bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality from peptic ulcer bleeding: the impact of comorbidity and the use of drugs that promote bleeding
Authors: Åhsberg K. , Höglund P. , Staël von Holstein C. 
Published: July 2010

SummaryBackground  Use of drugs promoting peptic ulcer bleed has increased several folds.Aim  To make a time‐trend analysis of peptic ulcer bleed patients and evaluate the impact of age, gender, comorbidity and use of drugs promoting peptic ulcer bleed on outcome.Methods  Retrospective review of hospitalizations for peptic ulcer bleed at Lund University Hospital during 1984, 1994 and 2004. Univariate analyses between years and multivariable logistic regression for risk factors of fatal outcome.Results  Incidence decreased from 62.0 to 32.1 per 100 000 inhabitants between 1984 and 2004. Mortality rates were stable. Median age (70–77 years; P = 0.001), number of comorbidities (mean ± s.d.: 0.88 ± 0.96 to 1.16 ± 0.77; P = 0.021), use of aspirin (16–57%; P < 0.001) and warfarin (5–17%; P = 0.02) increased. Pharmacological and endoscopic therapy improved. Age above 65 years (OR: 1.11, 95% CI: 1.02–1.23) and number of comorbidities (OR: 6.00, 95% CI: 2.56–17.4) were independent risk factors for in‐hospital mortality. Bleeding promoting drugs did not influence outcome negatively. Aspirin decreased the risk of fatal outcome (OR: 0.12, 95% CI: 0.012–0.67).Conclusions  Incidence of peptic ulcer bleed decreased despite higher prescription rates of bleeding promoting drugs. The in‐hospital mortality remained unchanged. The effect of improved therapy against peptic ulcer bleed is probably outweighed by older and more comorbid patients. The decreased risk of fatal outcome in aspirin users warrants further investigations.
The extension of epidural blockade for emergency Caesarean section: a survey of current UK practice*
Authors: Regan K. J. , O'Sullivan G. 
Published: July 2010

SummaryThe conversion of epidural analgesia during labour to surgical anaesthesia for Caesarean section can have important medical and medicolegal implications. This survey sought to establish the current management for extending epidural blockade for emergency Caesarean section. A postal questionnaire was sent to the lead obstetric anaesthetist in all maternity units in the UK (n = 254). The response rate was 82% (n = 209). Of those surveyed, 68% (136) give the full dose of the local anaesthetic mixture in the delivery room, whilst 12.5% (25) initiate the top‐up in the delivery room and give the remainder of the dose in theatre. Fifteen per cent (30) transfer the woman to theatre before commencing anaesthesia and 34% (68) give a test dose before the full anaesthetic dose. Guidelines for converting labour analgesia to anaesthesia for emergency Caesarean section were available in 64% (128) units. Bupivacaine 0.5% was the most commonly used agent, being used as the sole agent by 41.5% (81) units and in combination by a further 18% (36). Adrenaline was added to the chosen local anaesthetic by 30% (60) whilst 12% (24) added bicarbonate. In all, 13 combinations of local anaesthetics and adjuncts were used. The mode time to transfer the patient to theatre was 1 min. Of the 161 respondents who commenced anaesthesia in the delivery room, 71% (114) did not monitor the patient during transfer, whilst 87% (140) had ephedrine immediately available. Thirty‐three respondents reported a total of 43 adverse incidents associated with the extension of epidural blockade. These included high blocks, inadequate blocks and possible intravascular injections, the latter resulting in two seizures and one cardiac arrest.
Point‐of‐care testing in haemostasis
Authors: Perry David J. , Fitzmaurice David A. , Kitchen Steve , Mackie Ian J. , Mallett Sue 
Published: July 2010

SummaryPoint‐of‐care testing (POCT) in haematology has seen a significant increase in both the spectrum of tests available and the number of tests performed annually. POCT is frequently undertaken with the belief that this will reduce the turnaround time for results and so improve patient care. The most obvious example of POCT in haemostasis is the out‐of‐hospital monitoring of the International Normalized Ratio in patients receiving a vitamin K antagonist, such as warfarin. Other areas include the use of the Activated Clotting Time to monitor anticoagulation for patients on cardio‐pulmonary bypass, platelet function testing to identify patients with apparent aspirin or clopidogrel resistance and thrombelastography to guide blood product replacement during cardiac and hepatic surgery. In contrast to laboratory testing, POCT is frequently undertaken by untrained or semi‐trained individuals and in many cases is not subject to the same strict quality control programmes that exist in the central laboratory. Although external quality assessment programmes do exist for some POCT assays these are still relatively few. The use of POCT in haematology, particularly in the field of haemostasis, is likely to expand and it is important that systems are in place to ensure that the generated results are accurate and precise.
Tanespimycin monotherapy in relapsed multiple myeloma: results of a phase 1 dose‐escalation study
Authors: Richardson Paul G. , Chanan‐Khan Asher A. , Alsina Melissa , Albitar Maher , Berman David , Messina Marianne , Mitsiades Constantine S. , Anderson Kenneth C. 
Published: July 2010

SummaryTanespimycin, a heat shock protein 90 (HSP90) inhibitor, induces apoptosis in drug‐sensitive and ‐resistant MM cell lines and in tumour cells from patients with relapsed MM. In this phase 1 dose‐escalation study, the safety, plasma pharmacokinetics, and biological/antitumour activity of tanespimycin were evaluated in heavily pretreated patients with relapsed/refractory MM. Tanespimycin (150–525 mg/m2) was given on days 1, 4, 8, and 11 of each 3‐week cycle for up to 8 cycles. Non‐haematological AEs included diarrhoea (59%), back pain (35%), fatigue (38%), and nausea (35%); haematological AEs included anaemia (24%) and thrombocytopenia (21%). One patient (3%) achieved minimal response (MR), with a progression‐free survival (PFS) of 3 months, a 41% decrease from baseline in urine M protein, and a 33% decrease from baseline in serum M protein. Fifteen patients (52%) achieved SD with a median PFS of 2·1 months; 5/15 had reductions in serum M protein ranging from 7% to 38% and in urine M protein ranging from 6% to 91%. Mean HSP70 levels increased from day 1 h 0 to day 1 h 4 with further increases on day 11 h 0 and day 11 h 4, consistent with a therapeutic treatment effect. Tanespimycin monotherapy was well tolerated and demonstrated activity across all doses tested.
Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes
Authors: Marin-Gallen S , Clemente-Casares X , Planas R , Pujol-Autonell I , Carrascal J , Carrillo J , Ampudia R , Verdaguer J , Pujol-Borrell R , Borràs F E , Vives-Pi M 
Published: July 2010

SummaryDendritic cells (DCs) are powerful antigen-presenting cells capable of maintaining peripheral tolerance. The possibility to generate tolerogenic DCs opens new therapeutic approaches in the prevention or remission of autoimmunity. There is currently no treatment inducing long-term tolerance and remission in type 1 diabetes (T1D), a disease caused by autoimmunity towards β cells. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow islet regeneration. Apoptotic cells – a source of autoantigens – are cleared rapidly by macrophages and DCs through an immunologically silent process that contributes to maintaining tolerance. Our aims were to prevent T1D and to evaluate the re-establishment of peripheral tolerance using autologous DCs pulsed in vitro with apoptotic bodies from β cells. Immature DCs derived from bone marrow of non-obese diabetic (NOD) mice were obtained and pulsed with antigen-specific apoptotic bodies from the β cell line NIT-1. Those DCs that phagocytosed apoptotic cells diminished the expression of co-stimulatory molecules CD40 and CD86 and reduced secretion of proinflammatory cytokines. Moreover, these cells were resistant to increase the expression of co-stimulatory molecules after lipopolysaccharide activation. The administration of these cells to NOD transgenic mice expressing interferon-β in their insulin-producing cells, a model of accelerated autoimmune diabetes, decreased diabetes incidence significantly and correlated positively with insulitis reduction. DCs pulsed with apoptotic cells that express disease-associated antigens constitutes a promising strategy to prevent T1D.
Functional differences between native and alien species: a global‐scale comparison
Authors: Ordonez Alejandro , Wright Ian J. , Olff Han 
Published: July 2010

Summary 1. A prevalent question in the study of plant invasions has been whether or not invasions can be explained on the basis of traits. Despite many attempts, a synthetic view of multi‐trait differences between alien and native species is not yet available. 2. We compiled a database of three ecologically important traits (specific leaf area, typical maximum canopy height, individual seed mass) for 4473 species sampled over 95 communities (3784 species measured in their native range, 689 species in their introduced range, 207 in both ranges). 3. Considering each trait separately, co‐occurring native and alien species significantly differed in their traits. These differences, although modest, were expressed in a combined 15% higher specific leaf area, 16% lower canopy height and 26% smaller seeds. 4. Using three novel multi‐trait metrics of functional diversity, aliens showed significantly smaller trait ranges, larger divergences and a consistent differentiation from the median trait combination of co‐occurring natives. 5. We conclude that the simultaneous evaluation of multiple traits is an important novel direction in understanding invasion success. Our results support the phenotypic divergence hypothesis that predicts functional trait differences contribute to the success of alien species.
‘A local habitation and a name’: how narrative evidence‐based medicine transforms the translational research paradigm
Authors: Goyal Rishi K. , Charon Rita , Lekas Helen‐Maria , Fullilove Mindy T. , Devlin Michael J. , Falzon Louise , Wyer Peter C. 
Published: July 2010

AbstractRationale We propose narrative evidence‐based medicine as a necessary elaboration of the NIH translational research roadmap. The roadmap defined two complex obstacles, T1 and T2, to the progress of research from the ‘bench’ or basic laboratory science to the ‘bedside’ or clinical application, the traversal of which requires emergence of complex transformative relationships between the parties and stakeholders. It fails to encompass patient interactions, hesitancies and alliances with medical care.Aims and Objectives We suggest a third transformative or translational step, T3, that begins at the point that practitioners have themselves elected to adopt and recommend strategies and interventions based on high‐level evidence and guidelines. In our model, T3 encompasses all aspects of care that converge on the practitioner–patient relationship and ultimately determine what therapies and choices patients actually make regarding their care.Results Learning from the biopsychosocial model, patient‐centred care and shared decision making while attending to the ethical injunction of Emmanuel Levinas to know the other, we have developed a medical practice and theory that unites the local and specific concerns of narrative medicine with the generalizability and power of evidence‐based medicine.Conclusions We offer innovative approaches to study, teach and improve the therapeutic intimacy and integrative effectiveness of the practitioner–patient relationship.
The applicability of the Kaufman Assessment Battery for Children (K‐ABC) with older adults (50+ years) with moderate, severe and profound intellectual impairment
Authors: Hogg J. , Moss S. 
Published: July 2010

AbstractTo define the intellectual characteristics of a population of older people (50+ years) with severe intellectual impairment who were the focus of a wider demographic study, participants were assessed on the Kaufman Assessment Battery for Children (K‐ABC). Test material was modified to make it age‐appropriate and culturally suitable. Of the 122 people in the population [chronological age (CA) = 63·5 years; range 50–90 years], 61 were successfully tested on the K‐ABC (CA = 60·9 years; range 51–81 years). Factor analysis closely replicated the factorial structure demonstrated for younger children. Separate Sequential and Simultaneous Mental Processing factors were identified, with subtests from the Achievement Scale loading on these factors and not constituting a separate factor. Application of hierarchical cluster analysis confirmed the factor structures. Inferences in relation to cognitive development from a Piagetian perspective are drawn, and the utility of information on mental processing for educational intervention with older persons with severe intellectual impairment is noted.
Psychotherapeutic approaches in the treatment of mental illness and behavioural disorders in mentally retarded people: the significance of a psychoanalytic perspective
Authors: Gaedt C. 
Published: July 2010

AbstractAs a result of the increasing preoccupation with pre‐oedipal disturbances, psychoanalytic theory has had to expand its basis. Through this new interpretation, better possibilities for the explanation and treatment of the various forms of psychopathology associated with mental retardation emerge. In this connection, the notion of a ‘persisting developmental deficit’ plays an important role based on ego‐psychology which includes object‐relation theory and psychoanalytic developmental psychology. Four specific issues illustrate the significance of a psychoanalytically orientated approach, namely: (1) the transformation of organic brain deficits into mental disorders; (2) ‘secondary psychosocial deficit'; (3) the significance of the therapeutic relationship; and (4) re‐enactments as expression of a pathological identity.
A small antisense RNA downregulates expression of an essential replicase protein of an Agrobacterium tumefaciens Ti plasmid
Authors: Chai Yunrong , Winans Stephen C. 
Published: July 2010

SummaryTumour‐inducing (Ti) plasmids of Agrobacterium tumefaciens replicate via the products of the repABC genes, which are highly conserved among plasmids of the alpha‐Proteobacteria. RepA and RepB direct stable partitioning of daughter plasmids, while the RepC directs replicative DNA synthesis. We have identified a new gene (repE) within the repB–repC intergenic region of an octopine‐type Ti plasmid. This gene encodes a small, non‐translated RNA that is transcribed in the direction opposite to the repABC mRNA. Increased expression of repE blocked plasmid replication of a repABC‐dependent miniplasmid, while decreased repE expression increased plasmid copy number. Direct RNA measurements and repC–lacZ fusions demonstrated that RepE inhibits the expression of RepC at the transcriptional level and possibly also at the translational level. Based on our experimental results and an RNA folding algorithm, we predict that RepE binding to the repABC mRNA would promote termination of the repABC transcript near the start codon of repC. Sequence analysis suggests that this phenomenon may be widespread among plasmids of this family.
Adaptational assistance in clusters of bacterial chemoreceptors
Authors: Li Mingshan , Hazelbauer Gerald L. 
Published: July 2010

SummarySensory adaptation of low‐abundance chemoreceptors in Escherichia coli requires assistance from high‐abundance receptors, because only high‐abundance receptors carry the carboxyl‐terminal pentapeptide sequence NWETF that enhances adaptational covalent modification. Using membrane vesicles containing both high‐abundance receptor Tar and low‐abundance receptor Trg, we observed effective assistance in vitro for all three adaptational modifications: methylation, demethylation and deamidation. These results demonstrated that adaptational assistance involves not only the previously documented assistance for methylation but also assistance for the two CheB‐catalysed reactions. We determined rates of assisted methylation and demethylation at many ratios of assisting to assisted receptor. Analysis by a model of assistance indicated one Tar dimer could assist seven Trg dimers in methylation or five in demethylation, defining assistance neighbourhoods. These neighbourhoods were larger than a trimer of homodimers, required only receptors and were minimally affected by formation of signalling complexes. Time courses of assisted Trg methylation in membranes with low amounts of Tar showed that assisting receptors did not diffuse beyond initial neighbourhoods for at least two hours. Taken together, these observations indicate that chemoreceptors can form stable neighbourhoods larger than trimers in the absence of other chemotaxis proteins. Such interactions are likely to occur in natural receptor clusters in vivo.
A secreted anti‐activator, OspD1, and its chaperone, Spa15, are involved in the control of transcription by the type III secretion apparatus activity in Shigella flexneri
Authors: Parsot Claude , Ageron Elisabeth , Penno Christophe , Mavris Maria , Jamoussi Kais , d’Hauteville Hélène , Sansonetti Philippe , Demers Brigitte 
Published: July 2010

SummaryBacteria of Shigella spp. are responsible for shigellosis in humans and use a type III secretion (TTS) system to enter epithelial cells and trigger apoptosis in macrophages. Transit of translocator and effector proteins through the TTS apparatus is activated upon contact of bacteria with host cells. Transcription of ≈15 genes encoding effectors is regulated by the TTS apparatus activity and controlled by MxiE, an AraC family activator, and its coactivator IpgC, the chaperone of IpaB and IpaC translocators. Using a genetic screen, we identified ospD1 as a gene whose product negatively controls expression of genes regulated by secretion activity. OspD1 associates with the chaperone Spa15 and the activator MxiE and acts as an anti‐activator until it is secreted. The mechanism regulating transcription in response to secretion activity involves an activator (MxiE), an anti‐activator (OspD1), a co‐anti‐activator (Spa15), a coactivator (IpgC) and two anti‐coactivators (IpaB and IpaC) whose alternative and mutually exclusive interactions are controlled by the duration of the TTS apparatus activity.
Deletion of GEL2 encoding for a β(1–3)glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus
Authors: Mouyna Isabelle , Morelle Willy , Vai Marina , Monod Michel , Léchenne Barbara , Fontaine Thierry , Beauvais Anne , Sarfati Jacqueline , Prévost Marie‐Christine , Henry Christine , Latgé Jean‐Paul 
Published: July 2010

SummaryThe first fungal glycosylphosphatidylinositol an‐chored β(1–3)glucanosyltranferase (Gel1p) has been described in Aspergillus fumigatus and its encoding gene GEL1 identified. Glycosylphosphatidylinositol‐anchored glucanosyltransferases play an active role in the biosynthesis of the fungal cell wall. We characterize here GEL2, a homologue of GEL1. Both homologues share common characteristics: (i) GEL1 and GEL2 are constitutively expressed during over a range of growth conditions; (ii) Gel2p is also a putative GPI‐anchored protein and shares the same β(1–3)glucanosyltransferase activity as Gel1p and (iii) GEL2, like GEL1, is able to complement the Δgas1 deletion in Saccharomyces cerevisiae confirming that Gelp and Gasp have the same enzymatic activity. However, disruption of GEL1 did not result in a phenotype whereas a Δgel2 mutant and the double mutant Δgel1Δgel2 exhibit slower growth, abnormal conidiogenesis, and an altered cell wall composition. In addition, the Δgel2 and the Δgel1Δgel2 mutant have reduced virulence in a murine model of invasive aspergillosis. These data suggest for the first time that β(1–3)glucanosyltransferase activity is required for both morphogenesis and virulence in A. fumigatus.
Overexpression of the COX2 translational activator, Pet111p, prevents translation of COX1 mRNA and cytochrome c oxidase assembly in mitochondria of Saccharomyces cerevisiae
Authors: Fiori Alessandro , Perez‐Martinez Xochitl , Fox Thomas D. 
Published: July 2010

SummaryDramatically elevated levels of the COX2 mitochondrial mRNA‐specific translational activator protein Pet111p interfere with respiratory growth and cytochrome c oxidase accumulation. The respiratory phenotype appears to be caused primarily by inhibition of the COX1 mitochondrial mRNA translation, a finding confirmed by lack of cox1Δ::ARG8m reporter mRNA translation. Interference with Cox1p synthesis depends to a limited extent upon increased translation of the COX2 mRNA, but is largely independent of it. Respiratory growth is partially restored by a chimeric COX1 mRNA bearing the untranslated regions of the COX2 mRNA, and by overproduction of the COX1 mRNA‐specific activators, Pet309p and Mss51p. These results suggest that excess Pet111p interacts unproductively with factors required for normal COX1 mRNA translation. Certain missense mutations in PET111 alleviate the interference with COX1 mRNA translation but do not completely restore normal respiratory growth in strains overproducing Pet111p, suggesting that elevated Pet111p also perturbs assembly of newly synthesized subunits into active cytochrome c oxidase. Thus, this severe imbalance in translational activator levels appears to cause multiple problems in mitochondrial gene expression, reflecting the dual role of balanced translational activators in cooperatively regulating both the levels and locations of organellar translation.
Accumulation of eosinophils in intestine‐draining mesenteric lymph nodes occurs after Trichuris muris infection
Authors: SVENSSON M. , BELL L. , LITTLE M. C. , DeSCHOOLMEESTER M. , LOCKSLEY R. M. , ELSE K. J. 
Published: July 2010

SummaryEosinophils have recently been demonstrated capable of localizing to lymph nodes that drain mucosal surfaces, in particular during T helper 2 (Th2) responses. Resistance of mice to infection with the gastrointestinal nematode Trichuris muris depends critically on mounting of a Th2 response and represents a useful model system to investigate Th2 responses. Following infection of resistant BALB/c mice with T. muris, we observed accumulation of eosinophils in intestine‐draining mesenteric lymph nodes (MLNs). The accumulation of MLN eosinophils was initiated during the second week of infection and peaked during worm expulsion. In contrast, we detected a comparably late and modest increase in eosinophil numbers in the MLNs of infected susceptible AKR mice. MLN eosinophils localized preferentially to the medullary region of the lymph node, displayed an activated phenotype and contributed to the interleukin‐4 (IL‐4) response in the MLN. Despite this, mice genetically deficient in eosinophils efficiently generated IL‐4‐expressing CD4+ T cells, produced Th2 cytokines and mediated worm expulsion during primary T. muris infection. Thus, IL‐4‐expressing eosinophils accumulate in MLNs of T. muris‐infected BALB/c mice but are dispensable for worm expulsion and generation of Th2 responses, suggesting a distinct or subtle role of MLN eosinophils in the immune response to T. muris infection.