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Showing papers by "University of Copenhagen published in 2003"


Journal ArticleDOI
TL;DR: A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.
Abstract: From the Steno Diabetes Center, Copenhagen (P.G., P.V., N.L., H.-H.P., O.P.); Herlev County Hospital, Herlev (N.L.); Amtssygehuset Roskilde, Roskilde (G.V.H.J.); and the Faculty of Health Science, Aarhus University, Aarhus (H.-H.P., O.P.) — all in Denmark. Address reprint requests to Dr. Pedersen at the Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark, or at oluf@steno.dk. N Engl J Med 2003;348:383-93. Copyright © 2003 Massachusetts Medical Society. background Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. methods The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. results The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). conclusions A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.

4,111 citations


Journal ArticleDOI
TL;DR: The International Standards for Neurological Classification of Spinal Cord Injury (ISC-II) as mentioned in this paper is a set of international standards for the classification of spinal cord injury that were developed by the International Association of Neurological Diseases and Pathology (IANS).
Abstract: (2003). International Standards For Neurological Classification Of Spinal Cord Injury. The Journal of Spinal Cord Medicine: Vol. 26, No. sup1, pp. S50-S56.

1,931 citations


Journal ArticleDOI
TL;DR: Top-class soccer players performed more high-intensity running during a game and were better at the Yo-Yo test than moderate professional players; fatigue occurred towards the end of matches as well as temporarily during the game, independently of competitive standard and of team position; defenders covered a shorter distance in high- intensity running than players in other playing positions.
Abstract: The aim of this study was to assess physical fitness, match performance and development of fatigue during competitive matches at two high standards of professional soccer. Computerized time-motion analyses were performed 2-7 times during the competitive season on 18 top-class and 24 moderate professional soccer players. In addition, the players performed the Yo-Yo intermittent recovery test. The top-class players performed 28 and 58% more (P < 0.05) high-intensity running and sprinting, respectively, than the moderate players (2.43 +/- 0.14 vs 1.90 +/- 0.12 km and 0.65 +/- 0.06 vs 0.41 +/- 0.03 km, respectively). The top-class players were better (11%; P < 0.05) on the Yo-Yo intermittent recovery test than the moderate players (2.26 +/- 0.08 vs 2.04 +/- 0.06 km, respectively). The amount of high-intensity running, independent of competitive standard and playing position, was lower (35-45%; P < 0.05) in the last than in the first 15 min of the game. After the 5-min period during which the amount of high-intensity running peaked, performance was reduced (P < 0.05) by 12% in the following 5 min compared with the game average. Substitute players (n = 13) covered 25% more (P < 0.05) ground during the final 15 min of high-intensity running than the other players. The coefficient of variation in high-intensity running was 9.2% between successive matches, whereas it was 24.8% between different stages of the season. Total distance covered and the distance covered in high-intensity running were higher (P < 0.05) for midfield players, full-backs and attackers than for defenders. Attackers and full-backs covered a greater (P < 0.05) distance in sprinting than midfield players and defenders. The midfield players and full-backs covered a greater (P < 0.05) distance than attackers and defenders in the Yo-Yo intermittent recovery test (2.23 +/- 0.10 and 2.21 +/- 0.04 vs 1.99 +/- 0.11 and 1.91 +/- 0.12 km, respectively). The results show that: (1) top-class soccer players performed more high-intensity running during a game and were better at the Yo-Yo test than moderate professional players; (2) fatigue occurred towards the end of matches as well as temporarily during the game, independently of competitive standard and of team position; (3) defenders covered a shorter distance in high-intensity running than players in other playing positions; (4) defenders and attackers had a poorer Yo-Yo intermittent recovery test performance than midfielders and full-backs; and (5) large seasonal changes were observed in physical performance during matches.

1,859 citations


Journal ArticleDOI
TL;DR: In this article, the authors used fluorescence excitation-emission spectroscopy and parallel factor analysis (PARAFAC) to characterise the fluorescent fraction of dissolved organic matter (DOM) in the catchment of a Danish estuary.

1,695 citations


Book
01 Jan 2003
TL;DR: In this article, the authors develop a regional approach to global security and present scenarios for the RSCs of the Americas, Europe, and Sub-Saharan Africa, respectively.
Abstract: Part I. Introduction: Developing a Regional Approach to Global Security: 1. Theories and histories about the structure of contemporary international security 2. Levels: distinguishing the regional from the global 3. Security complexes: a theory of regional security Part II. Asia: 4. South Asia: inching towards internal and external transformation 5. Northeast and southeast Asian security complexes during the Cold War 6. The 1990s and beyond: an emergent east Asian complex Conclusion Part III. The Middle East and Africa: Introduction 7. The Middle East: a perennial conflict formation 8. Sub-saharan Africa: security dynamics in a setting of weak and failed states Conclusions Part IV. The Americas: 9. North America: the sole superpower and its surroundings 10. South America: an under-conflictual anomaly? Conclusion: scenarios for the RSCs of the Americas Part V. The Europes: Introduction: 11. EU-Europe: the European Union and its 'near abroad' 12. The Balkans and Turkey 13. The post-Soviet space: a regional security complex around Russia Conclusion: scenarios for the European supercomplex Part VI. Conclusions: 14. Regions and powers: summing up and looking ahead 15. Reflections on conceptualising international security.

1,537 citations


Journal ArticleDOI
19 Jun 2003-Nature
TL;DR: In this article, the authors reported evidence for a very energetic supernova (a hypernova), temporally and spatially coincident with a gamma-ray burst at redshift z=0.1685.
Abstract: Over the past five years evidence has mounted that long-duration (greater than 2s) gamma-ray bursts (GRBs), the most brilliant of all astronomical explosions, signal the collapse of massive stars in our Universe. This evidence, originally based on the probable association of one unusual GRB with a supernova, now includes the association of GRBs with regions of massive star-formation in distant galaxies, tantalizing evidence of supernova-like light-curve 'bumps' in the optical afterglows of several bursts, and lines of freshly synthesized elements in the spectra of a few X-ray afterglows. These observations support, but do not yet conclusively validate, models based upon the deaths of massive stars, presumably associated with core collapse. Here we report evidence for a very energetic supernova (a hypernova), temporally and spatially coincident with a GRB at redshift z=0.1685. The timing of the supernova indicates that it exploded within a few days of the GRB, strongly suggesting that core-collapse events can give rise to GRBs. Amongst the GRB central engine models proposed to-date, the properties of this supernova thus favour the collapsar model.

1,415 citations


Book ChapterDOI
TL;DR: A conceptual model of the spatial and temporal dominance of group-specific primary producers, and hence the basic fatty acid patterns available to higher trophic levels is presented and is based on stratification.
Abstract: Fatty acids have been used as qualitative markers to trace or confirm predator-prey relationships in the marine environment for more than thirty years. More recently, they have also been used to identify key processes impacting the dynamics of some of the world's major ecosystems. The fatty acid trophic marker (FATM) concept is based on the observation that marine primary producers lay down certain fatty acid patterns that may be transferred conservatively to, and hence can be recognized in, primary consumers. To identify these fatty acid patterns the literature was surveyed and a partial least squares (PLS) regression analysis of the data was performed, validating the specificity of particular microalgal FATM. Microalgal group specific FATM have been traced in various primary consumers, particularly in herbivorous calanoid copepods, which accumulate large lipid reserves, and which dominate the zooplankton biomass in high latitude ecosystems. At higher trophic levels these markers of herbivory are obscured as the degree of carnivory increases, and as the fatty acids originate from a variety of dietary sources. Such differences are highlighted in a PLS regression analysis of fatty acid and fatty alcohol compositional data (the components of wax esters accumulated by many marine organisms) of key Arctic and Antarctic herbivorous, omnivorous and carnivorous copepod species. The analysis emphasizes how calanoid copepods separate from other copepods not only by their content of microalgal group specific FATM, but also by their large content of long-chain monounsaturated fatty acids and alcohols. These monounsaturates have been used to trace and resolve food web relationships in, for example, hyperiid amphipods, euphausiids and fish, which may consume large numbers of calanoid copepods. Results like these are extremely valuable for enabling the discrimination of specific prey species utilized by higher trophic level omnivores and carnivores without the employment of invasive techniques, and thereby for identifying the sources of energetic reserves. A conceptual model of the spatial and temporal dominance of group-specific primary producers, and hence the basic fatty acid patterns available to higher trophic levels is presented. The model is based on stratification, which acts on phytoplankton group dominance through the availability of light and nutrients. It predicts the seasonal and ecosystem specific contribution of diatom and flagellate/microbial loop FATM to food webs as a function of water column stability. Future prospects for the application of FATM in resolving dynamic ecosystem processes are assessed.

1,357 citations


Journal ArticleDOI
TL;DR: A synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing and inhibited virulence factor expression in a mouse pulmonary infection model.
Abstract: Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip® microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.

1,319 citations


Journal ArticleDOI
TL;DR: The Yo-Yo intermittent recovery test was a valid measure of fitness performance in soccer and had a high reproducibility and sensitivity, allowing for detailed analysis of the physical capacity of athletes in intermittent sports.
Abstract: KRUSTRUP, P, M MOHR, T AMSTRUP, T RYSGAARD, J JOHANSEN, A STEENSBERG, P K PEDERSEN, and J BANGSBO The Yo-Yo Intermittent Recovery Test: Physiological Response, Reliability, and Validity Med Sci Sports Exerc, Vol 35, No 4, pp 697–705, 2003PurposeTo examine the physiological

1,175 citations


Journal ArticleDOI
TL;DR: This review summarises current knowledge of granule biology and highlights the effects of neutrophil degranulation in the acute inflammatory response.

1,117 citations


Book
31 Dec 2003
TL;DR: The present thesis deals with the physiological demands of soccer, with a particular focus on the physiological response to repeated intense exercise, and performs physiological measurements in connection with soccer matches.
Abstract: The present thesis is based on 14 original articles published in international journals (I-XIV, see page 8) and a summarizing review. The thesis deals with the physiological demands of soccer, with a particular focus on the physiological response to repeated intense exercise. In chapter I the specific issues are presented and in chapter II the physiological demands in soccer are discussed based on the results of the studies performed. Chapter III contains a short survey of the experiments performed to study specifically muscle metabolism and muscle fatigue with repeated intense muscle contractions. With reference to the topics covered in chapters II and III, fatigue during a soccer match is discussed in chapter IV, and chapter V deals with applications for physical training in soccer. Measurements have been performed during soccer matches and training, as well as in experiments simulating the activities of a soccer match. The information obtained has been compared to results from studies of the physical capacity of top-class soccer players and from laboratory experiments aimed at investigating metabolism and fatigue in intermittent exercise. Studies with whole-body and single muscle group exercises have been performed, the latter mainly with the application of a knee-extension model. In the studies on isolated muscle groups, biopsies taken from exercising muscles as well as arterial and femoral venous blood samples have allowed for detailed analysis of muscle ionic transportation and metabolism. In addition, the magnetic resonance technique has been used for the continuous determination of changes in muscle metabolites and pH during intermittent exercise. Analysis of activities during soccer matches showed that a top-class soccer player covers an average distance of approximately 11 km during a match. The distance differs highly between players and is partly related to the position in a team. Midfield players run more at low speed than defenders and forwards, whereas no difference appears to exist between groups when comparing the distance covered at high speed. The distance covered at high speed is the same in the beginning as in the end of a match. The total distance covered by a player during a soccer match is only to a limited extent a measure of the physiological demands on the player during the match. In addition to running, a player is engaged in many other energy demanding activities, i.e. tackling, jumping, accelerating and turning. A more precise evaluation of the total energy demand during a soccer match may be achieved by performing physiological measurements in connection with soccer matches (I).(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: The difference in predictive performance between the neural network methods and that of the matrix‐driven methods is found to be most significant for peptides that bind strongly to the HLA molecule, confirming that the signal of higher order sequence correlation is most strongly present in high‐binding peptides.
Abstract: In this paper we describe an improved neural network method to predict T-cell class I epitopes. A novel input representation has been developed consisting of a combination of sparse encoding, Blosum encoding, and input derived from hidden Markov models. We demonstrate that the combination of several neural networks derived using different sequence-encoding schemes has a performance superior to neural networks derived using a single sequence-encoding scheme. The new method is shown to have a performance that is substantially higher than that of other methods. By use of mutual information calculations we show that peptides that bind to the HLA A*0204 complex display signal of higher order sequence correlations. Neural networks are ideally suited to integrate such higher order correlations when predicting the binding affinity. It is this feature combined with the use of several neural networks derived from different and novel sequence-encoding schemes and the ability of the neural network to be trained on data consisting of continuous binding affinities that gives the new method an improved performance. The difference in predictive performance between the neural network methods and that of the matrix-driven methods is found to be most significant for peptides that bind strongly to the HLA molecule, confirming that the signal of higher order sequence correlation is most strongly present in high-binding peptides. Finally, we use the method to predict T-cell epitopes for the genome of hepatitis C virus and discuss possible applications of the prediction method to guide the process of rational vaccine design.

Journal ArticleDOI
TL;DR: IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise-induced leukocyte trafficking.
Abstract: The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received...

Journal ArticleDOI
TL;DR: Dynamics and selection during biofilm formation were investigated by tagging the wild type and flagella/type IV mutants with Yfp and Cfp and performing time‐lapse confocal laser scanning microscopy in mixed colour biofilms, which revealed dynamic compositions with extensive motility, competition and selection occurring during development.
Abstract: Summary Biofilm formation by Gfp-tagged Pseudomonas aeruginosa PAO1 wild type, flagella and type IV pili mutants in flow chambers irrigated with citrate mini- mal medium was characterized by the use of confocal laser scanning microscopy and COMSTAT image anal- ysis. Flagella and type IV pili were not necessary for P. aeruginosa initial attachment or biofilm formation, but the cell appendages had roles in biofilm develop- ment, as wild type, flagella and type IV pili mutants formed biofilms with different structures. Dynamics and selection during biofilm formation were investi- gated by tagging the wild type and flagella/type IV mutants with Yfp and Cfp and performing time-lapse confocal laser scanning microscopy in mixed colour biofilms. The initial microcolony formation occurred by clonal growth, after which wild-type P. aeruginosa bacteria spread over the substratum by means of twitching motility. The wild-type biofilms were dynamic compositions with extensive motility, com- petition and selection occurring during development. Bacterial migration prevented the formation of larger microcolonial structures in the wild-type biofilms. The results are discussed in relation to the current model for P. aeruginosa biofilm development.

Journal ArticleDOI
TL;DR: This work proposes a scheme in which DNA would be the scaffold of a taxonomic reference system, whilst maintaining the importance of the morphological information associated with whole specimens.
Abstract: Taxonomy underpins all biological research, with implications for many basic scientific and applied fields. Insights into the stability or change of animal and plant guilds require species identification on a broad scale and biodiversity questions have become a major public issue. But this comes at a time when taxonomy is facing a crisis, because ever fewer specialists are available. Here, we explore the possibility of using DNA-based methodology to overcome these problems. The utility of DNA sequences for taxonomic purposes is well established. However, all current taxonomic approaches intend to use DNA, at best, as an auxiliary criterion for identifying a species or a taxon, but have not given it a central role. We propose a scheme in which DNA would be the scaffold of a taxonomic reference system, whilst maintaining the importance of the morphological information associated with whole specimens.

Journal ArticleDOI
TL;DR: It is demonstrated that exercise induces a dramatic transient increase in PGC‐1α transcription and mRNA content in human skeletal muscle, consistent with its role as a transcriptional coactivator, and suggest that PGC•1α may coordinate the activation of metabolic genes in human muscle in response to exercise.
Abstract: Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1α (PGC-1α) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1α transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1α was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1α in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor α, and calcineurin Aα and Aβ mRNA were elevated (≈2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1α transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1α may coordinate the activation of metabolic genes in human muscle in response to exercise.

Journal ArticleDOI
TL;DR: The theory of electroporation is outlined, the use of short high-voltage pulses to overcome the barrier of the cell membrane is described, and data on safety and efficacy is summed up on delivery of chemotherapy to tumours in cancer patients.
Abstract: Electroporation designates the use of short high-voltage pulses to overcome the barrier of the cell membrane. By applying an external electric field, which just surpasses the capacitance of the cell membrane, transient and reversible breakdown of the membrane can be induced. This transient, permeabilized state can be used to load cells with a variety of different molecules, either through simple diffusion in the case of small molecules, or through electrophoretically driven processes allowing passage through the destabilized membrane--as is the case for DNA transfer. Initially developed for gene transfer, electroporation is now in use for delivery of a large variety of molecules: From ions to drugs, dyes, tracers, antibodies, and oligonucleotides to RNA and DNA. Electroporation has proven useful both in vitro, in vivo and in patients, where drug delivery to malignant tumours has been performed. Whereas initial electroporation procedures caused considerable cell damage, developments over the past decades have led to sophistication of equipment and optimization of protocols. The electroporation procedures used in many laboratories could be optimized with limited effort. This review (i) outlines the theory of electroporation, (ii) discusses factors of importance for optimization of electroporation protocols for mammalian cells, (iii) addresses particular concerns when using electroporation in vivo, e.g. effects on blood flow and considerations regarding choice of electrodes, (iv) describes DNA electrotransfer with emphasis on use in the in vivo setting, and (v) sums up data on safety and efficacy of electroporation used to enhance delivery of chemotherapy to tumours in cancer patients.

Journal ArticleDOI
16 Oct 2003-Nature
TL;DR: A single-electron transistor where the electronic levels of a single π-conjugated molecule in several distinct charged states control the transport properties is described, leading to a very significant reduction of the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital.
Abstract: A combination of classical Coulomb charging, electronic level spacings, spin, and vibrational modes determines the single-electron transfer reactions through nanoscale systems connected to external electrodes by tunnelling barriers1. Coulomb charging effects have been shown to dominate such transport in semiconductor quantum dots2, metallic3 and semiconducting4 nanoparticles, carbon nanotubes5,6, and single molecules7,8,9. Recently, transport has been shown to be also influenced by spin—through the Kondo effect—for both nanotubes10 and single molecules8,9, as well as by vibrational fine structure7,11. Here we describe a single-electron transistor where the electronic levels of a single π-conjugated molecule in several distinct charged states control the transport properties. The molecular electronic levels extracted from the single-electron-transistor measurements are strongly perturbed compared to those of the molecule in solution, leading to a very significant reduction of the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital. We suggest, and verify by simple model calculations, that this surprising effect could be caused by image charges generated in the source and drain electrodes resulting in a strong localization of the charges on the molecule.

Journal ArticleDOI
TL;DR: Physical exercise and rhIL‐6 infusion at physiological concentrations inhibit endotoxin‐induced TNF‐α production in humans and suggest that the mechanism include IL‐6, which is produced by and released from exercising muscles.
Abstract: During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli lipopolysaccharide endotoxin (0.06 ng/kg) i.v. to induce low-grade inflammation. In CON, plasma TNF-alpha increased significantly in response to endotoxin. In contrast, during EX, which resulted in elevated IL-6, and rhIL-6, the endotoxin-induced increase in TNF-alpha was totally attenuated. In conclusion, physical exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced by and released from exercising muscles.

Journal Article
TL;DR: The 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists is described, developed by an international MRI-OMERACT group.
Abstract: This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.

Journal ArticleDOI
TL;DR: In this article, a nomenclature for restriction endonucleases, DNA methyltransferases, homing endon nucleases and related genes and gene products is described.
Abstract: A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genomes.

Journal ArticleDOI
TL;DR: High interobserver agreement rates for the identification of synovitis and bone erosions are achieved using an introduced semiquantitative scoring system for ultrasonography of finger and toe joints in RA.
Abstract: Objective To evaluate the interobserver agreement of ultrasonographic assessment of finger and toe joints in patients with rheumatoid arthritis (RA) by 2 investigators with different medical backgrounds. Methods Ultrasonography and clinical examination were performed on 150 small joints of 30 patients with active RA. A General Electric LOGIQ 500 ultrasound unit with a 7–13-MHz linear array transducer was used. In each patient, 5 preselected small joints (second and third metacarpophalangeal, second proximal interphalangeal, first and second metatarsophalangeal) were examined independently on the same day by 2 ultrasound investigators (an experienced musculoskeletal radiologist and a rheumatologist with limited ultrasound training). Joint effusion, synovial thickening, bone erosions, and power Doppler signal were evaluated in accordance with an introduced 4-grade semiquantitative scoring system, on which the investigators had reached consensus prior to the study. Results Exact agreement between the 2 observers was seen in 91% of the examinations with regard to bone erosions, in 86% with regard to synovitis, in 79% with regard to joint effusions, and in 87% with regard to power Doppler signal assessments. Corresponding intraclass correlation coefficient values were 0.78, 0.81, 0.61, and 0.72, respectively, while unweighted kappa values were 0.68, 0.63, 0.48, and 0.55, respectively. Ultrasonography showed signs of inflammation in 94 joints, while clinical assessment revealed tenderness and/or swelling in 64 joints. Conclusion An experienced radiologist and a rheumatologist with limited ultrasound training achieved high interobserver agreement rates for the identification of synovitis and bone erosions, using an introduced semiquantitative scoring system for ultrasonography of finger and toe joints in RA. Signs of inflammation were more frequently detected with ultrasound than with clinical examination. Ultrasonography may improve the assessment of RA patients by radiologists and rheumatologists.

Journal ArticleDOI
TL;DR: The data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia.
Abstract: Although IL-6 is a key modulator of immune function, it also plays a role in regulating substrate metabolism. To determine whether IL-6 affects lipid metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of recombinant human IL-6 (rhIL-6). The IL-6 concentration during Con, Low-rhIL6, and High-rhIL6 was at a steady state after 30 min of infusion at approximately 4, 140, and 320 pg/ml, respectively. Either dose of rhIL-6 was associated with a similar increase in fatty acid (FA) concentration and endogenous FA rate of appearance (R(a)) from 90 min after the start of the infusion. The FA concentration and FA R(a) continued to increase until the cessation of rhIL-6 infusion, reaching levels approximately 50% greater than Con values. The elevated levels reached at the end of rhIL-6 infusion persisted at least 3 h postinfusion. Triacylglycerol concentrations were unchanged during rhIL-6 infusion, whereas whole body fat oxidation increased after the second hour of rhIL-6 infusion. Of note, during Low-rhIL6, the induced elevation in FA concentration and FA R(a) occurred in the absence of any change in adrenaline, insulin, or glucagon, and no adverse side effects were observed. In conclusion, the data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia.

Journal ArticleDOI
TL;DR: Body site largely explains the variation in epidermal thickness, but also a significant individual variation was observed, and thickness of the stratum corneum and cellular epidermis correlated positively to blood content and was greater in males than in females.
Abstract: Epidermal thickness and its relationship to age, gender, skin type, pigmentation, blood content, smoking habits and body site is important in dermatologic research and was investigated in this study. Biopsies from three different body sites of 71 human volunteers were obtained, and thickness of the stratum corneum and cellular epidermis was measured microscopically using a preparation technique preventing tissue damage. Multiple regressions analysis was used to evaluate the effect of the various factors independently of each other. Mean (SD) thickness of the stratum corneum was 18.3 (4.9) microm at the dorsal aspect of the forearm, 11.0 (2.2) microm at the shoulder and 14.9 (3.4) microm at the buttock. Corresponding values for the cellular epidermis were 56.6 (11.5) microm, 70.3 (13.6) microm and 81.5 (15.7) microm, respectively. Body site largely explains the variation in epidermal thickness, but also a significant individual variation was observed. Thickness of the stratum corneum correlated positively to pigmentation (p = 0.0008) and negatively to the number of years of smoking (p < 0.0001). Thickness of the cellular epidermis correlated positively to blood content (P = 0.028) and was greater in males than in females (P < 0.0001). Epidermal thickness was not correlated to age or skin type.

Journal ArticleDOI
TL;DR: Investigation in six European countries found medical end-of-life decisions frequently precede dying in all participating countries, with large variations in the extent to which decisions were discussed with patients, relatives, and other caregivers.

Journal ArticleDOI
TL;DR: A combination of L rhamnosus 19070-2 and L reuteri DSM 122460 was beneficial in the management of AD, and the effect was more pronounced in patients with a positive skin prick test response and increased IgE levels.
Abstract: Background: Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis (AD). Objective: The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD. Methods: In a double-blind, placebo-controlled, crossover study, 2 probiotic Lactobacillus strains (lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) were given in combination for 6 weeks to 1- to 13-year-old children with AD. The patients' evaluations were registered after each intervention (ie, better, unchanged, or worse). The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis (SCORAD) score. As inflammatory markers, eosinophil cationic protein in serum and cytokine production by PBMCs were measured. Results: After active treatment, 56% of the patients experienced improvement of the eczema, whereas only 15% believed their symptoms had improved after placebo ( P = .001). The total SCORAD index, however, did not change significantly. The extent of the eczema decreased during active treatment from a mean of 18.2% to 13.7% ( P = .02). The treatment response was more pronounced in allergic patients (at least one positive skin prick test response and elevated IgE levels), and in this group the SCORAD score decreased ( P = .02 compared with nonallergic patients). During active treatment, serum eosinophil cationic protein levels decreased ( P = .03). No significant changes in the production of the cytokines IL-2, IL-4, IL-10, or IFN-γ were found. Conclusions: A combination of L rhamnosus 19070-2 and L reuteri DSM 122460 was beneficial in the management of AD. The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels. (J Allergy Clin Immunol 2003;111:389-95.)

Journal ArticleDOI
TL;DR: In this article, the authors compared phytoplankton and periphyton productivity along a eutrophication gradient in Greenland, U.S., and Danish lakes.
Abstract: Benthic community responses to lake eutrophication are poorly understood relative to pelagic responses. We compared phytoplankton and periphyton productivity along a eutrophication gradient in Greenland, U.S., and Danish lakes. Phytoplankton productivity increased along the phosphorus gradient (total phosphorus [TP] 5 2‐430 mg m 23 ), but whole-lake benthic algal productivity decreased, substantially depressing increases in primary productivity at the whole-lake scale. In shallow, oligotrophic Greenland lakes, periphyton was responsible for 80‐98% of primary production, whereas in Danish lakes with TP . 100 mg m 23 , phytoplankton were responsible for nearly 100% of primary production. Benthic contributions ranged from 5 to 80% depending on morphometry and littoral habitat composition in lakes with intermediate phosphorus concentrations. Thus, eutrophication was characterized by a switch from benthic to pelagic dominance of primary productivity. Carbon stable isotope analysis showed that the redistribution of primary production entailed a similar shift from periphyton to phytoplankton in the diets of zoobenthos. Benthic and pelagic habitats were energetically linked through food web interactions, but eutrophication eroded the benthic primary production pathway.

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TL;DR: Aging is associated with chronic low-grade increases in circulating levels of inflammatory markers, such as TNF-alpha and IL-6, which are associated with morbidity and mortality in the elderly.

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TL;DR: In this article, a thermal bipolar seesaw model was proposed to explain a large fraction of the millennial climate variability measured in the isotopic composition of Antarctic ice cores, and the model resolved the apparent confusion whether northern and southern climate records are in or out of phase, synchronous or time lagged.
Abstract: [1] The simplest possible model is proposed to explain a large fraction of the millennial climate variability measured in the isotopic composition of Antarctic ice cores. The model results from the classic bipolar seesaw by coupling it to a heat reservoir. In this "thermal bipolar seesaw" the heat reservoir convolves northern time signals with a characteristic timescale. Applying the model to the data of GRIP and Byrd, we demonstrate that maximum correlation can be obtained using a timescale of about 1000-1500 years. Higher correlations are obtained by first filtering out the long-term variability which is due to astronomical and greenhouse gas forcing and not part of the thermal bipolar seesaw. The model resolves the apparent confusion whether northern and southern climate records are in or out of phase, synchronous, or time lagged.

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TL;DR: Eleven studies of electrochemotherapy of malignant cutaneous or subcutaneous lesions, e.g., metastases from melanoma, breast or head- and neck cancer, are reviewed, finding the treatment was well tolerated and could be performed on an out-patient basis.