bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust multiple suppression using adaptive beamforming
Authors: Hu T. , White R.E.
Published: October 2010

Minimum variance unbiased (MVU) beamforming is a type of multichannel filtering which extracts coherent signals without distortion, whilst minimizing residual noise power. Adaptive beamforming estimates signal and noise characteristics as part of the extraction process. The adaptive beamformer used here is designed from models of primary and multiple reflection signals having parametrically specified moveout and amplitude variation with offset (MVO and AVO). Phase variation with offset (PVO) can also be included but it is not usually justified in practice. The resulting analysis provides data for input into AVO and PVO schemes for obtaining lithological information. Synthetic data examples illustrate details of implementation of parametric adaptive MVU beamforming and the response characteristics of the resultant design. Real data examples show that data‐adaptive beamforming is more flexible and more effective in attenuating multiples in prestack common‐midpoint seismic data than Radon transform methods. In common with other prestack multichannel processes, the advantages of beamforming are shown to best effect in data with a good signal‐to‐noise ratio.
A semi‐empirical velocity‐porosity‐clay model for petrophysical interpretation of P‐ and S‐velocities
Authors: Goldberg Igor , Gurevich Boris
Published: October 2010

We design a velocity–porosity model for sand‐shale environments with the emphasis on its application to petrophysical interpretation of compressional and shear velocities. In order to achieve this objective, we extend the velocity–porosity model proposed by Krief et al., to account for the effect of clay content in sandstones, using the published laboratory experiments on rocks and well log data in a wide range of porosities and clay contents.

The model of Krief et al. works well for clean compacted rocks. It assumes that compressional and shear velocities in a porous fluid‐saturated rock obey Gassmann formulae with the Biot compliance coefficient. In order to use this model for clay‐rich rocks, we assume that the bulk and shear moduli of the grain material, and the dependence of the compliance on porosity, are functions of the clay content.

Statistical analysis of published laboratory data shows that the moduli of the matrix grain material are best defined by low Hashin–Shtrikman bounds. The parameters of the model include the bulk and shear moduli of the sand and clay mineral components as well as coefficients which define the dependence of the bulk and shear compliance on porosity and clay content. The constants of the model are determined by a multivariate non‐linear regression fit for P‐ and S‐velocities as functions of porosity and clay content using the data acquired in the area of interest.

In order to demonstrate the potential application of the proposed model to petrophysical interpretation, we design an inversion procedure, which allows us to estimate porosity, saturation and/or clay content from compressional and shear velocities.

Testing of the model on laboratory data and a set of well logs from Carnarvon Basin, Australia, shows good agreement between predictions and measurements. This simple velocity‐porosity‐clay semi‐empirical model could be used for more reliable petrophysical interpretation of compressional and shear velocities obtained from well logs or surface seismic data.
3D geoelectric tomography and archaeological applications1
Authors: Mauriello Paolo , Monna Dario , Patella Domenico
Published: October 2010

Following a previous paper in which the principles of a 3D ground‐surface tomographic processing of self‐potential data were established, we extend the method to active source geoelectric surveying. The main purpose of the new tomographic approach is to obtain a physical image reconstruction of the induced electric charges distributed over buried resistivity discontinuities. The information is produced in a probabilistic sense, as the mathematical formulation underlying the method treats only the intrinsic physical nature of the generated electric field underground and the method of its ground‐surface detection, independently of the geometry of the unknown structures. In practice, a 3D tomography is realized by cross‐correlating a set of distributed electric‐field ground‐surface data with a scanning function, representing a unit positive point charge located anywhere in the lower half‐space. The resolution of the method is tested on the synthetic response of a 3D structural simulation of an archaeological target, consisting of an infinitely resistive prismatic body immersed in a half‐space, including surface inhomogeneities and layering. Finally, the field response of a 3D structure consisting of a hypogeal dromos‐chamber tomb inside the Sabine Necropolis at Colle del Forno, close to Rome, is presented and discussed.
Caring for parents of hospitalized children: a hidden area of nursing work
Authors: Callery Peter
Published: October 2010

Children are the recognized patients when admitted to hospital but their parents can also present demands for care by nurses. Involvement in care can be stressful for parents, particularly when children are required to undergo unpleasant procedures. Parents turn to their families for support in the first instance but some also look for care from nurses. Consequently parents can present a need for care of themselves to nurses whose primary patients are children. In this paper the experiences of a group of parents who became co‐clients of nurses are considered along with the views of nurses working on the same ward. The discussion arises out of a larger study of the experiences of the parents of children admitted to a surgical ward in a children's hospital. The principal purpose of the study was to examine parents' and nurses' perceptions of their participation in the care of hospitalized children. The work of caring for parents is found to be ad hoc and unpredictable. The implications of the study for practice and policy are considered.
Evolutionary change in the use of skills within the district nursing team: a study in two Health Board areas in Scotland
Authors: McIntosh Jean , Moriarty Deirdre , Lugton Jean , Carney Orla
Published: October 2010

Evolutionary change in the use of skills within the district nursing team: a study in two Health Board areas in Scotland

Grade mix within the district nursing team in the United Kingdom has changed markedly over the last 10 years but the relationship between grade mix and skill mix has received only intermittent research attention. This study adopted an ethnographic approach and aimed to explore the way in which grade and skill are taken into account in the delegation of nursing care. After gaining ethical approval, a total of 76 members of 21 district nursing teams in two areas were observed and interviewed. Delegation practices were found to vary both within and between areas and considerable differences were uncovered in the responsibilities allocated to more junior and unqualified team members. The developing role of nursing auxiliaries is discussed in relation to the role of the G grade sister, resource constraints and the standards of patient care. The paper concludes by arguing that the supervision and leadership role provided by the G grade sister should be fully recognized and safeguarded.
Which terminally ill cancer patients in the United Kingdom receive care from community specialist palliative care nurses?
Authors: Addington‐Hall Julia , Altmann Dan
Published: October 2010

Which terminally ill patients in the United Kingdom receive care from community specialist palliative care nurses?

This study investigates how cancer patients who receive care from community specialist palliative care (CSPC) nurses differ from those who do not. This was achieved by secondary data analyses from the Regional Study of Care for the Dying, a retrospective interview survey of deaths in 1990 in 20 nationally representative health districts. Interviews were obtained for 2074/2915 (71%) of randomly selected cancer deaths; 574 (27·8%) were reported to have received care from a Macmillan nurse, hospice home‐care nurse, or other community specialist palliative care nurse. Using logistic regression analysis 10 factors were found to predict independently CSPC use. Being dependent with dressing/undressing, needing help at night, having constipation, experiencing vomiting/nausea, being mentally confused, having breast cancer and being under the age of 75 years increased the likelihood of receiving CSPC. Having a lymphoma, leukaemia or myeloma, a brain tumour and being dependent on others for help with self‐care for more than 1 year decreased the likelihood. The use of CSPC nurses to provide expertise in symptom control and to support families of dependent patients is consistent with the aims of palliative care, and therefore appears appropriate. Further research is, however, needed to investigate the apparent age bias in access to these services, and to ensure that CSPC services are provided on the basis of need, irrespective of patient age.
Nursing in the public sphere: breaching the boundary between research and policy
Authors: West Elizabeth , Scott Cherill
Published: October 2010

Nursing in the public sphere: breaching the boundary between research and policy

Nurses and nursing are associated traditionally with activities in a private sphere. This paper argues that, if clinical care is to be improved, nurses need to take a more active public role in making and implementing health policy at both local and national levels. In the current climate, empirical evidence is one of the most important tools for influencing health policy. This paper discusses contemporary models of the policy‐making process before outlining a number of strategies that could be used to increase the policy impact of nursing research. Finally, while the current climate in the United Kingdom health‐care arena presents opportunities for researchers to have an impact on policy, the growth of health policy research as a distinct field of scholarship also poses a number of challenges and dangers.
Some dilemmas of master's level nurse education
Authors: Gerrish Kate , Ashworth Peter D. , McManus Mike
Published: October 2010

Some dilemmas of master's level nursing education

Despite an increase in the growth of master's level provision for qualified nurses in the United Kingdom uncertainty exists regarding the characteristics of master's level performance in respect of professional practice. This paper presents selected findings from a multidisciplinary study that sought to examine the characteristics of master's level performance in health professional courses that had an expressed practice orientation. It focuses specifically on dilemmas nurse educators encountered in relation to British master's level nurse education. Following an initial pilot stage involving focus group interviews with separate groups of nurses, occupational therapists and physiotherapists, an interview agenda was developed to explore participants’ perspectives of the characteristics of master's level performance. Individual in‐depth interviews were undertaken with a purposive sample of 18 nurse educators drawn from eight universities in England. Interview transcripts were coded and thematically analysed. Six kinds of dilemma emerged from the interviews. These were breadth vs. depth in the conceptualization of master's level for nursing, relevance to practice vs. academic detachment, facilitating creative thinking vs. reinforcing rigidity, encouraging or suppressing different modes of critical thinking, postgraduate nurses as loyal change agents vs. the problem of well‐qualified mavericks, and professional experience as facilitating or hindering master's level performance. These dilemmas raise important questions about course design and the role of stakeholders in determining curriculum content. Moreover, a pervasive tension between a utilitarian emphasis on the application and utility of knowledge on one hand, and aspirations to promote creativity and critical thinking which look to alternative possibilities on the other hand, suggests that nurse educators exercise a degree of conservatism in relation to master's level. It is concluded that this apparent quest to maintain a safe variant of the status quo as the best way of promoting the wellbeing of patients should be subject to profound questioning.
Limitations, frustrations and opportunities: a follow‐up study of nursing graduates from the University of Birmingham, England
Authors: Wheeler Herman H. , Cross Vinette , Anthony Denis
Published: October 2010

Limitations, frustrations and opportunities: a follow‐up study of nursing graduates from the University of Birmingham, England

This paper reports an ongoing study of the progress of nursing graduates from the University of Birmingham, England. The aim of the research was to follow‐up early graduates from the programme, to assess their progress and study feedback indicators that could help further the development of this relatively new programme. The study also aims to contribute to the growing body of knowledge about United Kingdom nursing graduates, following the recent shift of nurse education from Schools/Colleges of Nursing into universities. Due to objection from some quarters as to the value of a university education for nurses, even such a small‐scale study is considered to be important. A questionnaire was sent to the first three cohorts of graduates. It revealed interesting findings in relation to work patterns, continuing professional and academic development and perceptions of the value of the degree in practice. The graduates made recommendations regarding changes that might enhance the quality of the Birmingham degree and nursing practice generally.
Communication and information needs of a random sample of community psychiatric nurses in the United Kingdom
Authors: Fakhoury Walid K.H. , Wright Donna
Published: October 2010

Communication and information needs of a random sample of community psychiatric nurses in the United Kingdom

This paper reports on a cross‐sectional survey investigating communication and information needs of community psychiatric nurses attached to community mental health teams in the United Kingdom. Community psychiatric nurses’ access to and communication with other professionals was also assessed. In total, 200 teams were randomly sampled UK‐wide, and postal questionnaires were sent to community psychiatric nurses attached to these teams; 110 questionnaires were completed and returned (55% response rate). Spearman's rho, Pearson's correlation and the chi‐square test were used in bivariate analyses and multiple logistic regression in multivariate analysis. Participants reported to be mainly in contact with psychiatrists (71%) and other community psychiatric nurses (52%). Eighty‐four per cent and 91% reported psychiatrists and community psychiatric nurses, respectively, to be quite/extremely helpful when consulted; the proportions were lower for general practitioners and counsellors/therapists (32% and 31%, respectively). All reported lack of time and 84% reported communication problems with other professionals as barriers to their work. Although 70% reported having the necessary training/skills for managing severe cases, 76% indicated they had information needs. Being a long‐serving community psychiatric nurse (OR=4·51, 95% CI=1·06–19·20), perceiving the discussion of cases with other professionals as less helpful (OR=4·82, 95% CI=1·16–20·01), being mainly in contact with other CPNs (OR=6·72, 95% CI=1·21–37·15), reporting not having the necessary training/skills (OR=7·78, 95% CI=1·37–44·25), and wanting information on mental health law (OR=12·27, 95% CI=1·75–86·36) were significant predictors of having information needs. This survey provided valuable information on problems facing these nurses and highlighted the need for training and for easier access to and increased communication with other professionals.
Hearing the voices of children with chronic illness
Authors: Sartain Samantha A. , Clarke Charlotte L. , Heyman R.
Published: October 2010

Hearing the voices of children with chronic illness

This qualitative study has aimed to explore children’s, parents’ and health professionals’ experience of childhood chronic illness. Seven families and their professional carers participated in semistrucured interviews. The children's interviews were augmented with a ‘drawing’ technique. A grounded theory approach facilitated data collection and analysis. This paper debates the perceived passivity of the voice of children in health care and research and illustrates data collection methods that seek to give children and other disadvantaged groups a voice. The children who participated in this study are described as competent interpreters of their world.
English nursing and medical students’ attitudes towards organ donation
Authors: Cantwell Michelle , Clifford Collette
Published: October 2010

English nursing and medical students’ attitudes towards organ donation

The purpose of the study reported in this paper was to examine nursing and medical students’ attitudes towards organ and corneal donation. A sample of 72 nursing and medical degree students from a British University, completed a 61‐item self‐administered quantitative questionnaire, adapted by Kent and Owens (1995) from an original tool devised by Parisi and Katz (1986). The findings revealed that all but one of the respondents had an overall positive attitude towards organ donation; a significant relationship was found to exist between the extent of this positive attitude held by each student and their personal willingness to donate organs. In total, 74% of the student nurses had already signed a donor card, compared to only 43% of the medical students, and the difference in the two groups’ personal commitment towards donation was significant (P=0·005). However, this disparity between the nursing and medical students was not evident when students were questioned about personally accepting organs, for survival. Most respondents agreed that they would take some form of transplanted organ or tissue into their body, if it was needed to maintain life.

Overall, the study revealed that although this group of student nurses seem to be in favour of organ donation, with many willing to sign a donor card, doubts still exist in the medical student group. Further work is required to understand this phenomena.

A comparison of the data with an earlier study completed by Kent and Owens (1995) indicate that student nurses may have a more positive orientation to donation than qualified staff.
Attitudes of nursing staff to the autopsy
Authors: Dziobon Mark D. , Roberts Ian S.D. , Benbow Emyr W.
Published: October 2010

Attitudes of nursing staff to the autopsy

We assessed the views of hospital nurses on the autopsy, using a questionnaire which was distributed by hand to all qualified nurses working at Manchester Royal Infirmary during a 48‐h period. We found that many respondents (43%) had had occasion to discuss autopsy with relatives, and the majority (90%) would like to learn more about counselling the bereaved. Few (15%) clearly understood the legal distinction between coroners’ and hospital autopsies. Almost all (97%) thought the main reason for autopsy was determination of the cause of death, and only 12% supported a role in clinical audit. More respondents saw benefits for doctors rather than for nurses, and only 56% perceived a benefit for relatives. In general, nursing staff have a more positive view of the autopsy than we anticipated, and we would advocate making more information about the benefits of autopsy available to nurses.
An accessible analytical approach for investigating what happens between the rounds of a Delphi study
Authors: Greatorex Jackie , Dexter Trevor
Published: October 2010

An accessible analytical approach for investigating what happens between the rounds of a Delphi study

The Delphi method is used to investigate consensus amongst a panel of experts using repeated rounds of a questionnaire, often in healthcare settings. However, many Delphi studies do not report any investigation into what happens to the stability of consensus or the convergence of agreement between the rounds in the study, which may be of importance. In this paper an accessible analytical approach is outlined using graphical presentations of means and standard deviations to identify what happens between rounds. For Delphi studies where the scale upon which experts are expressing their opinions can be considered to be interval, the mean will represent the group opinion whilst the standard deviation will represent the level of agreement. An example Delphi study from a healthcare setting is used to illustrate the methodology.
Classifying clinical decision making: interpreting nursing intuition, heuristics and medical diagnosis
Authors: Buckingham Christopher D. , Adams Ann
Published: October 2010

Classifying clinical decision making: interpreting nursing intuition, heuristics and medical diagnosis

This is the second of two linked papers exploring decision making in nursing. The first paper, ‘Classifying clinical decision making: a unifying approach’ investigated difficulties with applying a range of decision‐making theories to nursing practice. This is due to the diversity of terminology and theoretical concepts used, which militate against nurses being able to compare the outcomes of decisions analysed within different frameworks. It is therefore problematic for nurses to assess how good their decisions are, and where improvements can be made. However, despite the range of nomenclature, it was argued that there are underlying similarities between all theories of decision processes and that these should be exposed through integration within a single explanatory framework. A proposed solution was to use a general model of psychological classification to clarify and compare terms, concepts and processes identified across the different theories. The unifying framework of classification was described and this paper operationalizes it to demonstrate how different approaches to clinical decision making can be re‐interpreted as classification behaviour. Particular attention is focused on classification in nursing, and on re‐evaluating heuristic reasoning, which has been particularly prone to theoretical and terminological confusion. Demonstrating similarities in how different disciplines make decisions should promote improved multidisciplinary collaboration and a weakening of clinical elitism, thereby enhancing organizational effectiveness in health care and nurses’ professional status. This is particularly important as nurses’ roles continue to expand to embrace elements of managerial, medical and therapeutic work. Analysing nurses’ decisions as classification behaviour will also enhance clinical effectiveness, and assist in making nurses’ expertise more visible. In addition, the classification framework explodes the myth that intuition, traditionally associated with nurses’ decision making, is less rational and scientific than other approaches.
Lack of Interferon‐γ Receptor does not Influence the Outcome of Infection in Murine Schistosomiasis mansoni
Authors: AKHIANI A. A. , LYCKE N. , NILSSON L.‐Å. , OLLING S. , OUCHTERLONY Ö.
Published: October 2010

Studies of vaccine‐induced immunity in experimental schistosomiasis in mice have suggested that interferon‐γ (IFN‐γ) is an important factor for the induction of protective immunity against schistosomiasis. The present study compares some parameters during primary schistosome infection in IFN‐γ receptor deficient mice and wild type mice. No significant difference in worm burden between the two groups was found. Almost the same number of eggs in the liver as well as typical granulomas with numerous macrophages and eosinophils were observed in both groups of mice. Furthermore, IFN‐γ receptor deficient mice infected with S. mansoni displayed a significant reduction in the number of IgG2a secreting cells in the spleen and a significant enhancement of IgA secreting cells in the spleen and in the lungs. These findings suggest that the lack of IFN‐γ activity may result in an enhanced dominance of Th2 cells which, however, does not influence the development of a primary schistosome infection.
Wallaby Serum Amyloid A Protein: cDNA Cloning, Sequence and Evolutionary Analysis
Authors: UHLAR C. M. , BLACK I. L. , SHIELDS D. C. , BRACK C. M. , SCHREIBER G. , WHITEHEAD A. S.
Published: October 2010

A serum amyloid A (SAA) clone was isolated from a Tammar wallaby cDNA library, the most distantly related mammalian species for which an SAA has been described to date. The clone predicts a premolecule of 127 amino acids with good homology to other mammalian SAAs, and consists of an 18 residue leader peptide and a mature protein of 109 amino acids. Evolutionary analysis at both the protein and nucleotide level indicate that the wallaby SAA clone clusters with the acute phase SAAs. However, as the SAA superfamily has undergone concerted evolution it is not possible to determine at this point which acute phase SAA it is most like. The grouping of wallaby SAA inside the acute phase SAA cluster demonstrates that at least some of the duplication events giving rise to multiple acute phase genes occured prior to the divergence of the eutherian and metatherian mammals.
Intravenous Immunoglobulin (IVIg) Modulates the Expansion of Vβ3+ and Vβ17+ T Cells Induced by Staphylococcal Enterotoxin B Superantigen In Vitro
Authors: BAUDET V. , HUREZ V. , LAPEYRE C. , KAVERI S. V. , KAZATCHKINE M. D.
Published: October 2010

The authors investigated the effect of IVIg on T‐cell proliferation induced by the superantigen, staphylococcal enterotoxin B (SEB). The addition of IVIg to normal PBMC stimulated with SEB resulted in a threefold increase in the proportion of CD3+ blast cells expressing Vβ3 and Vβ17, two subsets of T cells that selectively expand in the presence of SEB. There was no increase in the proportion of T‐cell blasts expressing Vβ2, Vβ8 and Vβ13.6 antigens that do not respond to SEB in the absence of IVIg. As described previously, IVIg inhibited T‐cell proliferation independently of Vβ specificity. The effects of IVIg were mediated by variable regions of immunoglobulins since they were reproduced with F(ab′)2 fragments of IVIg but not with purified Fc fragments of IgG. The observation that SEB‐activated T cells are rescued from inhibition of proliferation by IVIg indicates that IVIg modulates the effects of superantigen on T cells. These results may be of relevance for understanding the mechanisms underlying the effects of IVIg in patients with diseases in which T‐cell superantigens are of pathophysiological significance.
Cancer Prevention by Adoptive Transfer of Antigen 60‐Activated Immunocompetent Cells
Authors: MAES H. , COCITO C
Published: October 2010

The authors have already shown that A60, the thermostable macromolecular antigen complex of Mycobacterium bovis BCG, induced resistance to tumour challenge in several murine systems. In the present work, the authors provided evidence that activated macrophages played a major role, and cytolytic T lymphocytes a minor one, in both in vivo and in vitro A60‐promoted cancer cell cytolysis. To identify the types of immunocompetent cells involved in this protective effect, macrophages and T lymphocytes from A60‐primed mice donors were adoptively transferred to irradiated recipients prior to EMT 6 tumour challenge. In some groups, A60‐primed donors were survivors of previous tumour challenges. Transfer of T lymphocytes from the spleen or lymph‐nodes of A60‐immunized mice induced 80–90% protection against tumour challenge. Conversely, transferred macrophages, although cyto lytically active, did not induce resistance to tumour implantation. Furthermore, adoptive transfer with T lymphocytes from A60‐immunized and EMT 6 challenge‐surviving donors induced 100% protection. It is concluded that stimulation of T lymphocytes by A60 is the key step which leads to activation of the immunocompetent cells involved in tumour rejection.
Blood Leucocyte Subsets of the Rat: Expression of Adhesion Molecules and Localization Within High Endothelial Venules
Authors: WESTERMANN J , WALTER S , NAGAHORI Y. , HEERWAGEN C , MIYASAKA M , PABST R
Published: October 2010

Although several distinct adhesion pathways are now well characterized, it is not clear whether analysis of adhesion molecule expression on leucocytes is sufficient to predict their interaction with endothelium in vivo. Therefore, in the present study this question was addressed by investigating the interaction between blood leucocyte subsets and high endothelial venules (HEV). The expression of different types of adhesion molecule (CD44, α4‐integrins, LFA‐1, ICAM‐1, CD2 and L‐selectin) on lymphocytes, NK cells, monocytes and granulocytes of rat blood was determined by flow cytometry. In the same animals the numbers of blood leucocyte subsets present in the HEV of axillary lymph nodes and Peyer’s patches were analysed using immunohistology. In the HEV of both axillary lymph nodes and of Peyer’s patches lymphocytes (> 10.000 per mm2), as well as small numbers of NK cells and monocytes (< 500 per mm2), were found. In contrast, granulocytes were not detected here. Lymphocytes, NK cells, monocytes and granulocytes each expressed CD44, α4‐integrins, LFA‐1, ICAM‐1, CD2 and L‐selectin in a pattern characteristic to cell type, but this did not correlate with the different ability of the leucocyte subsets to interact with the two types of HEV. In conclusion, determining the expression of CD44, α4‐integrins, LFA‐1, ICAM‐1, CD2 and L‐selectin on blood leucocytes alone is not sufficient to predict leucocyte/endothelium interaction in vivo
Oestrogen Treatment Depletes Extrathymic T Cells from Intestinal Lymphoid Tissues
Authors: BOLL G. , REIMANN J.
Published: October 2010

Different lineages of thymic and extrathymic T cells are found in the epithelial layer and in the lamina propria of the small and large intestine of euthymic and athymic mice. A single subcutaneous injection of oestradiolvalorat (Progynon®‐Depot‐10, Schering, Berlin, Germany) into athymic mice led to a dose‐dependent depletion of extrathymic T cells from the intraepithelial and lamina propria compartments of the small and large intestine. TCRαβ and TCRγδ, CD4+ and CD8α+ T cell subsets were affected. The depletion of intraepithelial, extrathymic T cells by oestradiol treatment was striking. Oestrogen, therefore, has an effect not only on genital mucous membranes, but also on the large, diffuse lymphoid tissues of the gut, in that it selectively depletes the intestinal, extrathymic T‐cell subsets.
Peripheral Blood Lymphocyte Adhesion Molecule Deployment in the Immune Response
Authors: PALLIS M. , ROBINS R. A. , POWELL R. J.
Published: October 2010

Using precise and reproducible flow cytometric measurements, the surface densities of the cell adhesion molecules (CAMs) CD29, CD2 and CD11a were studied on the CAMhigh (primed) subsets of peripheral blood CD4+ and CD8+ lymphocytes in 56 healthy subjects; 18 patients with acute bacterial infections, 19 with acute viral infections and 18 with chronic inflammatory conditions. By Mann–Whitney analysis, with significant P values adjusted for multiple comparisons to <0.0007, patients with viral infections were found to have increased CD11a on CAMhigh cells (an increase in median values of 13.7% for CD4+ lymphocytes and 15.8% for CD8+ lymphocytes); patients with chronic conditions have increased CD29 on CD8+CAMhigh lymphocytes (an increase in the median of 19%); and patients with bacterial infections have increased CD2 on CD8+CAMhigh cells (an increase in the median of 8%). There were marked individual increases in CD29 density: eight (15%) patients had CD29 gender‐adjusted density on CD4+ cells greater than the control mean + 3 standard deviations (SD). CD29 densities on CD8+ cells were elevated to > control mean + 3 SD in 12 (22%) patients. By multiple regression analysis CD11a density on CD8+ and CD4+ cells and CD2 density on CD4+ cells were found to be associated with HLA‐DR expression, but not with CD25 expression. Using standardized intercepts the authors demonstrated that there are very few circulating CD11ahighCD25+ cells, suggesting that these are rapidly extravasated. This study demonstrates that in disease, lymphocyte adhesion molecules are not deployed in concert and there are characteristic deployment patterns for different types of immune response.
Altered Allogeneic Response in Neonatally Anti‐MHC Class I‐Treated Mice
Authors: MARUŠIĆ‐GALEŠIĆ S. , SPARBIER K. , KNEZEVIC N. , WALDEN P.
Published: October 2010

Neonatal treatment of C3H mice (H‐2k) with anti‐Kk monoclonal antibodies results in altered cytotoxic responses against allogeneic targets. After 2–3 weeks of antibody treatment, no difference in the number of CD4+8− or CD4− 8+ T cells was observed between the antibody‐ and saline‐treated mice. However, antibody‐treated mice had a significantly reduced cytotoxic response against various allogeneic major histocompatibility complex (MHC) class I‐expressing targets. The strongest reduction was observed in very young mice (up to 2 weeks of age). As the mice got older, the allo MHC‐specific responses reached control levels. No significant changes in T‐cell receptor (TCR)‐V‐region usage was observed even in young antibody‐treated mice. The results suggest that the reduction in the number of positively selecting elements reduces alloreactivity and most likely also the diversity of TCR‐repertoire. However, the reduced alloresponsiveness was not restricted to either allogeneic K‐ or D‐encoded molecules, suggesting that self MHC‐D‐region encoded molecules can mediate positive selection of T cells able to react against both K and D region‐encoded allogeneic MHC class I molecules.
Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls
Authors: MOLBERG Ø . , KETT K. , SCOTT H. , THORSBY E. , SOLLID L. M. , LUNDIN K. E. A.
Published: October 2010

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten‐free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin‐2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti‐HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA‐DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA‐DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA‐DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non‐coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.
An insulin‐resistant hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the euglycaemic hyperinsulinaemic clamp in combination with the stable isotope technique
Authors: Bailhache E. , Ouguerram K. , Gayet C. , Krempf M. , Siliart B. , Magot T. , Nguyen P.
Published: October 2010

Many studies have shown that in humans insulin resistance (IR) is associated with obesity and hypertriglyceridaemia. The aim of our study was to develop slowly dietary‐induced obesity in dogs through long‐term overfeeding of a high‐fat diet, and to characterize this IR, hypertriglyceridaemic and normotensive model. Insulin resistance was assessed by the euglycaemic hyperinsulinaemic clamp technique. The contribution of hepatic glucose production during the clamp was evaluated using a constant stable‐isotope‐labelled glucose infusion.

Overfeeding a high‐fat diet for 7 months was associated with a 43 ± 5% body weight increase. Insulin resistance was characterized by hyperinsulinaemia in the unfed state (10 ± 1 vs. 24 ± 1 μU/ml, in healthy and obese dogs, respectively, p < 0.02) and by a reduction of the insulin‐mediated glucose uptake (28 ± 3 vs. 16 ± 1 mg/kg/min, p < 0.02). Hepatic glucose production suppression under insulin infusion allowed to conclude that this reduced glucose uptake resulted from a decrease of insulin sensitivity in obese dogs. Furthermore, animals remained normotensive and exhibited a marked hypertriglyceridaemia (0.26 ± 0.04 vs. 0.76 ± 0.15 mmol/l, in healthy and obese dogs, respectively, p < 0.02). Because hypertriglyceridaemia is the most common lipid abnormality in insulin‐resistant humans, this dog with slowly induced obesity may constitute a good model to study the consequences of IR in lipid metabolism independently of vascular changes.
Gene therapy: Recent advances and applications in gastroenterology and hepatology
Authors: OUYANG EDWIN , WU GEORGE
Published: October 2010

The advantages and disadvantages of viral and non‐viral vectors for gene delivery are reviewed. Advances in systems for introduction of new gene expression are described, including self‐deleting retroviral transfer vectors, chimeric viruses and chimeric oligonucleotides. Systems for inhibition of gene expression are also discussed including antisense oligonucleotides, ribozymes and dominant‐negative genes. Examples of the use of these systems in animal models and clinical trials for gastrointestinal disorders are discussed.
Role of growth factors in oesophageal mucosal healing: A work in progress
Authors: YOUNES ZIAD , DUNCAN MARK , HARMON JOHN
Published: October 2010

Reflux of gastroduodenal contents into the oesophagus results in dynamic cycles of injury followed by cell proliferation and repair. These processes are receiving increased attention due to the high incidence of gastro‐oesophageal reflux disease and the rising incidence of adenocarcinoma of the oesophagus. Repeated cycles of injury and repair may lead to abnormal differentiation followed by abnormal growth. This article summarizes the research performed by our group in the field of oesophageal injury and repair. We initially developed an in vivo perfused rabbit oesophagus model that served to study the effects of various components of the gastroduodenal juice on several parameters of oesophageal injury. We have shown that pepsin causes severe morphological oesophagitis at an acidic pH but is ineffective at an alkaline pH. We have also demonstrated that trypsin causes severe morphological oesophagitis at an alkaline pH but not at an acidic pH. Bile salts were found to disrupt the oesophageal barrier at both pH levels. We have also studied the effects of epidermal growth factor (EGF) and insulin‐like growth factor‐I (IGF‐I) on oesophageal regeneration. We used an ex vivo oesophageal explant model for these experiments. Both EGF and IGF‐I cause a dose‐dependent increase in oesophageal DNA synthesis, cell proliferation and mucosal growth. These effects are synergistic and can be inhibited by specific tyrphostins. We are currently studying the role of growth factors as therapeutic agents and the role of growth factors in the development of Barrett’s oesophagus and adenocarcinoma.
Variceal haemorrhage: An update on treatment
Authors: SUNG JOSEPH
Published: October 2010

Recent advances in the management of variceal haemorrhage include injection of cyanoacrylate and the use of banding ligation. New pharmacological agents, such as somatostatin and octreotide, have also proved to be effective in controlling variceal haemorrhage. The transjugular intrahepatic porto‐systemic shunt (TIPS) represents an effective rescue when other treatment modalities fail. A multi‐disciplinary approach should be emphasized in the management of this high‐risk complication of portal hypertension.
Non‐steroidal anti‐inflammatory drugs that cause relatively little gastric damage
Authors: TAVARES IGNATIUS , BENNETT ALAN
Published: October 2010

Gastrointestinal damage by non‐steroidal anti‐inflammatory drugs (NSAID), which is common and sometimes fatal, involves inhibition of prostaglandin (PG) synthesis. The damage is less with NSAID that inhibit inflammatory cyclo‐oxygenase (COX)‐2 but not gastroprotective COX‐1. We have compared nimesulide and acemetacin, two NSAID that cause relatively little gastric damage, with indomethacin for effects on purified COX‐1 and COX‐2. The results are related to findings on human gastric mucosa and leucocytes. With purified COX‐1, inhibition was absent with nimesulide, weak with acemetacin (inhibitory concentration of 50%[IC50] 85 μmol/L), and potent with indomethacin (IC500.6 μmol/L). Inhibition of purified COX‐2 occurred with nimesulide and indomethacin (IC50values 90 and 4.1 μmol/L, respectively) but not acemetacin. All results with nimesulide are consistent with a preferential block of COX‐2 that contributes to relatively little gastric damage in patients. However, our previous report on acemetacin needs re‐evaluation. Acemetacin did not inhibit sheep COX‐2 and only weakly inhibited COX‐1. Our previous leucocyte (COX‐2) experiments required 24 h incubation, and hydrolysis of acemetacin to indomethacin presumably accounted for the COX‐2 inhibition. In the few minutes of enzyme incubation, virtually no hydrolysis would be expected. Acemetacin itself presumably causes relatively little gastric damage mainly because it only weakly inhibits COX‐1.
Aged gastric mucosa: Mechanisms of vulnerability
Authors: MALCONTENTI‐WILSON CATHY , SCHULZ SONIA , PENNEY ANGELA , ANDREWS FIONA , O’BRIEN PAUL
Published: October 2010

The incidence, frequency of complications and mortality of gastric ulcer disease are increased four‐fold in the elderly taking non‐steroidal anti‐inflammatory drugs (NSAID). There is controversy as to whether this reflects increased usage of NSAID or specific vulnerability associated with age. We have investigated two possible mechanisms for this increase in gastrointestinal effects in the elderly: (i) increased susceptibility to acute gastrotoxicity; and (ii) reduced adaptation to NSAID, in a model of young (2 month), mature (12 month) and aged (24 month) rats. Aspirin damaged 7.7% of the volume of gastric mucosa in the young rat. In mature and aged rats, this increased to 11.3% (P< 0.002 compared to control) and 21.9% (P< 0.005 compared to control), respectively. Thus, aspirin caused a three‐fold increase in the severity of acute gastric mucosal injury in aged animals. However, indomethacin, ibuprofen and L745 337 did not produce any significant acute gastric mucosal damage in 2‐, 12‐ or 24‐month‐old rats. Significant gastric adaptation to diclofenac treatment occurred in both aged and young rats as measured by gastric mucosal damage. The aged gastric mucosa adapted equally as well as the young gastric mucosa to diclofenac. The findings of this study provide only modest support to the hypothesis of increased vulnerability of the stomach in the aged. Aspirin was associated with greater damage in the aged. Adaptation to diclofenac‐induced damage was not reduced in the aged and there was not an increased susceptibility to damage by the non‐aspirin NSAID tested. The selective cyclo‐oxygenase‐2 inhibitor, L745 337, was the least toxic agent and may represent a group of NSAID which cause fewer gastrointestinal complications in the elderly.
Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury
Authors: TACHÉ Y , KANEKO H , KAWAKUBO K , KATO K , KIRÁLY Á , YANG H
Published: October 2010

Activation of medullary thyrotropin‐releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane‐anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin‐sensitive splanchnic afferents leading to calcitonin gene‐related peptide (CGRP)‐ and nitric oxide (NO)‐dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal‐dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal‐dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non‐adrenergic, non‐cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal‐dependent mechanisms which increase the resistance of the gastric mucosa to injury.
Gastrointestinal motor function in diabetes mellitus: Relationship to blood glucose concentrations
Authors: HOROWITZ MICHAEL , RAYNER CHRIS , KONG MARIE‐FRANCE , JONES KAREN , WISHART JUDITH , SUN WEI‐MING , FRASER ROBERT
Published: October 2010

The application of novel investigative techniques has established that there is a high prevalence of disordered gastrointestinal motor function in patients with diabetes mellitus and has provided insights into its pathogenesis and clinical significance. Acute changes in the blood glucose concentration, even within the normal postprandial range, affect both gastrointestinal motor function and the perception of sensations arising from the gastrointestinal tract. Gastric emptying is slower during hyperglycaemia and accelerated during hypoglycaemia; the perception of gastric distension is greater during hyperglycaemia than euglycaemia. The pathways mediating the effects of the blood glucose concentration on gut motility and sensation are poorly defined. The rate of gastric emptying is an important determinant of postprandial blood glucose concentrations and there is increasing evidence that gastric emptying can be modulated therapeutically in order to optimize glycaemic control in patients with diabetes.