bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐sampling of vaginal fluid and high‐risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening
Authors: Lindell M , Sanner K , Wikström I , Wilander E 
Published: October 2011

Please cite this paper as: Lindell M, Sanner K, Wikström I, Wilander E. Self‐sampling of vaginal fluid and high‐risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. BJOG 2012;119:245–248.Objectives  To study the value of self‐sampling of vaginal fluid at home in combination with high‐risk human papillomavirus (HPV) testing in a cohort of older women not attending Papanicolaou (Pap) smear screening.Design  Women (n = 3618), aged 50–65 years, who had not attended screening for at least 6 years were offered self‐sampling of vaginal fluid at home (study cohort). The collected material was analysed for the presence of high‐risk HPV (using Hybrid capture 2; Hc2). Women with a positive HPV test were referred for colposcopy. These results were compared with the results of Pap smear screening in a corresponding age group of women (controls). The end point of the study was identification of a histological cervical intraepithelial neoplasia stage 2 (CIN2) and above (CIN2+).Results  In all, 39.4% (n = 1426) women participated and 4.6% (n = 66) were high‐risk HPV positive. Of the HPV‐positive women 56 chose to attend a surgery (84.8%) after a mean time of 2.1 months and ten of these women (17.9%) showed CIN2+, corresponding to 0.70% of all participating women. In the controls, who participated in organised Pap smear screening, the prevalence of CIN2+ was 0.25% (15/6048). The odds ratio for identification of CIN2+ in women aged 50 years or older performing self‐sampling and HPV test in comparison with Pap smear was: 2.84 (95% CI 1.14–6.77, P = 0.0174). In older women primary high‐risk HPV testing (Hc2) and Pap smear screening showed equal specificity of around 96%.Conclusions  Self‐sampling of vaginal fluid in combination with high‐risk HPV testing appears to be an attractive method to improve screening coverage and decrease the prevalence of cervical cancer in women aged 50 years or older.
Ports and complications for intraperitoneal chemotherapy delivery
Authors: Helm CW 
Published: October 2011

Please cite this paper as: Helm C. Ports and complications for intraperitoneal chemotherapy delivery. BJOG 2012;119:150–159.Intraperitoneal access ports are essential to the delivery of chemotherapy agents into the peritoneal cavity of women with ovarian cancer, but their malfunction and adverse effects are frequently responsible for the failure to complete planned therapy. Complications, such as obstruction of the catheter, infection, leakage, rotation, retraction, and pain, together with bowel and vaginal perforation, cause delays in treatment, patient suffering and the expenditure of medical resources. A wide variety of ports have been used, including vascular access devices and intraperitoneal access devices. This paper reviews the development and use of ports for intraperitoneal chemotherapy, their complications and reported methods of prevention.
Is complex gastroschisis predictable by prenatal ultrasound?
Authors: Kuleva M , Khen‐Dunlop N , Dumez Y , Ville Y , Salomon LJ 
Published: October 2011

Please cite this paper as: Kuleva M, Khen‐Dunlop N, Dumez Y, Ville Y, Salomon L. Is complex gastroschisis predictable by prenatal ultrasound? BJOG 2012;119:102–109.Objective  To establish a correlation between prenatal ultrasound findings and postnatal outcome in neonates with gastroschisis (GS).Design  Retrospective case–control study.Setting  Prenatal ultrasound reports, labour and neonatal intensive care unit notes, and paediatric surgical clinic records were reviewed.Population  Neonates with an antenatal diagnosis of isolated GS.Methods  The neonates were divided into two groups: one with associated bowel complications including intestinal atresia, perforation, necrosis or volvulus (‘complex’ GS), and the second without bowel complication (‘simple’ GS). Prenatal ultrasound markers: small‐for‐gestational‐age, intra‐abdominal and extra‐abdominal bowel dilatation (>6 mm), thickened intestinal wall and stomach dilatation were correlated with outcome.Main outcome measures  Fetal or neonatal death in complex versus simple GS. Time on parenteral nutrition and duration of hospital stay were also noted.Results  In all, 105 cases were eligible for analysis. Survival rate was 101/105 (96.2%). None of the ultrasound markers was predictive of fetal or neonatal death. Fourteen of 103 live‐born babies (14.6%) had complex GS, which was associated with longer time on parenteral nutrition [8.0 (51.5–390) versus 33.5 (25.3–53.3) days, P < 0.001] and longer duration of hospital stay [85.3 (55.5–210) versus 41.5 (33.0–64.8) days, P < 0.001]. Infants with complex GS were more likely to require bowel resection and stoma placement (P < 0.05). Intra‐abdominal bowel dilatation was the only predictive ultrasound marker of complex GS (odds ratio 4.13, 95% CI 1.32–12.90; P = 0.018). Receiver operating characteristic curve for observed/expected bowel diameter yielded 6 as the cutoff value for predicting complex GS (odds ratio 7.9, 95% CI 2.3–27.3; P = 0.001) with 54% and 88% for sensibility and specificity, respectively.Conclusions  Intra‐abdominal bowel dilatation is the only ultrasound marker predictive of complex GS but it is a strong marker.
The antiretroviral protease inhibitors indinavir and nelfinavir stimulate Mrp1‐mediated GSH export from cultured brain astrocytes
Authors: Brandmann Maria , Tulpule Ketki , Schmidt Maike M. , Dringen Ralf 
Published: October 2011

J. Neurochem. (2012) 120, 78–92.AbstractCombinations of antiretroviral drugs are successfully used for the treatment of acquired immune deficiency syndrome and reduce the incidence of severe human immunodeficiency virus (HIV)‐associated dementia. To test whether such drugs affect the GSH metabolism of brain cells, we have exposed astrocyte‐rich primary cultures to various antiretroviral compounds. Treatment of the cultures with the protease inhibitors indinavir or nelfinavir in low micromolar concentrations resulted in a time‐ and concentration‐dependent depletion of cellular GSH from viable cells which was accompanied by a matching increase in the extracellular GSH content. In contrast, the reverse transcriptase inhibitors zidovudine, lamivudine, efavirenz or nevirapine did not alter cellular or extracellular GSH levels. Removal of indinavir from the medium by washing the cells terminated the stimulated GSH export immediately, while the nelfinavir‐induced accelerated GSH export was maintained even after removal of nelfinavir. The stimulation of the GSH export from viable astrocytes by indinavir or nelfinavir was completely prevented by the application of MK571, an inhibitor of the multidrug resistance protein 1. These data demonstrate that indinavir and nelfinavir stimulate multidrug resistance protein 1‐mediated GSH export from viable astrocytes and suggest that treatment of patients with such inhibitors may affect the GSH homeostasis in brain.
Comparative effects of different modes of renin angiotensin system inhibition on hypercholesterolaemia‐induced atherosclerosis
Authors: Lu Hong , Balakrishnan Anju , Howatt Deborah A , Wu Congqing , Charnigo Richard , Liau Gene , Cassis Lisa A , Daugherty Alan 
Published: October 2011

BACKGROUND AND PURPOSE Inhibition of the renin angiotensin system (RAS) has been consistently demonstrated to reduce atherosclerosis. However, there has been no direct comparison among the three available pharmacological modes of inhibiting the RAS, which are inhibitors of renin, ACE and angiotensin II type 1 receptor. The purpose of this study was to determine the relative effects of these three modes of pharmacological RAS inhibition in reducing atherosclerosis by determining the dose–response relationships.EXPERIMENTAL APPROACH Male LDL receptor ‐/‐ mice were administered either vehicle or any of three doses of aliskiren, enalapril or losartan through s.c. infusion for 12 weeks. All mice were fed a saturated fat‐enriched diet during drug infusions. Systolic and diastolic BPs were measured during the study using a non‐invasive tail‐cuff system. Plasma cholesterol and renin concentrations, atherosclerotic lesions, and renal angiotensin II concentrations were determined at the termination of the study.KEY RESULTS Plasma renin concentrations were increased by all three drugs. None of the drugs changed plasma cholesterol concentrations. All drugs produced a dose‐related decrease in BP. All three drugs also profoundly reduced atherosclerosis in a dose‐dependent manner. The highest dose of each drug markedly attenuated lesion size, with no significant differences between the different drugs. The highest dose of each drug also similarly reduced renal angiotensin II concentrations.CONCLUSION AND IMPLICATIONS Drugs that inhibit the RAS, irrespective of their mode of inhibition, profoundly affect atherosclerotic lesion development in a dose‐dependent manner.
Glucagon and a glucagon‐GLP‐1 dual‐agonist increases cardiac performance with different metabolic effects in insulin‐resistant hearts
Authors: Axelsen LN , Keung W , Pedersen HD , Meier E , Riber D , Kjølbye AL , Petersen JS , Proctor SD , Holstein‐Rathlou N‐H , Lopaschuk GD 
Published: October 2011

BACKGROUND AND PURPOSE The prevalence of heart disease continues to rise, particularly in subjects with insulin resistance (IR), and improved therapies for these patients is an important challenge. In this study we evaluated cardiac function and energy metabolism in IR JCR:LA‐cp rat hearts before and after treatment with an inotropic compound (glucagon), a glucagon‐like peptide‐1 (GLP‐1) receptor agonist (ZP131) or a glucagon‐GLP‐1 dual‐agonist (ZP2495).EXPERIMENTAL APPROACH Hearts from IR and lean JCR:LA rats were isolated and perfused in the working heart mode for measurement of cardiac function and metabolism before and after addition of vehicle, glucagon, ZP131 or ZP2495. Subsequently, cardiac levels of nucleotides and short‐chain CoA esters were measured by HPLC.KEY RESULTS Hearts from IR rats showed decreased rates of glycolysis and glucose oxidation, plus increased palmitate oxidation rates, although cardiac function and energy state (measured by ATP/AMP ratios) was normal compared with control rats. Glucagon increased glucose oxidation and glycolytic rates in control and IR hearts, but the increase was not enough to avoid AMP and ADP accumulation in IR hearts. ZP131 had no significant metabolic or functional effects in either IR or control hearts. In contrast, ZP2495 increased glucose oxidation and glycolytic rates in IR hearts to a similar extent to that of glucagon but with no concomitant accumulation of AMP or ADP.CONCLUSION AND IMPLICATIONS Whereas glucagon compromised the energetic state of IR hearts, glucagon‐GLP‐1 dual‐agonist ZP2495 appeared to preserve it. Therefore, a glucagon‐GLP‐1 dual‐agonist may be beneficial compared with glucagon alone in the treatment of severe heart failure or cardiogenic shock in subjects with IR.
Development of a radioiodinated apoptosis–inducing ligand, rhTRAIL, and a radiolabelled agonist TRAIL receptor antibody for clinical imaging studies
Authors: Duiker EW , Dijkers ECF , Lambers Heerspink H , de Jong S , van der Zee AGJ , Jager PL , Kosterink JGW , de Vries EGE , Lub‐de Hooge MN 
Published: October 2011

BACKGROUND AND PURPOSE The TNF‐related apoptosis inducing ligand (TRAIL) induces apoptosis through activation of the death receptors, TRAIL‐R1 and TRAIL‐R2. Recombinant human (rh) TRAIL and the TRAIL‐R1 directed monoclonal antibody mapatumumab are currently clinically evaluated as anticancer agents. The objective of this study was to develop radiopharmaceuticals targeting the TRAIL‐R1, suitable for clinical use to help understand and predict clinical efficacy in patients.EXPERIMENTAL APPROACH rhTRAIL was radioiodinated with 125I, and conjugated mapatumumab was radiolabelled with 111In. The radiopharmaceuticals were characterized, their in vitro stability and death receptor targeting capacities were determined and in vivo biodistribution was studied in nude mice bearing human tumour xenografts with different expression of TRAIL‐R1.KEY RESULTS Labelling efficiencies, radiochemical purity, stability and binding properties were optimized for the radioimmunoconjugates. In vivo biodistribution showed rapid renal clearance of [125I]rhTRAIL, with highest kidney activity at 15 min and almost no detectable activity after 4 h. Activity rapidly decreased in almost all organs, except for the xenografts. Radiolabelled mapatumumab showed blood clearance between 24 and 168 h and a reduced decrease in radioactivity in the high receptor expression xenograft.CONCLUSIONS AND IMPLICATIONS rhTRAIL and mapatumumab can be efficiently radiolabelled. The new radiopharmaceuticals can be used clinically to study pharmacokinetics, biodistribution and tumour targeting, which could support evaluation of the native targeted agents in phase I/II trials.
Novel cAMP signalling paradigms: therapeutic implications for airway disease
Authors: Billington Charlotte K , Hall Ian P 
Published: October 2011

Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs‐coupled receptor to adenylyl cyclase (AC) to cAMP to PKA to biological effect. After a brief description of this canonical cAMP signalling pathway, a snapshot is provided of the novel paradigms of cAMP signalling. As in the airway the cAMP pathway relays the major bronchorelaxant signal and as such is the target for frontline therapy for asthma and COPD, particular emphasis is given to airway disease and therapy. Areas discussed include biased agonism, continued signalling following internalization, modulation of cAMP by AC, control of cAMP degradation, cAMP and calcium crosstalk, Epac‐mediated signalling and finally the implications of altered genotypes will be considered.LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐2
Blockade of ICa suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure
Authors: Milberg P , Fink M , Pott C , Frommeyer G , Biertz J , Osada N , Stypmann J , Mönnig G , Koopmann M , Breithardt G , Eckardt L 
Published: October 2011

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca2+ overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether ICa blockade was anti‐arrhythmic in an intact perfused heart model of CHF.EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham‐operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K+] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model.KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham‐operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block IKr in CHF hearts. After lowering [K+] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non‐sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state‐dependent block than a simple block of ICa.CONCLUSIONS AND IMPLICATIONS Blockade of ICa was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure.LINKED ARTICLE This article is commented on by Stams et al., pp. 554–556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01818.x
S(+)amphetamine induces a persistent leak in the human dopamine transporter: molecular stent hypothesis
Authors: Rodriguez‐Menchaca Aldo A , Solis Jr Ernesto , Cameron Krasnodara , De Felice Louis J 
Published: October 2011

BACKGROUND AND PURPOSE Wherever they are located, dopamine transporters (DATs) clear dopamine (DA) from the extracellular milieu to help regulate dopaminergic signalling. Exposure to amphetamine (AMPH) increases extracellular DA in the synaptic cleft, which has been ascribed to DAT reverse transport. Increased extracellular DA prolongs postsynaptic activity and reinforces abuse and hedonic behaviour.EXPERIMENTAL APPROACH Xenopus laevis oocytes expressing human (h) DAT were voltage‐clamped and exposed to DA, R(‐)AMPH, or S(+)AMPH.KEY RESULTS At ‐60mV, near neuronal resting potentials, S(+)AMPH induced a depolarizing current through hDAT, which after removing the drug, persisted for more than 30 min. This persistent leak in the absence of S(+)AMPH was in contrast to the currents induced by R(‐)AMPH and DA, which returned to baseline immediately after their removal. Our data suggest that S(+)AMPH and Na+ carry the initial S(+)AMPH‐induced current, whereas Na+ and Cl‐ carry the persistent leak current. We propose that the persistent current results from the internal action of S(+)AMPH on hDAT because the temporal effect was consistent with S(+)AMPH influx, and intracellular S(+)AMPH activated the effect. The persistent current was dependent on Na+ and was blocked by cocaine. Intracellular injection of S(+)AMPH also activated a DA‐induced persistent leak current.CONCLUSIONS AND IMPLICATIONS We report a hitherto unknown action of S(+)AMPH on hDAT that potentially affects AMPH‐induced DA release. We propose that internal S(+)AMPH acts as a molecular stent that holds the transporter open even after external S(+)AMPH is removed. Amphetamine‐induced persistent leak currents are likely to influence dopaminergic signalling, DA release mechanisms, and amphetamine abuse.
Investigating the Impact of Contrasting Paradigms of Knowledge on the Emancipatory Aims of Gallery Programmes for Young People
Authors: Sayers Esther 
Published: October 2011

AbstractWithin an emerging philosophy of contemporary gallery education, new pedagogies are required to meet the demands of looking at art, with increasingly varied constituent groups. Strategies that aim to empower young learners come from an ideological framework in which knowledge is negotiated and local significances are produced conversationally by learners and facilitators. Tension exists between the ideological position and the role of the gallery as ‘expert’: this conflict creates ambivalence towards the learner. The discourse of the ‘expert’ and the discourse of ‘local negotiation’ employ different pedagogic strategies, creating tension in the ways in which knowledge is reproduced for the visitor and participant. This article explores interrogatory pilot work with young people at Tate Modern. I use a hermeneutical approach to explore the interpretive roles of facilitator and participant when language‐based strategies are used to look at art. This research aims to construct a pedagogy that enables young people to learn about art in ways that take account of their situation as learners.
Effects of Withdrawal from Chronic Intermittent Ethanol Vapor on the Level and Circadian Periodicity of Running‐Wheel Activity in C57BL/6J and C3H/HeJ Mice
Authors: Logan Ryan W. , McCulley Walter D. , Seggio Joseph A. , Rosenwasser Alan M. 
Published: October 2011

Background:  Alcohol withdrawal is associated with behavioral and chronobiological disturbances that may persist during protracted abstinence. We previously reported that C57BL/6J (B6) mice show marked but temporary reductions in running‐wheel activity, and normal free‐running circadian rhythms, following a 4‐day chronic intermittent ethanol (CIE) vapor exposure (16 hours of ethanol vapor exposure alternating with 8 hours of withdrawal). In the present experiments, we extend these observations in 2 ways: (i) by examining post‐CIE locomotor activity in C3H/HeJ (C3H) mice, an inbred strain characterized by high sensitivity to ethanol withdrawal, and (ii) by directly comparing the responses of B6 and C3H mice to a longer‐duration CIE protocol.
Methods:  In Experiment 1, C3H mice were exposed to the same 4‐day CIE protocol used in our previous study with B6 mice (referred to here as the 1‐cycle CIE protocol). In Experiment 2, C3H and B6 mice were exposed to 3 successive 4‐day CIE cycles, each separated by 2 days of withdrawal (the 3‐cycle CIE protocol). Running‐wheel activity was monitored prior to and following CIE, and post‐CIE activity was recorded in constant darkness to allow assessment of free‐running circadian period and phase.
Results:  C3H mice displayed pronounced reductions in running‐wheel activity that persisted for the duration of the recording period (up to 30 days) following both 1‐cycle (Experiment 1) and 3‐cycle (Experiment 2) CIE protocols. In contrast, B6 mice showed reductions in locomotor activity that persisted for about 1 week following the 3‐cycle CIE protocol, similar to the results of our previous study using a 1‐cycle protocol in this strain. Additionally, C3H mice showed significant shortening of free‐running period following the 3‐cycle, but not the 1‐cycle, CIE protocol, while B6 mice showed normal free‐running rhythms.
Conclusions:  These results reveal genetic differences in the persistence of ethanol withdrawal‐induced hypo‐locomotion. In addition, chronobiological alterations during extended abstinence may depend on both genetic susceptibility and an extended prior withdrawal history. The present data establish a novel experimental model for long‐term behavioral and circadian disruptions associated with ethanol withdrawal.