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| 2. |
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| 3. |
- Castro-Giner, F, et al.
(författare)
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TNFA -308G>A in two international population-based cohorts and risk of asthma
- 2008
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Ingår i: European Respiratory Journal. - Sheffield : European respiratory society journals. - 0903-1936 .- 1399-3003. ; 32:2, s. 350-361
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
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| 7. |
- Alvarsson, M, et al.
(författare)
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Effects of insulin vs. glibenclamide in recently diagnosed patients with type 2 diabetes: a 4-year follow-up
- 2008
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 10:5, s. 421-429
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To compare effects of early insulin vs. glibenclamide treatment on beta-cell function, metabolic control and quality of life (QL) in recently diagnosed patients with type 2 diabetes. Methods: Forty-nine patients with type 2 diabetes diagnosed 0-2 years before inclusion were randomized to two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide at six diabetic clinics in Sweden. C-peptide-glucagon tests were performed yearly after 3 days of withdrawal of treatment. Results: Thirty-four patients completed 4 years of study. Daily dose of insulin was increased from 20.4 +/- 1.8 U at year 1 to 26.1 +/- 2.9 U at year 4 (p = 0.005). Glibenclamide dosage increased from 2.7 +/- 0.4 mg at year 1 to 4.5 +/- 0.8 mg at year 4 (p = 0.02). Weight increased more in insulin than in glibenclamide treated (+4.4 +/- 0.8 vs. +0.3 +/- 1.0 kg, p < 0.005). Following short-term withdrawal of treatment, the C-peptide responses to glucagon were significantly higher in the insulin vs. glibenclamide group at years 1 (p < 0.01) and 2 (p < 0.02). HbA1c improved identical during the first year but thereafter deteriorated in the glibenclamide group (p < 0.005 for difference at year 4). Ratios of proinsulin to insulin were higher during treatment in glibenclamide- vs. insulin-treated patients after year 2. QL after 4 years as measured by the MOS 36-item Short-Form Health Survey (SF-36) form was not significantly altered. Conclusions: In a 4-year perspective, beta-cell function deteriorated in both groups. However, deterioration occurred faster in the glibenclamide group, indicating that alleviating demands on secretion by insulin treatment is beneficial.
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| 8. |
- Gustavsson, B., et al.
(författare)
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Electron gyroharmonic effects in ionization and electron acceleration during high-frequency pumping in the ionosphere
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:19, s. 195002-
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Tidskriftsartikel (refereegranskat)abstract
- Optical emissions and incoherent scatter radar data obtained during high-frequency electromagnetic pumping of the ionospheric plasma from the ground give data on electron energization in an energy range from 2 to 100 eV. Optical emissions at 4278 angstrom from N-2(+) that require electrons with energies above the 18 eV ionization energy give the first images ever of pump-induced ionization of the thermosphere. The intensity at 4278 angstrom is asymmetric around the ionospheric electron gyroharmonic, being stronger above the gyroresonance. This contrasts with emissions at 6300 angstrom from O(D-1) and of electron temperature enhancements, which have minima at the gyroharmonic but have no apparent asymmetry. This direct evidence of pump-induced ionization contradicts previous indirect evidence, which indicated that ionization is most efficiently produced when the pump frequency was below the gyroharmonic.
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| 9. |
- Herlitz, Johan, 1949, et al.
(författare)
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Post resuscitation care: what are the therapeutic alternatives and what do we know?
- 2006
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 69:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of deaths in the Western World are caused by ischaemic heart disease. Among these patients a majority die outside hospital due to sudden cardiac death. The prognosis among these patients is in general, poor. However, a significant proportion are admitted to a hospital ward alive. The proportion of patients who survive the hospital phase of an out of hospital cardiac arrest varies considerably. Several treatment strategies are applicable during the post resuscitation care phase, but the level of evidence is weak for most of them. Four treatments are recommended for selected patients based on relatively good clinical evidence: therapeutic hypothermia, beta-blockers, coronary artery bypass grafting, and an implantable cardioverter defibrillator. The patient's cerebral function might influence implementation of the latter two alternatives. There is some evidence for revascularisation treatment in patients with suspected myocardial infarction. On pathophysiological grounds, an early coronary angiogram is a reasonable alternative. Further randomised clinical trials of other post resuscitation therapies are essential.
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| 14. |
- Nazli, Aisha, et al.
(författare)
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Enterocyte cytoskeleton changes are crucial for enhanced translocation of nonpathogenic Escherichia coli across metabolically stressed gut epithelia
- 2006
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:1, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Substantial data implicate the commensal flora as triggers for the initiation of enteric inflammation or inflammatory disease relapse. We have shown that enteric epithelia under metabolic stress respond to non-pathogenic bacteria by increases in epithelial paracellular permeability and bacterial translocation. Here we assessed the structural basis of these findings. Confluent filter-grown monolayers of the human colonic T84 epithelial cell line were treated with 0.1 mM dinitrophenol (which uncouples oxidative phosphorylation) and noninvasive, nonpathogenic Escherichia coli (strain HB101, 106 CFU) with or without pretreatment with various pharmacological agents. At 24 h later, apoptosis, tight-junction protein expression, transepithelial resistance (TER, a marker of paracellular permeability), and bacterial internalization and translocation were assessed. Treatment with stabilizers of microtubules (i.e., colchicine), microfilaments (i.e., jasplakinolide) and clathrin-coated pit endocytosis (i.e., phenylarsine oxide) all failed to block DNP+E. coli HB101-induced reductions in TER but effectively prevented bacterial internalization and translocation. Neither the TER defect nor the enhanced bacterial translocations were a consequence of increased apoptosis. These data show that epithelial paracellular and transcellular (i.e., bacterial internalization) permeation pathways are controlled by different mechanisms. Thus, epithelia under metabolic stress increase their endocytotic activity that can result in a microtubule-, microfilament-dependent internalization and transcytosis of bacteria. We speculate that similar events in vivo would allow excess unprocessed antigen and bacteria into the mucosa and could evoke an inflammatory response by, for example, the activation of resident or recruited immune cells. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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| 15. |
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| 18. |
- Elmlund, Hans, et al.
(författare)
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The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:43, s. 15788-15793
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Tidskriftsartikel (refereegranskat)abstract
- CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II.
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| 19. |
- Frenneaux, M, et al.
(författare)
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Hemodynamics of cardiac arrest.
- 2007
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Ingår i: Cardiac arrest. The science and practice of resuscitation medicine. - 9780521847001 ; , s. 347-368
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Bokkapitel (refereegranskat)
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| 20. |
- Holst, Birgitte, et al.
(författare)
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G Protein-Coupled Receptor 39 Deficiency Is Associated with Pancreatic Islet Dysfunction
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150, s. 2577-2585
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptor (GPR)-39 is a seven-transmembrane receptor expressed mainly in endocrine and metabolic tissues that acts as a Zn++ sensor signaling mainly through the G(q) and G(12/13) pathways. The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1 alpha and HNF-4 alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. The expression and localization of GPR39 were characterized in the endocrine pancreas and pancreatic cell lines. Gpr39(-/-) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. Immunohistochemistry demonstrated that GRP39 is localized selectively in the insulin-storing cells of the pancreatic islets as well as in the duct cells of the exocrine pancreas. Gpr39(-/-) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1 alpha was reduced. Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. It is concluded that GPR39 is involved in the control of endocrine pancreatic function, and it is suggested that this receptor could be a novel potential target for the treatment of diabetes. (Endocrinology 150: 2577-2585, 2009)
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| 21. |
- Häggmark, Sören, et al.
(författare)
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ST-segment deviations during pacing-induced increased heart rate in patients without coronary artery disease.
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:4, s. 246-522
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In order to interpret ST-segment changes as an indicator of ischemia in patients with higher heart rates (HRs), the relation between ST-segment levels and HR needs to be well defined in subjects without coronary artery disease. METHODS: Eighteen patients with normal ECGs in the catheterization laboratory, after radiofrequency ablation of AV nodal re-entry tachycardia or an accessory pathway were included. Computerized online vectorcardiography (VCG) was performed during step-wise atrial pacing-induced increases in HR up to 150 beats min(-1) (bpm). The ST-vector magnitude (ST-VM) and the relative ST change vector magnitude (STC-VM) were analysed at the J point, J + 20 and J + 60 ms. RESULTS: There was no divergence in the course of ST-VM or STC-VM based on J point + 0, 20, or 60 ms during increasing HR. The STC-VM mean values increased progressively during increases in HR above 100 bpm, with an average increase in STC-VM of 15-20 microV per 10 bpm increases in HR. The ST-VM response during HR increases showed a heterogeneous and unpredictable pattern. CONCLUSION: The STC-VM increases linearly with rising HRs above 100 bpm. The STC-VM can exceed widely recognized ischemic thresholds during higher HRs in the absence of ischemia. The choice of J point time to ST-VM measurements as tested here is not important for the STC-VM relation to HR at these HR levels. Further clinical testing is needed to improve the diagnostic specificity of STC-VM measurements during increased HRs.
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| 22. |
- Hörnsten, Rolf, et al.
(författare)
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Outcome of heart rate variability and ventricular late potentials after liver transplantation for familial amyloidotic polyneuropathy
- 2008
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 15:3, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Reduced heart rate variability (HRV) is common in familial amyloidotic polyneuropathy (FAP), as well as cardiac arrhythmias. We examined the effects of liver transplantation (LTx) on 24-h HRV and ventricular late potentials. Twenty-one liver-transplanted FAP patients underwent Holter-ECG recordings and signal average electrocardiography recordings (SAECG) before and after LTx. Mean follow-up time after LTx was 21.7 months. Three patients had marked increased HRV after LTx, but this was in all cases caused by the development of subtle atrial arrhythmia and did not reflect an improvement in the cardiac autonomic control. In total, ten patients were excluded from analysis of HRV because of arrhythmia. Spectral analysis of HRV showed no significant differences before and after LTx in the remaining 11 patients. Positive late potentials were found in 33% of patients before LTx and this proportion was unchanged after LTx. Reduced HRV and positive late potentials are common in Swedish FAP patients, and remain stable, at least within the short term after transplantation. If an increase of HRV after transplantation is observed, it should raise the suspicion that the patient has developed subtle atrial arrhythmia.
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| 23. |
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| 26. |
- Kesek, Milos, et al.
(författare)
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U22, a protocol to quantify symptoms associated with supraventricular tachycardia.
- 2009
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Ingår i: Pacing and Clinical Electrophysiology. - : Wiley. - 0147-8389 .- 1540-8159. ; 32:S1, s. S105-S108
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The main indication for ablation of supraventricular tachyarrhythmias (SVTA) is symptomatic relief. Specific paroxysmal symptoms cannot be quantified with general measures of quality of life, such as with the SF-36 questionnaire. U22 is a new protocol which measures the effects of arrhythmia on well-being, the intensity of discomfort during an episode, the type and temporal characteristics of dominant symptoms, and the duration and frequency of episodes. Discrete 0-10 scales are used. Unlike SF-36, U22 can be used in individual patients. METHODS: U22 and SF-36 protocols were used in the symptomatic evaluation of 88 patients (mean age = 49.6 +/- 16.4 years; 43 men), who underwent catheter ablation of SVTA. Results: The U22 scores (SD) for (a) well-being (10 being best), (b) effects of arrhythmia on well-being (10 being worst), and (c) discomfort during arrhythmia (10 being worst) were 5.6 (2.7), 7.5 (2.8), and 8.0 (2.4), respectively. For comparison, the physical and mental component summaries of SF-36 were 45.3 (11.0) and 45.2 (12.1), respectively, slightly lower than the expected normal of 50. The intensity of dominant symptom scored by U22 was 9.7 (1.2), 10 being worst. In 29% of patients > or =4 symptoms were equally dominant. Multiple dominant symptoms in U22 were associated with a low general well-being in SF-36. CONCLUSION: We found U22 useful to quantify symptoms associated with SVTA.
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| 27. |
- Kjaergaard, Magnus, et al.
(författare)
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Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris.
- 2007
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 16:9
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Tidskriftsartikel (refereegranskat)abstract
- The cysteine-rich somatomedin B domain (SMB) of the matrix protein vitronectin is involved in several important biological processes. First, it stabilizes the active conformation of the plasminogen activator inhibitor (PAI-1); second, it provides the recognition motif for cell adhesion via the cognate integrins (alpha(v)beta(3), alpha(v)beta(5), and alpha(IIb)beta(3)); and third, it binds the complex between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR). Previous structural studies on SMB have used recombinant protein expressed in Escherichia coli or SMB released from plasma-derived vitronectin by CNBr cleavage. However, different disulfide patterns and three-dimensional structures for SMB were reported. In the present study, we have expressed recombinant human SMB by two different eukaryotic expression systems, Pichia pastoris and Drosophila melanogaster S2-cells, both yielding structurally and functionally homogeneous protein preparations. Importantly, the entire population of our purified, recombinant SMB has a solvent exposure, both as a free domain and in complex with PAI-1, which is indistinguishable from that of plasma-derived SMB as assessed by amide hydrogen ((1)H/(2)H) exchange. This solvent exposure was only reproduced by one of three synthetic SMB products with predefined disulfide connectivities corresponding to those published previously. Furthermore, this connectivity was also the only one to yield a folded and functional domain. The NMR structure was determined for free SMB produced by Pichia and is largely consistent with that solved by X-ray crystallography for SMB in complex with PAI-1.
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| 28. |
- Langhelle, A., et al.
(författare)
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Recommended guidelines for reviewing, reporting, and conducting research on post-resuscitation care: the Utstein style
- 2005
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 66:3, s. 271-83
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this report is to establish recommendations for reviewing, reporting, and conducting research during the post-resuscitation period in hospital. It defines data that are needed for research and more specialised registries and therefore supplements the recently updated Utstein template for resuscitation registries. The updated Utstein template and the out-of-hospital "Chain of Survival" describe factors of importance for successful resuscitation up until return of spontaneous circulation (ROSC). Several factors in the in-hospital phase after ROSC are also likely to affect the ultimate outcome of the patient. Large differences in survival to hospital discharge for patients admitted alive are reported between hospitals. Therapeutic hypothermia has been demonstrated to improve the outcome, and other factors such as blood glucose, haemodynamics, ventilatory support, etc., might also influence the result. No generally accepted, scientifically based protocol exists for the post-resuscitation period in hospital, other than general brain-oriented intensive care. There is little published information on this in-hospital phase. This statement is the result of a scientific consensus development process started as a symposium by a task force at the Utstein Abbey, Norway, in September 2003. Suggested data are defined as core and supplementary and include the following categories: pre-arrest co-morbidity and functional status, cause of death, patients' quality of life, in-hospital system factors, investigations and treatment, and physiological data at various time points during the first three days after admission. It is hoped that the publication of these recommendations will encourage research into the in-hospital post-resuscitation phase, which we propose should be included in the chain-of-survival as a fifth ring. Following these recommendations should enable better understanding of the impact of different in-hospital treatment strategies on outcome.
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| 29. |
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| 30. |
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| 31. |
- Rönn, Folke, et al.
(författare)
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Long-term follow-up of patients treated with ICD : benefit in patients with preserved left ventricular function.
- 2008
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 42:2, s. 125-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Most major defibrillator trials have short follow-up and may neither capture the benefit for those with preserved function nor the progressive nature of advanced heart disease. We intended to investigate the long-term outcome in an unselected population of patients treated with ICD. DESIGN: We followed 124 consecutive patients that received an ICD during 1993-2002 at our institution for a median of 6.1 years. Information about heart disease, index arrhythmia, follow-up and death was extracted from medical records. RESULTS: The crude mortality was 26% (32/124). One- and two-year mortality was 6% and 12%, estimated 5- and 10-year mortality 20% and 33%. The cause of death was heart failure in 75% of deaths. The ejection fraction was below 35% in 91% of the 32 patients who died. We estimated that 28% of the patients received lifesaving therapy. The relative number of saved lives and complications was not related to the ejection fraction. CONCLUSION: Patients with preserved left ventricular function are excellent candidates for ICD, with life-saving ICD therapies in a substantial proportion, low mortality and good quality of life.
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| 32. |
- Steen, Bengt, 1944, et al.
(författare)
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Development of interpretation keys for environmental product declarations
- 2008
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 16:5, s. 598-604
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Tidskriftsartikel (refereegranskat)abstract
- Certified environmental product declarations (EPD) are beginning to be used in several countries. To date, user experience indicates that the EPD results are difficult for professional purchasers and salespeople to understand. In order to improve understanding, three interpretation keys have been developed. They recalculate the EPD results to other numbers, which are easier to value. One key calculates the degree of satisfaction of environmental goals, another calculates the damage cost and yet another compares with what is normal in economic activity. The three interpretation keys represent different ethical views of the environment. Intended users, people having some knowledge of environmental issues without being specialists, have tested the keys on several occasions after which the keys were redesigned. We concluded that the interpretation keys offer increased understanding. (c) 2007 Elsevier Ltd. All rights reserved.
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| 33. |
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| 34. |
- Trobos, Margarita, 1980, et al.
(författare)
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Characterization of sulphonamide-resistant Escherichia coli using comparison of sul2 gene sequences and multilocus sequence typing.
- 2009
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Ingår i: Microbiology (Reading, England). - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 155:Pt 3, s. 831-836
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Tidskriftsartikel (refereegranskat)abstract
- The sul2 gene encodes sulphonamide resistance (Sul(R)) and is commonly found in Escherichia coli from different hosts. We typed E. coli isolates by multilocus sequence typing (MLST) and compared the results to sequence variation of sul2, in order to investigate the relation to host origin of pathogenic and commensal E. coli strains and to investigate whether transfer of sul2 into different genomic lineages has happened multiple times. Sixty-eight E. coli isolated in Denmark and Norway from different hosts and years were MLST typed and sul2 PCR products were sequenced and compared. PFGE was performed in a subset of isolates. All isolates were divided into 45 different sequence types (STs), with clonal complexes CC10, CC23, CC168, CC350 and CC69 being the most frequent. The sul2 gene from the majority of E. coli strains had only two point mutations, at positions 159 and 197, leading to a synonymous and a non-synonymous change, respectively. Five strains had extra single mutations. All poultry, poultry meat, and Danish human blood isolates had the same sul2 ST and some of these strains clustered under the same MLST STs, indicating that they shared habitats. Most PFGE profiles clustered according to source, but some included different sources. Sul(R) E. coli from different animals, food, human faeces and infections did not cluster according to their origin, suggesting that these habitats share E. coli and sul2 gene types. However, while pig isolates on one occasion clustered with urinary tract infection isolates, poultry isolates seemed more related to isolates from bloodstream infections in humans. Presence of mainly two types of the sul2 gene in both human and animal isolates, irrespective of date and geography, and the presence of both types in the same clonal lineages, suggest horizontal transfer of sul2.
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| 35. |
- Wallentin, Lars, 1943-, et al.
(författare)
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Ticagrelor versus clopidogrel in patients with acute coronary syndromes
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 361:11, s. 1045-1057
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel. METHODS: In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. RESULTS: At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types. CONCLUSIONS: In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding.
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| 36. |
- Wierup, P, et al.
(författare)
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Ex vivo evaluation of nonacceptable donor lungs
- 2006
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:2, s. 460-466
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Tidskriftsartikel (refereegranskat)abstract
- Background. Only a minority of the potential candidates for lung donation are considered suitable, using current evaluation methods. A new method for ex vivo evaluation, with the potential for reconditioning of marginal and nonacceptable lungs, has been developed. This is a report of the ex vivo evaluation of six donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by the Scandiatransplant, Eurotransplant, and UK transplant organizations. Methods. The lungs are perfused ex vivo with Steen solution, a lung evaluation-preservation solution, mixed with red blood cells to a hematocrit of 15%. This extracellular solution is designed to have an optimal colloid osmotic pressure so that physiologic pressure and flow can be maintained without development of pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains a normal mixed venous blood gas level in the perfusate. The lungs are ventilated and evaluated through analyses of pulmonary vascular resistance, oxygenation capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide difference. Results. The arterial oxygen pressure (inspired oxygen fraction, 1.0) increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation. The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in the range of 1 to 2.5 kPa. Conclusions. The arterial oxygen pressure improves significantly in this model. This ex vivo evaluation model is a valuable addition to the armamentarium in finding acceptable lungs in a donor population with inferior arterial oxygen pressure values.
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| 37. |
- Wierup, Per, et al.
(författare)
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Moderate mitral regurgitation in patients undergoing CABG--the MoMIC trial.
- 2009
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Ingår i: Scandinavian cardiovascular journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 43:1, s. 50-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The presence of mild to moderate ischemic mitral regurgitation (IMR) marks a significantly reduced long-term survival and increased hospitalizations due to heart-failure. However, it is common practice in many institutions to refrain from repairing the mitral valve in these patients. There are no available conclusive data to support this practice, and thus there is a need for an adequately powered randomized trial. STUDY DESIGN: The Moderate Mitral Regurgitation In Patients Undergoing CABG (MoMIC) trial is the first international multi-center, large-scale study to clarify whether moderate IMR in CABG patients should be corrected. A total of 550 CABG patients with moderate IMR are to be randomized to treatment of either CABG alone or CABG plus mitral valve correction. The primary end point is a composite end point of mortality and rehospitalization for heart failure at five years. The inclusion and randomization of patients started in February 2008. IMPLICATION: If correction of moderate IMR in CABG patients proves to be the superior strategy, most patients should be treated accordingly.
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| 38. |
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| 39. |
- Winbo, Annika, 1978-, et al.
(författare)
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Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population
- 2009
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Ingår i: Circulation. - Philadelphia, PA : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 2:6, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- Background: A 10% cumulative incidence and a 0.3% per year incidence rate of sudden cardiac death in patients younger than 40 years and without therapy have been reported in type 1 long-QT syndrome. The Y111C-KCNQ1 mutation causes a severe phenotype in vitro, suggesting a high-risk mutation. This study investigated the phenotype among Y111C-KCNQ1 mutation carriers in the Swedish population with a focus on life-threatening cardiac events.Methods and Results: We identified 80 mutation carriers in 15 index families, segregating the Y111C-KCNQ1 mutation during a national inventory of mutations causing the long-QT syndrome. Twenty-four mutation carriers <40 years experienced syncope (30%). One mutation carrier had an aborted cardiac arrest (1.25%). No case of sudden cardiac death was reported during a mean nonmedicated follow-up of 25±20 years. This corresponds to a low incidence rate of life-threatening cardiac events (0.05%/year versus 0.3%/year, P=0.025). In 8 Y111C families connected by a common ancestor, the natural history of the mutation was assessed by investigating the survival over the age of 40 years for 107 nonmedicated ascertained mutation carriers (n=24) and family members (n=83) born between 1873 and 1968. In total, 4 deaths in individuals younger than 40 years were noted: 1 case of noncardiac death and 3 infant deaths between 1873 and 1915.Conclusions: The dominant-negative Y111C-KCNQ1 mutation, associated with a severe phenotype in vitro, presents with a low incidence of life-threatening cardiac events in a Swedish population. This finding of discrepancy emphasizes the importance of clinical observations in the risk stratification of long-QT syndrome.
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- Zhu, Xuefeng, et al.
(författare)
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Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions
- 2006
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 22:2, s. 169-178
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Tidskriftsartikel (refereegranskat)abstract
- Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use chromatin immunoprecipitation (ChIP) and DNA microarrays to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator occupancy in the coding region. We propose that Mediator coordinates transcription initiation with transcriptional events in the coding region of eukaryotic genes.
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