bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of intra‐ocular pressure by ocular compression before combined peri‐ and retrobulbar block
Authors: Kallio H. , Harju M. P. , Ihanamäki T. , Vesti E. T. , Kivelä T. 
Published: February 2011

SummaryThe intra‐ocular pressure immediately before glaucoma surgery can be raised. We wished to investigate if ocular compression for 20 min before a combined peri‐ and retrobulbar injection would result in a lower pressure after the block. Sixty consecutive patients scheduled for filtration surgery were randomly assigned to receive ocular compression using an external pressure device for 20 min before combined peri‐ and retrobulbar injection (intervention group, who also received compression after the block) or to a control group in whom pressure was applied only after the block was completed. The intra‐ocular pressure was measured at baseline, after the 20‐min pre‐injection compression (intervention group), after injecting the block, and after the 10‐min post‐injection compression. The pressure did not differ between groups at baseline, after the block or after the post‐injection compression. In the intervention group, the compression before the block reduced the median (IQR [range]) pressure from 21.0 (17.0–25.0 [12.0–40.0]) mmHg to 16.8 (12.5–22.5 [7.5–33.5]) mmHg (p < 0.001). We conclude that external ocular compression reduces the intra‐ocular pressure, but applying an additional compression for 20 min before injecting the block is not beneficial.
Ultrasound‐guided supra‐inguinal fascia iliaca block: a cadaveric evaluation of a novel approach
Authors: Hebbard P. , Ivanusic J. , Sha S. 
Published: February 2011

SummaryExisting descriptions of ultrasound‐guided fascia iliaca block focus on injection of local anaesthetic inferior to the inguinal ligament, relying on supra‐inguinal spread to block the lateral femoral cutaneous nerve in the iliac fossa. In this study, we explored injectate spread and nerve involvement in a cadaveric dye‐injection model, using a supra‐inguinal ultrasound‐guided technique that places local anaesthetic directly into the iliac fossa. Bilateral injections of 20 ml 0.25% aniline blue dye were made in six unembalmed cadavers. The femoral nerve was stained by the dye in all twelve injections. The lateral femoral cutaneous nerve was stained bilaterally in five cadavers, but the nerve was absent on both sides in the sixth cadaver. The ilio‐inguinal nerve passed into the iliac fossa over the iliacus muscle in eight of the hemi‐pelvi and was stained in seven of these occasions. We have performed more than 150 blocks in patients using this approach without complications. Injection using this technique in cadavers leads to extensive fluid spread throughout the iliac fossa. In patients this approach may allow a lower volume block of the femoral nerve and lateral femoral cutaneous nerve while still injecting at a distance from the femoral nerve.
Evaluation of a single‐use intubating videoscope (Ambu aScopeTM) in three airway training manikins for oral intubation, nasal intubation and intubation via three supraglottic airway devices
Authors: Scutt S. , Clark N. , Cook T. M. , Smith C. , Christmas T. , Coppel L. , Crewdson K. 
Published: February 2011

SummaryWe compared the Ambu aScope™ with a conventional fibrescope in two simulated settings. First, 22 volunteers performed paired oral and nasal fibreoptic intubations in three different manikins: the Laerdal Airway Trainer, Bill 1 and the Airsim (a total of 264 intubations). Second, 21 volunteers intubated the Airway Trainer manikin via three supraglottic airways: classic and intubating laryngeal mask airways and i‐gel (a total of 66 intubations). Performance of the aScope was good with few failures and infrequent problems. In the first study, choice of fibrescope had an impact on the number of user‐reported problems (p = 0.004), and user‐assessed ratings of ease of endoscopy (p < 0.001) and overall usefulness (p < 0.001), but not on time to intubate (p = 0.19), or ease of railroading (p = 0.72). The manikin chosen and route of endoscopy had more consistent effects on performance: best performance was via the nasal route in the Airway Trainer manikin. In the second study, the choice of fibrescope did not significantly affect any performance outcome (p = 0.3), but there was a significant difference in the speed of intubation between the devices (p = 0.02) with the i‐gel the fastest intubation conduit (mean (SD) intubation time i‐gel 18.5 (6.8) s, intubating laryngeal mask airway = 24.1 (11.2) s, classic laryngeal mask airway = 31.4 (32.5) s, p = 0.02). We conclude that the aScope performs well in simulated fibreoptic intubation and (if adapted for untimed use) would be a useful training tool for both simulated fibreoptic intubation and conduit‐assisted intubation. The choice of manikin and conduit are also important in the success of such training. This manikin study does not predict performance in humans and a clinical study is required.
Comparison of pharmacokinetic variability of fesoterodine vs. tolterodine extended release in cytochrome P450 2D6 extensive and poor metabolizers
Authors: Malhotra Bimal , Darsey Edress , Crownover Penelope , Fang Juanzhi , Glue Paul 
Published: February 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Tolterodine and 5‐hydroxymethyl tolterodine (5‐HMT) are equipotent active moieties of tolterodine; 5‐HMT is the singular active moiety of fesoterodine. The formation of 5‐HMT from tolterodine occurs via CYP2D6, and some subjects are poor metabolizers CYP2D6. On the other hand, the formation of 5‐HMT from fesoterodine occurs via ubiquitous esterases. Cross‐study comparisons of data from phase 1 studies suggest that active moiety exposures are considerably more variable following tolterodine extended release vs. fesoterodine.WHAT THIS STUDY ADDS• This head‐to‐head study confirmed the findings of reduced pharmacokinetic variability of fesoterodine and further delineates that tolterodine, and not 5‐HMT, was the principal source of variability after administration of tolterodine extended release. The data suggest that fesoterodine delivers 5‐HMT consistently, regardless of CYP2D6 status, with up to 40% higher bioavailability compared with tolterodine.AIMS Tolterodine and 5‐hydroxymethyl tolterodine (5‐HMT) are equipotent active moieties of tolterodine; 5‐HMT is the singular active moiety of fesoterodine. Formation of 5‐HMT from fesoterodine and tolterodine occurs via esterases and CYP2D6 respectively. This randomized, crossover, open‐label, multiple‐dose study in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) compared the pharmacokinetics of fesoterodine vs. tolterodine extended release (ER).METHODS Subjects received fesoterodine and tolterodine ER with a ≥3‐day washout period. Treatment comprised 4‐mg once daily doses for 5 days escalated to 8‐mg once daily for 5 days. Pharmacokinetics of active moieties were compared by drug, dose and genotype.RESULTS Active moiety exposures following fesoterodine and tolterodine ER increased proportional to dose in EMs and PMs. In EMs only, coefficients of variation for AUC and Cmax following fesoterodine (up to 46% and 48% respectively) were lower than those following tolterodine ER (up to 87% and 87% respectively). Following fesoterodine and tolterodine ER administration, active moiety exposures ranged up to sevenfold and 40‐fold respectively. Mean urinary excretion of 5‐HMT following fesoterodine 4 and 8 mg, respectively, was 0.44 and 0.89 mg in EMs and 0.60 and 1.32 mg in PMs. Following tolterodine ER 4 and 8 mg, it was 0.38 and 0.71 mg respectively (EMs only). Renal clearance was similar regardless of administered drug, dose or genotype.CONCLUSIONS Tolterodine, not 5‐HMT, was the principal source of variability after tolterodine ER administration. Fesoterodine delivers 5‐HMT with less variability than tolterodine, regardless of CYP2D6 status, with up to 40% higher bioavailability. The pharmacokinetics of fesoterodine were considerably less variable than TER.
Dasatinib inhibits B cell receptor signalling in chronic lymphocytic leukaemia but novel combination approaches are required to overcome additional pro‐survival microenvironmental signals
Authors: MCCaig Alison M. , Cosimo Emilio , Leach Michael T. , Michie Alison M. 
Published: February 2011

SummaryAs antigenic stimulation of the B cell antigen receptor (BCR) is key to chronic lymphocytic leukaemia (CLL) pathogenesis, targeting dysregulated kinases involved in BCR signalling is an attractive therapeutic approach. We studied the effects of the Src/c‐Abl tyrosine kinase inhibitor dasatinib on BCR signal transduction in CLL cells. Treatment of CLL cells with 100 nmol/l dasatinib induced apoptosis by an average reduction in viability of 33·7% at 48 h, with dasatinib sensitivity correlating with inhibition of SykY348 phosphorylation. Dasatinib inhibited calcium flux, phosphatidylinositol‐3‐kinase and mitogen‐activated protein kinase activation following BCR crosslinking, and blocked the Mcl‐1‐dependent increase in CLL cell survival on prolonged BCR stimulation. However, the pro‐apoptotic effect of dasatinib was abrogated by stromal cell contact alone or in the presence of CD154 and interleukin (IL)‐4 (CD154L/IL‐4 system). Whilst dasatinib retained the ability to sensitize CLL cells in stromal co‐culture to both fludarabine and chlorambucil, the addition of CD154 and IL‐4 rendered cells resistant to these drug combinations. We demonstrate that the HSP90 inhibitor 17‐DMAG exhibited synergy with dasatinib in vitro, and moreover, induced apoptosis of CLL cells in the CD154L/IL‐4 system. Our data provide evidence that dasatinib would be most clinically effective in combination with agents able to target antigen‐independent microenvironmental signals.
A pilot study evaluating the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers
Authors: Lemery Steven J. , Hsieh Matthew M. , Smith Aleah , Rao Sheila , Khuu Hanh M. , Theresa Donohue , Viano Jennifer M. , Cook Lisa , Goodwin Rose , Boss Carol , Calandra Gary , Geller Nancy , Tisdale John , Childs Richard 
Published: February 2011

SummaryThis study evaluated the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers. Three cohorts of six subjects received two different doses of plerixafor separated by at least 2 weeks to allow for adequate pharmacodynamic wash‐out. The following dosing cohorts were evaluated: 0·24 and 0·32 mg/kg (Cohort 1); 0·32 and 0·40 mg/kg (Cohort 2); and 0·40 and 0·48 mg/kg (Cohort 3). Circulating CD34+ cells were measured 0, 2, 4, 6, 8, 10, 12, 14, 18 and 24 h after each dose. Blood colony‐forming units were measured at baseline and 6 h after each dose. Common adverse events were diarrhoea, injection site erythema, perioral numbness, sinus tachycardia, headache, nausea, abdominal distention and injection site pain. No dose limiting toxicities occurred. When higher doses of plerixafor were administered, there was a trend towards higher peak CD34+ counts and CD34+ area under the curves, although these differences did not achieve statistical significance, perhaps due to intra‐subject variability. Together, these data show that the higher doses of plerixafor evaluated in this study are reasonably safe and suggest that a larger study should be performed to definitively answer whether increased numbers of CD34+ cell are mobilized with higher doses of plerixafor.
CD4+ T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes
Authors: Muller N G , Alencar R , Jamal L , Hammer J , Sidney J , Sette A , Brindeiro R M , Kalil J , Cunha-Neto E , Moraes S L 
Published: February 2011

SummaryHuman immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4–23, 45–64 and 73–95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.
Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharide-induced acute lung injury in mice
Authors: Yin H , Li X Y , Yuan B H , Zhang B B , Hu S L , Gu H B , Jin X B , Zhu J Y 
Published: February 2011

Summary
Acute lung injury is characterized by a diffuse inflammatory parenchymal process, implicated in the context of significant morbidity and mortality. Previously, we have reported that soluble ST2 (sST2), a member of the Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production of macrophage exposed to lipopolysaccharide (LPS). In this study, we examined the possibility of modulating LPS-induced murine inflammatory pulmonary damage by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc led to a profound decrease in LPS-induced bronchoalveolar lavage leucocyte exudation and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with inflammatory cell infiltration and alveolar haemorrhage in the alveolar airspace was less severe in Ad-sST2-Fc-treated mice when compared with control groups. In addition, high levels of sST2-Fc in vivo reduced the transcription of tumour necrosis factor-α, IL-6 and Toll-like receptor-4 gene remarkably, and suppressed the nuclear translocation of nuclear factor-κB in lung tissues in response to LPS challenge. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of LPS-mediated inflammatory lung injury.
A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells
Authors: Zhang F , Huang G , Hu B , Song Y , Shi Y 
Published: February 2011

SummaryRecent studies show that thymic stromal lymphopoietin (TSLP) plays a critical role in the upstream phase of the allergic cascade to induce T helper type 2 cell (Th2)-dominant allergic diseases. However, the effect of blocking TSLP signalling with the soluble TSLP receptor (TSLPR), TSLPR-immunoglobulin (Ig), on asthma development needs further investigation. Here, we examined the effects of TSLPR-Ig on asthmatic airway inflammation and dendritic cell (DC) function. TSLPR-Ig (comprising the extracellular domain of murine TSLPR and an IgG2a Fc tail) purified from transfected COS-7 cells reduced the expression of CD40, CD80 and CD86 on TSLP-activated DCs in vitro. We also investigated the mechanisms underlying TSLPR-Ig-mediated amelioration of allergic airway inflammation in a murine asthma model. When TSLP signalling was blocked by intratracheal administration of TSLPR-Ig prior to sensitization, allergen-specific serum IgE levels, airway tissue inflammation, inflammatory cell infiltration and Th2 cytokine levels in the bronchiolar lavage fluid (BALF) were reduced significantly. This was because of the TSLP-Ig-mediated down-regulation of co-stimulatory molecule expression on pulmonary DCs. We also transferred bone marrow-derived mature DCs (mDCs) into the airways of asthmatic mice. Intratracheal administration of TSLPR-Ig prior to the transfer of mDCs reduced eosinophilic airway inflammation and Th2 differentiation significantly. Collectively, these data suggest that local use of TSLPR-Ig prevents airway inflammation, at least in part, by regulating DC function, and that blocking TSLP signalling using TSLPR-Ig may be a novel strategy for the treatment of asthma bronchiale.
Incomplete activation of peripheral blood dendritic cells during healthy human pregnancy
Authors: Della Bella S , Giannelli S , Cozzi V , Signorelli V , Cappelletti M , Cetin I , Villa M L 
Published: February 2011

Summary
Successful pregnancy relies on the adaptation of immune responses that allow the fetus to grow and develop in the uterus despite being recognized by maternal immune cells. Dendritic cells (DCs) are central to the control of immune tolerance, and their state of activation at the maternal–decidual interface is critical to the feto–maternal immunological equilibrium. So far, the involvement of circulating DCs has been investigated poorly. Therefore, in this study we investigated whether, during healthy human pregnancy, peripheral blood DCs (PBDCs) undergo changes that may be relevant to the adaptation of maternal immune responses that allow fetal tolerance. In a cross-sectional study, we analysed PBDCs by six-colour flow cytometry on whole blood samples from 47 women during healthy pregnancy progression and 24 non-pregnant controls. We demonstrated that both myeloid and plasmacytoid PBDCs undergo a state of incomplete activation, more evident in the third trimester, characterized by increased expression of co-stimulatory molecules and cytokine production but lacking human leucocyte antigen (HLA)-DR up-regulation. To investigate the contribution of soluble circulating factors to this phenomenon, we also performed culture experiments showing that sera from pregnant women added to control DCs conditioned a similar incomplete activation that was associated with reduced DC allostimulatory capacity, supporting the in vivo relevance of our findings. We also obtained evidence that the glycoprotein hormone activin-A may contribute to DC incomplete activation. We suggest that the changes of PBDCs occurring during late pregnancy may aid the comprehension of the immune mechanisms operated by the maternal immune system to maintain fetal tolerance.
What is the best approach to suspected cyclical Cushing syndrome? Strategies for managing Cushing’s syndrome with variable laboratory data
Authors: Atkinson Brew , Mullan Karen R. 
Published: February 2011

SummaryCyclical Cushing’s syndrome is a pattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. This syndrome is often associated with fluctuating symptoms and signs. It is now being increasingly recognized. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. The techniques and criteria, protocols and dynamic biochemical tools to detect cycling in patients with hypercortisolism are discussed as are the strategies for diagnosing and managing this important subgroup of patients with hypercortisolism.
Artificial immune systems for the detection of credit card fraud: an architecture, prototype and preliminary results
Authors: Wong Nicholas , Ray Pradeep , Stephens Greg , Lewis Lundy 
Published: February 2011

AbstractSome biological phenomena offer clues to solving real‐life, complex problems. Researchers have been studying techniques such as neural networks and genetic algorithms for computational intelligence and their applications to such complex problems. The problem of security management is one of the major concerns in the development of eBusiness services and networks. Recent incidents have shown that the perpetrators of cybercrimes are using increasingly sophisticated methods. Hence, it is necessary to investigate non‐traditional mechanisms, such as biological techniques, to manage the security of evolving eBusiness networks and services. Towards this end, this paper investigates the use of an Artificial Immune System (AIS). The AIS emulates the mechanism of human immune systems that save human bodies from complex natural biological attacks. The paper discusses the use of AIS on one aspect of security management, viz. the detection of credit card fraud. The solution is illustrated with a case study on the management of frauds in credit card transactions, although this technique may be used in a range of security management applications in eBusiness.
Perceived discontinuities and constructed continuities in virtual work
Authors: Watson‐Manheim Mary Beth , Chudoba Katherine M. , Crowston Kevin 
Published: February 2011

AbstractBoundaries such as time, distance, organisation and culture have been a useful conceptual tool for researchers to unpack changes in the virtual work environment, moving from a dichotomous perspective that contrasts face‐to‐face and virtual work to a more nuanced hybrid perspective. However, researchers may tacitly assume that all members of a virtual team and virtual teams collectively will respond to a boundary in a similar way. We posit instead that boundaries are a dynamic phenomenon and may have different consequences under different circumstances. We offer organisational discontinuity theory as a tool for more focused investigation of the virtual work environment. Discontinuities and continuities describe the setting in which individuals in a virtual team operate, both actual work practices and the perceptions of the individuals in the virtual work environment. The terms offer a starting point to identify and understand what may otherwise seem to be paradoxical differences in how virtual team members respond to boundaries.
Survival of biogenic amine‐producing dairy LAB strains at pasteurisation conditions
Authors: Ladero Victor , Sánchez‐Llana Esther , Fernández María , Alvarez Miguel A. 
Published: February 2011

SummaryBiogenic amines (BAs) are low molecular weight organic bases with biological activity, synthesised by the microbial decarboxylation of precursor amino acids such as histidine, tyrosine or arginine. The consumption of food and beverages containing large amounts of BA can have toxicological effects. This paper reports the resistance of aminogenic lactic acid bacteria strains to pasteurisation (63 °C for 30 min). Skimmed milk inoculated with histamine‐ and tyramine‐producing strains of Enterococcus and Lactobacillus was subjected to pasteurisation. The viable number of Enterococcus durans IPLA 655 was reduced by 1 log, while that of Enterococcus faecalis BA64 was reduced by 3 logs. Lactobacillus brevis CECT 3810 did not survive pasteurisation, while the other Lactobacillus strains examined were more resistant; their viable numbers were reduced by about 2 logs. The two most resistant strains, E. durans IPLA 655 and Lactobacillus curvatus VI6, were subjected to higher temperatures. Enterococcus durans was completely inactivated at 78 °C, while some live cells of Lb. curvatus were observed. These results show that some native, metabolically active BA producers could be found in pasteurised milk owing to their resistance to the thermal treatment; their presence could have a negative impact on the final content of BAs in dairy products made from such milk.