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  • 251.
    Ajanovic, Dina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology. Linköping University, Faculty of Health Sciences.
    Korjenic, Dalida
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology. Linköping University, Faculty of Health Sciences.
    Utarbetning av språkpillerböcker skrivna på bosniska/kroatiska/serbiska för barn med BKS som modersmål: En kontrastiv grammatisk analys2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Projektet ”Språkpiller” har utformats genom ett samarbete mellan logopeder och biblioteken i Östergötland. Projektet syftar till att stimulera språket hos barn med språkstörning och fungerar i första hand som ett komplement till logopedisk behandling (Linköpings kommun, 2012).

    Föreliggande studie syftar till att undersöka om bilderböcker skrivna på bosniska/kroatiska/serbiska (BKS) tränar samma grammatiska struktur som motsvarande bilderböcker på svenska gör. Syftet är även att granska huruvida böckerna i föreliggande studie går att rekommendera som träningsmaterial för barn med språkliga svårigheter.

    En kontrastiv analys mellan BKS och svenska har genomförts av totalt tre bilderböcker. Böckerna i studien innehåller skillnader mellan BKS och svenska inom de flesta grammatiska kategorier och stämmer väl överrens med vad som beskrivits i litteraturen. Det föreliggande materialet antas därför kunna användas som träningsmaterial till vissa grammatiska strukturer.

  • 252. Ajari, A
    et al.
    Bergqvist, D
    Elfström, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery.
    Örtenvall, P
    Troeng, T
    Hedberg, B
    Ljungström, KG
    Norgren, L
    Diabetes mellitus as a risk factor for early outcome after carotid endarterectomy - a population study.1999In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, Vol. 18, 122-126 p.Article in journal (Refereed)
  • 253.
    Akanda, Nesar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.

  • 254.
    Akanda, Nesar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Biophysical properties of the apoptosis-inducing plasma membrane voltage-dependent anion channel2006In: Biophysical Journal, ISSN 0006-3495, Vol. 90, no 12, 4405-4417 p.Article in journal (Refereed)
    Abstract [en]

    Ion channels in the plasma membrane play critical roles in apoptosis. In a recent study we found that a voltage-dependent anion channel in the plasma membrane (VDACpl) of neuronal hippocampal cell line (HT22) cells was activated during apoptosis and that channel block prevented apoptosis. Whether or not VDACpl is identical to the mitochondrial VDACmt has been debated. Here, we biophysically characterize the apoptosis-inducing VDACpl and compare it with other reports of VDACpls and VDACmt. Excised membrane patches of apoptotic HT22 cells were studied with the patch-clamp technique. VDACpl has a large main-conductance state (400 pS) and occasionally subconductance states of µ28 pS and 220 pS. The small subconductance state is associated with long-lived inactivated states, and the large subconductance state is associated with excision of the membrane patch and subsequent activation of the channel. The open-probability curve is bell shaped with its peak around 0mV and is blocked by 30µM Gd3+. The gating can be described by a symmetrical seven-state model with one open state and six closed or inactivated states. These channel properties are similar to those of VDACmt and other VDACpls and are discussed in relation to apoptosis.

  • 255.
    Akanda, Nesar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Tofighi, Roshan
    Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden .
    Brask, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Tamm, Christoffer
    Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden .
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ceccatelli, Sandra
    Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden .
    Voltage-dependent anion channels (VDAC) in the plasma membrane play a critical role in apoptosis in differentiated hippocampal neurons but not in neural stem cells2008In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 7, no 20, 3225-3234 p.Article in journal (Refereed)
    Abstract [en]

    microRNAs (miRNAs) are small non-coding RNAs that regulate a large variety of cellular processes including differentiation, apoptosis and proliferation. Several miRNAs display defective expression patterns in human tumors with the consequent alteration of target oncogene or tumor suppressor genes. Many of these miRNAs modulate the major proliferation pathways through direct interaction with critical regulators such as RAS, PI3K/PTEN or ABL, as well as members of the retinoblastoma pathway, Cyclin-CDK complexes or cell cycle inhibitors of the INK4 or Cip/Kip families. A complex interplay between miRNAs and MYC or E2F family members also exists to modulate cell cycle-dependent transcription during normal or tumoral proliferation. The ability of miRNAs to modulate these proliferation pathways may have relevant implications not only in physiological or developmental processes but also in tumor progression or cancer therapy.

  • 256.
    Akcan, Derya
    et al.
    Swedish Council Health Technology Assessment SBU, Sweden .
    Axelsson, Susanna
    Swedish Council Health Technology Assessment SBU, Sweden .
    Bergh, Christina
    Gothenburg University, Sweden Sahlgrens University Hospital, Sweden .
    Davidson, Thomas
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Rosen, Mans
    Swedish Council Health Technology Assessment SBU, Sweden Karolinska Institute, Sweden .
    Methodological quality in clinical trials and bibliometric indicators: no evidence of correlations2013In: Scientometrics, ISSN 0138-9130, E-ISSN 1588-2861, Vol. 96, no 1, 297-303 p.Article in journal (Refereed)
    Abstract [en]

    Citation frequencies and journal impact factors (JIFs) are being used more and more to assess the quality of research and allocate research resources. If these bibliometric indicators are not an adequate predictor of research quality, there could be severe negative consequences for research. To analyse to which extent citation frequencies and journal impact factors correlate with the methodological quality of clinical research articles included in an SBU systematic review of antibiotic prophylaxis in surgery. All 212 eligible original articles were extracted from the SBU systematic review "Antibiotic Prophylaxis in Surgery" and categorized according to their methodological rigourness as high, moderate or low quality articles. Median of citation frequencies and JIFs were compared between the methodological quality groups using Kruskal-Wallis non-parametric test. An in-depth study of low-quality studies with higher citation frequencies/JIFs was also conducted. No significant differences were found in median citation frequencies (p = 0.453) or JIFs (p = 0.185) between the three quality groups. Studies that had high citation frequencies/JIFs but were assessed as low-quality lacked control groups, had high dropout rates or low internal validity. This study of antibiotic prophylaxis in surgery does not support the hypothesis that bibliometric indicators are a valid instrument for assessing methodological quality in clinical trials. This is a worrying observation, since bibliometric indicators have a major influence on research funding. However, further studies in other areas are needed.

  • 257.
    Akefeldt, Selma O
    et al.
    Karolinska University Hospital Solna, Sweden .
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Gavhed, Desiree
    Karolinska University Hospital Solna, Sweden .
    Henter, Jan-Inge
    Karolinska University Hospital Solna, Sweden .
    Langerhans cell histiocytosis in children born 1982-2005 after in vitro fertilization2012In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 101, no 11, 1151-1155 p.Article in journal (Refereed)
    Abstract [en]

    Aim: In a recent Swedish study, comparing data from the Swedish Cancer Register with the Medical Birth Register including data on IVF, an increased risk of Langerhans cell histiocytosis (LCH) was found in children born 19822005 after IVF. Here, we aimed to verify the LCH diagnoses and examine whether any special forms of the disease were overrepresented in this population. Methods: Medical records for all children with LCH conceived by IVF were acquired and the diagnosis confirmed or discarded. Disease characteristics were compared with data from children diagnosed with LCH 19922001 in the Stockholm County. Results: We verified LCH in seven children born after IVF, all born prior to 2002. These children did not have milder disease forms. The odds ratio (OR) to develop LCH for the whole group born after IVF was 3.2 [95% confidence interval (CI), 1.47.3] and for children born before 2002, 5.2 [95% CI, 2.311.9], compared with children in Stockholm County 19922001. Conclusion: LCH was overrepresented in children born after IVF prior to 2002. Affected children did not have milder disease forms. These findings may be valuable to understand LCH aetiology. Additional studies on a putative correlation between IVF and LCH in the offspring are encouraged.

  • 258.
    Akerblom, Axel
    et al.
    University Uppsala Hospital.
    James, Stefan K
    University Uppsala Hospital.
    Koutouzis, Michael
    Sahlgrens University Hospital.
    Lagerqvist, Bo
    University Uppsala Hospital.
    Stenestrand, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Svennblad, Bodil
    University Uppsala Hospital.
    Oldgren, Jonas
    University Uppsala Hospital.
    Eptifibatide is Non-inferior to Abciximab in Acute Coronary Syndromes: Results From the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) in CIRCULATION, vol 120, issue 18, pp S1027-S10272009In: CIRCULATION, 2009, Vol. 120, no 18, S1027-S1027 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 259.
    Akerblom, Axel
    et al.
    Uppsala University.
    James, Stefan K
    Uppsala University.
    Koutouzis, Michail
    Sahlgrens University Hospital.
    Lagerqvist, Bo
    Uppsala University.
    Stenestrand, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Svennblad, Bodil
    Uppsala University.
    Eptifibatide Is Noninferior to Abciximab in Primary Percutaneous Coronary Intervention Results From the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)2010In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, ISSN 0735-1097, Vol. 56, no 6, 470-475 p.Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to test the noninferiority of eptifibatide relative to abciximab in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Background Glycoprotein IIb/IIIa inhibitors are recommended by international guidelines in patients with acute coronary syndromes undergoing PCI. Abciximab is recommended with a higher level of evidence than eptifibatide in patients with STEMI. No large, prospective, randomized trial comparing abciximab and eptifibatide has been published. Methods All (n = 11,479) STEMI patients in Sweden who underwent primary PCI and received either eptifibatide or abciximab from 2004 to 2007 were derived from the SCAAR ( Swedish Coronary Angiography and Angioplasty Registry). The primary end point was death or myocardial infarction (MI) during 1-year follow-up, with adjustment for baseline differences with a multivariate logistic regression analysis including propensity score. The pre-specified noninferiority margin was set to 1.29. Results The combined end point occurred in 353 of 2,355 patients (15.0%) treated with eptifibatide and in 1,432 of 9,124 patients (15.7%) treated with abciximab. The unadjusted odds ratio ( OR) for eptifibatide versus abciximab was 0.95 (95% confidence interval [CI]: 0.84 to 1.08). Multivariate adjustment (n = 11,317) confirmed noninferiority, with an OR of 0.94 ( 95% CI: 0.82 to 1.09). The adjusted secondary end points of death and MI separately also showed noninferiority, with ORs of 0.99 ( 95% CI: 0.82 to 1.19) and 0.88 ( 95% CI: 0.73 to 1.05), respectively. Conclusions This large registry study suggests that eptifibatide is noninferior to abciximab in patients with STEMI undergoing primary PCI with respect to death or MI during 1 year, thereby supporting the use of either drug in clinical practice.

  • 260.
    Akerblom, H.K.
    et al.
    Åkerblom, H.K., Biomedicum Helsinki Institute, B.P. 700, Haartmaninkatu 8, FIN-00029 HUS, Finland, Department of Pediatrics, University of Helsinki.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Hyoty, H.
    Hyöty, H., Department of Virology, University of Tampere, Finland.
    Ilonen, J.
    Institute of Microbiology and Pathology, University of Turku.
    Knip, M.
    Department of Pediatrics, University of Helsinki.
    Environmental factors in the etiology of type 1 diabetes2002In: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 115, no 1, 18-29 p.Article, review/survey (Refereed)
    Abstract [en]

    Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes. © 2002 Wiley-Liss, Inc.

  • 261.
    Akerstedt, Anita
    et al.
    Child and Youth Habilitat, Eksjo, Sweden .
    Risto, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Ödman, Pia
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Public Health Sciences.
    Evaluation of single event multilevel surgery and rehabilitation in children and youth with cerebral palsy - A 2-year follow-up study2010In: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 32, no 7, 530-539 p.Article in journal (Refereed)
    Abstract [en]

    Method. A prospective single-subject study with AB design and 2-year follow-up, included 11 children between 8 and 18 years old with CP, Gross Motor Function Classification System I-III. Visual analyses were used to present physical function with Physical Cost Index (PCI). Descriptive statistics were used to present number of children with a clinically important change in Gross Motor Function Measure (GMFM), self-reported walking ability, and HRQOL with child health questionnaire (CHQ). Results. PCI showed a trend of lower energy cost during gait in six children and GMFM was unchanged for 10 children and improved for one child. Walking ability was improved in 10 children. Gait distance increased in all 11. Both physical and psychosocial dimensions of CHQ improved in six of nine (two missing data). Expectations of outcomes were fulfilled in seven and partly fulfilled in four. Satisfaction with care was fulfilled in 10 of 11. Conclusion. Self-reported walking ability improved after multilevel surgery and intensive rehabilitation. This result was partly supported by lower energy cost and improved HRQOL. Expectations and satisfaction were fulfilled for the majority of children.

  • 262.
    Akesson, K.
    et al.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Tompa, A.
    Jonköping University, Sweden; Jonköping University, Sweden.
    Ryden, A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Novo Nordisk Inc, WA USA.
    Faresjo, M.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Low expression of CD39(+)/CD45RA(+) on regulatory T cells (T-reg) cells in type 1 diabetic children in contrast to high expression of CD101(+)/CD129(+) on T-reg cells in children with coeliac disease2015In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 180, no 1, 70-82 p.Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) and coeliac disease are both characterized by an autoimmune feature. As T1D and coeliac disease share the same risk genes, patients risk subsequently developing the other disease. This study aimed to investigate the expression of T helper (Th), T cytotoxic (Tc) and regulatory T cells (T-reg) in T1D and/or coeliac disease children in comparison to healthy children. Subgroups of T cells (Th:CD4(+) or Tc:CD8(+)); naive (CD27(+)CD28(+)CD45RA(+)CCR7(+)), central memory (CD27(+)CD28(+)CD45RA(-)CCR7(+)), effector memory (early differentiated; CD27(+)CD28(+)CD45RA(-)CCR7(-) and late differentiated; CD27(-)CD28(-)CD45RA(-)CCR7(-)), terminally differentiated effector cells (TEMRA; CD27(-)CD28(-)CD45RA(+)CCR7(-)) and T-reg (CD4(+)CD25(+)FOXP3(+)CD127(-)) cells, and their expression of CD39, CD45RA, CD101 and CD129, were studied by flow cytometry in T1D and/or coeliac disease children or without any of these diseases (reference group). Children diagnosed with both T1D and coeliac disease showed a higher percentage of TEMRA CD4(+) cells (Pless than005), but lower percentages of both early and late effector memory CD8(+) cells (Pless than005) compared to references. Children with exclusively T1D had lower median fluorescence intensity (MFI) of forkhead box protein 3 (FoxP3) (Pless than005) and also a lower percentage of CD39(+) and CD45RA(+) within the T-reg population (CD4(+)CD25(+)FOXP3(+)CD127(-)) (Pless than005). Children with exclusively coeliac disease had a higher MFI of CD101 (Pless than001), as well as a higher percentage of CD129(+) (Pless than005), in the CD4(+)CD25(hi) lymphocyte population, compared to references. In conclusion, children with combined T1D and coeliac disease have a higher percentage of differentiated CD4(+) cells compared to CD8(+) cells. T1D children show signs of low CD39(+)/CD45RA(+) T-reg cells that may indicate loss of suppressive function. Conversely, children with coeliac disease show signs of CD101(+)/CD129(+) T-reg cells that may indicate suppressor activity.

  • 263. Akner, Gunnar
    et al.
    Bosaeus, Ingvar
    Forsum, Elisabet
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Nutrition.
    Thesleff, Peter
    Diagnostiskt prov i klinisk nutrition för läkarstuderande. Provresultat visar att utbildningen i klinisk nutrition måste förbättras.2001In: Läkartidningen, ISSN 0023-7205, Vol. 98, 2604-2610 p.Article in journal (Other academic)
  • 264.
    Aksenova, Vasilisa
    et al.
    Russian Academy of Sciences, St. Petersburg, Russia.
    Turoverova, Lidia
    Russian Academy of Sciences, St. Petersburg, Russia.
    Khotin, Mikhail
    Russian Academy of Sciences, St. Petersburg, Russia.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Tulchinsky, Eugene
    University of Leicester, UK.
    Melino, Gerry
    Saint-Petersburg Technological Institute, Russia.
    Pinaev, George P.
    Russian Academy of Sciences, St. Petersburg, Russia.
    Barlev, Nicolai
    Russian Academy of Sciences, St. Petersburg, Russia.
    Tentler, Dmitri
    Russian Academy of Sciences, St. Petersburg, Russia.
    Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB2013In: OncoTarget, ISSN 1949-2553, Vol. 4, no 2, 362-372 p.Article in journal (Refereed)
    Abstract [en]

    ACTN4 is an actin-binding protein that participates in cytoskeleton organisation. It resides both in the cytoplasm and nucleus and physically associates with various transcription factors. Here, we describe an effect of ACTN4 expression on transcriptional activity of the RelA/p65 subunit of NF-kB. We demonstrate that ACTN4 enhances RelA/p65-dependant expression of c-fos, MMP-3 and MMP-1 genes, but it does not affect TNC, ICAM1 and FN1 expression. Importantly, actin-binding domains of ACTN4 are not critical for the nuclear translocation and co-activation of RelA/p65-dependent transcription. Collectively, our data suggest that in the nucleus, ACTN4 functions as a selective transcriptional co-activator of RelA/p65.

  • 265. Al Hilli, S.M.
    et al.
    Willander, Magnus
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Öst, Anita
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Strålfors, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    ZnO nanorods as an intracellular sensor for pH measurements2007In: Journal of Applied Physics, ISSN 0021-8979, Vol. 102, no 8Article in journal (Refereed)
    Abstract [en]

    ZnO nanorods with 80 nm diameter and 700 nm length and grown on the tip of a borosilicate glass capillary (0.7 μm in diameter) were used to create a highly sensitive pH sensor for monitoring in vivo biological process within single cells. The ZnO nanorods, functionalized by proton H3 O+ and hydroxyl O H- groups, exhibit a pH -dependent electrochemical potential difference versus a AgAgCl microelectrode. The potential difference was linear over a large dynamic range (4-11), which could be understood in terms of the change in surface charge during protonation and deprotonation. These nanoelectrode devices have the ability to enable analytical measurements in single living cells and have the capability to sense individual chemical species in specific locations within a cell. © 2007 American Institute of Physics.

  • 266.
    Al-Ahmad, A.
    et al.
    Cardiac Arrhythmia Service, Stanford University Medical School, Stanford, CA, United States.
    Wigström, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Sandner-Porkristl, D.
    Siemens AG, Medical Solutions, Forchheim, Germany.
    Wang, P.J.
    Cardiac Arrhythmia Service, Stanford University Medical School, Stanford, CA, United States.
    Zei, P.C.
    Cardiac Arrhythmia Service, Stanford University Medical School, Stanford, CA, United States.
    Boese, J.
    Siemens AG, Medical Solutions, Forchheim, Germany.
    Lauritsch, G.
    Siemens AG, Medical Solutions, Forchheim, Germany.
    Moore, T.
    Siemens AG, Medical Solutions, Forchheim, Germany.
    Chan, F.
    Department of Radiology, Stanford University Medical School, Stanford, CA, United States.
    Fahrig, R.
    Department of Radiology, Stanford University Medical School, Stanford, CA, United States.
    Time-resolved three-dimensional imaging of the left atrium and pulmonary veins in the interventional suite-A comparison between multisweep gated rotational three-dimensional reconstructed fluoroscopy and multislice computed tomography2008In: Heart Rhythm, ISSN 1547-5271, Vol. 5, no 4, 513-519 p.Article in journal (Refereed)
    Abstract [en]

    Background: Cardiac computed tomography (CT) is commonly used to visualize left atrial (LA) anatomy for ablation of atrial fibrillation. We have developed a new imaging technique that allows acquisition and visualization of three-dimensional (3D) cardiac images in the catheter lab. Objective: We sought to compare LA and pulmonary vein (PV) dimensions acquired using gated multisweep rotational fluoroscopy (C-arm CT) system and multislice computed tomography (MSCT) in an in vivo porcine model. Methods: A Siemens AXIOM Artis dTA C-arm system (Siemens AG, Medical Solutions) was modified to allow acquisition of four bidirectional sweeps during synchronized acquisition of the electrocardiogram signal to allow retrospective gating. C-arm CT image volumes were then reconstructed. Gated MSCT (SOMATOM Sensation 16 and 64, Siemens AG, Medical Solutions) and C-arm CT images were acquired in six animals. The two main PV diameters were measured in orthogonal axes. LA volumes were calculated. C-arm CT measurements were compared with the MSCT measurements. Results: The average PV diameters using the C-arm CT were 2.24 × 1.35 cm, versus 2.27 × 1.38 cm for CT. The average difference was 0.034 cm (1.9%) between the C-arm CT and standard CT. The average LA volume using MSCT was 49.1 ± 12.7 cm3, as compared with 51.0 ± 8.7 cm3 obtained by the C-arm CT. The average difference between the C-arm CT and the MSCT was 1.9 cm3 (3.7%). There were no significant differences in either the PV or LA measurements. Conclusions: Visualization of 3D cardiac anatomy during ablation procedures is possible and highly accurate. The 3D cardiac reconstructions acquired during ablation procedures will be valuable for procedural planning and guidance. © 2008 Heart Rhythm Society.

  • 267.
    Alarcon, Emilio I
    et al.
    University of Ottawa.
    Udekwu, Klas
    Karolinska Institute.
    Skog, Mårten
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Pacioni, NataliL
    University of Ottawa.
    Stamplecoskie, Kevin G
    University of Ottawa.
    Gonzalez-Bejar, Maria
    University of Ottawa.
    Polisetti, Naresh
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Wickham, Abeni
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Richter-Dahlfors, Agneta
    Karolinska Institute.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Scaiano, Juan C
    University of Ottawa.
    The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles2012In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 19, 4947-4956 p.Article in journal (Refereed)
    Abstract [en]

    Spherical 3.5 nm diameter silver nanoparticles (AgNP) stabilized in type I collagen (AgNP@collagen) were prepared in minutes (5-15 min) at room temperature by a photochemical method initiated by UVA irradiation of a water-soluble non-toxic benzoin. This biocomposite was examined to evaluate its biocompatibility and its anti-bacterial properties and showed remarkable properties. Thus, while keratinocytes and fibroblasts were not affected by AgNP@collagen, it was bactericidal against Bacillus megaterium and E. coli but only bacteriostatic against S. epidermidis. In particular, the bactericidal properties displayed by AgNP@collagen were proven to be due to AgNP in AgNP@collagen, rather than to released silver ions, since equimolar concentrations of Ag are about four times less active than AgNP@collagen based on total Ag content. This new biocomposite was stable over a remarkable range of NaCl, phosphate, and 2-(N-morpholino)ethanesulfonic acid concentrations and for over one month at 4 degrees C. Circular dichroism studies show that the conformation of collagen in AgNP@collagen remains intact. Finally, we have compared the properties of AgNP@collagen with a similar biocomposite prepared using alpha-poly-L-Lysine and also with citrate stabilized AgNP; neither of these materials showed comparable biocompatibility, stability, or anti-bacterial activity.

  • 268.
    Alavian, S.M.
    et al.
    Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Tehran.
    Ande, S.R.
    University of Manitoba.
    Coombs, K.M.
    University of Manitoba.
    Yeganeh, B.
    University of Manitoba.
    Davoodpour, Padideh
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hashemi, M.
    Zahedan University of Medical Sceince, Iran.
    Los, Marek Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Ghavami, S.
    University of Manitoba.
    Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development2011In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 18, no 12, 821-830 p.Article, review/survey (Refereed)
    Abstract [en]

    . Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed.

  • 269.
    Al-Ayoubi, Fawzi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eriksson, Helene
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?2012In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, Vol. 20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subspecialisation within general surgery has today reached further than ever. However, on-call time, an unchanged need for broad surgical skills are required to meet the demands of acute surgical disease and trauma. The introduction of a new subspecialty in North America that deals solely with acute care surgery and trauma is an attempt to offer properly trained surgeons also during on-call time. To find out whether such a subspecialty could be helpful in Sweden we analyzed our workload for emergency surgery and trauma. METHODS: Linkoping University Hospital serves a population of 257 000. Data from 2010 for all patients, diagnoses, times and types of operations, surgeons involved, duration of stay, types of injury and deaths regarding emergency procedures were extracted from a prospectively-collected database and analyzed. RESULTS: There were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency interventions, 641 (41.1%) were made outside office hours, and of 453 minor or intermediate procedures (including appendicectomy, cholecystectomy, or proctological procedures) 276 (60.9%) were done during the evenings or at night. Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%) required operation, of whom general surgeons operated on eight (3.1%). Thirteen consultants and 11 senior registrars were involved in 138 bowel resections and 164 cholecystectomies chosen as index operations for standard emergency surgery. The median (range) number of such operations done by each consultant was 6 (3--17) and 6 (1--22). Corresponding figures for senior registrars were 7 (0--11) and 8 (1--39). CONCLUSION: There was an uneven distribution of exposure to acute surgical problems and trauma among general surgeons. Some were exposed to only a few standard emergency interventions and most surgeons did not operate on a single patient with trauma. Further centralization of trauma care, long-term positions at units for emergency surgery and trauma, and subspecialisation in the fields of emergency surgery and trauma, might be options to solve problems of low volumes.

  • 270.
    Alberth, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology.
    Kettissen, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Lisander, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Blood loss in prosthetic hip replacement is not influenced by the AB0 blood group2001In: European Journal of Surgery, ISSN 1102-4151, Vol. 167, no 9, 652-655 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To find out if there is a correlation between AB0 type and the amount of blood lost at operation. Design: Retrospective study. Setting: One county and one university hospital, Sweden. Subjects: 540 patients who underwent primary prosthetic hip replacement under regional anaesthesia. Albumin (n = 298) or dextran (n = 242) were used as plasma substitutes. Main outcome measures: Estimated blood loss and number of units of red cell concentrates transfused. Results: The characteristics of the study groups were similar. In patients given albumin, the mean (SD) intraoperative loss with blood group 0 (n = 100) was 718 (413) ml and 2.7 (1.9) red cell units were given. Those with other blood groups (n = 198) lost 713 (469) ml and were given 2.5 (2.0) units. In patients given dextran with blood group 0 (n = 82), the intraoperative blood loss was 650 (337) ml, the postoperative loss 480 (222) ml and they received 2.1 (2.1) units. The corresponding values in the patients with other blood groups (n = 160) were 665 (351), 498 (208) and 2.5 (2.1) units. Conclusion: Blood group 0 was not associated with increased blood loss.

  • 271.
    Albertsson, Pontus
    et al.
    Umeå Universitet.
    Björnstig, Ulf
    Umeå Universitet.
    Petzäll, Jan
    Vägverket.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Näsman, Yvonne
    Räddningsverket, Sandö.
    Utrymningsförsök av passagerare ur buss vid brand och brandtillbud samt antalet bränder och brandtillbud i bussar i Sverige2006In: Akuttjournalen: Tidsskrift for avansert akuttmedisin, ISSN 0805-6129, Vol. 14, 85-91 p.Article in journal (Refereed)
    Abstract [sv]

       

  • 272.
    Albertsson, Pontus
    et al.
    Umeå Universitetet.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Is there a pattern in European bus and coach incidents? A literature analysis with special focus on injury causation and injury mechanisms2005In: Accident Analysis and Prevention, ISSN 0001-4575, Vol. 37, no 2, 225-233 p.Article in journal (Refereed)
    Abstract [en]

    In order to identify and describe a pattern in bus and coach incident related injuries and fatalities, and to suggest possible future measures for improvement of bus and coach safety, a literature analysis was performed. The results formed a multi-faceted pattern, which briefly can be described as follows, women travelled more frequently by bus as compared to men. Injuries sustained predominantly affected women 60 years of age and older. Of all traffic fatalities in Europe, bus and coach fatalities represented 0.3-0.5%. In the OECD countries, the risk of being killed or seriously injured was found to be seven to nine times lower for bus and coach occupants as compared to those of car occupants. Despite the fact that fatalities were more frequent on rural roads, a vast majority of all bus and coach casualties occurred on urban roads and in dry weather conditions. Boarding and alighting caused about one-third of all injury cases. Collisions were a major injury-contributing factor. Buses and coaches most frequently collided with cars, but unprotected road users were hit in about one-third of all cases of a collision, the point of impact on the bus or the coach being typically frontal or side. Rollovers occurred in almost all cases of severe coach crashes. In this type of crash projection, total ejection, partial ejection, intrusion and smoke inhalation were the main injury mechanisms and among those, ejection being the most dangerous. A 2-point belt may prevent passenger ejection, but in frontal crashes when the upper abdominal parts and the head hit the seatback in front, it could, however, contribute to head and thoracic injuries. Hence, a 3-point belt provides the best restraint in rollovers and frontal crashes. © 2004 Elsevier Ltd. All rights reserved.

  • 273.
    Albertsson, Pontus
    et al.
    Umeå Universitet.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Kirk, Alan
    Loughborough University, UK.
    Mayrhofer, Erich
    University of Technology, Graz, Austria.
    Björnstig, Ulf
    Umeå Universitet.
    Case study: 128 Injured in rollover coach crashes in Sweden - Injury outcome, mechanisms and possible effects of seat belts2006In: Safety Science, ISSN 0925-7535, Vol. 44, no 2, 87-109 p.Article in journal (Refereed)
    Abstract [en]

    The risk for injuries in rollover coach crashes are dependent on whether the occupants are belted or not. However, the influence of the different belt systems for reducing injuries has remained unclear. Since many injuries sustained are caused by impacts with the interior, passenger interactions or ejection through a window, the advantages by proper seat belt systems are evident. In this study, representing the most common serious crash scenario for serious injury, 128 injured in rollover cases were analysed with regard to the injury outcome, mechanisms and the possible injury reduction for occupants when using a safety belt. Furthermore, the different belt systems were compared to explain their contribution to increased safety. Based on medical reports and questioning of the passengers, the injuries sustained are recorded according to the AIS classification. The next step was the identification of the injury mechanisms, using the passenger statements as well as results from numerical occupant simulations. It is important to mention that this study was purely focused on detection of the injury mechanism to avoid the reported injuries. The possibility of additional injuries due to the wearing of a belt were not taken into account. However, the analysis of the 128 injured showed a considerable increase in safety for belted occupants through limiting interior contacts, minimising passenger interaction and reducing the possibility of ejection. © 2005 Elsevier Ltd. All rights reserved.

  • 274. Albertsson Wikland, K
    et al.
    Alm, F
    Aronsson, S
    Gustafsson, J
    Hagenäs, L
    Häger, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ivarsson, S
    Kriström, B
    Marcus, C
    Moell, C
    Nilsson, KO
    Ritzén, M
    Tuvemo, T
    Westergren, U
    Westphal, O
    Åman, J
    Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens. 1999In: Acta Paediatrica, ISSN 0803-5253, Vol. 428, 80-84 p.Article in journal (Other (popular science, discussion, etc.))
  • 275.
    Albin, Björn
    et al.
    Linnaeus University, Växjö, Sweden .
    Hjelm, Katarina
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Linnaeus University, Växjö, Sweden .
    Elmståhl, Sölve
    Lund University, Universitetssjukhuset MAS, Malmö, Sweden .
    Comparison of Stroke Mortality in Finnish-Born Migrants Living in Sweden 1970-1999 and in Swedish-Born Individuals2013In: Journal of Immigrant and Minority Health, ISSN 1557-1912, Vol. 17Article in journal (Refereed)
    Abstract [en]

    A limited number of studies have been found on stroke mortality in migrants showing higher mortality for some groups. Influence of time of residence has been studied by a previous  research group. A previous study showed a significantly higher number of deaths in Diseases of the circulatory system in Finnish migrants compared to native Swedes. The aim was to test the hypothesis of a higher mortality in and a decrease in mortality over time in stroke among Finnish migrants in Sweden. The study was based on National Population registry data. The study population included 321,407 Swedish and 307,174 foreign born persons living in Sweden 1987-1999. Mean age was lower at time for death for Finnish migrants than native Swedes, men 5.1 years difference and women 2.3 years. The dissimilarity decreased over time. The risk of death by stroke was higher for migrants with short time of residence in Sweden than with long time (≤10 years, OR 1.61-1.36 vs ≥11 year, OR 1.18). Migrants with short time of residence in Sweden died 9.8-5.3 years earlier than native Swedes. The hypothesis was confirmed and an indication of adjustment to life in the new host country was found. International studies show similar results for other migrant groups but further studies are needed to verify if a similar pattern can be found in other migrant groups living in Sweden and to be able to generalise the findings.

  • 276.
    Albrecht, Matthew A.
    et al.
    Curtin University, Australia .
    Stuart, Geoffrey W.
    La Trobe University, Australia .
    Falkmer, Marita
    Curtin University, Australia, Jonköping University, Sweden .
    Ordqvist, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Leung, Denise
    Curtin University, Australia .
    Foster, Jonathan K.
    Curtin University, Australia Health Department WA, Australia .
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Brief Report: Visual Acuity in Children with Autism Spectrum Disorders2014In: Journal of autism and developmental disorders, ISSN 0162-3257, E-ISSN 1573-3432, Vol. 44, no 9, 2369-2374 p.Article in journal (Refereed)
    Abstract [en]

    Recently, there has been heightened interest in suggestions of enhanced visual acuity in autism spectrum disorders (ASD) which was sparked by evidence that was later accepted to be methodologically flawed. However, a recent study that claimed children with ASD have enhanced visual acuity (Brosnan et al. in J Autism Dev Disord 42:2491-2497, 2012) repeated a critical methodological flaw by using an inappropriate viewing distance for a computerised acuity test, placing the findings in doubt. We examined visual acuity in 31 children with ASD and 33 controls using the 2 m 2000 Series Revised Early Treatment Diabetic Retinopathy Study chart placed at twice the conventional distance to better evaluate possible enhanced acuity. Children with ASD did not demonstrate superior acuity. The current findings strengthen the argument that reports of enhanced acuity in ASD are due to methodological flaws and challenges the reported association between visual acuity and systemising type behaviours.

  • 277.
    Aldonyte, R
    et al.
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Tunaitis, V
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Surovas, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Suriakaite, K
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Jarmalaviciute, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Magnusson, Karl-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Pivoriunas, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth2010In: e-biomed: Journal of Regenerating Medicine, ISSN 1524-8909, Vol. 5, no 4, 633-643 p.Article in journal (Refereed)
    Abstract [en]

    AIM: Intrinsic tissue regeneration mechanisms are still not fully understood. The destruction/reconstruction processes are usually in fine balance; however, this can be easily destroyed, for example in the environment of chronic inflammation. One of the major proteins present at the inflammatory sites is the multifunctional protein alpha-1-antitrypsin (AAT). In this study, potential therapeutic effects of this major human antiprotease on progenitor cells are assessed.

    MATERIALS & METHODS: Stromal cells from human exfoliated deciduous teeth (SHEDs) were used, which are similar to the mesenchymal stromal cells isolated from other tissues. SHEDs were cultivated in the presence of subphysiological, physiological and inflammatory concentrations of AAT, and their proliferation and motility traits were assayed. Some intracellular signaling pathways, AAT internalization by SHEDs and their matrix metalloprotease profile were studied in parallel.

    RESULTS: Physiologic and inflammatory concentrations of AAT significantly increased the cell proliferation rate, induced phosphorylation of several key protein kinases and increased the amount of secreted active gelatinases. Moreover, cells exposed to physiologic and inflammatory levels of AAT were able to invade and migrate more efficiently. Subphysiologic AAT levels did not change cell behavior significantly.

    CONCLUSION: AAT at physiologic and inflammatory concentrations positively modulates the proliferation and motility of SHEDs in vitro. These results suggest the importance of AAT in the maintenance and regulation of tissue progenitor cells in vivo.

  • 278. Aldén, Anna
    et al.
    Ohlson, Sten
    Påhlsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Rydén, Ingvar
    HPLC analysis of carbohydrate deficient transferrin isoforms isolated by the Axis-Shield %CDT method2005In: Clinica Chimica Acta, ISSN 0009-8981, Vol. 356, no 1-2, 143-146 p.Article in journal (Refereed)
    Abstract [en]

    Background: Carbohydrate-deficient transferrin (CDT) is elevated during prolonged overconsumption of alcohol and CDT is considered to be the most specific biochemical marker for alcohol overconsumption. However, an accurate method for analysing CDT is necessary because the test is frequently used for example in legal matters. Methods: Patient serum samples were analysed with the Axis-Shield %CDT and eluates were pooled together. Transferrin was purified from the pool by affinity chromatography and further analysed with HPLC to determine the ratios of different transferrin isoforms. Results: In the eluates using the Axis-Shield %CDT method, a substantial amount of trisialo transferrin was found, which is generally not considered a CDT isoform. Conclusions: The fact that trisialo transferrin is present may generate falsely elevated CDT results and it could at least partly explain the discrepancy between results of the Axis-Shield %CDT assay and HPLC in routine analysis. © 2005 Elsevier B.V. All rights reserved.

  • 279.
    Alehagen, Siw
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Fear pain stress hormones during labor2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.

    The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.

    Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.

    The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.

    The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.

    In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.

  • 280.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Chamberlain Wilmoth, Margaret
    School of Nursing, College of Health and Human Services, UNC Charlotte, Charlotte, North Carolina, USA.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Defining and Clarifying Sexual Health: A Simultaneous Concept analysis2012In: Advances in Medicine and Biology vol 28 / [ed] Leon V. Berhardt, Nova Science Publishers, Inc., 2012, 177-198 p.Chapter in book (Refereed)
    Abstract [en]

    Purpose: The concepts of health and sexuality are complex and the discussion of how to clarify them seems to be ongoing. This continuing work is essential also according to the joined concept sexual health as it is central in national and international public health programs. Hence, the aim of this paper was to clarify the concept of sexual health by making a simultaneous concept analysis of sexuality and health.

    Methods: A qualitative content analysis defined the meanings, the major concepts and the components of the superior concepts Sexuality and Health, respectively. The data for this analysis were dictionaries, definitions, reports, guidelines, books and articles. Next, a simultaneous concept analysis (SCA) was chosen in order to answer the research questions and develop a process model of sexual health.

    Findings: The definitions of the processed concepts and the developing outcome from sexual health were: Prime mover, Interconnectedness, Interdependence, Norms, Completeness, Functional physiology, Insight, Relatedness, Adaptiveness and Contentedness. These outcomes are presented in a process model.

    Conclusions: This study adds a theoretical perspective clarifying the concept sexual health. The clarifications of this study contribute with knowledge, which can be used in practise, enabling health care professionals promoting sexual health and develop sexual health issues in further research.

  • 281.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Somasunduram, Konduri
    Centre for Social Medicine, Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Bangal, Vidyadhar
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Patil, Ashok
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Chandekar, Pratibha
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Nurse-based antenatal and child health care in rural India, implementation and effects - an Indian-Swedish collaboration2012In: Rural and remote health, ISSN 1445-6354, Vol. 12, no 3Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Improving maternal and child health care are two of the Millennium Development Goals of the World Health Organization. India is one of the countries worldwide most burdened by maternal and child deaths. The aim of the study was to describe how families participate in nurse-based antenatal and child health care, and the effect of this in relation to referrals to specialist care, institutional deliveries and mortality.

    METHODS:

    The intervention took place in a remote rural area in India and was influenced by Swedish nurse-based health care. A baseline survey was performed before the intervention commenced. The intervention included education program for staff members with a model called Training of Trainers and the establishment of clinics as both primary health centers and mobile clinics. Health records and manuals, and informational and educational materials were produced and the clinics were equipped with easily handled instruments. The study period was between 2006 and 2009. Data were collected from antenatal care and child healthcare records. The Chi-square test was used to analyze mortality differences between years. A focus group discussion and a content analysis were performed.

    RESULTS:

    Families' participation increased which led to more check-ups of pregnant women and small children. Antenatal visits before 16 weeks among pregnant women increased from 32 to 62% during the period. Women having at least three check-ups during pregnancy increased from 30 to 60%. Maternal mortality decreased from 478 to 121 per 100 000 live births. The total numbers of children examined in the project increased from approximately 6000 to 18 500 children. Infant mortality decreased from 80 to 43 per 1000 live births. Women and children referred to specialist care increased considerably and institutional deliveries increased from 47 to 74%.

    CONCLUSION:

    These results suggest that it is possible in a rural and remote area to influence peoples' awareness of the value of preventive health care. The results also indicate that this might decrease maternal and child mortality. The education led to a more patient-friendly encounter between health professionals and patients.

  • 282.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hägg, Monica
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Kalén-Enterlöv, Maria
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Experiences of community health nurses regarding father participation in child health care2011In: Journal of Child Health Care, ISSN 1367-4935, E-ISSN 1741-2889, Vol. 15, no 3, 153-162 p.Article in journal (Refereed)
    Abstract [en]

    Traditionally child health care (CHC) has been an arena where mothers and nurses meet, but in recent years fathers are entering CHC with increasing frequency. The aim of this study was to describe nurses’ experiences of fathers’ participation in CHC. Nine Swedish nurses working in CHC were interviewed and asked to give a description of their experiences from meetings with fathers in CHC. Phenomenology according to Giorgi was used for the analysis and the essence of the findings was that father participation was seen from the perspective of mother participation and was constantly compared to mother participation in CHC. The essence is explicated in the following themes: participation through activities; equal participation although diverse; influence of structures in society; and strengthening participation. Clinical implications include the need for creating a separate identity in CHC for fathers and more communication directed at fathers.

  • 283.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wambui, Theresah
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Perceptions of family planning among low-income men in Western Kenya: Original Article2009In: International Nursing Review, ISSN 0020-8132, E-ISSN 1466-7657, Vol. 56, no 3, 340-345 p.Article in journal (Refereed)
    Abstract [en]

    Background: Men have rarely been involved in either receiving or providing information on sexuality, reproductive health or birth spacing. They have also been ignored or excluded in one way or the other from participating in many family planning programmes as family planning is viewed as a womans affair.

    Aim: To describe the perceptions of family planning among low-income men in Western Kenya. Methods: A qualitative study using focus group interviews and content analysis was conducted, with 64 men aged 15-54 years participating actively.

    Findings: Perceptions of family planning were manifold. For example, some perceived it as meaning having the number of children one is able to provide for. Most men knew about traditional and modern methods of birth control, although their knowledge was poor and misconceived. Modern methods were thought to give side effects, discouraging family planning. Low instances of family planning were also because of the fact that culturally, children are considered wealth. A law advocating family size limitation was regarded as necessary for the future.

    Conclusion: Mens perceptions of family planning are manifold. Their knowledge about contraception is poor and sometimes misconceived. Preferences regarding a childs gender are strong, thus attitudes and cultural beliefs that might hinder family planning have to be considered. A policy on male contraception and contraceptive services is seen as necessary.

  • 284.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Ulf
    Division of Biological Psychology, Department of Psychology, Stockholm University, Stockholm, Sweden.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear, pain and stress hormones during childbirth2005In: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 26, no 3, 153-165 p.Article in journal (Refereed)
    Abstract [en]

    Aims. To investigate the course of fear, pain and stress hormones during labor, and the associations between fear, pain, stress hormones and duration of labor in nulliparous women with and without epidural analgesia (EDA).

    Method.  One day during gestation weeks 37–39, urinary and salivary samples were collected to measure catecholamines and cortisol. Hourly during labor, the participants answered the Delivery Fear Scale and a pain intensity scale, and urinary and salivary samples were collected to measure stress hormones.

    Results. The course of fear, pain and stress hormones differed throughout labor in women with and without EDA. Pain and cortisol increased throughout labor in women without EDA. Women who received EDA had more fear, but not more pain, before the administration of the EDA than women who did not receive EDA. Pain, fear and catecholamines decreased when women received EDA, but fear and pain increased again later in labor. Fear and pain correlated, as well as levels of fear in the different phases of labor. During phase one of labor epinephrine and duration of the phase were negatively correlated.

    Conclusion.  The course of fear, pain and concentrations of stress hormones differed, highly influenced by the administration of EDA. Fear and pain correlated more pronounced than stress hormones and fear, pain and duration of labor.

  • 285.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear of childbirth before, during, and after childbirth2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 1, 56-62 p.Article in journal (Refereed)
    Abstract [en]

    Background. Only scanty research exists about the relationship between women's expectations during pregnancy and their experiences as reported during the actual process of labor and afterwards. The aims of the present study were: 1. to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during early active labor (phase 1: cervix dilatation 3–5 cm), and 2. to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia during labor.

    Methods. Fear of childbirth was measured in 47 nulliparous women during gestation weeks 37–39 by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ version A). During early active labor we measured women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale). Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

    Results. A positive correlation appeared between fear of childbirth during pregnancy, postpartum, and early active labor. There were no differences in fear of childbirth during late pregnancy between women who received epidural analgesia and those who did not. Postpartum fear was higher in the women who had received epidural analgesia.

    Conclusions. Pregnant women who fear childbirth are prone to report fear during the actual labor and postpartum. The administration of epidural analgesia is not a sufficient response to women's fear during the process of labor.

  • 286.
    Alehagen, Siw
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Lundberg, Ulf
    Department of Psychology, Stockholm University.
    Melin, Bo
    Department of Psychology, Stockholm University.
    Wijma, Barbro
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Catecholamine and cortisol reaction to childbirth2001In: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 8, no 1, 50-65 p.Article in journal (Refereed)
    Abstract [en]

    One way to study the stressfulness of childbirth is to examine the output of stress hormones. In this study, urinary catecholamines and salivary cortisol from 50 primiparous women were collected for 1 day during gestational weeks 37 to 39, hourly during labor and delivery, and 2 hr and 2 days postpartum. All three stress hormones increased statistically significantly from pregnancy to labor. The increase in adrenaline and cortisol was more than 500%, and the increase in noradrenaline was about 50%. After labor, the output decreased but not statistically significantly below the levels during late pregnancy. Hormone levels during late pregnancy, during labor and delivery, and during the period postpartum mostly did not correlate systematically. However, noradrenaline and adrenaline, as well as adrenaline and cortisol, were positively correlated during labor. After administration of epidural analgesia, there was a moderate but significant decrease in noradrenaline and adrenaline, whereas cortisol did not change. In conclusion, the results of this study support the assumption that childbirth is a very stressful event and that the stress responses vary considerably among women. The substantial increase of adrenaline and cortisol compared with noradrenaline indicates that mental stress is more dominant than physical stress during labor.

  • 287.
    Alehagen, Siw
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Can women's cognitive appraisals be registered throughout childbirth?2000In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002x, Vol. 49, no 1, 31-35 p.Article in journal (Refereed)
    Abstract [en]

    The aims of the present study were: (a) to examine whether it was possible to measure women’s cognitive appraisals hourly during the whole process of labor and delivery, and (b) to explore how the appraisals varied during labor. Measurements from 12 nulliparous women are presented. The findings indicate that it is possible to study psychological appraisals directly, in detail and continuously during the process of labor and delivery. The women’s cognitive appraisals varied throughout labor both per individual woman and between the participating women.

  • 288.
    Alehagen, Siw
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Fear during labor2001In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 80, no 4, 315-320 p.Article in journal (Refereed)
    Abstract [en]

    Background. The aims of the present study were to compare primiparous and multiparous women’s experiences of fear of delivery during an early stage of active labor (cervix dilatation 3–5 centimeters) and to study whether fear of delivery, measured during the early stage of active labor, was a predictor of the amount of pain relief received during the remaining part of labor (cervix dilatation 5 cm – partus), of the duration of the remaining part of labor, and of the occurrence of instrumental vaginal delivery and emergency cesarean section.

    Method. Thirty-five primiparous and 39 multiparous women answered the Delivery Fear Scale (DFS) once during the early stage of labor and before they had received any pain relief.

    Results. Primiparous women reported higher levels of fear than multiparous women did. Fear during the first phase of labor predicted only the total amount of pain relief received during labor.

    Conclusion. The clinical implications of the study are that the delivery staff should consider women’s fear during labor and pay attention especially to primiparous women’s increased risk of higher levels of fear during an early stage of active labor, as compared with multiparous women’s. The challenge for staff of a delivery ward is to support the woman in labor in a way that decreases fear, which in turn might reduce the woman’s need of pain relief.

  • 289.
    Alehagen, Siw
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Pre- and postpartum fear of childbirth and fear and pain during laborManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: The aims of the present study were 1) to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during labor (phase 1: cervix dilatation 3-5 cm), and 2) to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia (EDA) during labor.

    Method. During gestation weeks 37-39, in 47 nulliparous women fear of childbirth was measured by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A. Early during labor (labor phase I = cervix dilatation 3-5cm) the women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale) were measured hourly. Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

    Results. Fear of childbirth during pregnancy and in the three postpartum measures was positively related to fear during labor, phase I. Pain during phase 1 of labor was neither associated with fear of childbirth measured during late pregnancy, nor with postpartum fear. There were no differences in fear of childbirth during late pregnancy between those women who received EDA and those who did not. Postpartum fear was higher in those women who had received EDA.

    Conclusion. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartum.

  • 290.
    Alehagen, Urban
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Heart failure in primary health care: special emphasis on natriuretic peptides in the elderly2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,

    Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.

    Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.

    Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.

    BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.

    In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.

    Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.

  • 291.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, N-2226 Kongsvinger, Norway.
    Selenium and coenzyme Q10 interrelationship in cardiovascular diseases - A clinician's point of view2015In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, Vol. 31, 157-162 p.Article in journal (Refereed)
    Abstract [en]

    A short review is given of the potential role of selenium deficiency and selenium intervention trials in atherosclerotic heart disease. Selenium is an essential constituent of several proteins, including the glutathione peroxidases and selenoprotein P. The selenium intake in Europe is generally in the lower margin of recommendations from authorities. Segments of populations in Europe may thus have a deficient intake that may be presented by a deficient anti-oxidative capacity in various illnesses, in particular atherosclerotic disease, and this may influence the prognosis of the disease. Ischemic heart disease and heart failure are two conditions where increased oxidative stress has been convincingly demonstrated. Some of the intervention studies of anti-oxidative substances that have focused on selenium are discussed in this review. The interrelationship between selenium and coenzyme Q10, another anti-oxidant, is presented, pointing to a theoretical advantage in using both substances in an intervention if there are deficiencies within the population. Clinical results from an intervention study using both selenium and coenzyme Q10 in an elderly population are discussed, where reduction in cardiovascular mortality, a better cardiac function according to echocardiography, and finally a lower concentration of the biomarker NT-proBNP as a sign of lower myocardial wall tension could be seen in those on active treatment, compared to placebo.

  • 292.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 2, 252-260 p.Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 293.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Can NT-proBNP predict risk of cardiovascular mortality within 10 years? Results from an epidemiological study of elderly patients with symptoms of heart failure2009In: International journal of cardiology, ISSN 0167-5273, Vol. 133, no 2, 233-240 p.Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure has a serious prognosis. However, among elderly patients the panorama of concomitant diseases makes it difficult to implement the results from epidemiological studies. The aim of this study was to evaluate the influence of different clinical variables on cardiovascular mortality during a long-term follow-up.

    Methods and results: In all, 474 elderly patients (age 65-82 years) in primary health care were evaluated and followed during a 10 year period. All patients had symptoms associated with heart failure and were examined by a cardiologist. Blood samples including NT-proBNP were analyzed, and ECG and Doppler echocardiography were assessed. Both the systolic and diastolic function was evaluated. Functional capacity was evaluated according to the NYHA classification.

    During the 10 years of follow-up those with the highest quartile of plasma concentration of NT-proBNP had almost four times increased risk of cardiovascular mortality. Impaired systolic function, diabetes and reduced functional capacity were all markers of increased risk of cardiovascular mortality. All variables were also evaluated after 5 years, with higher risk ratios for a majority of variables.

    Conclusion: In this study 474 patients with symptoms of heart failure were followed during 10 years. High plasma concentration of NT-proBNP could predict almost four times increased risk of cardiovascular mortality up to 10 years. Also, impaired cardiac function according to echocardiography, and reduced functional capacity as well as diabetes all had influence on risk of cardiovascular mortality up to 10 years.

     

  • 294.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Rehfeld, J. F.
    University of Copenhagen, Denmark .
    Gotze, J. P.
    University of Copenhagen, Denmark .
    Combined measurement of copeptin, high sensitivity Troponin T, and NT-proBNP improves the identification of elderly patients at risk of cardiovascular death in REGULATORY PEPTIDES, vol 177, issue , pp S14-S142012In: REGULATORY PEPTIDES, Elsevier , 2012, Vol. 177, S14-S14 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 295.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Cartensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Refeld, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Goetze, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Combined measurement of copeptin, high-sensitivity troponin T, and N-terminal proBNP improves the identification of patients at risk of cardiovascular death2012In: Cardiovascular Endocrinology, ISSN 2162-688X, Vol. 1, no 4, 68-73 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: A multimarker strategy for the handling of patients with heart failure has been suggested in the literature. Therefore, the potential prognostic relevance of combined copeptin, high-sensitivity troponin T (HS-TnT), and N-terminal proBNP (NT-proBNP) measurement in plasma from elderly patients with symptoms of heart failure was evaluated

    Methods: This study included 470 elderly patients (mean age 73 years) from a rural municipality with symptoms of heart failure. Clinical examination, echocardiography, and biomarker measurements were performed. All patients were followed for 13 years and all mortality was registered. Cardiovascular mortality was evaluated using Kaplan-Meier plots and multivariate Cox proportional hazard regression analyses.

    Results: Copeptin, HS-TnT, and NT-proBNP measurements provided independent prognostic information in a multivariate setting over 5 years (hazard ratio, HR: 3.66; 95% confidence interval, CI 1.27-10.53, HR: 2.52; 95% CI 1.20-5.28, HR: 2.73; 95% CI 1.19-6.26, respectively). Also, the group with all three biomarkers below cut-off values had a low risk for cardiovascular death (1.8% of the patients in this group died in the 5-year follow-up period). In the 13-year follow-up, combined copeptin and HS-TnT measurement did not provide independent prognostic information.

    Conclusion: Combined copeptin, HS-TnT, and NT-proBNP plasma measurements provide prognostic information on cardiovascular mortality that is superior to single biomarker use.

  • 296.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care2009In: EUROPEAN JOURNAL OF HEART FAILURE, ISSN 1388-9842, Vol. 11, no 4, 354-360 p.Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker. Four hundred and sixty-four primary health-care patients (mean age 73 years, range 65-87) with symptoms of HF were examined. All patients were evaluated using Doppler echocardiography and blood samples, including measurement of cystatin C and NT-proBNP. The patients were followed over a 10-year period. Patients with serum cystatin C levels within the highest quartile had almost three times the risk (HR: 2.92; 95% CI: 1.23-4.90) of CV mortality compared with those patients who had levels within the first, second, or third quartiles. If, at the same time, the patient had a plasma concentration of NT-proBNP within the highest quartile, the risk increased to andgt; 13 times (HR: 13.61; 95% CI: 2.56-72.24) during 10 years of follow-up or andgt; 17 times (HR: 17.04; 95% CI: 1.80-163.39) after 5 years of follow-up. Combined analysis of cystatin C and NT-proBNP could provide important prognostic information among elderly patients in the community with symptoms of HF.

  • 297.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure2004In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 92, no 6, 1250-1258 p.Article in journal (Refereed)
    Abstract [en]

    D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.

  • 298.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.2010In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, ISSN 1473-5733, Vol. 21, no 1, 62-9 p.Article in journal (Refereed)
    Abstract [en]

    Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

  • 299.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F
    University of Copenhagen, Denmark.
    Goetze, Jens P
    University of Copenhagen, Denmark.
    Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure2011In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, ISSN 0098-7484, Vol. 305, no 20, 2088-2095 p.Article in journal (Refereed)
    Abstract [en]

    Context Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. Objective To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Design, Setting, and Participants Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. Main Outcome Measures All-cause mortality and cardiovascular mortality. Results After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P=.01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; Pandlt;.001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P=.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; Pandlt;.001). Conclusion Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

  • 300.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark .
    Goetze, Jens P.
    University of Copenhagen, Denmark .
    Pro-A-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal Pro-B-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure2013In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 19, no 1, 31-39 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP), midregional pro A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care. less thanbrgreater than less thanbrgreater thanMethods and Results: The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echocardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with andgt;4-fold increased risk for cardiovascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT-proBNP 3-fold increased risk within 5 years. In the 5-13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) andlt;40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF andgt;50% NT-proBNP exhibited andgt;3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients. less thanbrgreater than less thanbrgreater thanConclusions: The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care. (J Cardiac Fail 2013;19:31-39)

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