bluuebunny/crossref_metadata_2025 huggingface dataset:
Case controlled study of the hospital stay and return to full activity following laparoscopic and open colorectal surgery before and after the introduction of an enhanced recovery programme
Authors: Raymond T. M. , Kumar S. , Dastur J. K. , Adamek J. P. , Khot U. P. , Stewart M. S. , Parker M. C.
Published: April 2009

Aim  The short‐term benefits of laparoscopic surgery are well established and in particular within an enhanced recovery programme. Early return to activity is to be expected but has not been quantified widely. The aim of this study was to measure the hospital stay and return to full activity following laparoscopic colorectal surgery and compare this with a matched group of patients undergoing open colorectal resections before and after the introduction of an enhanced recovery programme.

Method  Retrospective analysis of all laparoscopic colorectal operations performed between January 2003 and June 2007 on an intention to treat basis compared with a matched group of patients undergoing elective open colorectal surgery at the same institution.

Results  The median hospital stay following 179 laparoscopic colorectal resections was 6 days whilst following 144 conventional open operations it was 8 days. Following the introduction of an enhanced recovery programme the hospital stay fell from 7 to 5 days and from 9 to 7 days for laparoscopic and open groups respectively. The median return to full activity from surgery for laparoscopic patients was 13 days in comparison to 56 days for patients undergoing open colorectal surgery.

Conclusions  Following laparoscopic colorectal resection, patients can be expected to have a hospital stay of under a week and return to their usual activities as early as a week after discharge from hospital and < 2 weeks from surgery in comparison to patients undergoing open surgery who take 8 weeks or more to recover.
A pilot study of ultrasound guided Durasphere injection in the treatment of faecal incontinence
Authors: Beggs A. D. , Irukulla S. , Sultan A. H. , Ness W. , Abulafi A. M.
Published: April 2009

Aim  To assess injection of Durasphere under direct endoanal ultrasound guidance as a treatment for faecal incontinence.

Method  A total of 23 patients with varying degrees of persistent faecal leakage and/or soiling were recruited. Durasphere was injected in the intersphincteric plane under direct ultrasound guidance. All patients were given a general anaesthetic. Patients had ano‐rectal physiology, endoanal ultrasound, continence scoring and quality of life measures assessed at 0, 1, 3, 6 and 12 months.

Results  A total of 21 patients were followed up for at least 12 months, with two being excluded at the follow‐up stage. Friedman two‐way analysis of variance of the Cleveland Clinic Score, Faecal Incontinence Quality of Life Score and Diary Response Score demonstrated a significant sustained improvement. There was no significant improvement in number of bowel movements. There was a significant difference in anal squeeze pressure after therapy, but no significant difference in anal resting pressure. Six patients reported no improvement after Durasphere therapy.

Conclusions  Durasphere gave sustained improvements in quality of life and continence scores in this study group. Strict criteria are needed to ascertain suitability for Durasphere therapy.
Colon and rectal cancer in Ibadan, Nigeria: an update
Authors: Irabor D. O. , Arowolo A. , Afolabi A. A.
Published: April 2009

Introduction Colorectal cancer was hitherto a rarity in the rural African in general and in Nigerians inclusive. Ibadan is a sprawling city in Western Nigeria with a population of about 2.5 million inhabitants. Lately, several publications from surgeons in this city have alluded to an increase in the number of colorectal cancer cases managed in the teaching hospital.

Objectives To examine the incidence of this disease over 10 years in order to confirm or exclude the apparent significant increase in colorectal cancer cases in Ibadan, Nigeria.

Method This is a retrospective study highlighting the age, sex, clinical features, operations performed and histopathological subtypes of patients who had surgery for colorectal cancer in the University College Hospital Ibadan between July 1995 and August 2004.

Results Two and sixty‐eight patients were seen over 10 years. The male:female ratio was 1.16:1. The mean age was 41 years and the peak age was the 51‐ to 60‐years group. Fourteen per cent of the patients were 30 years and below. Sixty‐two per cent of the patients had rectal carcinoma while 33.2% had colonic carcinoma. Around 60.7% of colonic lesions were right‐sided. The most common histopathological subtype was adenocarcinoma (78.8%), mucinous adenocarcinoma was 10.8% and signet ring type was 2.6%.

Conclusion Colorectal cancer is a disease on the increase in Ibadan. The mean age of 41 years is much lower than in the Western world. The male:female ratio still favours male patients slightly. About one in seven patients are 30 years and below. Adenomatous polyps were absent in the resected specimens.
The promiscuous receptor
Authors: Newsom‐Davis Thomas E. , Kenny Laura M. , Ngan Sarah , King Judith , Waxman Jonathan
Published: April 2009

OBJECTIVE

To determine the effectiveness of vitamin D therapy in patients with asymptomatic, prostate‐specific antigen (PSA)‐progression of prostate cancer.

PATIENTS AND METHODS

Twenty‐six patients with locally advanced or metastatic prostate cancer were treated with vitamin D. Vitamin D therapy was discontinued on disease progression as assessed by symptoms or serum PSA increase. The response to therapy was judged from changes in PSA level from the pretreatment baseline to 3 months after starting vitamin D therapy.

RESULTS

Of the 26 patients, five (20%) responded to vitamin D; the mean (range) reduction in PSA level was 45.3 (15.9–95.1)%, and mean duration of response was 4–5 months. Patients in whom the PSA level was stabilized, but not reduced, after vitamin D treatment had a duration of response of up to 36 months. Treatment was well tolerated and was not associated with elevation of serum calcium levels. There was no significant correlation between response to therapy and stage of disease, Gleason grade, previous treatments or PSA level at diagnosis or initiation of vitamin D therapy.

CONCLUSION

Vitamin D therapy is an effective and well tolerated treatment for patients with asymptomatic progressive prostate cancer, and is a useful addition to the therapeutic options.
THE HUMAN WORLD
Authors: Kekes John
Published: April 2009

We do not have to choose between belief in a divinely ordained cosmic moral order and the arbitrariness of our moral commitments. The alternative is a secular view that accepts that there is a natural cosmic order, denies that the order is moral, and relies on the values of the human world to provide a moral order by which we can reasonably live. These values are human constructions. Reliance on them is reasonable if they have passed the test of critical reflection. Our well‐being depends on living according to the values that passed that test. Natural necessities, the contingencies of life, and our fallibility, however, limit the extent to which we can control how we live. We cannot free ourselves from necessities, but we can reduce the extent to which we are vulnerable to contingencies, and we can, within limits, increase the control we have by correcting mistakes we make when we are insufficiently critical of our attitudes, commitments, and values.
INDEFENSIBLE MIDDLE GROUND FOR LOCAL REDUCTIONISM ABOUT TESTIMONY
Authors: Gelfert Axel
Published: April 2009

Local reductionism purports to defend a middle ground in the debate about the epistemic status of testimony‐based beliefs. It does so by acknowledging the practical ineliminability of testimony as a source of knowledge, while insisting that such an acknowledgment need not entail a default‐acceptance view, according to which there exists an irreducible warrant for accepting testimony. The present paper argues that local reductionism is unsuccessful in its attempt to steer a middle path between reductionism and anti‐reductionism about testimonial justification. In particular, it challenges local reductionism ‘from within’, without appealing to anti‐reductionist intuitions. By offering novel arguments to the effect that local reductionism fails by its own standards, the present paper considerably strengthens the case against this version of reductionism. Local reductionism, it is argued, fails for three main reasons. First, it cannot account for the rationality of testimonial rejection in paradigmatic cases, even though the possibility of rational rejection is thought to be of central justificatory importance. Second, it does not provide a sufficiently distinct non‐testimonial basis to which testimonial justification can be successfully reduced. Finally, local reductionism is shown to be an intrinsically unstable position, in danger of collapsing into full‐fledged ‘credulism’ of the kind historically associated with Thomas Reid.
THE MODAL ARGUMENT FOR A PRIORI JUSTIFICATION
Authors: Horvath Joachim
Published: April 2009

Kant famously argued that, from experience, we can only learn how something actually is, but not that it must be so. In this paper, I defend an improved version of Kant's argument for the existence of a priori knowledge, the Modal Argument, against recent objections by Casullo and Kitcher. For the sake of the argument, I concede Casullo's claim that we may know certain counterfactuals in an empirical way and thereby gain epistemic access to some nearby, nomologically possible worlds. But I maintain that our beliefs about metaphysical necessities still cannot be justified empirically. Furthermore, I reject Casullo's deflationary thesis about the significance of such justification. Kitcher's most troublesome objection is that we can gain any modal justification whatsoever through testimony, i.e. in an experiential way. This can be countered by distinguishing between productive sources of justification, like perception, and merely reproductive sources, like testimony. Thus, some productive a priori source will always be needed somewhere.1
‘DEMONSTRATIVE’ COLOUR CONCEPTS: RECOGNITION VERSUS PRESERVATION
Authors: Textor Mark
Published: April 2009

Arguments for and against the existence of demonstrative concepts of shades and shapes turn on the assumption that demonstrative concepts must be recognitional capacities. The standard argument for this assumption is based on the widely held view that concepts are those constituents of propositional attitudes that account for an attitude's inferential potential. Only if demonstrative concepts of shades are recognitional capacities, the standard argument goes, can they account for the inferential potential of demonstrative judgements about shades. Shades are conceived as colour universals. Shade a is different from shade b iff it is possible to distinguish a from b visually. In this paper I will argue that the standard argument is based on a mistaken view of inference. We can correctly draw inferences from a demonstrative judgement about something x, even if we are not able to recognise or re‐identify the previously demonstrated x during our reasoning. We are prima facie entitled to rely on our preservative memory as retaining our initial demonstrative apprehension of x. The fact that preservative memory entitles us to assume sameness of referent over time is linguistically manifest in the use of anaphoric pronouns: if we can no longer recognise and demonstrate our original demonstratum, we can use anaphoric expressions to pick it up, thereby ensuring sameness of reference. (‘That is a nice bird. Now it has vanished. So there is a nice bird that has just vanished.’) Since preservation of the initial episode of apprehending x grounds our reasoning from demonstrative judgements, there is no longer a reason to require demonstrative concepts to be recognitional capacities. The standard argument does not get off the ground.1
A Vest Reinvested in The Gift
Authors: IVLEVA VICTORIA
Published: April 2009

They held the universe to be a large suit of clothes, which invests everything: that the earth is invested by the air; the air is invested by the stars; and the stars are invested by the primum mobile. Look on this globe of earth, you will find it to be a very complete and fashionable dress. What is that which some call land, but a fine coat faced with green? or the sea, but a waistcoat of watertabby? Proceed to the particular works of the creation, you will find how curious Journeyman Nature hath been, to trim up the vegetable beaux; observe how sparkish a periwig adorns the head of a beech, and what a fine doublet of white satin is worn by the birch. To conclude from all, what is man himself but a microcoat, or rather a complete suit of clothes with all its trimmings?
The debts of James VI of Scotland1
Authors: GOODARE JULIAN
Published: April 2009

James VI (1567–1625) was chronically indebted, and this caused him frequent problems. This article presents two series of systematic data that together indicate the main contours of his indebtedness: (1) end‐of‐year deficits, and (2) hived‐off debts which the Crown left unpaid for long periods (sometimes permanently). The hived‐off debts, reconstructed individually, constitute a narrative of fiscal policy‐making. Instead of a large and catastrophic bankruptcy, James in effect had numerous small bankruptcies. He benefited from an emerging structure of Scottish domestic credit. He eventually repaid many of his debts after succeeding to the English throne in 1603.
Equity Home‐Bias: A Suboptimal Choice for UK investors?
Authors: Antoniou Antonios , Olusi Olasupo , Paudyal Krishna
Published: April 2009

In spite of the popularity of international portfolio diversification theory, extant empirical literature shows that investors prefer domestic assets and as a result, many studies argue that investors' portfolios are largely suboptimal. This paper examines whether British investors need to diversify their portfolios internationally to gain performance benefits from international markets or can they obtain these benefits by mimicking the portfolios with domestically traded assets. The results confirm that it is possible to mimic the performance of foreign equity with domestic equity. Indeed, the pay‐offs from homemade portfolios outperform those from international portfolios regardless of the periodic variation in the overall performance of the UK market vis‐à‐vis foreign markets. The superiority of homemade portfolio is more prominent in recent years and is enhanced by the increased internationalisation of developed capital markets. Therefore, investors' home bias is not suboptimal.
Liquidity and Optimal Market Transparency
Authors: Dumitrescu Ariadna
Published: April 2009

In this paper I explore some of the consequences of greater market transparency for market performance in the presence of a strategic specialist. Although numerous studies have dealt with this issue, previous work has only considered either fully transparent or fully opaque markets. My model allows for different levels of transparency, and therefore sheds light on how transparency affects market performance. I show that an intermediate level of transparency can improve market performance relative to the more extreme cases of full transparency or no transparency at all.
Does Global Liquidity Matter for Monetary Policy in the Euro Area?*
Authors: Berger Helge , Harjes Thomas
Published: April 2009

Global excess liquidity prevalent across the world's financial markets (or its sudden absence) is sometimes believed to limit sovereign monetary policy even in large economies such as the euro area. However, there is still discussion about what constitutes global excess liquidity and how exactly it shapes the policy environment. Our approach adjusts liquidity for a longer‐term interest rate and output effects and focuses on US and Japanese liquidity as relevant proxies for global developments from a euro area perspective. We find that, in particular, excess liquidity in the US tends to lead developments in euro area liquidity. US excess liquidity is also consistently positive as a determinant of euro area inflation and is shown to be Granger‐causal for euro area inflation in an out‐of‐sample forecasting exercise. There is some evidence that, at least in part, this result seems to be related to a weakening of the effectiveness of monetary policy in the euro area interest during times of excessive US liquidity. In contrast, the influence of euro area excess liquidity on euro area inflation is more limited.
The effects of sales promotion strategy, product appeal and consumer traits on reminder impulse buying behaviour
Authors: Liao Shu‐Ling , Shen Yung‐Cheng , Chu Chia‐Hsien
Published: April 2009

This article investigates factors of marketing communications and consumer characteristics that induce reminder impulse buying behaviour. Study 1 applies the antecedent, process and consequence approach to investigate the essential differences between reminder impulse buying and pure impulse buying. The results of Study 1 reveal that reminder impulse buying significantly differs from pure impulse buying on motivation, buying goal and decision evaluation. Study 2 further examines how sales promotion strategy might affect reminder impulse buying, with product appeal and consumer traits as moderating factors. Both sales promotion strategy and its interaction effects with product appeal are found to have significant influences on reminder impulse buying. Specifically, an instant‐reward promotion promotes stronger reminder impulse buying than a delayed‐reward promotion. Furthermore, both a utilitarian product appeal with a price discount promotion and a hedonic product appeal with a premium promotion can encourage greater reminder impulse buying.
Neuroprotection of microglial conditioned medium on 6‐hydroxydopamine‐induced neuronal death: role of transforming growth factor beta‐2
Authors: Polazzi Elisabetta , Altamira Luis Emiliano Peña , Eleuteri Simona , Barbaro Raffaella , Casadio Chiara , Contestabile Antonio , Monti Barbara
Published: April 2009

Microglia, the immune cells of the CNS, play essential roles in both physiological and pathological brain states. Here we have used an in vitro model to demonstrate neuroprotection of a 48 h‐microglial conditioned medium (MCM) towards cerebellar granule neurons (CGNs) challenged with the neurotoxin 6‐hydroxydopamine, which induces a Parkinson‐like neurodegeneration, and to identify the protective factor(s). MCM nearly completely protects CGNs from 6‐hydroxydopamine neurotoxicity and at least some of the protective factor(s) are peptidic in nature. While the fraction of the medium containing molecules < 30 kDa completely protects CGNs, fractions containing molecules < 10 kDa or > 10 kDa are not neuroprotective. We further demonstrate that microglia release high amounts of transforming growth factor‐β2 (TGF‐β2) and that its exogenous addition to the fraction of the medium not containing it (< 10 kDa) fully restores the neuroprotective action. Moreover, MCM neuroprotection is significantly counteracted by an inhibitor of TGF‐β2 transduction pathway. Our results identify TGF‐β2 as an essential neuroprotective factor released by microglia in its culture medium that requires to be fully effective the concomitant presence of other factor(s) of low molecular weight.
Mechanism of rhodopsin kinase regulation by recoverin
Authors: Komolov Konstantin E. , Senin Ivan I. , Kovaleva Nadezda A. , Christoph Mathias P. , Churumova Valeriya A. , Grigoriev Ilya I. , Akhtar Muhammad , Philippov Pavel P. , Koch Karl‐Wilhelm
Published: April 2009

Recoverin is suggested to inhibit rhodopsin kinase (GRK1) at high [Ca2+] in the dark state of the photoreceptor cell. Decreasing [Ca2+] terminates inhibition and facilitates phosphorylation of illuminated rhodopsin (Rh*). When recoverin formed a complex with GRK1, it did not interfere with the phosphorylation of a C‐terminal peptide of rhodopsin (S338‐A348) by GRK1. Furthermore, while GRK1 competed with transducin on interaction with rhodopsin and thereby suppressed GTPase activity of transducin, recoverin in the complex with GRK1 did not influence this competition. Constructs of GRK1 that encompass its N‐terminal, catalytic or C‐terminal domains were used in pull‐down assays and surface plasmon resonance analysis to monitor interaction. Ca2+‐recoverin bound to the N‐terminus of GRK1, but did not bind to the other constructs. GRK1 interacted with rhodopsin also by its N‐terminus in a light‐dependent manner. No interaction was observed with the C‐terminus. We conclude that inhibition of GRK1 by recoverin is not the result of their direct competition for the same docking site on Rh*, although the interaction sites of GRK1/Rh* and GRK1/recoverin partially overlap. The N‐terminus of GRK1 is recognized by Rh* leading to a conformational change which moves the C‐terminus of Rh* into the catalytic kinase groove. Ca2+‐recoverin interacting with the N‐terminus of GRK1 prevents this conformational change and thus blocks Rh* phosphorylation by GRK1.
The α5(H105R) mutation impairs α5 selective binding properties by altered positioning of the α5 subunit in GABAAreceptors containing two distinct types of α subunits
Authors: Balic Ela , Rudolph Uwe , Fritschy Jean‐Marc , Mohler Hanns , Benke Dietmar
Published: April 2009

GABAAreceptors are pentameric ligand‐gated ion channels that are major mediators of fast inhibitory neurotransmission. Clinically relevant GABAAreceptor subtypes are assembled from α5(1‐3, 5), β1‐3 and the γ2 subunit. They exhibit a stoichiometry of two α, two β and one γ subunit, with two GABA binding sites located at the α/β and one benzodiazepine binding site located at the α/γ subunit interface. Introduction of the H105R point mutation into the α5 subunit, to render α5 subunit‐containing receptors insensitive to the clinically important benzodiazepine site agonist diazepam, unexpectedly resulted in a reduced level of α5 subunit protein in α5(H105R) mice. In this study, we show that the α5(H105R) mutation did not affect cell surface expression and targeting of the receptors or their assembly into macromolecular receptor complexes but resulted in a severe reduction of α5‐selective ligand binding. Immunoprecipitation studies suggest that the diminished α5‐selective binding is presumably due to a repositioning of the α5(H105R) subunit in GABAAreceptor complexes containing two different α subunits. These findings imply an important role of histidine 105 in determining the position of the α5 subunit within the receptor complex by determining the affinity for assembly with the γ2 subunit.
The role of ubiquitin linkages on α‐synuclein induced‐toxicity in a Drosophila model of Parkinson’s disease
Authors: Lee Francesca K. M. , Wong Azaria K. Y. , Lee Yuk Wa , Wan Oi Wan , Edwin Chan H. Y. , Chung Kenny K. K.
Published: April 2009

Parkinson’s disease (PD) is a common movement disorder marked by the loss of dopaminergic (DA) neurons in the brain stem and the presence of intraneuronal inclusions designated as Lewy bodies (LB). The cause of neurodegeneration in PD is not clear, but it has been suggested that protein misfolding and aggregation contribute significantly to the development of the disease. Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and autophagy lysosomal pathway (ALP). Recent studies suggested that different types of ubiquitin linkages can modulate these two pathways in the process of protein degradation. In this study, we found that co‐expression of ubiquitin can rescue neurons from α‐syn‐induced neurotoxicity in a Drosophila model of PD. This neuroprotection is dependent on the formation of lysine 48 polyubiquitin linkage which is known to target protein degradation via the proteasome. Consistent with our results that we observed in vivo, we found that ubiquitin co‐expression in the cell can facilitate cellular protein degradation by the proteasome in a lysine 48 polyubiquitin‐dependent manner. Taken together, these results suggest that facilitation of proteasomal protein degradation can be a potential therapeutic approach for PD.
Credit Losses in Australasian Banking
Authors: HESS KURT , GRIMES ARTHUR , HOLMES MARK
Published: April 2009

We analyse the determinants of bank credit losses in Australasia. Despite sizeable credit losses over the past two decades, ours is the first systematic study to do so. Analysis is based on a comprehensive dataset retrieved from original financial reports of 32 Australasian banks (1980–2005). Credit losses rise when the macro economy is weak. Asset markets, particularly the equity market, are also important. Larger banks provide more for credit losses while banks with high cost‐income‐ratios show greater loan loss provisions. Strong loan growth translates into significantly higher credit losses with a lag of 2–4 years. Finally, the results show strong evidence of income smoothing activities by banks.
The Publication Decisions of Judges on the County Court of Victoria*
Authors: SMYTH RUSSELL , MISHRA VINOD
Published: April 2009

This study examines the determinants of whether judges of the County Court of Victoria publish their judgements. Methodologically, it improves on existing US studies because it uses data on all published judgements over a decade and it exploits the panel properties of the data. The results suggest that there is a nonlinear relationship between ageing and the number of judgements published with productivity peaking at age 61; and judges who are adjunct professors, judges who manage more lists and judges who hear cases in the work cover list publish more judgements.
Receptors for NPY and PACAP differ in expression and activity during adipogenesis in the murine 3T3‐L1 fibroblast cell line
Authors: Gericke Martin T , Kosacka Joanna , Koch Daniela , Nowicki Marcin , Schröder Thomas , Ricken Albert M , Nieber Karen , Spanel‐Borowski Katharina
Published: April 2009

Background and purpose:  Neuropeptides are involved in the regulation of food intake in the central nervous system, but they might also act on peripheral fat tissue via neuropeptide receptors.

Experimental approach:  We investigated the receptor expression and activity of pituitary adenylate cyclase‐activating polypeptide (PACAP) and of neuropeptide Y at the mRNA and protein levels in the 3T3‐L1 fibroblast line during differentiation into adipocytes. Intracellular calcium concentration was measured by calcium imaging.

Key results:  The PACAP receptors PAC1 and VPAC2 as well as the neuropeptide Y1 receptor were expressed at the mRNA level in fibroblasts, pre‐adipocytes and adipocytes. The mRNA profile of the PAC1 receptor isoforms showed the HOP sequence, whereas the HIP‐isoform was present in subconfluent 3T3‐L1 fibroblasts only. At the protein level, the mature 3T3‐L1 adipocytes produced the PAC1 and Y1 receptors; only the PAC1 receptor showed carbohydrate residues. Both neuropeptides induced an increase of intracellular calcium in mature adipocytes, which was absent in the precursor cells. These changes in calcium were mediated by Y1 and PAC1 receptors as demonstrated by the effects of specific receptor agonists and antagonists.

Conclusions and implications:  As the PAC1‐HOP receptor variant seems to be responsible for PACAP‐mediated calcium influx in many cell types, the HOP sequence might also mediate the increase in intracellular calcium in adipocytes. Because a high intracellular calcium level is associated with lipogenesis, peptidergic innervation of adipose tissue might be involved in stress‐induced obesity.

British Journal of Pharmacology (2009) 157, 620–632; doi:10.1111/j.1476‐5381.2009.00164.x; published online 27 April 2009
SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor
Authors: Bradley ME , Bond ME , Manini J , Brown Z , Charlton SJ
Published: April 2009

Background and purpose: In several previous studies, the C‐X‐C chemokine receptor (CXCR)2 antagonist 1‐(2‐bromo‐phenyl)‐3‐(7‐cyano‐3H‐benzotriazol‐4‐yl)‐urea (SB265610) has been described as binding competitively with the endogenous agonist. This is in contrast to many other chemokine receptor antagonists, where the mechanism of antagonism has been described as allosteric.

Experimental approach: To determine whether it displays a unique mechanism among the chemokine receptor antagonists, the mode of action of SB265610 was investigated at the CXCR2 receptor using radioligand and [35S]‐GTPγS binding approaches in addition to chemotaxis of human neutrophils.

Key results: In equilibrium saturation binding studies, SB265610 depressed the maximal binding of [125I]‐interleukin‐8 ([125I]‐IL‐8) without affecting theKd. In contrast, IL‐8 was unable to prevent binding of [3H]‐SB265610. Kinetic binding experiments demonstrated that this was not an artefact of irreversible or slowly reversible binding. In functional experiments, SB265610 caused a rightward shift of the concentration‐response curves to IL‐8 and growth‐related oncogene α, but also a reduction in maximal response elicited by each agonist. Fitting these data to an operational allosteric ternary complex model suggested that, once bound, SB265610 completely blocks receptor activation. SB265610 also inhibited basal [35S]‐GTPγS binding in this preparation.

Conclusions and implications: Taken together, these data suggest that SB265610 behaves as an allosteric inverse agonist at the CXCR2 receptor, binding at a region distinct from the agonist binding site to prevent receptor activation, possibly by interfering with G protein coupling.
Effects of NXY‐059 in experimental stroke: an individual animal meta‐analysis
Authors: Bath PMW , Gray LJ , Bath AJG , Buchan A , Miyata T , Green AR
Published: April 2009

Background and purpose:  Disodium 2,4‐disulphophenyl‐N‐tert‐butylnitrone (NXY‐059) was neuroprotective in experimental stroke models but ineffective in a large clinical trial. This first‐ever individual animal meta‐analysis was used to assess the preclinical studies.

Experimental approach:  Studies were obtained from AstraZeneca and PubMed searches. Data for each animal were obtained from the lead author of each study and/or AstraZeneca. Published summary data were used if individual data were not available. Infarct volume and motor impairment were standardized to reflect different species and scales. Standardized mean difference (SMD), coefficients from multilevel models and 95% confidence intervals (95% CI) are presented.

Key results:  Fifteen studies (26 conditions, 12 laboratories) involving rats (544), mice (9) and marmosets (32) were identified (NXY‐059: 332, control: 253) with individual data for 442 animals. Four studies were unpublished. Studies variably used randomization (40%), blinding of surgeon (53%) and outcome assessor (67%). NXY‐059 reduced total (SMD −1.17, 95% CI −1.50 to −0.84), cortical (SMD −2.17, 95% CI −2.99 to −1.34) and subcortical (−1.43, 95% CI −2.20 to −0.86) lesion volume; efficacy was seen in transient, permanent and thrombotic ischaemia, up to 180 min post occlusion. NXY‐059 reduced motor impairment (SMD −1.66, 95% CI −2.18 to −1.14) and neglect. Evidence for performance, attrition and publication bias was present.

Conclusions and implications:  NXY‐059 was neuroprotective in experimental stroke although bias may have resulted in efficacy being overestimated. Efficacy in young, healthy, male animals is a poor predictor of clinical outcome. We suggest the use of preclinical meta‐analysis before initiation of future clinical trials.
The Piano as Cultural Symbol in Colonial New Zealand
Authors: Moffat Kirstine
Published: April 2009

The piano was an important cultural symbol in colonial New Zealand, yet although there is a significant body of international scholarship on the social and cultural history of the instrument in Britain, America, Canada, Norway, Spain and India there is a dearth of scholarly criticism relating to New Zealand. Research to redress this absence has revealed that the piano was central to settler culture, demonstrating a migrant desire to replicate the known and familiar but also highlighting settler innovations and an emerging nationalism. International connections between New Zealand, Britain, Western Europe, America and Australia are also apparent in relation to migrant patterns, the importation of instruments and sheet music and networks of musical performance and study. The instrument played a role in the complex dynamic of cultural encounter between Maori and settler, with an initial indigenous negativity and bemusement giving way to an interest in the piano and an appropriation of the instrument into Maori cultural contexts and spaces, including the marae. Prevailing perceptions of gender roles and identity are also challenged by research on the piano. Likewise, an examination of piano and class reveals that the instrument was popular with New Zealanders from all socio‐economic backgrounds.
‘A School Said to Resemble a Luxury Hotel’: Historicizing African Women's Quest for Education before Oprah's School
Authors: Charumbira Ruramisai
Published: April 2009

The public reception of the Oprah Winfrey Leadership Academy for Girls (OWLA) in South Africa and the United States is a recent example of a historical pattern historians have often called the ‘civilizing mission’ on behalf of girls and women in Africa. One of the greatest missed opportunities by founders (and critics) of such schools, past and the present, has been the glaring omission of highlighting contemporary African women's achievements so the girls can see themselves as connected to a long line of female strivers and achievers with varied personal histories. This study utilizes African women's novels and memoirs to historicize African women's quest for (higher) education as well as emphasize the importance of historically grounded international development aid to Africa so as to avoid the pitfalls of neocolonialism that reproduce stereotypes about Africans, and women in particular. Texts highlighted include: Tsitsi Dangarembga'sNervous Conditions, Mariama Bâ'sSo Long a Letter, Mamphela Ramphele'sAcross Boundaries, and Wangari Maathai'sUnbowed.
How Well Do Headache Patients Remember? A Comparison of Self‐Report Measures of Headache Frequency and Severity in Patients with Migraine
Authors: McKenzie Jeff A. , Cutrer F. Michael
Published: April 2009

Objective.— To compare patient recall of migraine headache frequency and severity over 4 weeks prior to a return visit as reported in an interval questionnaire vs a daily diary.

Background.— Many therapeutic decisions in the management of migraine patients are based on patient recall of response to treatment. As consistent completion of a daily headache diary is problematic, we have assessed the reliability of patient recall in a 1‐time questionnaire.

Methods.— Headache frequency and average severity (0 to 3‐point scale) were reported in an interval questionnaire by 209 patients who had also maintained a daily diary over the same 4‐week period.

Results.— Headache frequency over the previous 4 weeks as reported in interval questionnaires (14.7) was not different from that documented in diaries (15.1), P = .056. However, reported average headache severity on a 0 to 3 scale as reported in the questionnaire (1.84) was worse than that documented in the diaries (1.63), P < .001.

Conclusions.— In the management of individual patients, the daily diary is still preferable when available. Aggregate assessment of headache frequency in groups of patients based on recall of the prior 4 weeks is equally as reliable as a diary. Headache severity reported in questionnaires tends to be greater than that documented in daily diaries and may be less reliable.
The antiepileptogenic effect of electrical stimulation at different low frequencies is accompanied with change in adenosine receptors gene expression in rats
Authors: Jahanshahi A. , Mirnajafi‐Zadeh Javad , Javan Mohammad , Mohammad‐Zadeh Mohammad , Rohani Razieh
Published: April 2009

Purpose:  Previous studies have shown that the anticonvulsant effects of low‐frequency stimulation (LFS) can be affected by activation of adenosine receptors. In the present study, the effect of LFS at different frequencies on kindling rate and adenosine receptors gene expression was investigated.

Methods:  Animals were kindled by perforant path stimulation in a rapid kindling manner. LFS (0.5, 1, and 5 Hz) was applied after termination of each kindling stimulation. Seizure severity was measured according to behavioral and electrophysiologic parameters. At the end of the experiments, adenosine A1 and A2A receptor gene expression were measured.

Results:  The inhibitory effect of LFS on kindling acquisition was observed at all frequencies. In addition, the inhibitory action of LFS on enhancement of field excitatory postsynaptic potential slope and population spike amplitude during kindling acquisition was not affected by the LFS frequency. However, the effects of LFS on paired‐pulse recordings were greater at frequency of 5 Hz. Application of LFS during kindling acquisition also prevented the kindling induced decrease in the A1 receptor gene expression and attenuated the level of A2A receptor gene expression in the dentate gyrus. These effects were also greater at the frequency of 5 Hz.

Discussion:  According to these data, it may be suggested that the antiepileptogenic effects of LFS, developed through inhibition of synaptic transmission in the dentate gyrus, is mediated somehow through preventing the decrease of A1 receptor and through attenuating the A2A receptor gene expression. These effects might be dependent on the frequency of LFS.
Coexistence of symptomatic focal and absence seizures: Video‐EEG and EEG‐fMRI evidence of overlapping but independent epileptogenic networks
Authors: Chassagnon Serge , Hawko Colin S. , Bernasconi Andrea , Gotman Jean , Dubeau François
Published: April 2009

The distinction between typical absences and hypomotor seizures in patients having frontal lesions is difficult. In focal epilepsy, generalized‐like interictal discharges can reflect either a coexistent generalized epileptic trait or a secondary bilateral synchrony. Using combined measures of the EEG and blood oxygenation level dependent (BOLD) activity, we studied a 50‐year‐old patient with both absence‐like and symptomatic focal motor seizures. Focal activity induced activation in the lesional area and deactivation in the contralateral central cortex. Generalized spike‐and‐wave discharges (GSWDs) resulted also in perilesional activation, and multifocal symmetrical cortical and thalamic activations, and deactivation in associative cortical areas. Although the central cortex was involved during both types of epileptic activity, electroencephalography (EEG)–functional magnetic resonance imaging (fMRI) revealed distinct neuronal networks at the time of the focal or generalized discharges, allowing a clear‐cut differentiation of the generators. Whether the patient had distinct epileptic syndromes or distinct electrographic patterns from the lesional trigger remains debatable.
Impaired function of GABABreceptors in tissues from pharmacoresistant epilepsy patients
Authors: Teichgräber Laura A. , Lehmann Thomas‐Nicolas , Meencke Heinz‐Joachim , Weiss Torsten , Nitsch Robert , Deisz Rudolf A.
Published: April 2009

Purpose: Effects of pre‐ and postsynaptic γ‐aminobutyric acid B (GABAB) receptor activation were characterized in human tissue from epilepsy surgery.

Methods: Slices of human cortical tissue were investigated in a submerged‐type chamber with intracellular recordings in layers II/III. Parallel experiments were performed in rat neocortical slices with identical methods. Synaptic responses were elicited with single or paired stimulations of incrementing intervals.

Results: Neurons in human epileptogenic tissue exhibited usually small inhibitory postsynaptic potentials (IPSP) mediated by GABABreceptor, verified by the sensitivity to the selective antagonist CGP 55845A. The IPSPBconductance averaged 5.8 nS in neurons from epileptogenic tissues and 15.9 nS in neurons from nonepileptogenic tissues (p < 0.0001). Application of baclofen caused small conductance increases in human neurons, which were linearly related to IPSPBconductances. Paired‐pulse stimulation revealed constant synaptic responses in human temporal lobe epilepsy (TLE) slices at all interstimulus intervals (ISIs). Pharmacologically isolated IPSPAin the human tissue exhibited a small paired‐pulse depression (average 10% at 500 ms ISI). Bicuculline‐induced paroxysmal depolarization shifts (PDSs) were transiently depressed by 24% in human TLE tissue; and by 74% in rat neocortical slices (200 ms ISI; p = 0.015). The depressions of bicuculline‐induced PDSs were antagonized by CGP 55845A in both species. Staining for GABABreceptors revealed significantly smaller numbers of immunopositive dots in human epileptogenic neurons versus human control neurons.

Discussion: The small IPSPB, baclofen‐conductances, and paired‐pulse depression of PDSs and IPSPs in human TLE tissue indicate a reduced density of post‐ and presynaptic GABABreceptors. The reduced efficacy of presynaptic GABABreceptors facilitates the occurrence of repetitive synaptic activity.
The effects of intracerebroventricular AM‐251, a CB1‐receptor antagonist, and ACEA, a CB1‐receptor agonist, on penicillin‐induced epileptiform activity in rats
Authors: Kozan Ramazan , Ayyildiz Mustafa , Agar Erdal
Published: April 2009

Purpose: Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM‐251 [N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide], a CB1‐receptor antagonist, and ACEA (arachidonyl‐2‐chloroethylamide), a CB1‐receptor agonist, on penicillin‐induced epileptiform activity in rats.

Methods: In the first set of experiments, 30 min after penicillin injection, AM‐251, at doses of 0.125, 0.25, 0.5, and 1 μg, was administered intracerebroventricularly (i.c.v.). In the second set of experiments, 30 min after penicillin injection, ACEA, at doses of 2.5, 5, 7.5, and 15 μg (i.c.v.), was administered. In the third set of experiments, AM‐251, at doses of 0.125 and 0.25 μg (i.c.v.), was administered 10 min before ACEA (7.5 μg, i.c.v.) injection.

Results: ACEA, at a dose of 7.5 μg, significantly decreased the frequency of penicillin‐induced epileptiform activity without changing the amplitude. ACEA, at doses of 2.5, 5, and 15 μg, had no impact on either frequency or amplitude of epileptiform activity. AM‐251, at doses of 0.25 and 0.50 μg, significantly increased the frequency of epileptiform activity. AM‐251, at a dose of 0.25 μg (i.c.v.), was the most effective in changing the frequency of penicillin‐induced epileptiform activity, and it also caused status epilepticus–like activity. AM‐251, at doses of 0.125 and 0.25 μg, 10 min before ACEA (7.5 μg), reversed the anticonvulsant action of ACEA.

Discussion: The results of the present study provide electrophysiologic evidence for the role of CB1 receptors in regulating the frequency of epileptiform activity in the model of penicillin‐induced epilepsy. To elucidate the precise mechanism of cannabinoid action in the brain during seizure, more advanced electrophysiologic and neurochemical studies are required.
Acceptability and effectiveness of a strategy for the communication of the diagnosis of psychogenic nonepileptic seizures
Authors: Hall‐Patch Lindsey , Brown Richard , House Allan , Howlett Stephanie , Kemp Steven , Lawton Gemma , Mayor Rebecca , Smith Phil , Reuber Markus ,   for the NEST collaborators
Published: April 2009

Purpose:  Communicating the diagnosis of psychogenic nonepileptic seizures (PNES) is a challenging task. This study was carried out to assess the acceptability and effectiveness of a new communication procedure consisting of a patient information leaflet and a communication strategy for neurologists.

Methods:  In a multicenter prospective study, 50 patients newly diagnosed with PNES were informed about the diagnosis by 10 different neurologists using the communication procedure. Follow‐up data were gathered by telephone interview and completion of a questionnaire about symptom attributions (psychological/physical) and illness cognitions (Illness Perception Questionnaire‐Revised, IPQ‐R).

Results:  Ninety‐four percent of patients found the leaflet easy to understand. Ninety‐four percent stated their questions were answered by the doctor; 70% got what they wanted from the consultation; only 4% reported feeling angry during the consultation. Eighty‐six percent of patients acknowledged that psychological factors were at least contributing to their seizures. On the IPQ‐R, “emotional” causes for the seizures were endorsed more commonly than “nonemotional” causes (p < 0.001). After 3 months, 14% of patients were seizure‐free and 63% reported a >50% reduction in seizure frequency.

Discussion:  We conclude that our procedure is acceptable and effectively communicates a psychological etiologic model for PNES.
Cerebral lesions can impair fMRI‐based language lateralization
Authors: Wellmer Jörg , Weber Bernd , Urbach Horst , Reul Jürgen , Fernandez Guillen , Elger Christian E.
Published: April 2009

Purpose:  Several small patient studies and case reports raise concerns that the reliability of functional magnetic resonance imaging (fMRI) may be impaired in the vicinity of cerebral lesions. This could affect the clinical validity of fMRI for presurgical language lateralization. The current study sets out to identify if a systematic effect of lesion type and localization on fMRI exists.

Methods:  We classify lesions typically occurring in epilepsy patients according to (1) their potential to disturb blood oxygenation level dependent (BOLD)–effect generation or detection or to disturb spatial brain normalization, and (2) the proximity of lesions to protocol‐specific volumes of interest (VOIs). The effect of lesions is evaluated through the examination of 238 epilepsy patients and a subgroup of 37 patients with suspected unilateral left‐language dominance according to the Wada test.

Results:  Patients with fMRI‐critical lesions such as cavernomas, gliomas, and mass defects close to VOIs, or with severe atrophy, show lower lateralization indices (LIs) and more often discordant language lateralization with the Wada test than do patients without such lesions.

Discussion:  This study points seriously toward fMRI‐language lateralization being sensitive to cerebral lesions. Some lesion types and locations are more critical than others. Our results question the noncritical application of fMRI in patients with cerebral lesions.