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Sökning: WFRF:(Jacob R) > (2005-2009)

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1.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Forskningsöversikt (refereegranskat)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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2.
  • Liu, Kui, et al. (författare)
  • Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
  • 2009
  • Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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3.
  • Namjou, Bahram, et al. (författare)
  • High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
  • 2009
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1085-1095
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
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4.
  • Purcell, Shaun M., et al. (författare)
  • Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 460:7256, s. 748-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
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5.
  • Douglas, K. B., et al. (författare)
  • Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing
  • 2009
  • Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 457-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant association with decreased risk of SLE (30.4% in cases vs 32.6% in controls, P=0.016, OR=0.90 (0.82-0.98)). Two of these SNPs are in exon 10, directly 5' of an alternatively spliced exon preferentially expressed in follicular dendritic cells (FDC), and the third is in the alternatively spliced exon. Effects of these SNPs and a fourth SNP in exon 11 (rs17616) on alternative splicing were evaluated. We found that the minor alleles of these SNPs decreased splicing efficiency of exon 11 both in vitro and ex vivo. These findings further implicate CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the maintenance of tolerance and autoantibody production in the secondary lymphoid tissues where B cells and FDCs interact.
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6.
  • Mason, R Preston, et al. (författare)
  • Loss of arterial and renal nitric oxide bioavailability in hypertensive rats with diabetes : effect of beta-blockers
  • 2009
  • Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 22:11, s. 1160-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Endothelial cell (EC) dysfunction contributes to hypertension and mechanisms of atherosclerosis. Agents that improve EC function may provide vascular protection, especially in patients with multiple risk factors. In this study, we examined the effects of beta(1)-selective antagonists, nebivolol and metoprolol, on vascular and renal EC function in spontaneously hypertensive (SH) rats with diabetes. METHODS: Male SH rats were treated with streptozotocin (STZ) to induce type 2 diabetes, followed by treatment with nebivolol or metoprolol at 2 mg/kg/day (vs. vehicle). After 4 weeks, aortic and glomerular ECs were isolated, stimulated with calcium ionophore (CaI), and assayed for nitric oxide (NO), and peroxynitrite (ONOO(-)) release using amperometric approaches. RESULTS: Glucose and mean blood pressure (BP) levels were significantly elevated in diabetic SH rats. In aortic ECs isolated from diabetic SH rats, NO production decreased by 20% whereas ONOO(-) increased by 16%, an effect linked to NAD(P)H oxidase and endothelial NO synthase (eNOS) uncoupling. Nebivolol treatment reduced glucose and BP levels and restored aortic EC function in diabetic SH rats, as indicated by a 30% increase and 23% decrease in NO and ONOO(-) levels, respectively. The NO/ONOO(-) ratio increased by more than twofold with nebivolol treatment in aortic and glomerular ECs. Despite similar reductions in glucose and mean BP levels, metoprolol had a smaller effect on the NO/ONOO(-) ratio in glomerular ECs but no effect in aortic ECs. CONCLUSIONS: Vascular and renal NO was significantly reduced in diabetic hypertensive rats and correlated with metabolic changes. Nebivolol reversed these effects in a manner consistent with enhanced endothelial function.
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7.
  • Nittby, Henrietta, et al. (författare)
  • Exposure to radiation from global system for mobile communications at 1,800 MHz significantly changes gene expression in rat hippocampus and cortex
  • 2008
  • Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 28:4, s. 458-465
  • Tidskriftsartikel (refereegranskat)abstract
    • We have earlier shown that radio frequency electromagnetic fields can cause significant leakage of albumin through the blood-brain barrier of exposed rats as compared to non-exposed rats, and also significant neuronal damage in rat brains several weeks after a 2 h exposure to a mobile phone, at 915 MHz with a global system for mobile communications (GSM) frequency modulation, at whole-body specific absorption rate values (SAR) of 200, 20, 2, and 0.2 mW/kg. We have now studied whether 6 h of exposure to the radiation from a GSM mobile test phone at 1,800 MHz (at a whole-body SAR-value of 13 mW/kg, corresponding to a brain SAR-value of 30 mW/kg) has an effect upon the gene expression pattern in rat brain cortex and hippocampus-areas where we have observed albumin leakage from capillaries into neurons and neuronal damage. Microarray analysis of 31,099 rat genes, including splicing variants, was performed in cortex and hippocampus of 8 Fischer 344 rats, 4 animals exposed to global system for mobile communications electromagnetic fields for 6 h in an anechoic chamber, one rat at a time, and 4 controls kept as long in the same anechoic chamber without exposure, also in this case one rat at a time. Gene ontology analysis (using the gene ontology categories biological processes, molecular functions, and cell components) of the differentially expressed genes of the exposed animals versus the control group revealed the following highly significant altered gene categories in both cortex and hippocampus: extracellular region, signal transducer activity, intrinsic to membrane, and integral to membrane. The fact that most of these categories are connected with membrane functions may have a relation to our earlier observation of albumin transport through brain capillaries.
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9.
  • Persson, Bertil R.R., et al. (författare)
  • Effects of microwaves from GSM mobile phones on the blood-brain barrier and neurons in rat brain
  • 2005
  • Ingår i: PIERS 2005 - Progress in Electromagnetics Research Symposium, Proceedings. - 1933077077 - 9781933077079 ; , s. 638-641
  • Konferensbidrag (refereegranskat)abstract
    • Our group has since 1988 studied the effects of different intensities and modulations of 915MHz RF in a rat model where the exposure takes place in a TEM-cell during various time periods and post exposure recovery times. The power fed into TEM-cells was 0.125, 1.25, 12.5 or 125mW corresponding to whole body SAR (determined experimentally): 0.2, 2, 20 or 200mW/kg. The rats were awake and not restrained during exposure and after the recovery period the animals were anaesthetized and sacrificed by perfusion-fixation with 4% formaldehyde. Paraffin embedded 5 μm. thick brain slices were stained for albumin by applying albumin antibodies (Dakopatts), by which albumin is revealed as brownish discolorations. Dark neurons were revealed by staining for RNA/DNA with cresyl violet. In series of more than 1800 Fisher rats, we have proven that sub thermal power levels from both pulse-modulated and continuous RF fields - including those from real GSM mobile phones - have the potency to significantly open the BBB for the animals' own albumin (but not fibrinogen) to pass out into the brain and to accumulate in the neurons and glial cells surrounding the capillaries. Albumin extravasations are most prominent at the lower SAR values. This dose-response behaviour suggests some kind of energy or electromagnetic field strength windowing effect. A linear dose-response relationship for dark neurons was found at 50 days after exposure, with most prominent occurrence at SAR 200mW/kg.
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10.
  • Salford, Leif G., et al. (författare)
  • Non-thermal effects of EMF upon the mammalian brain : The Lund experience
  • 2007
  • Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 27:4, s. 493-500
  • Tidskriftsartikel (refereegranskat)abstract
    • The environment in which biology exists has dramatically changed during the last decades. Life was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation and the terrestrial magnetism. The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity and during the very last decades, microwaves of the modern communication society spread around the world. Today one third of the world's population is owner of the microwave-producing mobile phones. The question is: to what extent are living organisms affected by these ubiquitous radio frequency fields? Since 1988 our group has studied the effects upon the mammalian blood-brain barrier (BBB) by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been revealed to cause significantly increased leakage of albumin through the BBB of exposed rats as compared to non-exposed animals-in a total series of about two thousand animals. One remarkable observation is the fact that the lowest energy levels give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz at non-thermal levels, gives rise to significant neuronal damage, seen 28 and 50 days after the exposure. In our continued research, the non-thermal effects (histology, memory functions) of long-term exposure for 13 months are studied as well as the effects of short term GSM 1,800 MHz upon gene expression. Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Studies from other laboratories in some cases find effects, while in other cases effects are not seen. Our conclusion is that all researchers involved in this field have the obligation to intensify this research in order to reduce, or avoid, the possible negative effects of the man made microwaves!
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12.
  • Aksentijevich, Ivona, et al. (författare)
  • An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
  • 2009
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
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13.
  • Beck, R., et al. (författare)
  • GPSDTN : Predictive velocity-enabled delay-tolerant networks for arctic research and sustainability
  • 2007
  • Ingår i: Second International Conference on Internet Monitoring and Protection (ICIMP 2007). - Los Alamitos, Calif : IEEE Computer Society Press. - 9780769529110
  • Konferensbidrag (refereegranskat)abstract
    • A Delay-Tolerant Network (DTN) is a necessity for communication nodes that may need to wait for long periods to form networks. The IETF Delay Tolerant Network Research Group is developing protocols to enable such networks for a broad variety of Earth and interplanetary applications. The Arctic would benefit from a predictive velocity-enabled version of DTN that would facilitate communications between sparse, ephemeral, often mobile and extremely power-limited nodes. We propose to augment DTN with power-aware, buffer-aware location- and time-based predictive routing for ad-hoc meshes to create networks that are inherently location and time (velocity) aware at the network level to support climate research, emergency services and rural education in the Arctic. On Earth, the primary source of location and universal time information for networks is the Global Positioning System (GPS). We refer to this Arctic velocity-enabled Delay-Tolerant Network protocol as "GPSDTN" accordingly. This paper describes our requirements analysis and general implementation strategy for GPSDTN to support Arctic research and sustainability efforts
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14.
  • Brose, Ulrich, et al. (författare)
  • Body sizes of consumers and their resources
  • 2005
  • Ingår i: Ecology. - : Ecological Society of America. - 0012-9658 .- 1939-9170. ; 86:9, s. 2545-2545
  • Tidskriftsartikel (refereegranskat)abstract
    • Trophic information—who eats whom—and species’ body sizes are two of the most basic descriptions necessary to understand community structure as well as ecological and evolutionary dynamics. Consumer–resource body size ratios between predators and their prey, and parasitoids and their hosts, have recently gained increasing attention due to their important implications for species’ interaction strengths and dynamical population stability. This data set documents body sizes of consumers and their resources. We gathered body size data for the food webs of Skipwith Pond, a parasitoid community of grass-feeding chalcid wasps in British grasslands; the pelagic community of the Benguela system, a source web based on broom in the United Kingdom; Broadstone Stream, UK; the Grand Caric¸aie marsh at Lake Neuchaˆtel, Switzerland; Tuesday Lake, USA; alpine lakes in the Sierra Nevada of California; Mill Stream, UK; and the eastern Weddell Sea Shelf, Antarctica. Further consumer–resource body size data are included for planktonic predators, predatory nematodes, parasitoids, marine fish predators, freshwater invertebrates, Australian terrestrial consumers, and aphid parasitoids. Containing 16 807 records, this is the largest data set ever compiled for body sizes of consumers and their resources. In addition to body sizes, the data set includes information on consumer and resource taxonomy, the geographic location of the study, the habitat studied, the type of the feeding interaction (e.g., predacious, parasitic) and the metabolic categories of the species (e.g., invertebrate, ectotherm vertebrate). The present data set was gathered with the intent to stimulate research on effects of consumer–resource body size patterns on food-web structure, interaction-strength distributions, population dynamics, and community stability. The use of a common data set may facilitate cross-study comparisons and understanding of the relationships between different scientific approaches and models.
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15.
  • Eberhardt, Jacob, et al. (författare)
  • Blood-brain barrier permeability and nerve cell damage in rat brain 14 and 28 days after exposure to microwaves from GSM mobile phones.
  • 2008
  • Ingår i: Electromagnetic Biology and Medicine. - : Informa UK Limited. - 1536-8386 .- 1536-8378. ; 27:3, s. 215-229
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier and signs of neuronal damage in rats using a real GSM programmable mobile phone in the 900 MHz band. Ninety-six non-anaesthetized rats were either exposed to microwaves or sham exposed in TEM-cells for 2 h at specific absorption rates of average whole-body Specific Absorption Rates (SAR) of 0.12, 1.2, 12, or 120 mW/kg. The rats were sacrificed after a recovery time of either 14 or 28 d, following exposure and the extravazation of albumin, its uptake into neurons, and occurrence of damaged neurons was assessed. Albumin extravazation and also its uptake into neurons was seen to be enhanced after 14 d (Kruskal Wallis test: p = 0.02 and 0.002, respectively), but not after a 28 d recovery period. The occurrence of dark neurons in the rat brains, on the other hand, was enhanced later, after 28 d (p = 0.02). Furthermore, in the 28-d brain samples, neuronal albumin uptake was significantly correlated to occurrence of damaged neurons (Spearman r = 0.41; p < 0.01).
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16.
  • Grafström, Gustav, et al. (författare)
  • Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation.
  • 2008
  • Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 77, s. 257-263
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to mimic the real life situation, with often life-long exposure to the electromagnetic fields emitted by mobile phones, we have investigated in a rat model the effects of repeated exposures under a long period to Global System for Mobile Communication-900MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed once weekly in a 2-h period, for totally 55 weeks, at different average whole-body specific absorption rates (SAR) (of in average 0.6 and 60mW/kg at the initiation of the experimental period). The animals were exposed in a transverse electromagnetic transmission line chamber (TEM-cell) to radiation emitted by a GSM-900 test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After behavioural tests, 5-7 weeks after the last exposure, the brains were evaluated for histopathological alterations such as albumin extravasation, dark neurons, lipofuscin aggregation and signs of cytoskeletal and neuritic neuronal changes of the type seen in human ageing. In this study, no significant alteration of any these histopathological parameters was found, when comparing the GSM exposed animals to the sham exposed controls.
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18.
  • Halgamuge, Malka N., et al. (författare)
  • Comparison Between Two Models for Interactions Between Electric and Magnetic Fields and Proteins in Cell Membranes
  • 2009
  • Ingår i: Environmental Engineering Science. - : Mary Ann Liebert Inc. - 1092-8758 .- 1557-9018. ; 26:10, s. 1473-1480
  • Forskningsöversikt (refereegranskat)abstract
    • Investigations on exposure to electromagnetic have generated conflicting results both in epidemiological and laboratory studies, leaving their possible health consequences largely inconclusive. One of the well-reported reasons for the discrepancies is that there is no generally accepted theory to describe the interactions between the very weak electromagnetic fields and the living cells. This work presents a critical evaluation of three theories that describes the effects of weak electromagnetic fields on channel proteins in the cell membrane. The forced ion vibration model appears to explain the opening of ion channel proteins for exposures to low-frequency magnetic fields in the mili-Tesla range. No resonance frequencies or amplitude window effects are predicted in this method. We identify inconsistencies in the forced vibration model and show that the environmental magnetic fields that would be required to elicit opening of channel proteins are much stronger than predicted by the proposers of this model. The Ion Parametric Resonance model predicts a biological response at well-defined resonance frequencies for magnetic fields exceeding about 10 micro-Tesla. The oscillating magnetic field is assumed to act on proteins together with the earth's static magnetic field. This model predicts amplitude windows. We explain how a purely magnetic interaction, where in a two-stage ion magnetic resonance model, the conformation of a protein is changed under the influence of ions attached to its surface, which in turn, changes the function of the protein, can overcome the inherent signal-to-noise problem caused by electric thermal noise. The hydrogen nuclear polarization model predicts a biological response for oscillating magnetic field strengths above 0.1 micro-Tesla. The presence of a static magnetic field is required, and biological effects can be expected for frequencies below a few hundred hertz. All models except the forced vibration model can be applied for amplitude modulated microwaves.
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19.
  • Harley, John B., et al. (författare)
  • Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:2, s. 204-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
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20.
  • Hollenberg, Jacob, et al. (författare)
  • Difference in survival after out-of-hospital cardiac arrest between the two largest cities in Sweden: a matter of time?
  • 2005
  • Ingår i: J Intern Med. - : Wiley. - 0954-6820 .- 1365-2796. ; 257:3, s. 247-54
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dramatic differences in survival after out-of-hospital cardiac arrests (OHCA) reported from different geographical locations require analysis. We therefore compared patients with OHCA in the two largest cities in Sweden with regard to various factors at resuscitation and outcome. SETTING: All patients suffering an OHCA in Stockholm and Goteborg between 1 January 2000 and 30 June 2001, in whom cardiopulmonary resuscitation (CPR) was attempted were included in this retrospective analysis. RESULTS: All together, 969 OHCA in Stockholm and 398 in Goteborg were registered during the 18-month study period. There were no differences in terms of age, gender, and percentage of witnessed cases or percentage of patients who had received bystander CPR. However, the percentage of patients with ventricular fibrillation (VF) at arrival of the ambulance crew was 18% in Stockholm versus 31% in Goteborg (P <0.0001). The percentage of patients who were alive 1 month after cardiac arrest was 2.5% in Stockholm versus 6.8% in Goteborg (P=0.0008). Various time intervals such as cardiac arrest to calling for an ambulance, cardiac arrest to the start of CPR and calling for an ambulance to its arrival were all significantly longer in Stockholm than in Goteborg. CONCLUSION: Survival was almost three times higher in Goteborg than in Stockholm amongst patients suffering an OHCA. This is primarily explained by a higher occurrence of VF at the time of arrival of the ambulance crew, which in turn probably is explained by shorter delays in Goteborg. The reason for the difference in time intervals is most likely multifactorial, with a significantly higher ambulance density in Goteborg as one possible explanation.
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21.
  • Lalani, Tahaniyat, et al. (författare)
  • Propionibacterium endocarditis: a case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study.
  • 2007
  • Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:10, s. 840-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with beta-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy.
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22.
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23.
  • Markljung, Ellen, et al. (författare)
  • ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth
  • 2009
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:12, s. e1000256-
  • Tidskriftsartikel (refereegranskat)abstract
    • A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (ChIP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth.
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24.
  • Mikkelsen, Tarjei S, et al. (författare)
  • Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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25.
  • Nittby, Henrietta, et al. (författare)
  • Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation
  • 2008
  • Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 29:3, s. 219-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).
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26.
  • Nittby, Henrietta, et al. (författare)
  • Increased blood-brain barrier permeability in mammalian brain 7 days after exposure to the radiation from a GSM-900 mobile phone.
  • 2009
  • Ingår i: Pathophysiology. - : Elsevier BV. - 1873-149X .- 0928-4680.
  • Tidskriftsartikel (refereegranskat)abstract
    • Microwaves were for the first time produced by humans in 1886 when radio waves were broadcasted and received. Until then microwaves had only existed as a part of the cosmic background radiation since the birth of universe. By the following utilization of microwaves in telegraph communication, radars, television and above all, in the modern mobile phone technology, mankind is today exposed to microwaves at a level up to 10(20) times the original background radiation since the birth of universe. Our group has earlier shown that the electromagnetic radiation emitted by mobile phones alters the permeability of the blood-brain barrier (BBB), resulting in albumin extravasation immediately and 14 days after 2h of exposure. In the background section of this report, we present a thorough review of the literature on the demonstrated effects (or lack of effects) of microwave exposure upon the BBB. Furthermore, we have continued our own studies by investigating the effects of GSM mobile phone radiation upon the blood-brain barrier permeability of rats 7 days after one occasion of 2h of exposure. Forty-eight rats were exposed in TEM-cells for 2h at non-thermal specific absorption rates (SARs) of 0mW/kg, 0.12mW/kg, 1.2mW/kg, 12mW/kg and 120mW/kg. Albumin extravasation over the BBB, neuronal albumin uptake and neuronal damage were assessed. Albumin extravasation was enhanced in the mobile phone exposed rats as compared to sham controls after this 7-day recovery period (Fisher's exact probability test, p=0.04 and Kruskal-Wallis, p=0.012), at the SAR-value of 12mW/kg (Mann-Whitney, p=0.007) and with a trend of increased albumin extravasation also at the SAR-values of 0.12mW/kg and 120mW/kg. There was a low, but significant correlation between the exposure level (SAR-value) and occurrence of focal albumin extravasation (r(s)=0.33; p=0.04). The present findings are in agreement with our earlier studies where we have seen increased BBB permeability immediately and 14 days after exposure. We here discuss the present findings as well as the previous results of altered BBB permeability from our and other laboratories.
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27.
  • Nittby, Henrietta, et al. (författare)
  • Radiofrequency and extremely low-frequency electromagnetic field effects on the blood-brain barrier.
  • 2008
  • Ingår i: Electromagnetic Biology and Medicine. - : Informa UK Limited. - 1536-8386 .- 1536-8378. ; 27:2, s. 103-126
  • Tidskriftsartikel (refereegranskat)abstract
    • During the last century, mankind has introduced electricity and during the very last decades, the microwaves of the modern communication society have spread a totally new entity--the radiofrequency fields--around the world. How does this affect biology on Earth? The mammalian brain is protected by the blood-brain barrier, which prevents harmful substances from reaching the brain tissue. There is evidence that exposure to electromagnetic fields at non thermal levels disrupts this barrier. In this review, the scientific findings in this field are presented. The result is a complex picture, where some studies show effects on the blood-brain barrier, whereas others do not. Possible mechanisms for the interactions between electromagnetic fields and the living organisms are discussed. Demonstrated effects on the blood-brain barrier, as well as a series of other effects upon biology, have caused societal anxiety. Continued research is needed to come to an understanding of how these possible effects can be neutralized, or at least reduced. Furthermore, it should be kept in mind that proven effects on biology also should have positive potentials, e.g., for medical use.
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28.
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29.
  • Salford, Leif, et al. (författare)
  • The mammalian brain in the electromagnetic fields designed by man with special reference to blood-brain barrier function, neuronal damage and possible physical mechanisms
  • 2008
  • Ingår i: PROGRESS OF THEORETICAL PHYSICS SUPPLEMENT. - 0375-9687. ; :173, s. 283-309
  • Konferensbidrag (refereegranskat)abstract
    • Life oil earth was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation, atmospheric electric fields and the terrestrial magnetism. The Schumann resonances at 7.4 Hz are all example of oscillations possibly important for life.(1)) The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity, in the early 20th century long-wave radio and in the 1940-ies short-wave radio. High frequency RF was introduced in the 50-ies as FM and television and during the very last decades, microwaves of the modern communication society spread around the world. Today, however, one third of the world's population is owner of the microwave-producing mobile phones and an even larger number is exposed to the cordless RF emitting systems. To what; extent are all living organisms affected by these, almost everywhere present radio frequency fields? And what will be the effects of many years of continuing exposure? Since 1989 Our group has studied the effects upon the mammalian blood-brain barrier (BBB) in rats by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been shown to cause significantly increased leak-age of the rats' own blood albumin through the BBB of exposed rats, at energy levels of 1W/kg and below, as compared to non-exposed animals in a total series of about two thousand animals.(2)-6)) One remarkable observation is the fact that the lowest energy levels, with whole-body average power densities below 10mW/kg, give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz, at non-thermal SAB-values of 0.2, 2 and 200 mW/kg, gives rise to significant neuronal damage, seen not only 50 days after the exposure 7) but also after 28 days but not after 14 days. Albumin extravasations and uptake into neurons was enhanced after 14 clays, but not after 28.(8)) in our continued research, also the non-thermal effects oil tissue structure and memory function of long-term exposure for 13 months are studied.(9)) We have also performed microarray analysis of brains from rats exposed to short term GSM both at 1,800 MHz and at 900MHz and have found significant effects upon gene expression of membrane associated genes as compared to control animals.(10),11)) Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Some other Studies agree while others find no effects. The mechanisms by which the EMFs may alter BBB permeability are not Well Understood. At low field strengths, the effects on body temperature are negligible and thus heating effects are not involved. A change in the physicochemical characteristics of membranes has been suggested as a cause.(12)) We have performed experiments to verify a quantum mechanical model for interaction with protein-bound ions. Our results show that controlled frequency and amplitude of ELF EM fields upon spinach plasma vesicles can steer transport over the membrane.(13)) This may be a first proof of a resonance phenomenon where appropriate levels of frequency and amplitude in the right combination have the potency to communicate with the biology of membranes and transport systems. Our study has prompted Lis to elaborate on magnetic resonance models; the Ion Cyclotron Resonance (ICR) model and the Ion Parametric Resonance (IPR) Model in an attempt to explain the occurrence of resonance frequencies. This is extensively described here under the heading: Mechanisms behind the effects of electromagnetical fields upon biology. We also bring forward the concept of solitons being active in membranes and DNA/RNA-transcription as a, possible mean to understand and prove the biological effects of EMF. The Nishinomiya-Yukawa International and Interdisciplinary Symposium 2007 raised the question: What is Life? An obvious and simple answer could be: It is DNA! The DNA strand can be looked upon as an antenna resonating in the microwave band 6GHz with its harmonics and subharmonics.(14)-18)) If this holds true, the dramatic situation might exist, that all living organisms have a receptor for the newly constructed and world-wide man-made microvaves, leading to a direct effect upon the function of DNA - in concordance with our experimental findings! Our generation invented the microwave emitters. We now have in imperative obligation to further investigate the links between EMF and biology in order to prevent possible detrimental effects of the microwaves.
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30.
  • Sandalova, T., et al. (författare)
  • A structural basis for CD8(+) T cell-dependent recognition of non-homologous peptide ligands - Implications for molecular mimicry in autoreactivity
  • 2005
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 280:29, s. 27069-27075
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (KAVYNFATC/ M), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM, has also been identified. We herein report the crystal structure of H-2D(b)center dot rDBM and a comparison with the crystal structures of the cross-reactive H-2D(b)center dot gp33 and non- cross- reactive H-2D(b)center dot gp33 (V3L) escape variant (KALYNFATM, 88% identity to gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented in nearly identical manners by H-2D(b), with a striking juxtaposition of the central sections of both peptides from residues p3 to p7. The structural similarity provides H-2D(b) in complex with either a virus-derived or a dopamine beta-mono-oxygenase-derived peptide with a shared antigenic identity that conserves the positioning of the heavy chain and peptide residues that interact with the T cell receptor (TCR). This stands in contrast to the structure of H-2D(b) center dot gp33 (V3L), in which a single conserved mutation, also present in rDBM, induces large movements of both the peptide backbone and the side chains that interact with the TCR. The TCR-interacting surfaces of the H-2D(b) center dot rDBM and H-2D(b) center dot gp33 major histocompatibility complexes are very similar with regard to shape, topology, and charge distribution, providing a structural basis for CD8 T cell activation by molecular mimicry and potential subsequent development of autoreactivity.
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31.
  • Thyssen, Jacob Pontoppidan, et al. (författare)
  • p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study
  • 2009
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 60:6, s. 314-319
  • Tidskriftsartikel (refereegranskat)abstract
    • Positive patch test reactions to p-phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary 'tattoos'. Cross-sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe reactions upon hair dyeing, there is a need for 'current' prevalence data on PPD sensitization. To compare PPD patch test results from dermatitis patients tested between 2003 and 2007 in 10 European patch test centres and to analyse the causes and determine relevance of positive PPD patch test reactions. Patch testing was performed using PPD (1% free base in petrolatum from Trolab (Almirall Hermal GmbH, Reinbeck, Germany) or Chemotechnique (Malmo, Sweden), equivalent to 0.090 mg/cm(2) in the TRUE (R) test from MEKOS Laboratories AS). Statistical analysis was performed using the chi-squared test. The weighted average prevalence was 4.6% among 21 515 patients. PPD sensitization occurred more often in centres located in Central and Southern Europe than in Scandinavian centres (odds ratio = 2.40; 95% confidence interval = 2.07-2.78). The overall proportion of positive patch test reactions to PPD that were registered as being of either current or 'past' relevance was high (weighted average 53.6% and 20.3%, respectively). Consumer hair dyeing was the most prominent cause of PPD sensitization (weighted average 41.8%). Furthermore, occupational hair dye exposure (10.6%) and cross-sensitization to textile dyes (12.6%) were frequently reported. PPD sensitization caused by exposure to hair dyes is frequent and remains a present problem for patients visiting contact dermatitis clinics, especially in patch test centres located in Central and Southern Europe.
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32.
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33.
  • Veith, Frank J., et al. (författare)
  • Collected world and single center experience with endovascular treatment of ruptured abdominal aortic aneurysms
  • 2009
  • Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 250:5, s. 818-824
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Case and single center reports have documented the feasibility and suggested the effectiveness of endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs), but the role and value of such treatment remain controversial. OBJECTIVE: To clarify these we examined a collected experience with use of EVAR for RAAA treatment from 49 centers. METHODS: Data were obtained by questionnaires from these centers, updated from 13 centers committed to EVAR treatment whenever possible and included treatment details from a single center and information on 1037 patients treated by EVAR and 763 patients treated by open repair (OR). RESULTS: Overall 30-day mortality after EVAR in 1037 patients was 21.2%. Centers performing EVAR for RAAAs whenever possible did so in 28% to 79% (mean 49.1%) of their patients, had a 30-day mortality of 19.7% (range: 0%-32%) for 680 EVAR patients and 36.3% (range: 8%-53%) for 763 OR patients (P < 0.0001). Supraceliac aortic balloon control was obtained in 19.1% +/- 12.0% (+/-SD) of 680 EVAR patients. Abdominal compartment syndrome was treated by some form of decompression in 12.2% +/- 8.3% (+/-SD) of these EVAR patients. CONCLUSION: These results indicate that EVAR has a lower procedural mortality at 30 days than OR in at least some patients and that EVAR is better than OR for treating RAAA patients provided they have favorable anatomy; adequate skills, facilities, and protocols are available; and optimal strategies, techniques, and adjuncts are employed.
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34.
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