bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Interventions: Art, Politics and Pedagogy
Authors: PINDER DAVID
Published: September 2008

Challenging perspectives on the urban question have arisen in recent years from beyond academic realms through the work of artists and cultural practitioners. Often in dialogue with urban theory and political activism, and employing a range of tactical practices, they have engaged critically with cities and with the spatialities of everyday urban life. They are typically concerned less with representing political issues than with intervening in urban spaces so as to question, refunction and contest prevailing norms and ideologies, and to create new meanings, experiences, understandings, relationships and situations. Such interventionist practices may rarely be seen as part of the traditional purview of urban studies. Yet in asserting their significance here, this essay argues that growing dialogues across and between urban and spatial theory, and artistic and cultural practice, have considerable potential for inspiring and developing critical approaches to cities. The essay highlights a number of specific challenges thrown up by such interconnections that are of political and pedagogical significance and in need of further debate.

Récemment, d’intéressantes perspectives sur la question urbaine se sont dégagées au‐delà des sphères de recherches, à travers le travail d’artistes et de professionnels de la culture. Dans un échange fréquent avec la théorie urbaine et le militantisme politique, et à l’aide de toute une panoplie de pratiques tactiques, ils se sont impliqués dans les villes et les spatialités de la vie urbaine au quotidien. En général, ils se soucient moins de représenter des thèmes politiques que d’intervenir dans les espaces urbains pour remettre en question, rediriger ou contester les normes et idéologies en vigueur, et pour créer de nouvelles significations, expériences, compréhensions, relations et situations. Il est rare de pouvoir inscrire ces modes interventionnistes dans le champ traditionnel des études urbaines. Toutefois, cet essai défend leur importance en soulignant le potentiel considérable d’une accentuation du dialogue à travers et entre les théories urbaine et spatiale, et les pratiques artistique et culturelle, pour inspirer et élaborer des approches critiques des villes. Ce travail met en avant plusieurs enjeux spécifiques nés de ces interconnexions, significatifs sur le plan politique et pédagogique, et appelant à un débat approfondi.
Aboriginal Cosmopolitanism
Authors: CLARK NIGEL
Published: September 2008

The current drought in Australia raises questions about the extent to which urban life depends on physical forces that come with their own dynamics and eccentric rhythms. I suggest that currently deepening understandings of the inherent volatility of earth processes might help us appreciate the accomplishments of those who have stayed in place for hundreds or thousands of years: peoples whose ‘nomadic’ journeys through deep time have taken them through major bio‐ or geo‐physical transformations in their environments. In this way, we might learn to recognize how most urban or settled life inherits terrains whose irregularities and extremes have been softened by the efforts of these prior inhabitants. In a world where we can expect major environmental changes to induce new waves of estrangement and displacement, I ask whether a sense of the immeasurable debt which we owe to those people who came before us might help inspire the kind of cosmopolitan sensibilities we would hope for.

La sécheresse que connaît actuellement l’Australie pousse à se demander dans quelle mesure la vie urbaine dépend de forces physiques qui obéissent à leur rythme excentrique et à leur dynamique propre. En approfondissant notre compréhension de la nature éphémère de la Terre, nous pourrions mieux apprécier les réalisations de ceux qui se sont implantés pendant des centaines ou des milliers d’années : des peuples que leur “nomadisme” par des temps reculés a fait traverser les grandes mutations biophysiques et géophysiques de leur environnement. Ainsi, nous pourrions apprendre à reconnaître comment la vie urbaine ou sédentaire hérite en grande partie de terrains dont les irrégularités et les excès ont été atténués par les efforts de ces habitants antérieurs. Dans un monde où nous pouvons nous attendre à ce que des changements environnementaux considérables provoquent de nouvelles vagues d’éloignement et de déplacement, la perception de l’incommensurable dette redevable à ces peuples arrivés avant nous pourrait peut‐être inspirer le genre de sensibilités cosmopolites que nous pourrions espérer.
An Unusual Clique of City‐Makers: Social Networks in the Production of a Neighborhood in Beirut (1950–75)
Authors: FAWAZ MONA
Published: September 2008

This article documents the early development of an informal settlement in Beirut (Lebanon) through the trajectories of the developers who participated in its production, looking specifically at the role that social networks played in the process. Drawing primarily on the methodological approach developed by Pierre Bourdieu, my analysis reveals that social networks play a central role as conduits for developers to access the necessary housing ingredients and market securities they need to conduct their businesses. Social networks also function as accumulated capital, enabling developers to strengthen their hold over the production of housing in the neighborhood. My analysis also indicates that while some of these networks were inherited, many were built through patient investments deployed by these developers within the changing limitations of the micro (neighborhood) and macro (city‐wide) contexts. Finally, the changing distribution of social networks in this neighborhood determined when and how different social agents were able to participate as developers in the production and exchange of housing. These findings are important since they generate new insights into how (informal land) markets work, the practices of developers in this type of neighborhood, as well as the yet unstudied mechanisms of informal housing production in the Lebanese context.

Cet article, qui présente la création d’un quartier informel de Beyrouth (Liban) au travers des trajectoires adoptées par les promoteurs ayant pris part à sa production, s’intéresse au rôle des réseaux sociaux dans ce processus. Utilisant principalement l’approche méthodologique de Pierre Bourdieu, l’analyse révèle que les réseaux sociaux jouent un rôle central comme canaux permettant aux promoteurs d’accéder aux ressources et aux cautionnements du marché dont ils ont besoin pour mener leur activité. Par ailleurs, les réseaux sociaux sont accumulés telle une forme de capital, ce qui permet aux promoteurs d’accentuer leur mainmise sur la production d’habitations dans le quartier. De plus, il apparaît que, si certains de ces réseaux ont été hérités, d’autres sont le fruit de patients investissements de ces promoteurs malgré les conditions changeantes des environnements micro (quartier) et macro (ville). Pour finir, la répartition évolutive des réseaux sociaux dans ce quartier a déterminé quand et comment les différents agents sociaux ont été en mesure de participer à la production et à l’échange d’habitations en tant que promoteurs. Ces résultats sont importants puisqu’ils ouvrent de nouvelles perspectives sur les modes opératoires des marchés (fonciers informels), les pratiques des promoteurs dans ce type de quartier, ainsi que les mécanismes de production d’habitat informel dans le contexte libanais, mécanismes qui n’ont jamais étéétudiés.
ARCHAEOMETRIC STUDY OF SHELLS OF HELICIDAE FROM THE EDERA CAVE (NORTHEASTERN ITALY)*
Authors: BONIZZONI L. , BRUNI S. , GIROD A. , GUGLIELMI V.
Published: September 2008

The Edera Cave, near Aurisina in the Trieste Karst, retains a stratigraphy that extends from the Mesolithic to the modern era. At Sauveterrian layers, many specimens ofHelix cinctaare present, which are considerably crushed, and a small percentage of which are also blackened. Chemical analyses show that the blackened specimens were exposed to a temperature of between 500 and 550°C, and suggest that many others were destroyed by fire at temperatures of above 700°C. Consequently, only a part of theHelix cinctashells is assumed to be the residue of human meals, since several factors render plausible an accidental combustion of shells already present in the ground before the lighting of Mesolithic hearths.
Cut‐offs, Knock‐ons and Welfare Payment Taper Changes: An Evaluation of the July 2000 Tax and Welfare Changes for Lone Mothers*
Authors: GREGORY ROBERT G. , KLUG EVA , THAPA PREM J.
Published: September 2008

High welfare withdrawal rates generate high effective marginal tax rates and work disincentives; but reducing withdrawal rates extends welfare to the better‐off. We analyse pension taper reduction effects for lone mothers subject to the Australian tax and welfare reforms of July 2000. The changes in work incentives were trivial. Taper reductions extended income support and provided larger family payments to high income lone mothers previously excluded from welfare. Approximately 90 per cent of the better‐off group now made eligible for income support had a long history of welfare reliance. The taper reduction encouraged them to stay on welfare longer.
Understanding the Drivers of Poverty Dynamics in Australian Households*
Authors: BUDDELMEYER HIELKE , VERICK SHER
Published: September 2008

This paper contributes to the growing literature on poverty dynamics in Australian households. The results reveal that a range of life‐changing events, household head, partner and demographic characteristics have an impact on both the likelihood of remaining poor and slipping into poverty. These findings have important implications for Australian policymakers: tertiary education and employment are key factors in keeping households out of poverty; having a disability or living in outer‐regional or remote areas increases the probability of becoming poor and remaining in such a situation; and finally, life‐changing events, especially becoming separated, can lead households into persistent poverty.
Private or Public? Towards a Taxonomy of Optimal Ownership and Management Regimes*
Authors: KING STEPHEN , PITCHFORD ROHAN
Published: September 2008

We develop a model to assist policy‐makers in their choice between private and public ownership for a broad range of activities, based on managers’ ability to divert resources through perks or pet projects. Qualitative information is always required to demonstrate that public ownership is optimal. More ‘public’ firms are synonymous with greater control of such actions, but generate greater bureaucracy costs. The flat incentives faced by public managers can be socially desirable when commercially productive activities generate large social harms relative to profit, but are undesirable when these activities are either benign or create external social benefits. Applications are discussed.
Government turnover: Concepts, measures and applications
Authors: HOROWITZ SHALE , HOFF KARLA , MILANOVIC BRANKO
Published: September 2008

Abstract.  While government turnover is often thought of as an adverse source of instability, it may also be viewed as a favourable source of competition and institution‐building. To articulate and test such hypotheses, this article describes two main concepts of government turnover: leadership turnover, or change in rulers, and ideological turnover, or change in the rulers' ideology. Refinements involve the mode, outcome and timing of turnover. The article discusses measurement issues that arise when there are multiple power institutions and when parliaments are controlled by changing majority coalitions. The measures of turnover are illustrated by examining the post‐communist world. The article considers the possibility that higher cumulative post‐transition turnover – in terms of leaderships or ideologies – has assisted in establishing the rule of law.
Relationship between psychiatric symptoms and regional cerebral blood flow in patients with mild Alzheimer's disease
Authors: NAKAJIMA Keisuke , TAKAHASHI Megumi , OISHI Satoru , INOUE Aya , SAWAYAMA Enami , KAMIYA Michiko , TANAKA Satomi , MIYAOKA Hitoshi
Published: September 2008

Background:  Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in patients with dementia and often cause serious problems. However, the cause of BPSD has not yet been elucidated. Moreover, the precise evaluation of BPSD in mild dementia has not been studied in any great detail. In the present study, we investigated the relationship between psychiatric symptoms and regional cerebral blood flow (rCBF) in patients with mild Alzheimer's disease (AD).

Methods:  The present study included 47 patients (20 men and 27 women) who were diagnosed with mild AD. Mean patient age was 72.8 ± 8.2 years. Single photon emission computed tomography (SPECT) with 99mTc‐ethyl cysteinate dimer (99mTc‐ECD) was performed in all patients. The SPECT data were analyzed using a three‐dimensional stereotactic region of interest template, which evaluated CBF in 24 segments. Psychiatric symptoms were evaluated in patients using the Brief Psychiatric Rating Scale. Each psychiatric symptom was designated as ‘symptom present’ in cases in which the BPRS item score was more than 3. We compared 10 segments of rCBF in symptom‐present patients with those in symptom‐absent patients.

Results:  Motor retardation was the most common psychiatric symptom (36.2%), followed by depression (19.1%), anxiety (17.0%), emotional withdrawal (17.0%), and somatic concern (14.9%). Alzheimer's disease patients with motor retardation exhibited a tendency towards lower rCBF in seven segments (left callosomarginal, bilateral parietal, bilateral angular, and bilateral temporal). However, no specific tendency was observed in depression, anxiety, and somatic concern.

Conclusions:  In the present study, we observed a tendency for decreased brain perfusion in patients with motor retardation. Further studies are necessary to confirm that this trend contributes to the appearance of psychiatric symptoms in patients with mild AD.
Kampo therapy as an alternative to pharmacotherapy using antipsychotic medicines for behavioral and psychological symptoms of dementia (BPSD)
Authors: MIZUKAMI Katsuyoshi
Published: September 2008

The behavioral and psychological symptoms of dementia (BPSD), including aggression, agitation, screaming, wandering, hallucinations, and delusions, occur in 50–90% of patients with dementia, and have a negative impact on the activity of daily living (ADL) of patients, as well as caregivers. Patients with severe BPSD often require management with antipsychotic medicines. However, an increased mortality rate has been reported in patients with dementia taking antipsychotic medicine and, thus, there is an urgent need to develop safer treatments for BPSD. Kampo medicines are an alternative to antipsychotic medicines and several Kampo medicines have been reported to be effective in the treatment of BPSD. Oren‐gedoku‐to has been reported to be effective for the treatment of irritability and sullenness in patients with vascular dementia, as well as improving excitement, depression, anxiety, and restlessness of patients with cerebrovascular lesions. Choto‐san has been reported to be effective in the treatment of delirium, insomnia, and hallucinations/delusions in patients with vascular dementia. Toki‐syakuyaku‐san has been reported to improve emotional lability, restlessness, and sleep disturbances in patients with dementia. Yokukan‐san has been reported to be effective for hallucinations, agitation/aggression, irritability/lability, and aberrant motor activity, as well as being effective in the treatment of visual hallucinations in patients with dementia with Lewy bodies (DLB). A multicenter randomized crossover study confirmed that Yokukan‐san is effective in the treatment of BPSD and is well‐tolerated. Kampo medicines do not induce extrapyramidal or anticholinergic symptoms and have no adverse effects on ADL or cognitive function. Thus, Kampo therapy is recommended for patients who cannot tolerate treatment with neuroleptics, patients who have extrapyramidal symptoms and gait disturbance, and patients with DLB. In future, to confirm the effectiveness of Kampo medicines in the treatment of BPSD, further studies, such as randomized control trials, are needed. In addition, basic studies are required to elucidate the processes by which Kampo medicines are metabolized, as well as any interactions between Western and Kampo medicines.
Behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies
Authors: KOSAKA Kenji
Published: September 2008

Behavioral and psychological symptoms of dementia (BPSD) bother patients with dementia with Lewy bodies (DLB) and their families so frequently that early diagnosis of DLB before the appearance of prominent cognitive impairment is important. Because BPSD in DLB can be reduced or improved by early intervention, medical intervention is important. Of BPSD in DLB, vivid visual hallucinations and delusions are most important. Other visual cognitive impairments and sleep disturbances, including disorders in rapid eye movement (REM) sleep, are also frequently seen. Cholinesterase inhibitors, including donepezil chloride, are the first choice for the therapy of BPSD; Yokukansan (a type of Kanpo (traditional Chinese herbal) medicine) is the second choice. When neither treatment is effective, atypical antipsychotics, such as quetiapine, risperidone, and aripiprazol, may be used.
Role of the home visit medical service for patients with behavioral and psychological symptoms of dementia (BPSD) living in the community
Authors: KINOSHITA Toru
Published: September 2008

Background:  It is important for patients with behavioral and psychological symptoms of dementia (BPSD) in the community, who refuse to go to clinics, to be medically served by means of home visits. However, there are a few clinics in Japan that are specialized in home visits for BPSD.

Methods:  The home visit medical service provided to several patients with BPSD was reviewed and the strategy for the treatment of BPSD was analyzed.

Results:  It was found that the medical approach of home visits for patients with BPSD needed to be based on daily life information as well as medical information.

Conclusions:  The medical service alone is not enough to provide appropriate care for patients with BPSD who are living in the community. Using the case studies presented herein, we have demonstrated the importance of ‘daily life information’ for medical intervention. Issues relating to the exacerbation of BPSD and the cooperation of caregivers in the drug monitoring system at home are also considered.
PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing
Authors: Barrientos Stephan , Stojadinovic Olivera , Golinko Michael S. , Brem Harold , Tomic‐Canic Marjana
Published: September 2008

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF‐β) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM‐CSF), platelet‐derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor nerosis factor‐α family. Currently, patients are treated by three growth factors: PDGF‐BB, bFGF, and GM‐CSF. Only PDGF‐BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.
The anti‐inflammatory agent Propolis improves wound healing in a rodent model of experimental diabetes
Authors: McLennan Susan V. , Bonner James , Milne Sgtephen , Lo Lisa , Charlton Ana , Kurup Savita , Jia Junhong , Yue Dennis K. , Twigg Stephen M.
Published: September 2008

Foot ulcers and poor wound healing are problematic for patients with diabetes. The beehive protectant Propolis can improve wound healing but whether it can improve healing in diabetic wounds has not been investigated. In this study, the effect of a single application of Propolis on epithelial closure, wound morphology, cellular infiltrate, and blood vessel density were investigated. Diabetes was induced in rats using streptozocin. After 6 weeks, diabetic and control animals were wounded and the wounds were treated with Propolis or saline as control. At days 6 and 12 animals were sacrificed and wounds were excised. Compared with controls, diabetes decreased epithelial closure and reepithelialization but had no effect on wound contraction. These delays were prevented by Propolis. At day 12, the impaired macrophage infiltration (C:1.49±0.09 vs. D:0.25±0.14), persistent neutrophil infiltration (C:0.22±0.19 vs. D:1.33±0.81), and increased myeloperoxidase activity (fourfold) in diabetic wounds were prevented by Propolis. Diabetes had no effect on wound volume, vessel number, or branch points. These novel data indicate that Propolis can accelerate wound healing in diabetes. As neutrophil infiltration is normalized, its mechanism of action may be through anti‐inflammatory pathways. This result and the established safety profile of Propolis provide a rationale for studying topical application of this agent in a clinical setting.
ORIGINAL RESEARCH – BASIC SCIENCE: Primary dermal fibroblasts derived from sdc‐1 deficient mice migrate faster and have altered αv integrin function
Authors: Jurjus Rosalyn A. , Liu Yueyuan , Pal‐Ghosh Sonali , Tadvalkar Gauri , Stepp Mary Ann
Published: September 2008

The goal of this study is to determine whether dermal fibroblasts lacking syndecan‐1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc‐1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in α‐smooth muscle actin were detected but sdc‐1 null cells expressed significantly more αv and β1 integrin than wildtype (wt) cells. Transforming growth factor β1 (TGFβ1) treatment at day 3 increased αv‐ and β1‐integrin expression in sdc‐1 null cells at day 5 whereas wt cells showed increased expression only of αv‐integrin. Using time‐lapse studies, we showed that the sdc‐1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFβ1 increased these migration differences, and treatment with a TGFβ1 antagonist caused sdc‐1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin‐coated surfaces. Additional time lapse studies with β1‐ and αv‐integrin antibody antagonists, showed that wt fibroblasts expressing sdc‐1 had activated integrins on their surface that impeded their migration whereas the null cells expressed αv‐containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of α2β1 and α3β1 on the sdc‐1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of α5β1, αvβ3, or αvβ5. Taken together, our data indicates that sdc‐1 functions in the activation of αv‐containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc‐1 null mice could be due to integrin‐mediated defects in fibroblast migration after injury.
Physiological Complexity Underlying Heart Rate Dynamics and Frailty Status in Community‐Dwelling Older Women
Authors: Chaves Paulo H. M. , Varadhan Ravi , Lipsitz Lewis A. , Stein Phyllis K. , Windham B. Gwen , Tian Jing , Fleisher Lee A. , Guralnik Jack M. , Fried Linda P.
Published: September 2008

OBJECTIVES: To assess whether less physiological complexity underlying regulation of heart rate dynamics, as indicated by lower approximate entropy for heart rate (ApEnHR), is associated with frailty. For supporting validity, relationships between frailty and traditional linear indices of heart rate variability (HRV) were also assessed.

DESIGN: Cross‐sectional.

SETTING: Women's Health and Aging Study I, a community‐based observational study, 1992 to 1995.

PARTICIPANTS: Subset of 389 community‐dwelling women aged years and older with moderate to severe disability with ApEnHR data (convenience sampling).

MEASUREMENTS: Electrocardiographic Holter recordings obtained over 2‐ to 3‐hour periods were processed for ApEnHR and HRV measures. ApEnHR is a nonlinear statistic that quantifies the regularity of heart rate fluctuations over time. Lower ApEnHR is characteristic of heart rate time series containing a high proportion of repetitive patterns. Frailty was defined according to validated phenotype criteria.

RESULTS: Median ApEnHR was lower in frail than in nonfrail subjects (P=.02). Lower ApEnHR (top quartile) was associated with lower likelihood of frailty than higher ApEnHR (bottom three quartiles) (odds ratio=0.47, 95% confidence interval=0.26–0.86), even after adjustment for major confounders. Frailty was consistently associated with lower HRV as assessed using time‐ and frequency‐domain indices.

CONCLUSION: This study supports the notion that less physiological complexity marks frailty and provides an empirical basis to the concept of frailty as a syndrome of homeostatic impairment. Future research will determine whether noninvasive measures of physiological complexity underlying heart rate dynamics might be useful for screening and monitoring of clinical vulnerability in older adults.
End‐of‐Life Decision‐Making, Decisional Conflict, and Enhanced Information: Race Effects
Authors: Allen Rebecca S. , Allen Jessica Y. , Hilgeman Michelle M. , DeCoster Jamie
Published: September 2008

OBJECTIVES: To examine the effect of enhanced information regarding the risks, benefits, and life‐sustaining treatment alternatives on hypothetical medical decisions and decisional conflict in older, community‐dwelling Caucasian and African‐American adults.

DESIGN: Two‐group (enhanced information; no information) between‐subjects design.

SETTING: Community‐based dwellings, two assisted living facilities, and one senior citizen center.

PARTICIPANTS: Seventy‐eight adults (aged 74.5±7.18) with a mean Telephone Interview for Cognitive Status—Modified (TICS‐m) score of 31.5±4.7 were recruited through personal contacts and informational talks held at the recruitment sites.

MEASUREMENTS: Measures included the Life Support Preferences/Predictions Questionnaire—modified (LSPQ‐m); the Decisional Conflict Scale; and enhanced information, including detailed descriptions of life‐sustaining treatment options for each LSPQ‐m illness scenario, risks of the treatment, benefits of the treatment, and alternatives for each treatment (called medical information stimuli).

RESULTS: Enhanced information (e.g., medical information stimuli) reduced decisional conflict (P=.049, d=0.47) for hypothetical life‐sustaining treatment decisions. A mixed analysis of variance with group and race as between‐subjects variables and illness and treatment as within‐subjects variables revealed significant main effects of race, illness, and treatment, as well as a significant race‐by‐illness‐by‐group interaction (Wilk's lambda=0.923, F(2, 73)=3.05, P=.05, partial η2=0.08). Enhanced information produced different patterns of desire for life‐sustaining treatments in African Americans and Caucasians.

CONCLUSION: Physicians and other healthcare professionals can reduce decisional conflict in patients by providing enhanced information regarding treatment risks, benefits, and alternatives. Such decision aids may provide new information or knowledge and thus reduce desire for treatment in African Americans.
A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase
Authors: Sakata Hidekatsu , Matsubayashi Keiji , Takeda Hiromi , Sato Shinichiro , Kato Toshiaki , Hino Satoru , Tadokoro Kenji , Ikeda Hisami
Published: September 2008

BACKGROUND: Although we reported two cases of transfusion‐transmitted hepatitis E in Japan, the prevalence of hepatitis E virus (HEV) in Japanese blood donors is not very clear.

STUDY DESIGN AND METHODS: Blood samples of donors who were deferred from donation because of elevated alanine aminotransferase (ALT) levels were collected from all Japanese Red Cross Blood Centers and subjected to HEV tests.

RESULTS: Among the 41 donors with elevated ALT levels higher than 500 IU per L in Hokkaido, HEV RNA was detected in 8 (19.5%) samples. In 1389 donor samples with ALT levels of higher than 200 IU per L in nationwide Japan, the numbers of positive HEV RNA, immunoglobulin M (IgM) anti‐HEV, and immunoglobulin G (IgG) anti‐HEV samples were 15 (1.1%), 14 (1.0%), and 45 (3.2%), respectively. Although RNA‐positive donors were predominantly male and found in any geographic area of Japan, they tended to be higher in number in eastern Japan including Hokkaido and lower in number in western Japan. Of the 23 HEV‐positive samples, 19 were Genotype 3 and 4 were Genotype 4. DNA sequences of the 9 isolates showed more than 98.5 percent homology with the known swine HEV isolates. In 1062 donor samples with ALT levels of 61 to 199 IU per L, the percentages of IgM and IgG anti‐HEV–positive samples were 0.1 and 2.7 percent, respectively, although there was no HEV RNA–positive sample.

CONCLUSION: HEV markers (HEV RNA and anti‐HEV) were detected in donors with elevated ALT levels who were widely distributed over Japan. The prevalence and incidence were higher in eastern Japan than in western Japan.
Membrane Time Constant During Internal Defibrillation Strength Shocks in Intact Heart: Effects of Na+ and Ca2+ Channel Blockers
Authors: MOWREY KENT A. , EFIMOV IGOR R. , CHENG YUANNA
Published: September 2008

Introduction:
We assessed defibrillation strength shock‐induced changes of the membrane time constant (τ) and membrane potential (ΔVm) in intact rabbit hearts after administration of lidocaine, a sodium (Na+) channel blocker, or nifedipine, a L‐type calcium (Ca2+) channel blocker.

Methods and Results:
We optically mapped anterior, epicardial, electrical activity during monophasic shocks (±100, ±130, ±160, ±190, and ±220 V; 150 μF; 8 ms) applied at 25%, 50%, and 75% of the action potential duration via a shock lead system in Langendorff‐perfused hearts. The protocol was run twice for each heart under control and after lidocaine (15 μM, n = 6) or nifedipine (2μM, n = 6) addition. τ in the virtual electrode area away from the shock lead was approximated with single‐exponential fits from a total of 121,125 recordings. The same data set was used to calculate ΔVm. We found (1) Under all conditions, there is inverse relationship between τ and ΔVm with respect to changes of shock strength, regardless of shock polarity and phase of application: a stronger shock resulted in a larger ΔVm, which corresponded to a smaller τ (faster cellular response); (2) Lidocaine did not cause appreciable changes in either τ or ΔVm versus control, and (3) Nifedipine significantly increased both τ and ΔVm in the virtual cathode area; in contrast, in the virtual anode area, this effect depended on the phase of shock application.

Conclusion:
τ and ΔVm are inversely related. Na+ channel blocker has minimal impact on either τ or ΔVm. Ca2+ blocker caused polarity and phase‐dependent significant changes in τ and ΔVm.
Catheter Ablation of Atrial Fibrillation in Patients with Diabetes Mellitus Type 2: Results from a Randomized Study Comparing Pulmonary Vein Isolation Versus Antiarrhythmic Drug Therapy
Authors: FORLEO GIOVANNI B. , MANTICA MASSIMO , DE LUCA LUCIA , LEO ROBERTO , SANTINI LUCA , PANIGADA STEFANIA , DE SANCTIS VALERIO , PAPPALARDO AUGUSTO , LAURENZI FRANCESCO , AVELLA ANDREA , CASELLA MICHELA , RUSSO ANTONIO DELLO , ROMEO FRANCESCO , PELARGONIO GEMMA , TONDO CLAUDIO
Published: September 2008

Introduction:
Atrial fibrillation (AF) and diabetes mellitus type 2 (DM2) often coexist; however, a small number of patients with DM2 undergoing catheter ablation (CA) of AF have been included in previous studies. The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF.

Methods and Results:
From January 2005 to September 2006, 70 patients with a diagnosis of DM2 and paroxysmal (n = 29) or persistent (n = 41) AF were randomized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment (ADT) with a 1‐year follow‐up. The primary endpoint was the time to first AF recurrence. By Kaplan‐Meier analysis, at the end of follow‐up, 42.9% of patients in the ADT group and 80% of patients who received a single ablation procedure and were without medications were free of AF (P = 0.001). In the ablation group, a significant improvement in quality‐of‐life (QoL) scores as compared with ADT group was observed. Six patients in the ADT group (17.1%) developed significant adverse drug effects. Hospitalization rate during follow‐up was higher in the ADT group (P = 0.01). The only complication attributable to ablation was one significant access‐site hematoma.

Conclusion:
In patients with DM2, CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility, effectiveness, and low procedural risk.
Successful Targeted Ablation of the Pathway Potential in the Noncoronary Cusp of the Aortic Valve in an Infant with Incessant Orthodromic Atrioventricular Reentrant Tachycardia
Authors: BALASUNDARAM RAMPRAKASH , RAO HYGRIV , ASIRVATHAM SAMUEL J. , NARASIMHAN CALAMBUR
Published: September 2008

A 4‐month‐old infant presented with incessant SVT and severe failure to thrive. At EP study, orthodromic‐reciprocating tachycardia using an anteroseptal accessory pathway was identified. Detailed mapping on the right atrial septum failed to disclose a distinctly early site of atrial activation or a near‐field pathway potential. Mapping in the noncoronary cusp of the aortic valve identified a discrete pathway potential that was successfully targeted for ablation. At 12‐month follow‐up after the procedure, there had been no recurrence of tachycardia.

Conclusion:
Myocardial fibers above the aortic valve cusps may constitute the atrioventricular bypass connection and can be identified and targeted for successful ablation even in infants.
Safe and Effective Ablation of Atrial Fibrillation: Importance of Esophageal Temperature Monitoring to Avoid Periesophageal Nerve Injury as a Complication of Pulmonary Vein Isolation
Authors: KUWAHARA TAISHI , TAKAHASHI ATSUSHI , KOBORI ATSUSHI , MIYAZAKI SHINSUKE , TAKAHASHI YOSHIHIDE , TAKEI ASUMI , NOZATO TOSHIHIRO , HIKITA HIROYUKI , SATO AKIRA , AONUMA KAZUTAKA
Published: September 2008

Introduction:
Catheter ablation on the left atrial posterior wall has been reported to potentially damage the esophagus or periesophageal vagal nerve. The aim of this study was to evaluate the efficacy of esophageal temperature monitoring (ETM) in preventing esophageal or periesophageal vagal nerve injury in patients with atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation.

Methods:
This study included 359 patients with drug‐refractory AF who underwent extensive PV isolation. The first 152 patients were treated without ETM (non‐ETM) and the last 207 with ETM. In the ETM group, the esophageal temperature (ET) was measured with a deflectable temperature probe that was placed close to the ablation electrode, and the radiofrequency energy applications were stopped when the ET reached 42°C.

Results:
In all patients in the ETM group, the ET increased to 42°C in at least one site by 28 ± 14 seconds, mostly along the right side of the left PVs, especially near the left inferior PV. Less energy (6.3 ± 1.9 × 104 J) was required for PV isolation in the ETM group than that in the non‐ETM (6.8 ± 1.9 ×104 J, P = 0.03). Gastric hypomotility owing to periesophageal nerve damage was observed in three patients in the non‐ETM group, but in none in the ETM (P = 0.02). The recurrence rates of AF did not differ between the two groups (non‐ETM, 29%; ETM, 27%).

Conclusion:
Titration of the duration of the ablation energy delivery while monitoring the ET could prevent periesophageal nerve injury due to the AF ablation, without decreasing the success rate of maintaining sinus rhythm.
Fluvastatin Reduces Pulmonary Vein Spontaneous Activity Through Nitric Oxide Pathway
Authors: HU YU‐FENG , CHEN YAO‐CHANG , CHENG CHEN‐CHUAN , HIGA SATOSHI , CHEN YI‐JEN , CHEN SHIH‐ANN
Published: September 2008

Introduction:
Pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The HMG‐CoA reductase inhibitors (statins) can reduce the occurrence of atrial fibrillation. The purposes of this study were to evaluate whether statins may inhibit the PV arrhythmogenic activity to prevent atrial arrhythmias from PVs and to investigate the link between fluvastatin, nitric oxide synthase (NOS) activity, mechanical activity, and electrical activity.

Methods:
Conventional microelectrodes and Western blot were used to record the electrical activity, diastolic tension, contractility and expression of Akt, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and phosphorylated Akt and eNOS before and after the administration of fluvastatin in rabbit PVs or atria.

Results:
Fluvastatin decreased the PV spontaneous activity, diastolic tension, and contractility, but did not change the action potential duration or resting membrane potential. The effects of fluvastatin on the PV firing rate and diastolic tension were attenuated in the presence of L‐NAME (100 μM), wortmannin (100 nM), and ODQ (3 μM). Fluvastatin (1 μM) increased the phosphorylated Akt and eNOS, but did not change the total Akt or eNOS in the PVs and atria. In contrast, fluvastatin (1 μM) decreased the total nNOS in the PVs and atria.

Conclusions and implications:
Fluvastatin produced nitric oxide through the PI3kinase/Akt pathway, thus reducing the PV vascular diastolic tension and PV spontaneous activity. These results may contribute to the beneficial effects of statins.
Variability of the Diagnostic ECG Pattern in an ICD Patient Population with Brugada Syndrome
Authors: RICHTER SERGIO , SARKOZY ANDREA , VELTMANN CHRISTIAN , CHIERCHIA GIAN‐BATTISTA , BOUSSY TIM , WOLPERT CHRISTIAN , SCHIMPF RAINER , BRUGADA JOSEP , BRUGADA RAMON , BORGGREFE MARTIN , BRUGADA PEDRO
Published: September 2008

Introduction:
The spontaneous presence of a coved‐type ECG is considered as an important risk factor in Brugada syndrome. However, diagnosis making and risk stratification may be hampered by the dynamic nature of the ECG abnormalities. The objective of this study was to determine the variability and predictive value of the electrocardiogram in Brugada patients implanted with a cardioverter‐defibrillator (ICD).

Methods and Results:
We analyzed consecutive 12‐lead ECGs from 89 ICD patients (44 ± 14 years, 69 males) with Brugada syndrome. A total of 1,161 ECGs were included for analysis (13 ± 8 ECGs/patient). Twenty‐four percent of the ECGs/patient were coved‐type I, 25% saddleback‐type II or III, and 51% normal. Fifty‐seven patients had a diagnostic coved‐type ECG spontaneously (group A), 32 patients only after drug challenge (group B). In group A, 38% of the ECGs/patient were diagnostic, 25% saddleback‐type, and 37% normal. Fifty‐five group A patients (96%) had transient normalization and/or conversion to saddleback‐type ECGs. During a mean follow‐up of 48 ± 35 months, 16 patients (18%) experienced appropriate shocks. All patients with appropriate shocks had spontaneous diagnostic ECGs. They tended to have more coved‐type ECGs (36 vs 22%, respectively, P = 0.05) than patients without appropriate shocks.

Conclusions:
Analysis of serial ECG recordings in an ICD patient population shows that the Brugada‐ECG pattern is highly variable over time. In patients with spontaneous coved‐type ECG, only every third ECG is diagnostic and every third ECG normal. Patients with spontaneous coved‐type ST‐segment elevation have a high incidence of appropriate shocks. Spontaneous saddleback‐type electrocardiograms are not helpful for risk stratification.
Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing
Authors: DEWEY FREDERICK E. , PEREZ MARCO , HADLEY DAVID , FREEMAN JAMES V. , WANG PAUL , ASHLEY EUAN A. , MYERS JONATHAN , FROELICHER VICTOR F.
Published: September 2008

Background:
Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise‐induced ventricular arrhythmias has not been investigated.

Methods and Results:
We evaluated the association between statin use and PVCs in 1,847 heart‐failure‐free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity‐adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37–0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30–0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise‐induced angina, or exercise capacity.

Conclusions:
Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.
ADAM15 modulates outside‐in signalling in chondrocyte–matrix interactions
Authors: Böhm Beate B. , Schirner Andrea , Burkhardt Harald
Published: September 2008

ADAM15 belongs to a family of transmembrane multi‐domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up‐regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin‐mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside‐in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co‐immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell‐adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease.
Hypoxia induces a hedgehog response mediated by HIF‐1α
Authors: Bijlsma Maarten F. , Groot Angelique P. , Oduro Jeremiah P. , Franken Rutger J. , Schoenmakers Saskia H. H. F. , Peppelenbosch Maikel P. , Spek C. Arnold
Published: September 2008

Recently, it has become clear that the developmental hedgehog pathway is activated in ischaemic adult tissue where it aids in salvaging damaged tissue. The exact driving force for the initial hedgehog response is unclear and as most physiological and cellular processes are disturbed in ischaemic tissue, hedgehog‐activating signals are hard to dissect. Here, we demonstrate that hypoxia per se is able to induce a rapid systemic hedgehog response in adult mice, as evident from expression of the pathway ligand, Sonic hedgehog, as well as the pathway activity marker Patched1 in various organs. Using in vitro models of hypoxia, we showed that the hedgehog response was transient and preceded by the accumulation of HIF‐1α, which we hypothesized to communicate between hypoxia and hedgehog expression. Indeed, pharmacological inhibition, knockdown or genetic ablation of HIF‐1α abolished hedgehog pathway activation. In conclusion, we have established that hypoxia is translated into a hedgehog response through HIF‐1α and this mechanism is likely to be responsible for the hedgehog response observed in various ischaemia models.
Lack of inhibitory effects of the anti‐fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
Authors: Venalis Paulius , Maurer Britta , Akhmetshina Alfiya , Busch Nicole , Dees Clara , Stürzl Michael , Zwerina Jochen , Jüngel Astrid , Gay Steffen , Schett Georg , Distler Oliver , Distler Jörg H.W.
Published: September 2008

Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti‐fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti‐fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real‐time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.