN C. , NONNENMACHER C. , MUTTERS R.
Published: June 2010

Introduction: Daily change of breathing circuits in the operating theatre requires a lot of resources and is time and labour consuming. The extended use of breathing circuits could reduce the workload of the staff and health care costs. The aim of the present study was to evaluate the contamination rate of anaesthesia breathing circuits changed after 24, 48 or 72 h of use.

Materials: The study was performed as an experimental observational study. Microbiological samples were taken from 112 breathing systems including both parts of the ventilator circuit (inspiration and expiration) and analysed using microbiological standard techniques. Breathing circuits were changed according to three different schedules. In the 24‐h group, breathing circuits were changed every day, whereas in the 48‐h group changing of the circuits took place on Mondays, Wednesdays and Fridays. A period of 72 h operating use was tested on weekends.

Results: A total of 112 breathing systems comprised of 224 samples from the ventilator circuit were tested for bacteria and yeast contamination. A non‐significant increase in the contamination rate was observed with the extended use for breathing circuits (24 h: 3.33%, 48 h: 4.35% and 72 h: 5.56%; P for trend=0.66). Similarly, no significant increase in contamination rate could be observed at the sample level (24 h: 1.67%, 48 h: 3.26% and 72 h: 2.78%; P for trend=0.71).

Conclusion: The extended use of breathing circuits for 48 and 72 h does not increase significantly the risk of contamination, provided that HME filters are changed separately for every patient.
Dispersion of the neurons expressing layer specific markers in the reeler brain
Authors: Dekimoto Hideyuki , Terashima Toshio , Katsuyama Yu
Published: June 2010

Neurons with similar functions including neuronal connectivity and gene expression form discrete condensed structures within the vertebrate brain. This is exemplified within the circuitry formed by the cortical layers and the neuronal nuclei. It is well known that the Reelin protein is required for development of these neuronal structures in rodents and human, but the function of Reelin remains controversial. In this report, we used “layer‐specific markers” of the cerebral cortex to carry out detailed observations of spatial distribution of the neuronal subpopulations in the brain of the Reelin deficient mouse, reeler. We observed a spatially dispersed expression of the markers in the reeler cerebral cortex. These markers are expressed also in other laminated and non‐laminated structures of brain, in which we observed similar abnormal gene expression. Our observations suggest that neurons within the brain structures (such as the layers and the nuclei), which normally exhibit condensed distribution of marker expressions, loosen their segregation or scatter by a lack of Reelin.
Objectively measured physical activity and obesity prevention in children, adolescents and adults: a systematic review of prospective studies
Authors: Wilks D. C. , Besson H. , Lindroos A. K. , Ekelund U.
Published: June 2010

This study aimed at synthesizing the prospective associations between measured physical activity (PA) and change in adiposity in children, adolescents and adults following from two previous reviews. Search terms were adapted and a systematic literature search was conducted (January 2000–September 2008) and later updated (up to October 2009), considering observational and intervention studies of weight gain that measured both PA and body composition. Sixteen observational studies (six comprising adults) and five trials (one comprising adults) were eligible. For consistency, whenever possible either baseline PA energy expenditure or accelerometer output (counts min−1) and change in per cent body fat were the extracted exposure and outcome measures. Results of observational studies suggest that PA is not strongly prospectively related with adiposity: five studies on children and three on adults reported no association between baseline PA and change in adiposity, one study found a weak positive association and the other studies observed a weak negative association. Negative associations were more frequently observed in studies that analysed the association between change in the exposure and outcome. Intervention studies show generally no effect on either PA or adiposity. In conclusion, despite the well‐established health benefits of PA, it may not be a key determinant of excessive gain in adiposity.
Question‐answering systems as efficient sources of terminological information: an evaluation
Authors: Olvera‐Lobo María‐Dolores , Gutiérrez‐Artacho Juncal
Published: June 2010

Background:  Question‐answering systems (or QA Systems) stand as a new alternative for Information Retrieval Systems. Most users frequently need to retrieve specific information about a factual question to obtain a whole document.

Objectives:  The study evaluates the efficiency of QA systems as terminological sources for physicians, specialised translators and users in general. It assesses the performance of one open‐domain QA system, START, and one restricted‐domain QA system, MedQA.

Method:  The study collected two hundred definitional questions (What is…?), either general or specialised, from the health website WebMD. Sources used by the open‐domain QA system, START, and the restricted‐domain QA system, MedQA, were studied to retrieve answers, and later a range of evaluation measures (precision, Mean Reciprocal Rank, Total Reciprocal Rank, First Hit Success) were applied to mark the quality of answers.

Results:  It was established that both systems are useful in the retrieval of valid definitional healthcare information, with an acceptable degree of coherent and precise responses from both. The answers supplied by MedQA were more reliable that those of START in the sense that they came from specialised clinical or academic sources, most of them showing links to further research articles.

Conclusions:  Results obtained show the potential of this type of tool in the more general realm of information access, and the retrieval of health information. They may be considered a good, reliable and reasonably precise alternative in alleviating the information overload. Both QA systems can help professionals and users can obtain healthcare information.
Ethics in operations research and sustainable development
Authors: Brans Jean‐Pierre , Kunsch Pierre L.
Published: June 2010

During the last 100 years, major social, economic, environmental and technical problems have arisen that today jeopardise mankind's very existence. The authors argue that operations research (OR) should be more strongly involved by developing models to face today's crucial challenges. OR should change drastically because it is traditionally involved mainly with optimisation problems, which are often counterproductive in the sense of ethical behaviour: new basic approaches are required. This paper provides some avenues on how to develop instruments for addressing mankind's sustainability problems, and for complying with ethical principles. It is proposed to have a mix of techniques, mainly: systems thinking, multi‐criteria decision‐making and dynamic control. A global framework, called ASMC (Adaptive, Systemic, Multi‐criteria, Control procedure), is proposed for developing these ideas. Some sustainable development applications are presented.
Différences de satisfaction au travail entre les travailleurs à salaire élevé et à bas salaires en Europe
Authors: POULIAKAS Konstantinos , THEODOSSIOU Ioannis
Published: June 2010

Les données de six vagues d'enquětes du Panel européen des ménages (1996–2001) collectées dans onze pays indiquent que les travailleurs à bas salaire de l'Europe du Sud sont, contrairement à ceux de l'Europe du Nord, nettement moins satisfaits de leur emploi que les travailleurs à salaire élevé. En calculant par approximation la satisfaction au travail pour évaluer la qualité de l'emploi, les auteurs montrent que, si bas salaire ne rime pas nécessairement avec emploi de mauvaise qualité, les travailleurs de certains pays sont néanmoins doublement pénalisés: ils sont mal rémunérés et ont un travail de mauvaise qualité. Selon les auteurs, ce dualisme des marchés du travail en Europe correspond à des approches différentes au niveau national du compromis entre flexibilité et sécurité, cette dernière devant ětre privilégiée au plan politique pour améliorer la qualité de l'emploi.
ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas
Authors: Silva SD , Cunha IW , Younes RN , Soares FA , Kowalski LP , Graner E
Published: June 2010

Oral Diseases (2010) 16, 774–780

Summary:  Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies.

Methods:  This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis.

Results:  Strong correlation among the expression of ErbB family receptors was found (ErbB1–ErbB2 P = 0.008, ErbB1‐ErbB4 P = 0.018, EbB2‐ErbB3 P = 0.001, ErbB2‐ErbB4 P = 0.006, ErbB3‐ErbB4 P = 0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006).

Conclusions:  The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1‐ErbB2, ErbB1‐ErbB4, ErbB2‐ErbB3, ErbB2‐ErbB4, and ErbB3‐ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.
Effects of smoking on trace metal levels in saliva
Authors: Kim Y‐J , Kim Y‐K , Kho H‐S
Published: June 2010

Oral Diseases (2010) 16, 823–830

Objectives:  To compare the salivary levels of trace metals between non‐smokers and smokers using inductively coupled plasma mass spectroscopy (ICP‐MS). The effect of pretreatment methods on the accuracy of ICP‐MS analysis and daily variations in trace metal levels in saliva were also investigated.

Subjects and methods:  The participants were 10 male non‐smokers (mean age: 27.4 ± 3.4 years) and 30 male smokers (mean age: 26.5 ± 4.1 years). Unstimulated whole saliva was collected. Salivary flow rate, the number of metal restorations in the oral cavity, the level of blood contamination in the saliva and the levels of cotinine and trace metals in the saliva of each participant were determined.

Results:  Direct dilution of saliva samples with nitric acid showed the most accurate ICP‐MS results. Trace metal levels in saliva showed wide daily variations. They were not affected by the number of metal restorations. Trace metal concentrations of saliva samples without blood contamination were much lower than the previously reported values. Salivary levels of cotinine and aluminum were significantly increased in smokers.

Conclusions:  Saliva can be a medium for trace metal analysis. Salivary levels of cotinine and aluminum can be useful markers to evaluate smoking status.
Confirmed Exposure to Tick‐Borne Encephalitis Virus and Probable Human Cases of Tick‐Borne Encephalitis in Central/Northern Anatolia, Turkey
Authors: Ergünay K. , Saygan M. B. , Aydoğan S. , Litzba N. , Şener B. , Lederer S. , Niedrig M. , Hasçelik G. , Us D.
Published: June 2010

Tick‐borne encephalitis virus (TBEV) is the aetiological agent of tick‐borne encephalitis (TBE), a potentially fatal central nervous system infection of humans. TBE is endemic in many areas of Europe and Asia; however, very scarce data on TBEV activity are available from Turkey. We aimed to identify TBEV exposure in healthy blood donors and the impact of TBEV in central nervous system infections in Central/Northern Anatolia. Two‐thousand four hundred and fifty four sera, collected from blood donors at Ankara, Konya, Eskişehir and Zonguldak branches of the Turkish Red Crescent Middle Anatolia Regional Blood Center, were analysed for TBEV serosurveillance. Paired serum and cerebrospinal fluid samples from 108 patients with the diagnosis of aseptic meningitis/encephalitis of unknown aetiology were also evaluated to identify TBE and neuroborreliosis cases. Commercial enzyme‐linked immunosorbent assays and indirect immunofluorescence tests were employed for antibody detection. Forty‐seven donor samples (1.9%) were reactive for TBEV IgG. In 25 persons with IgG reactivity (53.1%), risk factors for tick‐borne infections were revealed. One sample from Zonguldak province (1/198; 0.5%) in the Black Sea region of Turkey was confirmed to possess neutralizing antibodies via plaque reduction neutralization test. TBEV IgM was detected in 9.2% (8/108) of the patients. IgM was accompanied by IgG reactivity in two persons where, in one, recent history of a tick bite was also identified. Intrathecal antibody production for TBEV could not be demonstrated. No evidence for Borrelia infections could be found. Confirmed exposure to TBEV and/or an antigenically similar tick‐borne flavivirus is documented for the first time in blood donors in Zonguldak in Northern Anatolia. Probable cases of TBE have also been identified from Central Anatolia. The epidemiology of TBEV activity in Turkey needs to be assessed and benefits of vaccination for general population, risk groups or travellers must be considered.
Nonlinear femtosecond laser processing of alkylsiloxane monolayers on surface-oxidized silicon substrates
Authors: Franzka Steffen , Koch Jürgen , Chichkov Boris N. , Hartmann Nils
Published: June 2010

Femtosecond laser patterning of octadecylsiloxane monolayers on surface-oxidized silicon substrates via single-pulse processing at λ=800nm, τ<30fs, and ambient conditions has been investigated. Depending on the laser pulse fluence, local irradiation results in circular spots of distinct size and morphology. At high fluences, a particular rich complexity of distinct surface morphologies is observed including hole, rim, and ripple formation, and a faint boundary area where monolayer decomposition sets in. At low fluences, subwavelength patterning of the organic monolayer is feasible. In particular, at a 1∕e laser spot diameter of 1.3μm, surface spots with a width down to 300nm are fabricated. Selective processing of the organic monolayer, though, is restricted to a very narrow range of fluences between 1.1 and 1.2J∕cm2. A significantly larger parameter range for selective processing is anticipated in the case of functional monolayers that incorporate aromatic groups. Promising perspectives in femtosecond laser processing of organic monolayers are discussed.
Fabrication of Bi2Te3/Sb2Te3 and Bi2Te3/Bi2Te2Se multilayered thin film-based integrated cooling devices
Authors: Xiao Z. , Hedgemen K. , Harris M. , DiMasi E.
Published: June 2010

In this article, the authors report on the development of solid-state integrated cooling devices using Bi2Te3/Sb2Te3 and Bi2Te3/Bi2Te2Se thermoelectric thin films fabricated using sputtering deposition. The multilayer thin films have a periodic structure consisting of alternating Bi2Te3 and Sb2Te3 layers or Bi2Te3 and Bi2Te2Se layers, where each layer is about 10 nm thick. The deposited Bi2Te3/Sb2Te3 multilayer thin film has a p-type conductivity and the deposited Bi2Te3/Bi2Te2Se multilayer thin film has an n-type conductivity. The multilayer structure of films and the interface of layers were analyzed by x-ray diffraction and reflectivity. Bi2Te3/Sb2Te3 and Bi2Te3/Bi2Te2Se multilayer thin film-based integrated cooling devices were fabricated using standard integrated circuit fabrication process. The temperature difference was measured from the fabricated cooling devices. The devices could be good candidates for the application of high-efficiency solid-state microcooling.
Nanopatterning of ultrananocrystalline diamond thin films via block copolymer lithography
Authors: Ramanathan Muruganathan , Darling Seth B. , Sumant Anirudha V. , Auciello Orlando
Published: June 2010

Nanopatterning of diamond surfaces is critical for the development of diamond-based microelectromechanical system/nanoelectromechanical system (MEMS/NEMS), such as resonators or switches. Micro-/nanopatterning of diamond materials is typically done using photolithography or electron beam lithography combined with reactive ion etching (RIE). In this work, we demonstrate a simple process, block copolymer (BCP) lithography, for nanopatterning of ultrananocrystalline diamond (UNCD) films to produce nanostructures suitable for the fabrication of NEMS based on UNCD. In BCP lithography, nanoscale self-assembled polymeric domains serve as an etch mask for pattern transfer. The authors used thin films of a cylinder-forming organic-inorganic BCP, poly(styrene-block-ferrocenyldimethylsilane), PS-b-PFS, as an etch mask on the surface of UNCD films. Orientational control of the etch masking cylindrical PFS blocks is achieved by manipulating the polymer film thickness in concert with the annealing treatment. We have observed that the surface roughness of UNCD layers plays an important role in transferring the pattern. Oxygen RIE was used to etch the exposed areas of the UNCD film underneath the BCP. Arrays of both UNCD posts and wirelike structures have been created using the same starting polymeric materials as the etch mask.
Photon- and electron-stimulated desorption from laboratory models of interstellar ice grains
Authors: Thrower J. D. , Abdulgalil A. G. M. , Collings M. P. , McCoustra M. R. S. , Burke D. J. , Brown W. A. , Dawes A. , Holtom P. J. , Kendall P. , Mason N. J. , Jamme F. , Fraser H. J. , Rutten F. J. M.
Published: June 2010

The nonthermal desorption of water from ice films induced by photon and low energy electron irradiation has been studied under conditions mimicking those found in dense interstellar clouds. Water desorption following photon irradiation at 250 nm relies on the presence of an absorbing species within the H2O ice, in this case benzene. Desorption cross sections are obtained and used to derive first order rate coefficients for the desorption processes. Kinetic modeling has been used to compare the efficiencies of these desorption mechanisms with others known to be in operation in dense clouds.
Fabrication of quantum dots using multicoated self-assembled monolayer
Authors: Kwon Namyong , Kim Kyohyeok , Chung Ilsub
Published: June 2010

The authors have fabricated quantum dots with various nanogaps by controlling the number of self-assembled molecular coatings. First, Au electrodes with a unique shape were obtained using conventional lithography. Then, a self-assembled multilayer, composed of alternating layers of 16-mercaptoalkanoic acids [HS(CH2)15COOH, 16-MHDA] and copper (II) ions, were deposited on Au electrode patterns to form the controllable gap between adjacent Au electrodes. After reaching a nanometer-scale gap, the second Au was deposited again using e-beam evaporation. Finally, both the second Au and molecular resist were removed by lift-off, thereby resulting in quantum dots with a nanogap between gold electrodes. Ellipsometry and cyclic voltammetry were used to find the number of self-assembled molecular layers. In addition, contact angle and x-ray photoelectron spectroscopy were used to analyze chemical properties between gold and the self-assembled multilayer. Field-emission scanning-electron microscopy was used for characterization of shapes of nanogaps and quantum dots.
Photothermally induced bromination and decomposition of alkylsiloxane monolayers on surface-oxidized silicon substrates
Authors: Klingebiel Benjamin , Schröter Anja , Franzka Steffen , Hartmann Nils
Published: June 2010

Photothermal laser processing of alkylsiloxane monolayers in gaseous bromine is investigated. Surface-oxidized silicon samples are coated with octadecylsiloxane monolayers and locally irradiated with a focused beam of an Ar+-laser at λ=514 nm and a 1/e2 spot diameter of 3 μm. For characterization, atomic force microscopy, scanning electron microscopy, and optical microscopy in conjunction with labeling techniques and condensation experiments are used. At low laser powers, monolayer bromination in micron-sized areas is observed. Additionally, at high laser powers, decomposition of the monolayer takes place at the center of the brominated areas. Prospects and limitations of this procedure in fabrication of multifunctional templates are discussed.
Ranitidine bismuth citrate with clarithromycin for the treatment of duodenal ulcer
Authors: Bardhan K D , Dallaire C , Eisold H , Duggan A E
Published: June 2010

Background/Aims—To investigate the effect of the new Helicobacter pylori eradication regimen, ranitidine bismuth citrate (RBC) and clarithromycin (CLAR) dual therapy, on duodenal ulcer healing and absence of ulcer recurrence during 24 weeks follow up (overall success).

Methods—Two hundred and thirty two H pylori positive patients with active duodenal ulcer received four weeks treatment with RBC 400 mg twice daily alone (RBC400) (n=82), or RBC 400 or 800 mg twice daily co-prescribed with clarithromycin 250 mg four times daily for 14 days, followed by 14 days of RBC 400 mg twice daily alone (RBC400+CLAR and RBC 800+CLAR, respectively, n=75 for each).

Results—The co-prescription regimens gave highH pylori eradication rates determined using two tests (CLOtest and 13C-urea breath test) for the presence of the organism. These rates were 92% and 81% for RBC400+CLAR (n=62) and RBC800+CLAR (n=63) respectively, compared with 2% for RBC400 (n=66) (p<0.001). With respect to overall success as estimated by life table analysis, RBC400+CLAR (89%) and RBC800+ CLAR (87%) were significantly more effective than RBC400 alone (51%) (p<0.001). All regimens were safe and well tolerated. Trough plasma bismuth concentrations at week 4 were low (treatment medians less than 6.6 ng bismuth/ml).

Conclusions—Ranitidine bismuth citrate is a well tolerated and efficacious ulcer healing drug which, when co-prescribed with clarithromycin, affords effective H pylorieradication therapy and prevents ulcer relapse in most patients with duodenal ulcer.
Oral budesonide is as effective as oral prednisolone in active Crohn’s disease
Authors: Campieri M , Ferguson A , Doe W , Persson T , Nilsson L-G ,   the Global Budesonide Study Group
Published: June 2010

Background—The use of corticosteroids in active Crohn’s disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.

Aims—To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn’s disease affecting the ileum and/or the ascending colon.

Patients and methods—One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less.

Results—After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p=0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p=0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p=0.0023).

Conclusions—Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn’s disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.
N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions
Authors: Hubbard A L , Harrison D J , Moyes C , Wyllie A H , Cunningham C , Mannion E , Smith C A D
Published: June 2010

Background—Genetic polymorphisms inN-acetyltransferase (NAT2) can change the normally fast acetylation of substrates to slow acetylation, and have been associated with the development of some cancers. The NAT2 locus may also suffer dysregulation during cancer progression, as the gene resides on chromosome 8p22, a region which is frequently deleted in colorectal cancer.

Subjects and Methods—A polymerase chain reaction based method was used to determine NAT2 genotype in 275 patients with colon cancer and 343 normal control DNAs. Within the cancer group, 65 cases known to contain deletions in chromosome 8p were examined for loss of heterozygosity at the NAT2 locus.

Results—Overall, there was no statistical difference in frequency or distribution of NAT2 alleles and genotype between colon cancer and control groups. There was a significant association between the slow acetylation genotype and early age of onset. NAT2 genotype did not vary with other clinical features of colon cancer, which included Dukes’s stage, site of tumour, and sex. Of 48 informative cases, only three (6%) showed loss of heterozygosity, indicating that the NAT2 locus is not commonly deleted in colorectal cancer. This suggests that NAT2 is retained during the process of allele loss possibly because of its proximity to a gene necessary for cell viability.

Conclusions—NAT2 does not play a major role in colorectal cancer risk, but may influence risk in some age groups. The nature of the loss of heterozygosity at the chromosome 8p site is complex and is worthy of further study.
Effect of cereal fibre source and processing on rectal epithelial cell proliferation
Authors: Macrae F A , Kilias D , Selbie L , Abbott M , Sharpe K , Young G P
Published: June 2010

Background—Low fat and wheat bran interventions significantly reduced the growth of small to large adenomas and modestly suppressed rectal epithelial cell proliferation in the Australian Polyp Prevention Project.

Aim—To study the effect of unprocessed wheat bran, unprocessed oat bran and processed wheat bran (Kellogg’s All Bran) on rectal epithelial cell proliferation.

Patients—Twenty subjects with recent adenomas and a high fat background diet were recruited.

Methods—Rectal biopsy specimens were taken at entry and at the end of three six-week periods of oat bran (64 g/day), wheat bran (25 g/day) and All Bran (38 g/day), all in association with a diet <25% energy as fat, in a randomised cross-over trial. Each of the bran supplements had a total of 11 g dietary fibre. The biopsy specimens were fixed in methacarn and stained immunohistochemically for presence of the proliferating cell nuclear antigen (PCNA). The kinetics used to measure proliferation were labelling index, whole distribution of labelled cells, and labelled cells in the top two-fifths of crypts using analysis of variance.

Results—There were no significant differences in mean labelling indexes between the four diets or in the percentage of labelled cells in the top two-fifths (p=0.59), but activity in the top two-fifths of crypts was lowest with wheat bran. The mean (SD) labelling indexes were 2.23 (0.11)% for control, 2.13 (0.08)% for wheat bran, 2.19 (0.09)% for oat bran, and 2.12 (0.08)% for All Bran. The proportion in the top two-fifths of the crypts was 2.6 (0.6)% for control, 2.15 (0.5)% for wheat bran, 3.3 (0.9)% for oat bran, and 3.1 (0.9)% for All Bran. On analysis of whole distribution, there was no significant overall effect of diets but there was a difference between subjects. Analysis including total fibre intake also did not identify effects on proliferation.

Conclusion—In this study of high risk subjects with initial high fat diets, dietary fibre in association with a low fat diet had no effect on rectal epithelial cell proliferation, although wheat bran had the greatest effect on percentage of labelled cells in the top two-fifths of crypts.
Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestine
Authors: Somasundaram S , Rafi S , Hayllar J , Sigthorsson G , Jacob M , Price A B , Macpherson A , Mahmod T , Scott D , Wrigglesworth J M , Bjarnason I
Published: June 2010

Background—The “topical” effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage.

Aim—To examine the possible mechanism of the “topical” phase of damage in the small intestine.

Methods—Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode.

Results—The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the “topical” phase of NSAID induced damage.

Conclusion—Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the “topical” phase of damage induction.
Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats
Authors: Yano Y , Yao H , Aoyagi K , Kawakubo K , Nakamura S , Doi K , Ibayashi S , Fujishima M
Published: June 2010

Background—Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon.

Aim—To establish a new model of photochemically induced ischaemic colitis in rats.

Methods—Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20  mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n=4), 12 hours (n=2), 24 hours (n=10), three days (n=4), seven days (n=4), 14 days (n=2), or 28 days (n=2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology.

Results—Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon.

Conclusion—This model may be useful for further investigation of the pathophysiology of ischaemic colitis.
The potential role of hepatitis C virus in the pathogenesis of the neurological syndrome in chronic hepatitis C
Authors: Caudai C , Maimone D , Almi P , Annunziata P , Bastianoni I , Boggiano C A , Guazzi G C , Padula M , Valensin P E
Published: June 2010

A 72 year old man developed chronic sensory neuropathy (CSN) during chronic hepatitis C (HCV) infection. Neurological symptoms began one year after acute HCV hepatitis and slowly worsened over three years. No conventional cause for CSN was found. Circulating antinervous tissue antibodies (including anti-Hu) and inflammatory infiltrates in sural nerve biopsy specimens were absent. However, the presence of anti-HCV antibody and HCV-RNA in cerebrospinal fluid indicated that HCV had reached the intrathecal compartment, suggesting the direct viral involvement in the pathogenesis of CSN.
Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese
Authors: Kinoshita Y , Kawanami C , Kishi K , Nakata H , Seino Y , Chiba T
Published: June 2010

Background—Gastric acid secretion in Japanese subjects decreases with aging. One of the possible causative mechanisms of this attenuated acid secretion is speculated to be aHelicobacter pylori induced chronic gastritis. The infection rate of this microorganism has decreased recently in Japan.

Aims—To investigate whether gastric acid secretion has altered over the past 20 years, and if so, what the influence of H pylori infection might be in the Japanese population.

Subjects and methods—Gastric acid secretion, serum gastrin and pepsinogen I and II concentrations, and H pylori infection were determined in 110 Japanese subjects in both the 1970s and 1990s.

Results—Basal acid output as well as maximal acid output have greatly increased over the past 20 years, not only in individuals with H pylori infection but also in those without infection. Furthermore, subjects with H pyloriinfection tended to show decreased gastric acid secretion in comparison with those without infection, particularly in geriatric subjects. There was a positive correlation between gastric acid secretion and serum pepsinogen I concentrations.

Conclusions—In Japan, both basal and stimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in H pylori infection may play an important role in this phenomenon.
Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide
Authors: Schwizer W , Borovicka J , Kunz P , Fraser R , Kreiss C , D’Amato M , Crelier G , Boesiger P , Fried M
Published: June 2010

Background—Exogenous cholecystokinin (CCK) inhibits antral motility and slows gastric emptying (GE) but the effect of endogenous CCK on the gastric motor mechanisms responsible for GE remains unclear.

Methods—The effect of the CCK-A antagonist loxiglumide (LOX) on GE and motility was studied using magnetic resonance imaging in six healthy volunteers after ingestion of 500 ml Intralipid 10% (550 kcal). Subjects were studied in the supine position on two occasions during intravenous infusion of LOX (66 μmol/kg/h for 10 min followed by 22 μmol/kg/h) or placebo. GE was determined every 15 minutes using transaxial abdominal scans and motility was studied by means of 120 coronal scans, 1.2 seconds apart. For each coronal image the proximal and distal (antral) diameters were measured at a fixed point in the stomach to determine contraction frequency (ACF) and amplitude (AMP).

Results—GE was faster during LOX infusion than placebo (t1/2 31 (22) versus 115 (67) minutes, p<0.03). There was little variation in the diameter of the proximal stomach with either LOX or placebo. In the distal stomach marked contractile activity was observed during LOX (ACF 2.9 (0.2) versus 1.5 (2.9) during placebo, p<0.01). AMP also increased during LOX compared with placebo (56 (22)% versus 27 (16)%, p<0.001).

Conclusion—The increases in antral motility are likely to contribute to the acceleration of GE and suggest that CCK may regulate GE by acting on the distal stomach although an effect on the proximal stomach cannot be excluded.
Evidence for two distinct perceptual alterations in irritable bowel syndrome
Authors: Naliboff B D , Munakata J , Fullerton S , Gracely R H , Kodner A , Harraf F , Mayer E A
Published: June 2010

Background and aims—Visceral hyperalgesia has been implicated as a factor contributing to symptom generation in irritable bowel syndrome (IBS). However, previous studies using intestinal balloon distension have used psychophysical procedures which do not provide adequate and unbiased measures of visceral sensitivity.

Methods—Three psychophysical tasks were examined in 45 patients with IBS (positive Rome criteria) and 14 controls using rectal balloon distension with a computerised distension device. Discomfort threshold and tolerance were assessed during an ascending series of phasic pressure stimuli and during an interactive threshold tracking procedure. In addition, stimulus response functions were generated from intensity and unpleasantness ratings of the rectal distensions.

Results—Discomfort threshold and tolerance for the ascending stimuli were significantly lower for the patients with IBS compared with the controls. In contrast, discomfort thresholds during the tracking procedure and stimulus response curves for the ascending series were not different between the groups. A factor analysis of the psychophysical data was consistent with the presence of two distinct and unrelated perceptual alterations related to rectal distension: hypervigilance for visceral stimuli, manifested as lowered response criteria for using the descriptor “discomfort”; and rectal hypersensitivity, manifested as a lower discomfort threshold and left shift of the stimulus response curves.

Conclusions—Patients with IBS as a group have a greater propensity to label visceral sensations negatively and show a lower tolerance for rectal balloon distension. A subgroup of patients also have baseline rectal hypersensitivity, assessed by unbiased measures of discomfort threshold and stimulus intensity judgements.
Gastric cancer below the age of 55: implications for screening patients with uncomplicated dyspepsia
Authors: Christie J , Shepherd N A , Codling B W , Valori R M
Published: June 2010

Aims—To test the hypothesis that gastric cancer presenting with uncomplicated dyspepsia is rare below the age of 55.

Patients and methods—The area studied was the postcode defined catchment area of a district general hospital (Gloucestershire Royal) serving a population of 280 500. An open access endoscopy service has been available in this district for more than 17 years. All cases of gastric cancer during a seven year period (1986–92) were drawn from the local pathology database. The database of the neighbouring hospital and the South West Cancer Registry were searched for missed cases from the postcoded area. Hospital and general practitioner records were retrospectively reviewed with respect to duration of symptoms, and previous consultation and investigation for dyspepsia; and alarming symptoms and signs suggestive of underlying malignancy (unexplained recent weight loss, dysphagia, haematemesis or melaena, anaemia, previous gastric surgery, palpable mass, and perforation).

Results—Twenty five of 319 cases of gastric cancer detected during the seven year period were aged less than 55. Twenty four of these 25 patients presented with one or more suspicious symptoms or signs. Only one patient (4%) aged less than 55 presented with uncomplicated dyspepsia. In two patients there was a delay in diagnosis of more than six months after first presenting to the general practitioner. Both these patients had significant symptoms at presentation.

Conclusion—Gastric cancer is rare below the age of 55 (7.8% of all cases) and, even in the presence of established open access endoscopy, presents with suspicious symptoms or signs in 96% of cases. The age limit for screening uncomplicated dyspepsia can be raised safely to 55.
Intestinal metaplasia at the squamocolumnar junction in patients attending for diagnostic gastroscopy
Authors: Trudgill N J , Suvarna S K , Kapur K C , Riley S A
Published: June 2010

Background—The incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing rapidly. Barrett’s oesophagus is the major risk factor. Intestinal metaplasia at the squamocolumnar junction in the absence of Barrett’s oesophagus is common but its relation to adenocarcinoma and gastro-oesophageal reflux disease is unclear.

Aims—To study the prevalence and clinical, endoscopic, and histological associations of intestinal metaplasia at the squamocolumnar junction.

Methods—Biopsy specimens were taken from 120 randomly selected patients undergoing routine diagnostic endoscopy. Eight biopsy specimens, taken from above and below the squamocolumnar junction, gastric fundus, and gastric antrum, were stained with haematoxylin/eosin, alcian blue/periodic acid-Schiff, and Gimenez, and graded independently by one pathologist.

Results—Intestinal metaplasia at the squamocolumnar junction was found in 21 patients (18%). Metaplasia was associated with increasing age (p<0.01) and antral intestinal metaplasia (p=0.04). Logistic regression analysis revealed that age was the only independent predictor (p<0.01). There was no association with symptomatic, endoscopic, or histological markers of gastro-oesophageal reflux disease.

Conclusions—Intestinal metaplasia at the squamocolumnar junction is a common finding. It is associated with increasing age but not gastro-oesophageal reflux disease.
Associations between different forms of gastro-oesophageal reflux disease
Authors: El-Serag H B , Sonnenberg A
Published: June 2010

Abstract

Aims—To study the epidemiology and natural history of gastro-oesophageal reflux disease (GORD).

Methods—Retrospective cohort study involving all 172 hospitals of the Department of Veterans Affairs. A total of 194 527 patients with GORD were followed between 1981 and 1994. Distribution of oesophagitis, oesophageal ulcer, oesophageal stricture, strictured hiatus hernia, hiatus hernia, and pyrosis by age, sex, and ethnicity were determined. The comorbid occurrence of various forms of GORD in identical patients was analysed by an age and race standardised morbidity ratio. The population of all hospitalised veterans was used for comparison.

Results—Severe forms of GORD associated with oesophageal erosions, ulcers, or strictures, affected elderly, white, male patients more often than their corresponding opposite demographic group. All forms of GORD clustered in the same patient population; on average, any form of GORD was 10 times more likely to occur in a patient with another form of GORD than without. The highest morbidity ratio (22) was found in oesophageal ulcer and stricture. About one third of all patients with oesophageal erosions, ulcers, or strictures also had hiatus hernia; 46% of patients with hiatus hernia were diagnosed as having other forms of GORD. While one third of all oesophageal strictures appeared in patients without other forms of GORD diagnosed at any time, oesophageal ulcers were always associated with some other form of GORD. No clear cut progression in different forms of GORD was found.

Conclusions—Older age, male sex, and white ethnicity are risk factors in the development of severe forms of GORD. The most severe grade of GORD is reached at the onset of the disease.
Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2
Authors: Andus T , Daig R , Vogl D , Aschenbrenner E , Lock G , Hollerbach S , Köllinger M , Schölmerich J , Gross V
Published: June 2010

Background—Interleukin 1 (IL-1) α and β are potent cytokines which play key roles in inflammation. They are controlled by IL-1 receptor antagonist (IL-1ra).

Aims—To investigate the influence of mucosal inflammation and IL-1ra genotype on the IL-1ra:IL-1 balance.

Patients and methods—IL-1α, IL-1β, and IL-1ra were measured by enzyme linked immunosorbent assay (ELISA) in biopsy specimens taken from inflamed and non-inflamed colon of 60 patients with Crohn’s disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotype was determined by polymerase chain reaction and gel electrophoresis.

Results—IL-1α and IL-1β were significantly increased in inflamed mucosa in inflammatory bowel disease (IBD) (CD: 53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2 (7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared with normal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CD IL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively; p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased in inflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and in non-inflamed mucosa in CD (369 (149); p<0.0001) compared with normal controls (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 had slightly but significantly reduced mucosal IL-1ra concentrations (p=0.003). The greatest difference was seen in colonic biopsy specimens from patients with inflamed Crohn’s disease.

Conclusion—Mucosal inflammation can modulate the balance of the IL-1:IL-1ra system in colonic mucosa.