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Sökning: WFRF:(Jacobson Stefan H.) > (2010-2014)

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1.
  • Olsson, Jenny, et al. (författare)
  • Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation : A potential cause of neutrophil dysfunction in chronic kidney disease
  • 2011
  • Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:7, s. 2195-2201
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Neutrophils from patients with chronic kidney disease (CKD) are dysfunctional and thus a contributing factor to the risk of infections. The mechanisms for leucocyte dysfunction in CKD are not fully understood. It is known that lipopolysaccharide (LPS) activates transcription of several genes encoding proinflammatory cytokines. We therefore aimed to study the effect of LPS on neutrophil expression of genes related to the inflammatory response to address the hypothesis that LPS-induced gene transcriptions are altered in CKD patients.Methods. We analysed gene expression of LPS-stimulated neutrophils from 30 patients with CKD and 15 healthy controls. Superoxide dismutase-2 (SOD2), IL1A, IL-1R1, IL-1R2 and IL8RA gene expression from both neutrophils and differentiated HL60 cells were measured by quantitative polymerase chain reaction. Differentiated HL60 cells were stimulated with phorbol-12-myristate-7- acetate (PMA) after inhibition of SOD2 by small interfering RNA followed by respiratory burst assessment using flow cytometry.Results. LPS stimulation induced a significant mobilization of CD11b on neutrophils from CKD and healthy controls. Upregulation of SOD2, IL1A, IL-1R1 and IL-1R2 gene expression in neutrophils from healthy controls after LPS stimulation was contrasted by no change in gene transcription (IL-1R1 and IL-1R2) or even a downregulation in patients with CKD (SOD2 and IL1A). Inhibition of SOD2 reduced the PMA-induced respiratory burst and IL1A, IL-1R1, IL-1R2 and IL8RA gene expression in neutrophil-differentiated HL60 cells.Conclusions. Because of the critical role of SOD2 in the generation of hydrogen peroxide during phagocytosis, downregulation of SOD2 gene expression after LPS stimulation in neutrophils from patients with CKD indicates a potential mechanism for neutrophil dysfunction and cytokine dysregulation in these patients.
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2.
  • Aljadi, Zenib, et al. (författare)
  • Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis
  • 2014
  • Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 38:11, s. 945-953
  • Tidskriftsartikel (refereegranskat)abstract
    • The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood-membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fc epsilon receptor I (Fc epsilon RI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-Fc epsilon RI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.
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3.
  • Axelsson, Lena, et al. (författare)
  • Living with haemodialysis when nearing end of life
  • 2012
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 26:1, s. 45-52
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS AND OBJECTIVES: The aim of this study was to describe and to elucidate the meanings of being severely ill living with haemodialysis when nearing end of life.INTRODUCTION: To have end stage renal disease and to be treated with maintenance haemodialysis implies being dependent on lifelong treatment. Several studies have reported that these patients suffer a high symptom burden and an impaired quality of life due to both disease and treatment. In the dialysis unit, where the focus is on handling technology and maintaining life, end of life care may be neglected or overlooked. Nevertheless, mortality rates show that about one-fourth of patients in haemodialysis care are in their last year of life.DESIGN: A qualitative interpretative design was used.METHODS: Serial qualitative interviews over a period of 12 months were conducted with eight patients (aged 66-87). Altogether text of 31 interviews was interpreted using a phenomenological hermeneutical method in three phases. The study is ethically approved.FINDINGS: The structural analysis resulted in 11 subthemes and thereafter the following three themes were formulated; being subordinate to the deteriorating body, changing outlook on life and striving for upheld dignity. The comprehensive interpretation revealed that being severely ill living with haemodialysis near the end of life means living with suffering simultaneously with reconciliation and well-being. Further, the meanings are understood as intertwined with being old.CONCLUSIONS: Findings contribute to an increased awareness of the complexities of these patients' life worlds and their meanings, and thus of the importance to listen to their experiences and their understandings. Findings suggest that to integrate the philosophy of palliative care in haemodialysis units may improve care for patients who are living with haemodialysis and approaching the end of their lives.
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4.
  • Axelsson, Lena, et al. (författare)
  • Thoughts on death and dying when living with haemodialysis approaching end of life
  • 2012
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 21:15-16, s. 2149-59
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS AND OBJECTIVES: To describe inner thoughts and feelings relating to death and dying when living with haemodialysis approaching end of life.BACKGROUND: Patients who undergo maintenance haemodialysis suffer a significant symptom burden and an impaired quality of life. The high mortality rate in these patients indicates that about one-fourth of them are in their last year of life, suggesting the presence of death and dying in the haemodialysis unit.DESIGN: A qualitative descriptive design was used. Methods.  A total of 31 qualitative interviews were conducted with eight patients (aged 66-87) over a period of 12 months. Qualitative content analysis was used to analyse data.RESULTS: The analysis revealed 10 subthemes that were sorted into three main themes. Being aware that death may be near comprises being reminded of death and dying by the deteriorating body, by the worsening conditions and deaths of fellow patients, and by knowing haemodialysis treatment as a border to death. Adapting to approaching death comprises looking upon death as natural, preparing to face death, hoping for a quick death and repressing thoughts of death and dying. Being alone with existential thoughts comprises a wish to avoid burdening family, lack of communication with healthcare professionals and reflections on haemodialysis withdrawal as an hypothetic option.CONCLUSIONS: Living with haemodialysis approaching, the end of life involves significant and complex existential issues and suffering, and patients are often alone with their existential thoughts.RELEVANCE TO CLINICAL PRACTICE: Nurses and other healthcare professionals in haemodialysis settings need to combine technical and medical abilities with committed listening and communication skills and be open to talking about death and dying, with sensitivity to individual and changeable needs.
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5.
  • Carrero, Juan Jesus, et al. (författare)
  • Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation
  • 2014
  • Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:9, s. 919-928
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24 317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m(2) [eGFR(<60)]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR(>30-60): event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR(>15-30): event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR(<= 15): event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR(>30-60) event rate, 6.8 forwarfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR(>15-30) event rate, 9.3 forwarfarin vs 10.4 for nowarfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR(<= 15) event rate, 9.1 forwarfarin vs 13.5 for nowarfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR(>60) event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR(>30-60) event rate, 53.6 forwarfarin vs 69.0 for nowarfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR(>15-30) event rate, 90.2 forwarfarin vs 117.7 for nowarfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR(<= 15) event rate, 86.2 forwarfarin vs 138.2 for nowarfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.
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6.
  • Fernström, Anders, et al. (författare)
  • Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol : An observational study
  • 2011
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:3, s. 196-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. Material and methods. This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. Results. Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of > 300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of > 300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (--45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium xx phosphorus product remained unchanged. Conclusions. This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150--300 pg/ml) and had minimal impact on serum minerals.
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7.
  • Jonasson, Mats, 1969-, et al. (författare)
  • Utilization of Actuators to Improve Vehicle Stability at the Limit : From Hydraulic Brakes Toward Electric Propulsion
  • 2011
  • Ingår i: Journal of Dynamic Systems Measurement, and Control. - : ASME. - 0022-0434 .- 1528-9028. ; 133:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The capability of over-actuated vehicles to maintain stability during limit handling is studied in this paper. A number of important differently actuated vehicles, equipped with hydraulic brakes toward more advanced chassis solutions, are presented. A virtual evaluation environment has specifically been developed to cover the complex interaction between the driver and the vehicle under control. In order to fully exploit the different actuators setup, and the hard nonconvex constraints they possess, the principle of control allocation by nonlinear optimization is successfully employed. The final evaluation is made by exposing the driver and the over-actuated vehicles to a safety-critical double lane change. Thereby, the differently actuated vehicles are ranked by a quantitative indicator of stability.
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8.
  • Szummer, Karolina, et al. (författare)
  • Association between statin treatment and outcome in relation to renal function in survivors of myocardial infarction
  • 2011
  • Ingår i: KIDNEY INTERNATIONAL. - : Nature Publishing Group. - 0085-2538 .- 1523-1755. ; 79:9, s. 997-1004
  • Tidskriftsartikel (refereegranskat)abstract
    • As statins are recommended at discharge to all patients following myocardial infarction (MI), we studied their use and efficacy in renal disease by analyzing the data, in the nationwide SWEDEHEART registry, of 42,814 consecutive survivors of MI with available creatinine/dialysis data but without statin therapy on admission. The estimated glomerular filtration rate (eGFR) was determined by the Modification of Diet in Renal Disease Study formula and the patients classified into the five traditional stages of kidney disease. The 1-year survival in relation to prescription of statin at discharge was assessed in a Cox regression analysis adjusted by a propensity score that described each individuals likelihood of being treated with a statin, established by 36 baseline characteristics and in-hospital therapies. Statin use at discharge decreased with increased renal impairment from 81% in eGFR stage 1 to 31% in eGFR stage 5. After adjusting for the propensity score and discharge medication, statin use was associated with a significant reduction in overall risk of death (hazard ratio 0.63), with a statistically significant interaction between statin therapy and the stage of renal function. Thus, statin use at discharge was associated with improved 1-year survival of patients in stages 2-4 (mild-to-severe) of renal insufficiency. This effect appears attenuated in those with stage 5 renal failure.
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9.
  • Szummer, Karolina, et al. (författare)
  • Cockcroft-Gault is better than the Modification of Diet in Renal Disease study formula at predicting outcome after a myocardial infarction : Data from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)
  • 2010
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:6, s. 979-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim was to examine whether the Modification of Diet in Renal Disease (MDRD) or the Cockcroft-Gault (CG) formula is better at predicting prognosis in myocardial infarction (MI) patients. Methods All consecutive MI patients entered in a nationwide registry between 2003 and 2006 with glomerular filtration rate (eGFR) estimated by both the MDRD and CG formula (N = 36,137) were analyzed. Results Cockcroft-Gault classified a larger proportion of patients as having at least a moderate (39.8% vs 31.1%, P<.001) or at least a severe renal dysfunction (7.6% vs 4.4%, P<.001) compared with the MDRD. The largest difference between the estimations was seen when patients were divided according to gender, age, and weight, where CG estimated a lower eGFR in women, the elderly, and those with low body weight. In a receiver operating characteristic analysis, CG had a stronger association to 1-year mortality (area under the curve 0.78, 95% CI 0.77-0.79) than MDRD (area under the curve 0.73, 95% CI 0.72-0.74). Within each renal function stage classified with the MDRD, there were patients identified with the CG as having both a worse renal function and a higher mortality. After multivariable adjustment, CG predicted 1-year mortality better than the MDRD (renal failure vs normal renal function: hazard ratio 3.00, 95% CI 2.42-3.71 with the CG; hazard ratio 2.56, 95% CI 2.10-3.11 with the MDRD). Conclusion Cockcroft-Gault is better than the MDRD equation at predicting mortality after a MI. This is mainly explained by differences in the coefficients and variables included in the eGFR equations, and less to differences in various subgroups of patients.
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10.
  • Tuyet Vuong, Mai, et al. (författare)
  • Genetic evidence for involvement of adaptive immunity in the development of IgA nephropathy: MHC class II alleles are protective in a Caucasian population
  • 2013
  • Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 74:8, s. 957-960
  • Tidskriftsartikel (refereegranskat)abstract
    • There is evidence suggesting that IgA nephropathy (IgAN) is an immunological disease. The role of FILA class II DR beta 1 (DRB1) has previously not been well studied. The aim of our study was to investigate the association of HLA-DRB1 variants with IgAN in a Swedish Caucasian cohort. Our study consisted of 213 patients with biopsy proven IgAN, all of self-reported Caucasian ancestry. As a control cohort, 1569 healthy subjects from the same population in Sweden were included. HLA-DRB1 low-resolution genotyping was performed and odds ratios were calculated to assess the risk. less thanbrgreater than less thanbrgreater thanIn an allelic model the HLA-DRB1*03 and *10, demonstrated association for IgAN after correction for multiple comparison, with subsequent OR = 0.54 (95% CI 0.37-0.78) and 3.44 (95% Cl 1.67-7.07). When the influence of risk allelic groups was adjusted for protective allelic groups and vice versa, only a protective effect of HLA-DRB1*03 remained significant. less thanbrgreater than less thanbrgreater thanIn conclusion, the variants of HLA-DRB1 were associated with IgAN of which the HLA-DRB1*03 revealed a strong protective effect for IgAN. Our data replicates finding from other Caucasian populations and suggest that involvement of adaptive immunity may be of importance in the development of the disease.
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