bluuebunny/crossref_metadata_2025 huggingface dataset:
Lats2 Is a Negative Regulator of Myocyte Size in the Heart
Authors: Matsui Yutaka , Nakano Noritsugu , Shao Dan , Gao Shumin , Luo Wenting , Hong Chull , Zhai Peiyong , Holle Eric , Yu Xianzhong , Yabuta Norikazu , Tao Wufan , Wagner Thomas , Nojima Hiroshi , Sadoshima Junichi
Published: October 2008

Mammalian sterile 20–like kinase (Mst)1 plays an important role in mediating apoptosis and inhibiting hypertrophy in the heart. Because Hippo, a
Drosophila
homolog of Mst1, forms a signaling complex with Warts, a serine/threonine kinase, which in turn stimulates cell death and inhibits cell proliferation, mammalian homologs of Warts, termed Lats1 and Lats2, may mediate the function of Mst1. We here show that Lats2, but not Lats1, dose-dependently increased apoptosis in cultured cardiac myocytes. Lats2 also dose-dependently reduced [
3
H]phenylalanine incorporation and cardiac myocyte size, whereas dominant negative Lats2 (DN-Lats2) increased them, suggesting that endogenous Lats2 negatively regulates myocyte growth. DN-Lats2 significantly attenuated induction of apoptosis and inhibition of hypertrophy by Mst1, indicating that Lats2 mediates the function of Mst1 in cardiac myocytes. Cardiac specific overexpression of Lats2 in transgenic mice significantly reduced the size of left and right ventricles, whereas that of DN-Lats2 caused hypertrophy in both ventricles. Overexpression of Lats2 reduced left ventricular systolic and diastolic function without affecting baseline levels of myocardial apoptosis. Expression of endogenous Lats2 was significantly upregulated in response to transverse aortic constriction. Overexpression of DN-Lats2 significantly enhanced cardiac hypertrophy and inhibited cardiac myocyte apoptosis induced by transverse aortic constriction. These results suggest that Lats2 is necessary and sufficient for negatively regulating ventricular mass in the heart. Although Lats2 is required for cardiac myocyte apoptosis in response to pressure overload, it was not sufficient to induce apoptosis at baseline. In conclusion, Lats2 affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy.
Factor V Leiden Mutation in Reocclusion After Intra-Arterial Thrombolysis
Authors: Kuruvilla Abraham , Norris Gregory M. , Manjila Sunil , Xavier Andrew R. , Chaturvedi Seemant
Published: October 2008

Background and Purpose—

Reocclusion of intracranial arteries after successful recanalization is associated with poor clinical outcome. The role of Factor V Leiden mutation in intracranial arterial thrombosis/rethrombosis is unclear.

Summary of Report—

We report the case of a patient who developed recurrent reocclusions of the middle cerebral artery after intra-arterial thrombolysis for acute ischemic stroke. The patient subsequently underwent transcatheter clot retrieval followed by successful stent-supported angioplasty of the occluded segment. He underwent a detailed workup for thrombophilia. The patient was detected to be heterozygous for Factor V Leiden mutation without any other cause for thrombophilia.

Conclusions—

Factor V Leiden mutation could be a contributing etiology for reocclusion after endovascular interventions in stroke. Systematic studies looking for thrombophilic mutations in patients with arterial reocclusion might be warranted.
Sequential Optimal Design of Neurophysiology Experiments
Authors: Lewi Jeremy , Butera Robert , Paninski Liam
Published: October 2008

Adaptively optimizing experiments has the potential to significantly reduce the number of trials needed to build parametric statistical models of neural systems. However, application of adaptive methods to neurophysiology has been limited by severe computational challenges. Since most neurons are high-dimensional systems, optimizing neurophysiology experiments requires computing high-dimensional integrations and optimizations in real time. Here we present a fast algorithm for choosing the most informative stimulus by maximizing the mutual information between the data and the unknown parameters of a generalized linear model (GLM) that we want to fit to the neuron's activity. We rely on important log concavity and asymptotic normality properties of the posterior to facilitate the required computations. Our algorithm requires only low-rank matrix manipulations and a two-dimensional search to choose the optimal stimulus. The average running time of these operations scales quadratically with the dimensionality of the GLM, making real-time adaptive experimental design feasible even for high-dimensional stimulus and parameter spaces. For example, we require roughly 10 milliseconds on a desktop computer to optimize a 100-dimensional stimulus. Despite using some approximations to make the algorithm efficient, our algorithm asymptotically decreases the uncertainty about the model parameters at a rate equal to the maximum rate predicted by an asymptotic analysis. Simulation results show that picking stimuli by maximizing the mutual information can speed up convergence to the optimal values of the parameters by an order of magnitude compared to using random (nonadaptive) stimuli. Finally, applying our design procedure to real neurophysiology experiments requires addressing the nonstationarities that we would expect to see in neural responses; our algorithm can efficiently handle both fast adaptation due to spike history effects and slow, nonsystematic drifts in a neuron's activity.
Positioning Classism Within Counseling Psychology's Social Justice Agenda
Authors: Smith Laura
Published: October 2008

Counseling psychologists have been instrumental in advancing a social justice agenda within the larger field of psychology. What is still missing within this agenda, however, is a fully developed consideration of classism within the spectrum of oppressions more commonly addressed in discussions of social justice and multiculturalism. The operations of classism can be difficult to see in a society that has long considered itself to be classless, and for counseling psychologists to undertake this work, they must initiate a deliberate effort to develop their awareness of classism as it affects their theory, research, and practice. In support of this end, the author presents a social justice conceptualization of classism, provides examples of classism at work, and outlines the resulting implications for counseling psychology practice.
Using Item Response Theory and Model—Data Fit to Conceptualize Differential Item and Person Functioning for Students With Disabilities
Authors: Engelhard George
Published: October 2008

The major purpose of this study is to describe a conceptual framework for examining differential item functioning (DIF) and differential person functioning (DPF) as types of model—data misfit within the context of assessing students with disabilities. Specifically, DIF and DPF can be viewed through the lens of residual analyses. Residual analyses can be used to explore DIF (item fit) as well as extended to explore DPF (person fit). One of the advantages of this conceptual framework is that the size of the subgroups can be quite small with interpretable results produced even for individuals. To illustrate this conceptual framework, Rasch measurement theory is used as the item response theory model. Methodological and theoretical issues are discussed. Data from a high-stakes assessment in mathematics in Georgia (Grade 7, geometry items) are used to illustrate the conceptual framework for students with disabilities. The substantive research questions used to illustrate the conceptual framework addresses whether modifications in test administration (use of resource guides or calculators) influence item functioning for students with disabilities (DIF analyses) and whether students with various disabilities differentially benefit from these modifications (DPF analyses).
Parents and Youth With Learning Disabilities
Authors: Heiman Tali , Zinck Lana C. , Heath Nancy L.
Published: October 2008

The study examined perceptions of family relationships and communication in 52 families who have an adolescent child diagnosed with learning disabilities (LD) with a matched group of 52 families who have a child without LD. Parents and youth completed a self-reported Family Relations and Communication Scales assessment. Findings revealed parents perceived their child as either overinvolved or underinvolved with their parents and not sharing the same values and norms as their parents. Findings indicated that parents of youth with and without LD share similar perceptions of both the openness and problematic aspects of family communication. Youth with and without LD reported higher levels of problematic maternal involvement than perceived by the mothers; youth without LD rated their mothers' affective expression higher than reported by their mothers; both groups of youth perceived their mothers' and their fathers' communication as less open and more problematic than reported by their parents.
Gentrification and Social Mixing: Towards an Inclusive Urban Renaissance?
Authors: Lees Loretta
Published: October 2008

Nearly 30 years ago now, Holcomb and Beauregard were critical of the way that it was assumed that the benefits of gentrification would 'trickle down' to the lower classes in a manner similar to that hypothesised in the housing market. Nevertheless, despite fierce academic debate about whether or not gentrification leads to displacement, segregation and social polarisation, it is increasingly promoted in policy circles both in Europe and North America on the assumption that it will lead to less segregated and more sustainable communities. Yet there is a poor evidence base for this policy of 'positive gentrification'-for, as the gentrification literature tells us, despite the new middle classes' desire for diversity and difference they tend to self-segregate and, far from being tolerant, gentrification is part of an aggressive, revanchist ideology designed to retake the inner city for the middle classes. In light of this, it is argued that these new policies of social mixing require critical attention with regard to their ability to produce an inclusive urban renaissance and the potentially detrimental gentrifying effects they may inflict on the communities they intend to help.
From London to Mumbai and Back Again: Gentrification and Public Policy in Comparative Perspective
Authors: Harris Andrew
Published: October 2008

Gentrification has become a global phenomenon over the past 15 years and has been understood as an increasingly important strategy within neo-liberal policy-making. Focusing on London and Mumbai, this paper details how public policies and planning regimes have been reconfigured and rescaled to facilitate and encourage new property speculation. However, against more generalised and abstract accounts of the neo-liberal city, the paper uses its comparative perspective to emphasise the geographically and historically specific manifestations and effects of gentrification processes. By highlighting different forms of state intervention and sharper socio-spatial impacts in Mumbai, the paper challenges the Eurocentric framing of a global spread of gentrification and argues that Mumbai can act as an important source of learning for gentrification research.
Gentrification—Gentle or Traumatic? Urban Renewal Policies and Socioeconomic Transformations in Copenhagen
Authors: Larsen Henrik Gutzon , Hansen Anders Lund
Published: October 2008

This article contrasts the intentions and outcomes of the publicly instigated and supported urban renewal of Copenhagen's Inner Vesterbro district. Apart from physically upgrading the decaying buildings, the municipality's aim was to include the inhabitants in the urban renewal process and, seemingly, to prevent the dislocation of people from the neighbourhood. However, due to ambiguous policies, the workings of the property market and the lack of sufficient deflecting mechanisms, middle-class inhabitants are now replacing the high concentration of socioeconomically vulnerable people that characterised Vesterbro before the urban renewal. This process may appear `gentle', but it is nonetheless an example of how state and market interact to produce gentrification with `traumatic' consequences for individuals and the city as a socially just space.
Spoiled Mixture: Where Does State-led `Positive' Gentrification End?
Authors: Davidson Mark
Published: October 2008

Over the past decade, policy-makers have introduced social mixing initiatives that have sought to address urban social problems by deconcentrating poor and working-class communities through attracting the middle classes back to the city. Such a policy objective clearly `smells like gentrification'. However, some commentators have warned against being critical of these policies, pointing out that the types of inner-city redevelopment generated by them is different from classical gentrification and that state-led gentrification offers benefits for many working-class communities. This paper draws upon research conducted in London to demonstrate how, despite having many commendable aspects, these policy agendas carry with them significant threats of displacement for lower-income communities. The paper also argues that, due to the mutating nature of gentrification, these threats are increasingly context-bound. In conclusion, the paper argues that those state mechanisms which might manage the unjust aspects of gentrification are inadequate.
Relevance, Gentrification and the Development of a New Hegemony on Urban Policies in Antwerp, Belgium
Authors: Loopmans Maarten
Published: October 2008

This paper applies a state-theoretical perspective to a historical analysis of gentrification and urban policies in Antwerp, Belgium. Before 1970, the city experienced a period of modernist hegemony, with urban development policies characterised by slum clearing, peripheral high-rise social housing construction and inner-city office development. After moving through a period of non-hegemony with intense debate and struggle about urban development, the city now appears to be experiencing another period of hegemony in urban policy of which state support for gentrification has become the centrepiece. A historical state-theoretical approach shows how this move has been the consequence of local institutionalisation and political conflicts following the collapse of modernism, and provides insight into the opportunities available for critical observers of gentrification to enhance policy relevance.
The Politics of Studentification and `(Un)balanced' Urban Populations: Lessons for Gentrification and Sustainable Communities?
Authors: Smith Darren
Published: October 2008

This paper explores the politics of studentification in the UK. It is argued that there is a paradox between New Labour's vision of sustainable communities and the geographical effects of the promotion of higher education—in a similar vein to policies to generate `positive' gentrification. This contention hinges on the absence of a national policy on the supply of student housing, which dictates how enlarged student populations should be integrated into established communities, or dispersed to other parts of towns and cities. It is asserted that the lack of government policy and the incapacity of institutional actors to intervene or regulate the residential geographies of students are yielding `unbalanced' populations. This is a factor in the rise of studentification and the fragmentation of established communities. Ironically, some activists argue these `lost' communities signified lucid exemplars that the sustainable communities policy seeks to engender. These new geographies also obscure the positives of a student population and may foster resentment and conflict between students and established residents. More specifically, the paper illustrates how debates of planning and housing legislation are integral for addressing the challenges of studentification. The paper concludes by considering some possible lessons of studentification for mitigating the negatives of gentrification.
The heat pipe heat exchanger: a review of its status and its potential for coolness recovery in tropical buildings
Authors: Yau YH
Published: October 2008

The heat pipe heat exchanger (HPHX) is a proven device for heat recovery in HVAC systems, and competes effectively with other available systems such as heat recovery wheels and run-around coils. This paper reviews major research work done on heat pipe heat exchangers (HPHXs) installed in HVAC systems since 1970. It reveals that research work on HPHXs for HVAC heat and coolness recovery has been done mostly in North America, Britain and Australia. Literature reviews further reveal that only limited research work on HPHXs for HVAC heat and coolness recovery has been conducted in subtropical and tropical climates and therefore, more HPHX research work for HVAC applications should be carried out in these regions in the interests of energy conservation and global green environment strategies.

Practical applications: The review on recover heat or coolness in HVAC systems since 1970 described in this paper enables necessarily good understanding on recover heat or coolness technologies for the impact of energy consumption and dehumidification in buildings before actual research or retrofitting is conducted to the space's conditioning system. The results obtained from a considerable number of research work in subtropical and tropical climates could serve as a preliminary guide for mechanical and electrical (M&E) engineers and researchers who are intending to apply heat pipe heat exchangers as `coolness' recovery and dehumidification devices in HVAC systems operating in tropical countries.
Analysis of uncertainty in natural ventilation predictions of high-rise apartment buildings
Authors: Hyun SH , Park CS , Augenbroe GLM
Published: October 2008

Quantification of natural ventilation rates is an important issue in HVAC system design. Natural ventilation in buildings depends on many parameters whose uncertainty varies significantly, and hence the results from a standard deterministic simulation approach could be unreliable and provide a false sense of security that natural ventilation will supply adequate amounts of fresh air. This study performed an uncertainty analysis to predict natural airflow rates. The paper presents relevant uncertainty in model and input parameters such as meteorological data, building properties (leakage areas of windows, doors, etc.), etc. Uncertainties of the aforementioned parameters were quantified based on data available from literature and on-site visits. The Monte-Carlo method with Latin Hypercube Sampling (LHS) was used for uncertainty propagation. The CONTAMW was chosen to simulate natural ventilation phenomena in a high-rise apartment building that is typical of residential buildings in Korea. It is shown that the uncertainty propagated through this process is not negligible and may significantly influence the prediction of the airflow rates. In the paper, the result of a sensitivity analysis is also addressed.

Practical application: The paper describes a probablistic approach to predict the natural airflow rates of high-rise apartment buildings under uncertainty and could eventually replace the current conventional deterministic approach.
Air-conditioned deployable force infrastructure as a strategy to combat sleep deprivation among troops in hot countries
Authors: van Hoof J
Published: October 2008

High-tech peacekeeping and humanitarian interventions form an increasing part of the range of duties of the military, dispatching troops to all parts of the world, with emphasis on hot climate areas. These missions call for fewer soldiers but with a more thorough, detailed and timely awareness level to reach predetermined goals. High ambient temperatures in the operational environment have a deleterious effect on performance, which is aggravated by poor sleep. Current deployable force infrastructure is often unable to support the restoration of body and brain sufficiently, while troop fitness is essential to the success of the mission. Supplying the peacekeepers with air-conditioned housing is becoming an increasingly important non-pharmacological strategy to counter the negative effects of heat. This paper investigates the influence of the military field environment, and high temperatures in particular, on sleep, comfort and performance of personnel and equipment, and looks at the benefits of installing air-conditioning systems and future trends in deployable force infrastructure.

Practical application: Results of this study can be used for innovations in designing comfortable mission housing and accompanying building services that do not only offer comfort to military personnel in field settings, but also provide better conditions for sleep. Improved comfort and sleep can in turn benefit operational performance. The results can also be used for a large range of civilian purposes, for instance, the creation of comfortable bedrooms and hotel rooms.
Equivalent diameters of rectangular and oval ducts
Authors: Koch P
Published: October 2008

To help engineers predict the pressure drop of a fluid passing along ducts of non-circular cross-section, the concept of `equivalent diameter' of a circular duct has been extensively used. This paper re-analyses two earlier sets of research data for non-circular ducts, such an analysis being easier now than at the time of the original research, 1948 and 1975. This new work reveals that equations for equivalent diameter of non-rectangular ducts lifted from the two prime sources are totally inapplicable; in short they are myths which should no longer be reiterated. In analysing the experimental results as constructively as possible to extract a more appropriate and correct relationship, the author finds that the experimental results are not sufficiently consistent to draw any reliable quantitative conclusions. Thus the experimental work needs to be repeated to verify whether hydraulic diameter may be used as an `equivalent diameter' or whether an alternative relationship can be found.

Practical application: In showing that there are no reliable practical results to guide engineers in calculating pressure drop along non-circular ducts, the paper demonstrates that further practical research is necessary. In showing that the relationships used in some texts and reputedly emanating from practical research, are both invalid, the author hopes that their future use will cease. Until a proven relationship for `equivalent diameter' is forthcoming, there is no other choice than to use the hydraulic diameter.
A review of the IPCC Assessment Report Four, Part 2: Mitigation options for residential and commercial buildings
Authors: Levermore GJ
Published: October 2008

The Intergovernmental Panel on Climate Change, (IPCC), Fourth Assessment Report, AR4, Climate Change 2007 consists of three volumes based on the work of three IPCC Working Groups (WGs). WG1 considered the scientific basis of climate change and what the climate models are showing. WG2 considered the consequences of climate change and possible adaptation to it. WG3 considered how the climate change could be mitigated. Within this WG3 volume is chapter 6 on the mitigation options for residential and commercial buildings. This paper reviews this chapter which discusses how the potential savings of greenhouse gases can be achieved through technical fixes and policies. The technical fixes are based on existing technology although it is recognised that existing building refurbishment is a major issue to be addressed and that there are a number of policies that can help achieve these reductions although some are in their infancy. Part 1 of this paper (The IPCC process and Greenhouse Gas Emission trends from Buildings worldwide) considered the history of the IPCC and the trends in emissions, particularly from buildings.

Practical application: Climate change is an important topic for building services engineers, resulting in the UK in the new, performance-based Building Regulations Part L. This paper reviews the technical options that have been identified by the IPCC as potentially carbon mitigating for buildings. The context of the world situation is also considered and the policies considered by the IPCC as relevant to buildings and plant that will ultimately affect the design of building services engineers in the UK and overseas.
A review of the IPCC Assessment Report Four, Part 1: the IPCC process and greenhouse gas emission trends from buildings worldwide
Authors: Levermore GJ
Published: October 2008

The Intergovernmental Panel on Climate Change, (IPCC), Fourth Assessment Report, AR4, Climate Change 2007 consists of three volumes based on the work of three IPCC Working Groups (WGs). WG1 considered the scientific basis of climate change and what the climate models are showing. WG2 considered the consequences of climate change and possible adaptation to it. WG3 considered how the climate change could be mitigated. This paper briefly outlines the history of the IPCC, its purpose and outputs, including the AR4 and its relation to the Kyoto Protocol, and the IPCC authoring process. The paper then reviews the trends in carbon emissions, especially from the built environment (which are a major source of greenhouse gas, GHG, emissions in the world), and the potential mitigation reductions in carbon emissions that are considered possible and the scenarios on which they are based.

Practical application: Climate change is an important topic for building services engineers, resulting in the UK in the new, performance-based Building Regulations Part L. This paper outlines the history and relevance of the IPCC for building services engineers as well as reviewing the world trends in carbon emissions from buildings and the future scenarios on which they are based. The paper emphasises the importance of buildings and building services in the context of climate change.
Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery
Authors: Allen Bradley S , Ilbawi Michael N
Published: October 2008

As cardiopulmonary bypass (CPB) in infants and neonates is becoming more frequent, the technical performance of these operations for congenital heart disease has made significant progress. However, little research has been carried out into the conduct of CBP in producing myocardial and pulmonary dysfunction. Postoperative organ dysfunction is a problem, particularly for cyanotic infants. This paper examines the experimental and clinical experience of injury brought about by abrupt reoxygenation of the hypoxic, or cyanotic, heart. The modalities of gradual reoxygenation and leukodepletion in limiting this injury are examined, leading to the conclusion that injury can be reduced and possibly ameliorated by changes in intraoperative management during CBP in children with cyanotic disease.
Timing of leukocyte filtration during cardiopulmonary bypass
Authors: Matheis G , Scholz M , Simon A , Henrich D , Wimmer-Greinecker G , Moritz A
Published: October 2008

The effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass (CPB) have been shown by numerous investigators. In the majority of cases a leukocyte filter is placed in the arterial line instead of a standard arterial line filter and used throughout CPB. However, protocols to optimize onset and duration of leukocyte filtration have not been sufficiently evaluated to date. In this paper, current efforts to improve such protocols are demonstrated and discussed. These efforts are based on studies of leukocyte pathogenicity during cardiac surgery. A first study (double-blind randomized) was performed in routine coronary artery bypass graft (CABG) patients to evaluate whether short-term leukocyte filtration during reperfusion by release of the aortic crossclamp would reduce reperfusion-associated myocardial damage. Further data compare the efficacy of three different filtration concepts to reduce CPB-and/or reperfusion-associated leukocyte pathogenicity. Clinical endpoints, standard laboratory variables and functional in vitro assays are provided and discussed.
Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute myocardial infarction
Authors: Patel Mrugesh B , Kilgore Kenneth S , Ortolano Girolamo A , Gryboski Cyndy L , Qureshi Mansoor A , Marcovitz Pamela , Naylor Keith B , Park James L , Wenz Barry , Gikakis Nicolas , Freedman Robert J , Lucchesi Benedict R , O’Neill William W
Published: October 2008

Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI.

The filter reduces leukocytes by 99.9998 ± 0.0002% (p<0.0001) and platelets by 99.9934 ± 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was ‘conditioned’ by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (1.64 ± 0.18 to 1.45 ± 0.15, p=0.02).

Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.
Effects of leukocyte depletion of blood transfusions on postoperative complications
Authors: van de Watering Leo
Published: October 2008

Postoperative complications associated with blood transfusions are frequently reported to be a result of the transfused leukocytes. This paper examines the effects of leukocyte depletion. Leukocyte depletion by filtration which can reduce leukocyte presence by more than 99.9%. The implications of this are postulated in terms of the results that may be obtained.
The effects of leucodepletion in patients who develop the systemic inflammatory response syndrome following cardiopulmonary bypass
Authors: Treacher D F , Sabbato M , Brown K A , Gant V
Published: October 2008

The development of the systemic inflammatory response syndrome (SIRS) is associated with increased morbidity and mortality. Numerous anticytokine trials have failed to demonstrate any outcome benefit and there has been little evidence of improvement in the prognosis of this condition over the past 20 years. This study examines the effect of using a white cell filter designed to remove polymorphonuclear cells (PMNs) in patients who developed SIRS 36 h after cardiopulmonary bypass (CPB). Twenty-four patients were randomized to receive either leucofiltration (LF) or control therapy (CT). The two groups were well matched at study entry in terms of age, severity of illness and length of time on CPB. LF patients received 60 min filtration periods using a venovenous extracorporeal circuit at a flow rate of 200 ml/min with the cycle repeated every 12 h while SIRS and other entry criteria were met. CT patients received standard therapy. LF patients received an average of 4.2 cycles (range 1-8) and, after 15 min filtration, the total leucocyte count had fallen from 16.2 ± 5.3 to 10.4 ± 3.3 × 109/l and PMN from 14.4 ± 5.2 to 8.3 ± 4.2 × 109/l. The mean platelet count changed from 127 ± 87 to 117 ± 82 × 109/l. No adverse effects related to leucodepletion were observed. There was no difference between the groups in either mortality or length of stay at the intensive care unit or at hospital discharge. Organ function was assessed regularly during the study period and significant changes occurred only in respiratory and renal function. In the LF patients, respiratory function assessed by change in hypoxaemia index from baseline and renal function assessed by serum creatinine showed significant treatment effects compared to CT patients (p < 0.01, <0.01 respectively); three CT patients, but no LF patients, received haemofiltration during the study period. Leucofiltration safely and effectively removes circulating PMNs from patients with SIRS following CPB. This may result in improved pulmonary and renal function in these patients. Further studies are required of the kinetics and phenotypic characteristics of PMN removal by leucofiltration and a larger multicentre study will be necessary to determine whether this novel therapy has a significant outcome benefit in critically ill patients with SIRS.
Leucodepletion and the interaction of polymorphonuclear cells with endothelium in systemic inflammatory response syndrome
Authors: Brown K A , Lewis S M , Hill T A , Macey M G , McCarthey D A , Grant V A , Treacher D F
Published: October 2008

The abnormal interaction of polymorphonuclear cells (PMNs) with blood vessel walls is considered to underlie the multiple organ failure of systemic inflammatory response syndrome (SIRS). This consideration is supported by the present finding that PMNs from patients with SIRS are activated, as assessed by an increased distribution of cells bearing CD64, enhanced expression of CD11b and decreased expression of CD62L, and are highly adhesive to endothelial monolayers. Passage of SIRS blood through leucodepletion filters in a laboratory-designed extracorporeal circuit resulted in a marked depletion of PMNs. Of the PMNs that remained in the blood, far fewer cells bound to cultured endothelial cells in comparison with PMNs prior to leucofiltration. We propose that leucofiltration of SIRS blood will limit the number of PMNs available for binding to blood vessel walls and, hence, reduce the pathological manifestations associated with this disorder.
Massive intractable pericardial effusion in a patient with systemic lupus erythematosus treated successfully with pericardial fenestration alone
Authors: Kamata Y , Iwamoto M , Aoki Y , Kishaba Y , Nagashima T , Nara H , Kamimura T , Tanaka A , Yoshio T , Okazaki H , Minota S
Published: October 2008

Systemic lupus erythematosus (SLE) is often complicated by pericarditis with effusion, which generally responds well to glucocorticoid. We report herein a Japanese patient with SLE who showed a sign of cardiac tamponade and severe chest and back pain because of massive intractable pericardial effusion. Pulse glucocorticoid and pulse cyclophosphamide gained marginal effects. Pericardial effusion accumulated again soon after ultrasound-guided pericardiocentesis and drainage. Pericardial fenestration performed surgically as a last resort, for draining pericardial fluid into the pleural space, was very effective, and only a much smaller amount of fluid was observed in the space thereafter in comparison with the volume before the surgery. Pathological examination of the retrieved pericardium unfolded intense hyperplasia of small vessels and capillaries. Levels of IL-6 and TNF-α in pericardial effusion were extremely higher than those in serum. Pericardial effusion with extensive capillary hyperplasia in SLE would be resistant to medical treatment and require surgical fenestration.
Progressive multifocal leukoencephalopathy – the importance of early diagnosis illustrated in four cases
Authors: Nived O , Bengtsson AA , Jönsen A , Sturfelt G
Published: October 2008

Progressive multifocal leukoencephalopathy (PML) is a rare, deadly demyelinating disease of the central nervous system, which is caused by a reactivation of the DNA polyomavirus JC and occurs in immunosuppressed individuals. So far, only 25 cases have been described in patients with SLE and none survived without antiviral therapy and only two cases in RA. We present four additional cases from a defined area, three in SLE, of which one survived without antiviral therapy, and one case in RA, also surviving after reduction of immunosuppressive treatment. In three of these cases, diagnosis could only be confirmed by stereotactical brain biopsy, including the two surviving cases. Thus, this article illustrates the difficulty in diagnosing progressive multifocal leukoencephalopathy, the need for brain biopsy in many cases, the importance of reduced immunosuppression as early as possible and the severe damage progressive multifocal leukoencephalopathy can cause. Furthermore, progressive multifocal leukoencephalopathy might be much more common in SLE than expected with 1 case in 800 patient-years.
Diabetes mellitus complicating systemic lupus erythematosus – analysis of the UCL lupus cohort and review of the literature
Authors: Cortes S , Chambers S , Jerónimo A , Isenberg D
Published: October 2008

Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients’ notes ( n = 485) was performed. At every outpatient appointment the patients’ urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.
Vascular responsiveness in the microcirculation of patients with systemic lupus erythematosus is not impaired
Authors: de Leeuw K , Blaauw J , Smit AJ , Kallenberg CG , Bijl M
Published: October 2008

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud’s phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.
Patients with familial and sporadic onset SLE have similar clinical profiles but vary profoundly by race
Authors: Sestak AL , Nath SK , Kelly JA , Bruner GR , James JA , Harley JB
Published: October 2008

Few large, multi-ethnic studies have examined the clinical and serologic differences between familial and sporadic SLE patients. Understanding these similarities and differences is critical for interpreting genetic studies and developing therapeutic strategies. We compiled information on 1915 patients with SLE in a large multi-racial cohort, including general demographics, pedigree structure and the specific American College of Rheumatology (ACR) criteria met. One patient was randomly selected from each multiplex family for analysis, yielding 554 European-Americans (EA), 373 African-Americans (AA), 193 Hispanics (HI) and 237 patients of other of mixed races. When comparing familial and sporadic patients stratified by race, lupus erythematosus (LE) cells and arthritis were increased in white familial cases ( P = 5.5 × 10−6 and P = 0.028, respectively), but no other significant differences between familial and sporadic patients were found. We found that there were profound differences in clinical profiles between races. For example, photosensitivity and malar rash were decreased in AA ( P = 1.3 × 10−13 and 1.4 × 10−7, respectively), whereas discoid rash was increased in AA ( P = 5.5×10−6). EA had significantly less renal disease ( P = 5.4×10−13), proteinuria ( P = 4 × 10−12) and anti-Sm ( P = 1.7 × 10−12) than AA or HI. We, therefore, conclude that familial and sporadic onset patients may be treated similarly with respect to clinical and genetic studies.
High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus
Authors: Juárez-Rojas JG , Medina-Urrutia AX , Posadas-Sánchez R , Jorge-Galarza E , Mendoza-Pérez E , Caracas-Portilla N , Cardoso-Saldaña G , Muñoz-Gallegos G , Posadas-Romero C
Published: October 2008

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL2b (−14.7%) and higher proportions of HDL3b (+8.8%) and HDL3c (+23.3%). Cholesteryl ester (−18%) and apolipoprotein AI (−9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL ( P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R2 = 0.327) and plasma total apo AI (R2 = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.
IgA antiphospholipid antibodies are an independent risk factor for thromboses
Authors: Shen YM , Lee R , Frenkel E , Sarode R
Published: October 2008

Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin and anti-β2-glycoprotein I antibodies, mostly IgG isotype) are strong risk factors for thrombosis. Because a paucity of information on IgA isotype exists in the literature, we retrospectively evaluated the thrombotic significance of IgA antiphospholipid antibodies. We included 472 patients with clinical information on thrombotic events and complete laboratory work-up for antiphospholipid antibodies syndrome. Odds ratios (OR) of various antiphospholipid antibodies for thrombosis were calculated by univariate and multivariate analyses. Lupus anticoagulant alone was detected in 57 (12%) patients, ELISA-based antibodies (IgG, IgM, IgA) against cardiolipin, phosphatidylserine or β2-glycoprotein-I alone were detected in 131 (28%) patients, whereas 80 (17%) patients had both. Antibody isotype distribution was IgG 32%, IgM 60% and IgA 56%. Univariate analysis showed a statistically significant risk of thrombosis in patients with elevated titres of IgA of any ELISA-based antiphospholipid antibodies (OR 1.77). Stepwise logistic regression (multivariate) analysis identified elevated titres of any ELISA-based IgA antiphospholipid antibodies as an independent risk factor for thrombosis (OR 1.6) in the entire cohort, and in the subgroup of patients without concurrent presence of lupus anticoagulant (OR 1.8). IgA antiphospholipid antibodies appear to be a significant independent risk factor for thrombosis, thereby meriting evaluation in patients with unexpected thrombosis.
Efficiency of the DNA repair and polymorphisms of the XRCC1, XRCC3 and XRCC4 DNA repair genes in systemic lupus erythematosus
Authors: Bassi CL , Xavier DJ , Palomino GM , Nicolucci P , Soares CP , Sakamoto-Hojo ET , Donadi EA
Published: October 2008

Impaired DNA repair efficiency in systemic lupus erythematosus (SLE) patients has been reported in some studies, mainly regarding the repair of oxidative damage, but little is known about repair kinetics towards primarily single-stranded DNA breaks. In the present study, we aimed to investigate: (a) the efficiency of SLE peripheral blood leucocytes in repairing DNA damage induced by ionizing radiation and (b) the association of DNA repair gene ( XRCC1 Arg399Gln, XRCC3 Thr241Met and XRCC4 Ile401Thr) polymorphisms in SLE patients, considering the whole group, or stratified sub-groups according to clinical and laboratory features. A total of 163 SLE patients and 125 healthy controls were studied. The kinetics of DNA strand break repair was evaluated by the comet assay, and genotyping for DNA repair genes was performed by PCR-RFLP. Compared with controls, SLE leucocytes exhibited decreased efficiency of DNA repair evaluated at 30 min following irradiation. A significant association with DNA repair gene polymorphisms was not observed for the whole group of SLE patients; however, the XRCC1Arg399Gln polymorphism was associated with the presence of anti-dsDNA antibody. The concomitance of two DNA repair polymorphic sites was associated with the presence of neuropsychiatric manifestations and antiphospholipid antibody syndrome. Taken together, these results indicated that SLE leucocytes repair less efficiently the radiation-induced DNA damage, and DNA repair polymorphic sites may predispose to the development of particular clinical and laboratory features.