bluuebunny/crossref_metadata_2025 huggingface dataset:
MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells
Authors: Lee Ying-Ray , Liu Ming-Tao , Lei Huan-Yao , Liu Ching-Chuan , Wu Jing-Ming , Tung Yi-Ching , Lin Yee-Shin , Yeh Trai-Ming , Chen Shun-Hua , Liu Hsiao-Sheng
Published: November 2006

Vascular leakage, one hallmark of dengue haemorrhagic fever (DHF) and dengue shock syndrome, has been linked to the mediators secreted from cells in the circulatory system. In this study, extremely high expression levels of monocyte chemoattractant protein-1 (MCP-1) were found in the plasma of DHF patients compared with low MCP-1 expression levels in the plasma of enterovirus 71-infected patients. It was also found that MCP-1 expression was induced in dengue virus 2 (DV2)-infected monocytes and lymphocytes, but not in liver or endothelial cells. Exposing monolayers of human umbilical vein endothelial cells (HUVECs) to recombinant human MCP-1 (rhMCP-1) or to the culture supernatant of DV2-infected human monocytes increased the vascular permeability of the cells. MCP-1-neutralizing monoclonal antibody only partially prevented monolayer permeability change. Consistently, the distribution of the tight junction protein ZO-1 on the cellular membranes of HUVECs was disrupted by rhMCP-1 or by the conditioned medium of DV2-infected monocytes. In summary, it was found that the increased permeability and disrupted tight junctions of human vascular endothelium cells were effected through a mechanism partially dependent on MCP-1, which was secreted by DV2-infected monocytes and lymphocytes.
A hepatitis C virus (HCV) NS3/4A protease-dependent strategy for the identification and purification of HCV-infected cells
Authors: Breiman Adrien , Vitour Damien , Vilasco Myriam , Ottone Catherine , Molina Sonia , Pichard Lydiane , Fournier Chantal , Delgrange David , Charneau Pierre , Duverlie Gilles , Wychowski Czeslaw , Maurel Patrick , Meurs Eliane F.
Published: November 2006

As a tool for the identification and/or purification of hepatitis C virus (HCV)-infected cells, a chimeric form of the Gal4VP16 transcription factor was engineered to be activated only in the presence of the HCV NS3/4A protease and to induce different reporter genes [choramphenical acetyltransferase (CAT), green fluorescent protein (GFP) and the cell-surface marker H-2Kk] through the (Gal4)5-E1b promoter. For this, the NS5A/5B trans-cleavage motif of HCV of genotype 1a was inserted between Gal4VP16 and the N terminus of the endoplasmic reticulum (ER)-resident protein PERK, and it was demonstrated that it could be cleaved specifically by NS3/4A. Accordingly, transient transfection in tetracycline-inducible UHCV-11 cells expressing the HCV polyprotein of genotype 1a revealed the migration of the Gal4VP16 moiety of the chimera from the ER to the nucleus upon HCV expression. Activation of the chimera provoked specific gene induction, as shown by CAT assay, first in UHCV-11 cells and then in Huh-7 cells expressing an HCV replicon of genotype 1b (Huh-7 Rep). In addition, the GFP reporter gene allowed rapid fluorescence monitoring of HCV expression in the Huh-7 Rep cells. Finally, the chimera was introduced into Huh-7.5 cells infected with cell culture-generated HCV JFH1 (genotype 2a), allowing the purification of the HCV-infected cells by immunomagnetic cell sorting using H-2Kk as gene reporter. In conclusion, the Gal4VP16 chimera activation system can be used for the rapid identification and purification of HCV-infected cells.
Competition and complementation between thymidine kinase-negative and wild-type herpes simplex virus during co-infection of mouse trigeminal ganglia
Authors: Chen Shih-Heng , Lin Yu-Wen , Griffiths Anthony , Huang Wen-Yen , Chen Shun-Hua
Published: November 2006

Laboratory strains of herpes simplex virus lacking thymidine kinase (TK) cannot replicate acutely to detectable levels in mouse trigeminal ganglia and do not reactivate from latency. However, many pathogenic clinical isolates that are resistant to the antiviral drug acyclovir are heterogeneous populations of TK-negative (TK−) and TK-positive (TK+) viruses. To recapitulate this in vivo, mice were infected with mixtures of wild-type virus and a recombinant TK− mutant in various ratios. Following co-infection, the replication, number of latent viral genomes and reactivation efficiency of TK+ virus in trigeminal ganglia were reduced in a manner related to the amount of TK− virus in the inoculum. TK+ virus did not always complement the acute replication or increase the number of latent viral genomes of TK− mutant in mouse ganglia. Even so, TK+ virus could still confer the pathogenic phenotype to a TK− mutant, somehow providing sufficient TK activity in trans to permit a TK− mutant to reactivate from latently infected ganglia.
Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells
Authors: Hoppe Sven , Schelhaas Mario , Jaeger Verena , Liebig Timo , Petermann Philipp , Knebel-Mörsdorf Dagmar
Published: November 2006

The aim of this study was to understand how molecular determinants of epithelial cells influence initial infection by herpes simplex virus type 1 (HSV-1). Upon infection of the epithelial MDCKII cell line, enhanced association of virus particles with cells forming actin protrusions was observed, suggesting a putative role of actin dynamics in HSV-1 infection. Thus, the impact of the small Rho-like GTPases Rac1, Cdc42 and RhoA acting as key regulators of actin dynamics was addressed. Endogenous Rac1 and Cdc42 were temporarily activated at 15 and 30 min after HSV-1 infection. When constitutively active Cdc42 or Rac1 mutants were expressed transiently, a significant decrease in infectivity was observed, whereas expression of RhoA mutants had no influence. Furthermore, dominant-negative Cdc42 led to decreased infectivity, whereas dominant-negative Rac1 had no effect. So far, the study of potential effectors indicated that Rac1/Cdc42 mutants inhibited infectivity independently of p21-activated kinase (Pak1). The inhibitory effect of Rac1/Cdc42 mutant expression on HSV-1 infection was characterized further and it was found that binding, internalization and transport of HSV-1 were not affected by expression of Rac1/Cdc42 mutants. Thus, these results provide the first evidence for a role of Rac1/Cdc42 signalling during early HSV-1 infection and suggest a mechanism relying on virus-induced regulation of Rac1/Cdc42 activities.
Exchange of P/V genes between two non-cytopathic simian virus 5 variants results in a recombinant virus that kills cells through death pathways that are sensitive to caspase inhibitors
Authors: Dillon Patrick J. , Wansley Elizabeth K. , Young Virginia A. , Alexander-Miller Martha A. , Parks Griffith D.
Published: November 2006

The paramyxovirus Simian virus 5 (SV5) is largely non-cytopathic in human epithelial and fibroblast cells. WF-PIV has been described previously as a naturally occurring SV5 variant that encodes P and V proteins differing from the wild-type (WT) SV5 proteins in eight and five amino acid positions, respectively. In this study, it is shown that WF-PIV is like WT SV5 by being largely non-cytopathic in A549 lung epithelial cells. However, substitution of the WF-PIV P/V gene into the background of WT SV5 resulted in a hybrid virus (P/V-WF) that induced apoptotic cell death not seen with either of the parental viruses. The kinetics of HeLa cell killing and induction of apoptosis by the P/V-WF chimera differed from those of the previously described P/V-CPI− chimera by being slower and less extensive. HeLa cell killing by the P/V-WF chimera was effectively reduced by inhibitors of caspase-9, but not of caspase-8. These results demonstrate that an exchange of P/V genes from two non-cytopathic SV5 variants can produce apoptosis-inducing chimeras, and that the role of the SV5 P/V gene products in limiting apoptosis can be dependent on expression in the context of a native viral genome.
A single amino acid substitution in the V protein of Nipah virus alters its ability to block interferon signalling in cells from different species
Authors: Hagmaier Kathrin , Stock Nicola , Goodbourn Steve , Wang Lin-Fa , Randall Richard
Published: November 2006

The V protein of the paramyxovirus Nipah virus (NiV) has been shown to antagonize the interferon (IFN) response in human cells via sequestration of STAT1 and STAT2. This study describes a mutant of the NiV V protein, referred to as V(AAHL), that is unable to antagonize IFN signalling and demonstrates that a single amino acid substitution is responsible for its inactivity. The molecular basis for this was identified as a failure to interact with STAT1 and STAT2. It was also shown that NiV V, but not V(AAHL), was functional as an IFN antagonist in human, monkey, rabbit, dog, horse, pig and bat cells, which suggests that the ability of NiV to block IFN signalling is not a major constraint that prevents this virus from crossing species barriers.
Multiple virus resistance at a high frequency using a single transgene construct
Authors: Bucher Etienne , Lohuis Dick , van Poppel Pieter M. J. A. , Geerts-Dimitriadou Christina , Goldbach Rob , Prins Marcel
Published: November 2006

RNA silencing is a natural antiviral defence in plants, which can be exploited in transgenic plants for preprogramming virus recognition and ensuring enhanced resistance. By arranging viral transgenes as inverted repeats it is thus possible to obtain strong repression of incoming viruses. Due to the high sequence specificity of RNA silencing, this technology has hitherto been limited to the targeting of single viruses. Here it is shown that efficient simultaneous targeting of four different tospoviruses can be achieved by using a single small transgene based on the production of minimal sized chimaeric cassettes. Due to simultaneous RNA silencing, as demonstrated by specific siRNA accumulation, the transgenic expression of these cassettes rendered up to 82 % of the transformed plant lines heritably resistant against all four viruses. Thus RNA silencing can be further improved for high frequency multiple virus resistance by combining small RNA fragments from a series of target viruses.
Tomato yellow spot virus, a tomato-infecting begomovirus from Brazil with a closer relationship to viruses from Sida sp., forms pseudorecombinants with begomoviruses from tomato but not from Sida
Authors: Andrade E. C. , Manhani G. G. , Alfenas P. F. , Calegario R. F. , Fontes E. P. B. , Zerbini F. M.
Published: November 2006

Geminiviruses are characterized by a circular, single-stranded DNA genome and twinned icosahedral particles. Begomoviruses (whitefly-transmitted geminiviruses) are a major constraint to crop production worldwide. In Brazil, tomato-infecting begomoviruses emerged as serious pathogens over the last 10 years, due to the introduction of a new biotype of the insect vector. Tomato yellow spot virus (ToYSV) is a newly described begomovirus originally isolated from tomato, but phylogenetically closer to viruses fromSidasp. A study was performed to determine the viability of pseudorecombinants formed between the DNA components of ToYSV and other weed- and tomato-infecting begomoviruses from Brazil. Despite its closer relationship to weed-infecting viruses, ToYSV was only capable of forming viable pseudorecombinants with tomato viruses. An infectious pseudorecombinant formed between ToYSV DNA-A and tomato crinkle leaf yellows virus (TCrLYV) DNA-B induced severe symptoms inNicotiana benthamiana. This was attributed, at least in part, to the fact that the origins of replication of both components had identical Rep-binding sequences. However, this was not the case for another infectious pseudorecombinant formed between tomato golden mosaic virus (TGMV) DNA-A and ToYSV DNA-B, which have different Rep-binding sequences. These results reinforce the notion that pseudorecombinant formation cannot be explained solely on the basis of phylogenetic relationships and conserved iteron sequences, and suggest that the TGMV Rep protein may be more versatile in terms of recognizing heterologous DNA components than that of ToYSV.
Genome sequences of two frog herpesviruses
Authors: Davison Andrew J. , Cunningham Charles , Sauerbier Walter , McKinnell Robert G.
Published: November 2006

The sequences of two frog herpesviruses, Ranid herpesvirus 1 and Ranid herpesvirus 2, were determined. They are respectively 220 859 and 231 801 bp in size and contain 132 and 147 predicted genes. The genomes are related most closely in the central regions, where 40 genes are conserved convincingly. Nineteen of these genes are also conserved in a fish herpesvirus, Ictalurid herpesvirus 1. The terminal regions of the genomes are largely not conserved and contain many of the 15 families of related genes present in each genome. The frog herpesviruses are unique among sequenced herpesviruses in that the three exons of the gene encoding the putative ATPase subunit of terminase are not specified by the same DNA strand and in that they encode a putative DNA (cytosine-5-)-methyltransferase and have extensively methylated genomes.
Isolation and characterization of the first American bottlenose dolphin papillomavirus: Tursiops truncatus papillomavirus type 2
Authors: Rehtanz Manuela , Ghim Shin-je , Rector Annabel , Van Ranst Marc , Fair Patricia A. , Bossart Gregory D. , Jenson Alfred B.
Published: November 2006

A novel papillomavirus (PV) was isolated from a genital condyloma of a free-ranging bottlenose dolphin inhabiting the coastal waters of Charleston Harbor, SC, USA: Tursiops truncatus papillomavirus type 2 (TtPV2). This novel virus represents the first isolated North American cetacean PV and the first American bottlenose dolphin PV. After the viral genome was cloned, sequenced and characterized genetically, phylogenetic analyses revealed that TtPV2 is most similar to the only published cetacean PV isolated and characterized thus far, Phocoena spinipinnis PV type 1 (PsPV1). A striking feature of the genome of TtPV2, as well as that of PsPV1, is the lack of an E7 open reading frame, which typically encodes one of the oncogenic proteins believed to be responsible for malignant transformation in the high-risk mucosotropic human papillomaviruses (HPVs). TtPV2 E6 contains a PDZ-binding motif that has been shown to be involved in transformation in the case of high-risk genital HPVs.
Gene discovery and annotation using LCM-454 transcriptome sequencing
Authors: Emrich Scott J. , Barbazuk W. Brad , Li Li , Schnable Patrick S.
Published: November 2006

454 DNA sequencing technology achieves significant throughput relative to traditional approaches. More than 261,000 ESTs were generated by 454 Life Sciences from cDNA isolated using laser capture microdissection (LCM) from the developmentally important shoot apical meristem (SAM) of maize (Zea mays L.). This single sequencing run annotated >25,000 maize genomic sequences and also captured ∼400 expressed transcripts for which homologous sequences have not yet been identified in other species. Approximately 70% of the ESTs generated in this study had not been captured during a previous EST project conducted using a cDNA library constructed from hand-dissected apex tissue that is highly enriched for SAMs. In addition, at least 30% of the 454-ESTs do not align to any of the ∼648,000 extant maize ESTs using conservative alignment criteria. These results indicate that the combination of LCM and the deep sequencing possible with 454 technology enriches for SAM transcripts not present in current EST collections. RT-PCR was used to validate the expression of 27 genes whose expression had been detected in the SAM via LCM-454 technology, but that lacked orthologs in GenBank. Significantly, transcripts from ∼74% (20/27) of these validated SAM-expressed “orphans” were not detected in meristem-rich immature ears. We conclude that the coupling of LCM and 454 sequencing technologies facilitates the discovery of rare, possibly cell-type-specific transcripts.
Possible interethnic differences in quinidine‐induced QT prolongation between healthy Caucasian and Korean subjects
Authors: Shin Jae‐Gook , Kang Won‐ku , Shon Ji‐Hong , Arefayene Million , Yoon Young‐Ran , Kim Kyung‐Ah , Kim Doo‐Il , Kim Dong‐Soo , Cho Kwang‐Hyun , Woosley Raymond L. , Flockhart David A.
Published: November 2006

Aims

The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of quinidine‐induced QT prolongation in healthy Caucasian and Korean subjects to investigate interethnic differences in susceptibility to drug‐induced arrhythmia.

Methods

A randomized, double‐blind crossover study was conducted in 24 (12 male and 12 female) Korean and 13 (seven male and six female) Caucasian subjects. After a 20 min infusion of quinidine (4 mg kg−1) or saline, the serum concentration of quinidine and the QT interval corrected by Bazett's formula (QTc) were monitored. The dynamic data were analyzed by means of a population modelling approach using NONMEM.

Results

There were no statistical differences in the pharmacokinetic profiles of quinidine between ethnic groups. The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in female subjects. According to an Emaxmodel, the population modelling approach revealed that E0(ms) was related to gender (408 + [34*(1 − Sex)]; 1 for male and 0 for female), ΔEmax(ms) was related to ethnicity ((136*fETHN) + Cfemale:fETHN = 1 for Koreans and 1.26 for Caucasians;Cfemalewas 106 only for Caucasian females), and EC50was estimated to be 3.13 µm.

Conclusions

These results suggest that Korean subjects were less sensitive to quinidine‐induced QT prolongation than Caucasian subjects, and that this trend was particularly true for females. Further population‐based studies are merited to characterize more completely the ethnic differences in drug‐induced QT prolongation between Asians and other ethnic groups.
Prey resource use by bluegill and channel catfish in small impoundments
Authors: MICHALETZ P. H.
Published: November 2006

Abstract  Channel catfish, Ictalurus punctatus (Rafinesque), are commonly stocked into small impoundments that contain bluegill, Lepomis macrochirus Rafinesque, and these species may compete for food resources because both prey on macroinvertebrates. Prey selectivity and diet overlap of sympatric bluegill and channel catfish were evaluated in two small impoundments. Both fish species fed primarily on macroinvertebrates; but diet overlap between the species generally was not extensive because channel catfish consumed a more diverse array of foods, including more crayfish, fish and plant material. The use of foods other than macroinvertebrates increased as channel catfish grew larger. Bluegill also ingested large quantities of plant material at times, and ingestion of plants increased with fish size. Results of this study suggest that food competition between bluegill and channel catfish may occur when small channel catfish are abundant because, like bluegill, they feed almost entirely on macroinvertebrates and may reduce macroinvertebrate abundance. Thus, overstocking channel catfish in small impoundments managed for bluegill should be avoided.
Near real‐time spatial management based on habitat predictions for a longline bycatch species
Authors: HOBDAY A. J. , HARTMANN K.
Published: November 2006

Abstract  Southern bluefin tuna (SBT), Thunnus maccoyii (Castelnau), is a quota‐managed species that makes annual winter migrations to the Tasman Sea off south‐eastern Australia. During this period it interacts with a year‐round tropical tuna longline fishery (Eastern Tuna and Billfish Fishery, ETBF). ETBF managers seek to minimise the bycatch of SBT by commercial ETBF longline fishers with limited or no SBT quota through spatial restrictions. Access to areas where SBT are believed to be present is restricted to fishers holding SBT quota. A temperature‐based SBT habitat model was developed to provide managers with an estimate of tuna distribution upon which to base their decisions about placement of management boundaries. Adult SBT temperature preferences were determined using pop‐up satellite archival tags. The near real‐time predicted location of SBT was determined by matching temperature preferences to satellite sea surface temperature data and vertical temperature data from an oceanographic model. Regular reports detailing the location of temperature‐based SBT habitat were produced during the period of the ETBF fishing season when interactions with SBT occur. The SBT habitat model included: (i) predictions based on the current vertical structure of the ocean; (ii) seasonally adjusted temperature preference data for the 60 calendar days centred on the prediction date; and (iii) development of a temperature‐based SBT habitat climatology that allowed visualisation of the expected change in the distribution of the SBT habitat zones throughout the season. At the conclusion of the fishing season an automated method for placing management boundaries was compared with the subjective approach used by managers. Applying this automated procedure to the habitat predictions enabled an investigation of the effects of setting management boundaries using old data and updating management boundaries infrequently. Direct comparison with the management boundaries allowed an evaluation of the efficiency and biases produced by this aspect of the fishery management process. Near real‐time fishery management continues to be a realistic prospect that new scientific approaches using novel tools can support and advance.
Immunological aspects of inhibitor development
Authors: REDING M. T.
Published: November 2006

Summary.  The development of inhibitor antibodies is perhaps the most serious complication of coagulation factor replacement therapy. A complex interaction of several variables leads to inhibitor formation in congenital haemophilia, while acquired haemophilia represents a failure of the immune tolerance mechanisms that regulate a normal immune response to factor VIII (FVIII). The immune response to FVIII is dependent upon the interaction of different CD4+ T‐cell subsets (Th1, Th2 and Th3) specific for FVIII. Failure to activate regulatory CD4+ cells likely plays a crucial role in the development of FVIII inhibitors. Although the basic mechanisms of the immune response to FVIII in the setting of factor replacement therapy are being elucidated, a clear understanding of the relevance of these mechanisms in the context of successful immune tolerance therapy and ultimately gene therapy, awaits further study.
Characteristics of inhibitors in mild/moderate haemophilia A
Authors: PEERLINCK K. , JACQUEMIN M.
Published: November 2006

Summary.  Patients with mild or moderate haemophilia A usually have a mild bleeding disorder requiring only occasional treatment with factor VIII (FVIII) concentrates. The frequency of inhibitor development in such patients has been the subject of several recent surveys, which significantly modified our appreciation of this complication. Studies of the anti‐FVIII antibodies provided an explanation for the different bleeding phenotypes observed in mild/moderate haemophilia A patients with inhibitors. Antibodies distinguishing between the patient's mutant FVIII and the normal wild‐type FVIII were characterized, in addition to antibodies inhibiting completely or only partially FVIII activity. T lymphocytes recognizing FVIII and likely involved in the development of the immune response to FVIII were successfully identified. The FVIII peptides recognized by those FVIII‐specific cells bind to many major histocompatibility complex (MHC) class II molecules, which may provide an explanation for the lack of strong association between MHC haplotypes and inhibitor development. Although these studies have advanced our understanding of the conditions leading to inhibitor development, further work is required to determine whether the mode of FVIII administration significantly influences inhibitor development. Further studies of the genetic factors are also required to fully understand the mechanisms leading to inhibitor development in patients with mild/moderate haemophilia A.
Options for treating acute bleeds in addition to bypassing agents: extracorporeal immunoadsorption, FVIII/FIX, desmopressin and antifibrinolytics
Authors: BERNTORP E.
Published: November 2006

Summary.   Inhibitor patients do not always respond satisfactorily to treatment with bypassing agents, and options to the standard practice are sometimes needed. Temporary inhibitor removal may be achieved using extracorporeal immunoadsorption. This technique uses a column system including either protein A or antihuman IgG. Immunoadsorption may be used as part of an immune tolerance protocol, or in the case of acute bleeds or prior to surgery, thus rendering the patient more responsive to ordinary replacement therapy with factor VIII or factor IX. Desmopressin is a valuable haemostatic agent in many situations and can be especially recommended in mild haemophilia complicated by an inhibitor. Antifibrinolytics are often administered as an adjunct therapy to the treatment protocol and have also been reported to have a direct anti‐inhibitor effect.
Immune tolerance: critical issues of factor dose, purity and treatment complications
Authors: DIMICHELE D. M.
Published: November 2006

Summary.  The current practice of immune tolerance induction (ITI) therapy has been largely influenced by the results of small institutional studies and three large registries. However, many questions remain. Successful outcome predictors for ITI in haemophilia A have been suggested by the analyses of two of these registries. Among these predictors, factor VIII (FVIII) dose/dosing regimen remains a controversial outcome parameter, demonstrating a strong direct relationship to ITI success in the international registry and a weaker inverse relationship in the North American registry. There is an international multicentre prospective randomized trial underway to further study the role of FVIII dose in successful ITI induction in a good risk haemophilia A inhibitor patient cohort. FVIII purity also remains an unproved ITI outcome predictor. Institutional experience with von‐Willebrand‐factor‐containing products has suggested its therapeutic advantage in both inhibitor development and eradication. The International ITI Study, although not designed to answer this particular question, may be able to determine an impact on outcome depending on the final distribution of investigator choice of product among the study subjects. Much less is known about the influence of factor IX (FIX) dose and purity on ITI success in haemophilia B. Importantly, nephrotic syndrome has been a major determinant of ITI failure in FIX inhibitor patients, particularly those with the allergic phenotype. Unfortunately, large prospective randomized trials in this group will not be feasible. Rather, we will have to rely on prospectively collected registry data to build our knowledge base of inhibitors and ITI in haemophilia B.
Quality guidelines for endodontic treatment: consensus report of the European Society of Endodontology
Authors:   European Society of Endodontology
Published: November 2006

The assurance of the quality of a service rendered by a member of the dental profession is an essential feature of any system of peer review in dentistry. This document addresses two essential elements: (i) appropriateness of treatment modality and (ii) quality or level of treatment rendered. In revising these guidelines the European Society of Endodontology is responding to a public and professional need. In receiving care of a specialized nature such as endodontic treatment, patients need and deserve treatment that meets the standard of care generally given by competent practitioners. The European Society of Endodontology has the expertise and professional responsibility necessary to assist the dental profession by instituting guidelines on the standard of care in the special area of Endodontics. In accepting this responsibility the European Society of Endodontology formulated treatment guidelines that are intended to represent current good practice. This document is the revised version of an earlier consensus report [International Endodontic Journal (1994) 27, 115–24]. As there is not one single way of performing treatment, these guidelines have been formulated in broad terms.
Assessing palliative care needs: views of patients, informal carers and healthcare professionals
Authors: McIlfatrick Sonja
Published: November 2006

Title. Assessing palliative care needs: views of patients, informal carers and healthcare professionals

Aim.  This paper reports a study to assess the palliative care needs of the adult population served by a healthcare provider organization in Northern Ireland from the perspectives of patients, informal carers and healthcare providers.

Background.  Assessing palliative care need is a key factor for health service planning. Traditionally, palliative care has been associated with end‐of‐life care and cancer. More recently, the concept has been extended to include care for both cancer and non‐cancer populations. Various approaches have been advocated for assessing need, including the exploration of professional provider and user perspectives of need.

Method.  Semi‐structured qualitative interviews were undertaken with a purposive sample of patients and lay carers receiving palliative care services (n = 24). Focus groups were also conducted with multi‐professional palliative care providers (n = 52 participants) and face to face interviews were undertaken with key managerial stakeholders in the area (n = 7). The focus groups and interviews concentrated on assessment of palliative care need. All the interviews were transcribed verbatim and analysed using Burnard's framework.

Findings.  Professional providers experienced difficulty in defining the term palliative care. Difficulties in communication and information exchange, and fragmented co‐ordination between services were identified. The main areas of need identified by all participants were social and psychological support; financial concerns; and the need for choice and information. All participants considered that there was inequity between palliative care service provision for patients with cancer and non‐cancer diseases.

Conclusion.  All patients, regardless of diagnosis, should be able to access palliative care appropriate to their individual needs. For this to happen in practice, an integrated approach to palliative care is essential. The study methodology confirms the value of developing a comprehensive approach to assessing palliative care need.
‘Preparative waiting’ and coping theory with patients going through gastric diagnosis
Authors: Giske Tove , Gjengedal Eva
Published: November 2006

Title. Preparative waiting’ and coping theory with patients going through gastric diagnosis

Aim. This paper reports a study of how hospitalized patients with gastro‐intestinal problems going through diagnostic workups experience and handle the situation. It presents a theory of ‘preparative waiting’ and discusses it in relation to Lazarus’ theory of appraisal, stress and coping.

Background. The pre‐diagnostic phase is reported to be the most stressful time of the illness for patients, but there is little research on this with patients in gastric units. According to Lazarus, appraisal and coping are concurrent, and stress must be understood as both an intra‐ and an inter‐personal process.

Method. A grounded theory design was chosen to conduct and analyse 18 in‐depth interviews with 15 patients in a gastric unit at a Norwegian university hospital. The data were collected in 2002–2003.

Findings. Participants’ main concern was found to be how to prepare themselves for the results of the investigation and for life afterwards. The substantive grounded theory of ‘Preparative waiting’ presented here explains how they acted to do so. To be in the diagnostic phase meant to be in a process of continuously attempting to make sense of one's situation. Participants could judge their case to be harmful, a threat, a challenge, a benefit, or combinations of these. Their searches for realistic interpretation were balanced with searches for hopeful signs. This, together with lowering and rising of awareness, prevented them from despair. The process of understanding and handling the situation was concurrent, and was influenced by their relationships with family, friends, fellow patients, healthcare personnel and God.

Conclusion. To the degree that patients trusted that nurses understood and were sensitive to the complex processes of appraising and coping, they became patients’ key support persons. By providing adjusted information, coordinating care and examinations, respecting privacy, and inquiring about existential concerns, nurses could promote patients’ ability to prepare for receiving the diagnosis and life after.
Electronic searching to locate qualitative research: evaluation of three strategies
Authors: Flemming Kate , Briggs Michelle
Published: November 2006

Title.Electronic searching to locate qualitative research: evaluation of three strategies

Aim.  This paper presents an evaluation of the effectiveness of three search strategies to identify research for a qualitative synthesis of patient experiences of living with a leg ulcer.

Background.  Systematic reviews of research are increasingly the form of evidence used for evaluation of health care. There are well‐established methods for conducting systematic reviews of effectiveness incorporating randomized controlled trials. Methods have been developed for the synthesis of qualitative research, but these are not widely used or evaluated. Searching for qualitative research is one of the least developed and tested areas in systematic reviewing of qualitative research.

Method.  The replication of three search strategies (free text, thesaurus and broad‐based terms) developed for identification of qualitative research papers within electronic databases is described. Each strategy was run in seven electronic databases: MEDLINE, CINAHL, EMBASE, British Nursing Index, Social Science Citation Index, Applied Social Sciences Index and Abstracts, PsychInfo. The effectiveness of these strategies for identifying qualitative research for a synthesis of patients’ experiences of living with a leg ulcer is discussed.

Findings.  Each of the three search strategies produced similar numbers of potentially and actually relevant papers from each of the seven databases. These results were most striking for CINAHL, when all of the papers ultimately included in the review were identified by each search strategy. No other database identified all included papers.

Conclusion.  A simple search strategy using broad‐based terms was as effective as a complex one (free text) in locating qualitative research examining patients’ experiences of living with a leg ulcer. For a question with a clear nursing focus, it may be sufficient to search only CINAHL in order to locate qualitative research. This result needs replicating with other nursing topics.
Impact of hospital nursing care on 30‐day mortality for acute medical patients
Authors: Tourangeau Ann E. , Doran Diane M. , Hall Linda McGillis , O'Brien Pallas Linda , Pringle Dorothy , Tu Jack V. , Cranley Lisa A.
Published: November 2006

Aim.  This paper reports on structures and processes of hospital care influencing 30‐day mortality for acute medical patients.

Background.  Wide variation in risk‐adjusted 30‐day hospital mortality rates for acute medical patients indicates that hospital structures and processes of care affect patient death. Because nurses provide the majority of care to hospitalized patients, we propose that structures and processes of nursing care have an impact on patient death or survival.

Method.  A model hypothesizing the impact of nursing‐related hospital care structures and processes on 30‐day mortality was tested. Patient data from the Ontario, Canada Discharge Abstract Database 2002–2003, nurse data from the Ontario Nurse Survey 2003, and hospital staffing data from the Ontario Hospital Reporting System 2002–2003 files were used to develop indicators for variables hypothesized to impact 30‐day mortality. Two multiple regression models were implemented to test the model. First, all variables were forced to enter the model simultaneously. Second, backward regression was implemented.

Findings.  Using backward regression, 45% of variance in risk‐adjusted 30‐day mortality rates was explained by eight predictors. Lower 30‐day mortality rates were associated with hospitals that had a higher percentage of Registered Nurse staff, a higher percentage of baccalaureate‐prepared nurses, a lower dose or amount of all categories of nursing staff per weighted patient case, higher nurse‐reported adequacy of staffing and resources, higher use of care maps or protocols to guide patient care, higher nurse‐reported care quality, lower nurse‐reported adequacy of manager ability and support, and higher nurse burnout.

Conclusion.  Just as hospitals and clinicians caring for patients focus carefully on completing accurate diagnosis and appropriate and effective interventions, so too should hospitals carefully plan and manage structures and processes of care such as the proportion of Registered Nurses in the staff mix, percentage of baccalaureate‐prepared nurses, and routine use of care maps to minimize unnecessary patient death.
Systematic reviews of bladder training and voiding programmes in adults: a synopsis of findings on theory and methods using metastudy techniques
Authors: Roe Brenda , Milne Jill , Ostaszkiewicz Joan , Wallace Sheila
Published: November 2006

Aim.  This paper reports a comparison of four Cochrane systematic reviews on bladder training and voiding programmes for the management of urinary incontinence using metastudy descriptive techniques. It presents a synopsis of findings on theory and methods for interventions.

Background.  From the mid‐1970s bladder training, prompted voiding, habit retraining and timed voiding have been developed and form the basis of nursing practice for the management of urinary incontinence in adults in institutional and community settings.

Methods.  A synopsis of four Cochrane systematic reviews was undertaken using metastudy techniques developed for qualitative research and has provided a discursive comparison and contrast of the selection and appraisal of primary research, meta‐theory and meta‐method.

Findings.  All programmes share a therapeutic focus on voiding and the degree and active participation of the client and caregiver. Bladder training focuses on the restoration of continence, while prompted voiding, habit retraining and timed voiding focus on the avoidance of incontinence. Bladder training and prompted voiding share the two characteristics of cognitive behavioural modification and active client participation. Habit retraining and timed voiding pre‐empt episodes and avoid incontinence using operant conditioning rather than modifying behaviour. Variability of methods and operational terminology makes comparison between studies difficult. Use of cognitive behavioural approaches and operant conditioning need to be better understood in relation to future theory, interventions and study design. Bladder training is aimed at people who are cognitively and physically able, while the other voiding programmes are mainly used with for people with cognitive and physical impairments reliant on caregivers.

Conclusion.  The theoretical approaches underpinning bladder training and voiding programmes, their components and suitability for patients need to be re‐considered when designing future studies. There is a need for long‐term follow‐up in future studies. Future trials should adhere to recognized standards of good practice and incorporate outcomes from existing systematic reviews to enable future meta‐analysis to be undertaken. Metastudy techniques for the synthesis of qualitative research provide useful methods for the descriptive synopsis of quantitative systematic reviews.
The effect of socioeconomic status on dietary intake, physical activity and Body Mass Index in Austrian pregnant women
Authors: Freisling H. , Elmadfa I. , Gall I.
Published: November 2006

Objectives  To examine the associations of socioeconomic status (SES) with dietary intake and health related factors in pregnant women.

Subjects  A total of 261 pregnant women attending maternity clinics in Austria.

Methods  Descriptive cross‐sectional survey using a self‐administered questionnaire in combination with an interview to assess dietary intake (24‐hour‐recall).

Results  In the linear regression models, women with a higher level of education showed a higher intake of dietary fibre (P = 0.015), folate (P = 0.048), beta‐carotene (P = 0.008), and calcium (P = 0.003), whereas the intake of total fat (P = 0.039) was lower. The mean reported prepregnancy Body Mass Index (BMI) of lower educated women (23.6 kg m−2) was significantly higher (p for trend = 0.018) than that of women with medium or high levels of education (21.7 and 21.6 kg m−2, respectively). The manual occupation group was more than four times less likely to engage in structured physical activity compared with the nonmanual occupation group (adjusted odds ratio for manual group = 0.23, 95% CI: 0.08; 0.87).

Conclusions  Education is a strong and independent predictor of nutrient intake and BMI in pregnant women. The use of occupation and household income in addition to education improves the description of socioeconomic inequalities in diet and health related factors.
A systematic review and economic evaluation of adefovir dipivoxil and pegylated interferon‐alpha‐2a for the treatment of chronic hepatitis B
Authors: Takeda A. , Jones J. , Shepherd J. , Davidson P. , Price A.
Published: November 2006

Summary.  Standard treatments for chronic hepatitis B (CHB) include interferon‐alpha (IFN‐α) and lamivudine (LAM), but these are associated with adverse effects and viral resistance, respectively. The aim of this systematic review and economic evaluation was to assess the clinical effectiveness and cost‐effectiveness of two alternative drugs for the treatment of adults with CHB: adefovir dipivoxil (ADV) and pegylated IFN‐α‐2a. We searched electronic databases, including Cochrane Systematic Reviews and Medline, for literature that met criteria defined in a research protocol. Retrieved articles were independently assessed for inclusion by two reviewers. We developed a Markov state transition model to estimate the cost‐effectiveness (cost‐utility) of pegylated IFN‐α‐2a and of ADV compared with nonpegylated IFN‐α‐2a, LAM and best supportive care. Seven randomized controlled trials and two systematic reviews met the inclusion criteria for our review of clinical effectiveness. ADV was significantly more effective than placebo or ongoing LAM in reducing levels of hepatitis B virus (HBV) DNA. Rates of hepatitis B e antigen (HBeAg) seroconversion were higher among patients receiving ADV than either placebo or ongoing LAM. Patients treated with pegylated IFN‐α‐2a, either as monotherapy or in combination with LAM, showed significantly reduced HBV DNA levels compared with patients treated with LAM monotherapy. HBeAg seroconversion rates at follow‐up were significantly higher for pegylated IFN‐α‐2a patients than for those receiving LAM monotherapy. Results of our cost‐effectiveness analysis demonstrate that incremental costs per quality adjusted life year (QALY) for a range of comparisons were between £5994 and £16 569, and within the range considered by NHS decision‐makers to represent good value for money.
Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases
Authors: Coco B. , Oliveri F. , Maina A. M. , Ciccorossi P. , Sacco R. , Colombatto P. , Bonino F. , Brunetto M. R.
Published: November 2006

Summary.  Liver stiffness was measured by transient elastography (FibroScan®) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6‐month follow‐up. We identified 8.3 and 14 kPa as the fibrosis ≥F2 and cirrhosis cut‐offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan® performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12‐month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3‐ to 3‐fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.
Hepatitis E virus infection among animals in northern India: an unlikely source of human disease
Authors: Shukla P. , Chauhan U. K. , Naik S. , Anderson D. , Aggarwal R.
Published: November 2006

Summary.  Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing countries. Based on data from nonendemic regions, an animal reservoir of HEV has been proposed; however, data from HEV‐endemic regions are limited. We tested sera from 200 pigs, 98 chickens, 86 goats, 58 sheep and 30 buffaloes for anti‐HEV IgG using two different enzyme immunoassays. Specificity of the detected antibodies was confirmed using inhibition assays. Stool specimens from 210 pigs, 94 piglets and 37 sheep were tested for HEV‐RNA using nested amplification methods; the polymerase chain reaction products were sequenced and compared with known human and swine HEV sequences. Of the 200 swine sera, 193 and 195, respectively, tested positive in the two assays. All goat sera showed anti‐HEV reactivity in both the assays. Inhibition studies confirmed the HEV specificity of antibodies detected in swine and goat sera using both the assays. Sera from sheep, buffalo and chickens also showed high rates of apparent reactivity, but inhibition studies were unable to confirm the specificity of reactions in these species. One faecal specimen showed amplification using Indian swine HEV‐specific primers. The genomic sequence of the amplicon from this isolate had only 76–79% nucleotide and 93% amino acid homology with human HEV isolates reported from India and other parts of the world, and most closely resembled swine HEV isolates from other parts of India. Infection with HEV or a related agent is widespread among animals in northern India. However, the swine HEV in India differs genetically from human HEV isolates, indicating that pigs may not play an important role in the spread of human hepatitis E in endemic regions.