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  • 1.
    Lundberg, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Department of Biochemistry, University of Sydney, Australia.
    Dudman, Nicholas P.
    Department of Cardiovascular Medicine, Prince Henry Hospital, University of New South Wales, Australia.
    Kuchel, Philip W.
    Department of Biochemistry, University of Sydney, Australia.
    Wilcken, David E. L.
    Present address: Department of Physical Chemistry, University of Umeå, Umeå, Sweden.
    1H NMR determination of urinary betaine in patients with premature vascular disease and mild homocysteinemia1995In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 41, no 2, 275-283 p.Article in journal (Refereed)
    Abstract [en]

    Urinary N,N,N-trimethylglycine (betaine) and N,N-dimethylglycine (DMG) have been identified and quantified for clinical purposes by proton nuclear magnetic resonance (1H NMR) measurement in previous studies. We have assessed these procedures by using both one-dimensional (1-D) and 2-D NMR spectroscopy, together with pH titration of urinary extracts to help assign 1H NMR spectral peaks. The betaine calibration curve linearity was excellent (r = 0.997, P = 0.0001) over the concentration range 0.2-1.2 mmol/L, and CVs for replicate betaine analyses ranged from 7% (n = 10) at the lowest concentration to 1% (n = 9) at the highest. The detection limit for betaine was < 15 mumol/L. Urinary DMG concentrations were substantially lower than those of betaine. Urinary betaine and DMG concentrations measured by 1H NMR spectroscopy from 13 patients with premature vascular disease and 17 normal controls provided clinically pertinent data. We conclude that 1H NMR provides unique advantages as a research tool for determination of urinary betaine and DMG concentrations.

  • 2.
    Mancia, Giuseppe
    et al.
    University of Milano Bicocca, Italy .
    Fagard, Robert
    University of Gdansk, Poland .
    Narkiewicz, Krzysztof
    University of Gdansk, Poland .
    Redon, Josep
    University of Valencia, Spain .
    Zanchetti, Alberto
    University of Milan, Italy .
    Boehm, Michael
    University of Saarlandes Kliniken, Germany .
    Christiaens, Thierry
    University of Ghent, Belgium .
    Cifkova, Renata
    Charles University of Prague, Czech Republic .
    De Backer, Guy
    University Hospital, Belgium .
    Dominiczak, Anna
    University of Glasgow, Scotland .
    Galderisi, Maurizio
    Federico II University Hospital, Italy .
    Grobbee, Diederick E.
    University of Medical Centre Utrecht, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Kirchhof, Paulus
    University of Birmingham, England .
    Kjeldsen, Sverre E.
    University of Oslo, Norway .
    Laurent, Stephane
    Hop Europeen Georges Pompidou, France .
    Manolis, Athanasios J.
    Asklepe Gen Hospital, Greece .
    Nilsson, Peter M.
    Lund University, Sweden .
    Ruilope, Luis Miguel
    Hospital 12 Octubre, Spain .
    Schmieder, Roland E.
    University Hospital, Germany .
    Sirnes, Per Anton
    Ostlandske Hjertesenter, Norway .
    Sleight, Peter
    John Radcliffe Hospital, England .
    Viigimaa, Margus
    Tallinn University of Technology, Estonia .
    Waeber, Bernard
    CHU Vaudois, Switzerland .
    Zannad, Faiez
    University of Lorraine, France .
    2013 ESH/ESC Guidelines for the management of arterial hypertension2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 28, -+ p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 3.
    Mancia, Giuseppe
    et al.
    University of Milano Bicocca, Italy .
    Fagard, Robert
    KU Leuven University, Belgium .
    Narkiewicz, Krzysztof
    Medical University of Gdansk, Poland .
    Redon, Josep
    University of Valencia, Spain .
    Zanchetti, Alberto
    University of Milan, Italy .
    Boehm, Michael
    University of Klinikum Saarlandes, Germany .
    Christiaens, Thierry
    University of Ghent, Belgium .
    Cifkova, Renata
    Charles University of Prague, Czech Republic .
    De Backer, Guy
    University Hospital, Belgium .
    Dominiczak, Anna
    University of Glasgow, Scotland .
    Galderisi, Maurizio
    Federico II University Hospital, Italy .
    Grobbee, Diederick E.
    University of Medical Centre Utrecht, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Kirchhof, Paulus
    University of Birmingham, England .
    Kjeldsen, Sverre E.
    University of Oslo, Norway .
    Laurent, Stephane
    Hop Europeen Georges Pompidou, France .
    Manolis, Athanasios J.
    Asklepeion Gen Hospital, Greece .
    Nilsson, Peter M.
    Lund University, Sweden .
    Ruilope, Luis Miguel
    Hospital 12 Octubre, Spain .
    Schmieder, Roland E.
    University Hospital, Germany .
    Sirnes, Per Anton
    Ostlandske Hjertesenter, Norway .
    Sleight, Peter
    John Radcliffe Hospital, England .
    Viigimaa, Margus
    Tallinn University of Technology, Estonia .
    Waeber, Bernard
    CHU Vaudois, Switzerland .
    Zannad, Faiez
    Centre Invest Clin 9501, France .
    2013 ESH/ESC Guidelines for themanagement of arterial hypertension The Task Force for the management ofarterial hypertension of the European Society ofHypertension (ESH) and of the European Society of Cardiology (ESC)2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 7, 1281-1357 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 4.
    Mancia, Giuseppe
    et al.
    University of Milano Bicocca, Italy IRCSS, Italy .
    Fagard, Robert
    KU Leuven University, Belgium .
    Narkiewicz, Krzysztof
    Medical University of Gdansk, Poland .
    Redon, Josep
    University of Valencia INCLIVA Research Institute, Spain CIBERobn, Spain .
    Zanchetti, Alberto
    University of Milan, Italy .
    Boehm, Michael
    University of Klinikum Saarlandes, Germany .
    Christiaens, Thierry
    University of Ghent, Belgium .
    Cifkova, Renata
    Charles University of Medical School I, Czech Republic Thomayer Hospital, Czech Republic .
    De Backer, Guy
    University Hospital, Belgium .
    Dominiczak, Anna
    University of Glasgow, Scotland .
    Galderisi, Maurizio
    University of Naples Federico II, Italy .
    Grobbee, Diederick E.
    University of Medical Centre Utrecht, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Kirchhof, Paulus
    University of Birmingham, England SWBH NHS Trust, England University of Munster, Germany .
    Kjeldsen, Sverre E.
    University of Oslo, Norway .
    Laurent, Stephane
    Hop Europeen Georges Pompidou, France Hop Europeen Georges Pompidou, France .
    Manolis, Athanasios J.
    Asklepe Gen Hospital, Greece .
    Nilsson, Peter M.
    Lund University, Sweden .
    Miguel Ruilope, Luis
    Hospital 12 Octubre, Spain .
    Schmieder, Roland E.
    University Hospital, Germany .
    Sirnes, Per Anton
    Ostlandske Hjertesenter, Norway .
    Sleight, Peter
    John Radcliffe Hospital, England .
    Viigimaa, Margus
    Tallinn University of Technology, Estonia .
    Waeber, Bernard
    CHU Vaudois, Switzerland .
    Zannad, Faiez
    INSERM, France University of Lorraine, France CHU, France .
    2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension2014In: Blood Pressure, ISSN 0803-7051, Vol. 23, no 1, 3-16 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 5.
    Mancia, Giuseppe
    et al.
    University of Milano Bicocca, Italy .
    Fagard, Robert
    KU Leuven University, Belgium .
    Narkiewicz, Krzysztof
    Medical University of Gdansk, Poland .
    Redon, Josep
    University of Valencia, Spain .
    Zanchetti, Alberto
    University of Milan, Italy .
    Boehm, Michael
    University of Saarlandes Kliniken, Germany .
    Christiaens, Thierry
    University of Ghent, Belgium .
    Cifkova, Renata
    Charles University of Prague, Czech Republic .
    De Backer, Guy
    University Hospital, Belgium .
    Dominiczak, Anna
    University of Glasgow, Scotland .
    Galderisi, Maurizio
    Federico II University Hospital, Italy .
    Grobbee, Diederick E.
    University of Medical Centre Utrecht, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Kirchof, Paulus
    University of Birmingham, England .
    Kjeldsen, Sverre E.
    University of Oslo, Norway .
    Laurent, Stephane
    Hop Europeen Georges Pompidou, France .
    Manolis, Athanasios J.
    Asklepe Gen Hospital, Greece .
    Nilsson, Peter M.
    Lund University, Sweden .
    Ruilope, Luis Miguel
    Hospital 12 Octubre, Spain .
    Schmieder, Roland E.
    University Hospital, Germany .
    Sirnes, Per Anton
    Ostlandske Hjertesenter, Norway .
    Sleight, Peter
    John Radcliffe Hospital, England .
    Viigimaa, Margus
    Tallinn University of Technology, Estonia .
    Waeber, Bernard
    CHU Vaudois, Switzerland .
    Zannad, Faiez
    University of Lorraine, France .
    2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC)2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 10, 1925-1938 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 6. Imura, M
    et al.
    Kuroda, T
    Oshiro, O
    Chihara, K
    Brandberg, Joakim
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    3-D flow visualization for construction of the model of the blood flow in the heart2000In: Japanese Journal of Applied Physics, ISSN 0021-4922, Vol. 39, no 5 B, 3246-3251 p.Article in journal (Refereed)
    Abstract [en]

    The authors have been developing a model of blood flow in the heart. The flow model of the heart enables us to estimate the entire blood flow of the heart from a couple of 2-D color Doppler images. Therefore, the load on patients is expected to be reduced. To develop the model of the heart, precise observation and an understanding of the blood flow are indispensable, because the flow is strongly related to the diagnosis of heart diseases. The visualization method must have the following features: (1) 3-D (2) objectivity (3) interactivity and (4) multi-aspect. The authors have developed visualization methods to meet the above-mentioned requirements and evaluated the proposed methods with the in-vitro flow data set. The results clearly reveal that the proposed system enables the researchers of the modeling group to obtain the state of entire flow, such as the occurrence of turbulence.

  • 7.
    Markwardt, Niklas
    et al.
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Hollnburger, Bastian
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Stepp, Herbert
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Zelenkov, Petr
    Burdenko Neurosurgery Institute, Moscow, Russia.
    Rühm, Adrian
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence-guided stereotactic biopsy of brain tumors2016In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 9, no 9, 901-912 p.Article in journal (Refereed)
    Abstract [en]

    Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis. In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20-40 µm between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy. PpIX signal attenuation through clinically relevant blood layers for 405 nm (violet) and 633 nm (red) excitation.

  • 8.
    Cahill, N
    et al.
    Uppsala University, Sweden.
    Bergh, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kanduri, M
    Uppsala University, Sweden.
    Göransson-Kultima, H
    Uppsala University, Sweden.
    Mansouri, L
    Uppsala University, Sweden.
    Isaksson, A
    Sahlgrenska University Hospital, Sweden.
    Ryan, F
    Institute of Technology, Dublin, Ireland.
    Smedby, K E
    Karolinska Institutet, Stockholm, Sweden.
    Juliusson, G
    Institute of Technology, Dublin, Ireland.
    Sundström, C
    Uppsala University, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rosenquist, R
    Uppsala University, Sweden.
    450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments2013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 1, 150-158 p.Article in journal (Refereed)
    Abstract [en]

    In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K-arrays, we provide the most comprehensive DNA methylation study of CLL to date, analysing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (e.g. CLLU1, LPL, ZAP70, NOTCH1), epigenetic regulator (e.g. HDAC9, HDAC4, DNMT3B), B-cell signaling (e.g. IBTK) and numerous TGF-ß and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.Leukemia accepted article preview online, 27 August 2012; doi:10.1038/leu.2012.245.

  • 9.
    Fredriksson, Alexandru G
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Zajac, Jakub
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Eriksson, Jonatan
    Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Bolger, Ann F
    University of California San Francisco.
    Ebbers, Tino
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    4-D blood flow in the human right ventricle2011In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 301, no 6, H2344-H2350 p.Article in journal (Refereed)
    Abstract [en]

    Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 +/- 0.3 mJ) than the other flow components (P andlt; 0.001 and P andlt; 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P andlt; 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

  • 10.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bissell, Malenka
    University of Oxford, England.
    Barker, Alex J.
    Northwestern University, IL 60611 USA.
    Bolger, Ann F
    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 Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    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 Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    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 Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Francios, Christopher J.
    University of Wisconsin, WI 53706 USA.
    Frydrychowicz, Alex
    University Hospital Schleswig Holstein, Germany.
    Geiger, Julia
    University of Childrens Hospital Zurich, Switzerland.
    Giese, Daniel
    University Hospital Cologne, Germany.
    Hope, Michael D.
    University of Calif San Francisco, CA USA.
    Kilner, Philip J.
    University of London Imperial Coll Science Technology and Med, England.
    Kozerke, Sebastian
    University of Zurich, Switzerland; ETH, Switzerland.
    Myerson, Saul
    University of Oxford, England.
    Neubauer, Stefan
    University of Oxford, England.
    Wieben, Oliver
    University of Wisconsin, WI 53706 USA.
    Markl, Michael
    Northwestern University, IL 60611 USA; Northwestern University, IL 60611 USA.
    4D flow cardiovascular magnetic resonance consensus statement2015In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 72Article, review/survey (Refereed)
    Abstract [en]

    Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

  • 11.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, 558-565 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

    MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

    RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

    CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

  • 12.
    Sundbom, Per
    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.
    Ahn, Henrik
    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 Thoracic and Vascular Surgery.
    Kornhall, B
    Skane University Hospital, Lund.
    Loebe, M
    Division of Transplant and Assist Devices at Methodist DeBakey Heart & Vascular Centre, Houston, Texas, USA.
    Granfeldt, Hans
    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 Thoracic and Vascular Surgery.
    (556) – Change in Acoustic Fingerprints at Increased Pump Speed During Echocardiographic Ramp Test2014Conference paper (Refereed)
    Abstract [en]

    Purpose

    The continuous flow mechanical circulatory support HeartMate II (Thoratec Corporation, Inc. Pleasanton, USA) (HMII), generates an auditory signal (acoustic fingerprint) that can be registered by routine auscultation. A temporary or permanent change in sound indicates a change in pump function. Previous mock loop studies have shown that changes in acoustic fingerprint are due to changes in speed, so the aim of this study was to see if the acoustic fingerprint changed during an echocardiographic ramp test.

    Methods

    Four stable, event-free patients included in the SoundMate study performed an echocardiographic ramp test. The speed was increased stepwise by 400 rpm between 8 000 and 12 000 rpm, and the left ventricular end diastolic diameter, flow, power consumption and blood pressure were measured. Sounds from HMII were recorded using an iPhone™ (Apple Inc. Cupertino, CA, USA) with the stethoscope application iStethPro™ (Dr. Peter J Bentley, UK) and the frequency map analyzed using the Audacity™ program (Unicode, Ash, Chinen and Crook, USA). The acoustic fingerprint is divided into regions (R1: 1 000-6 500, R2: 8 500-14 000, R3: 15 000-21 000 Hz) and peaks (P1: 0-1 000, P2: 6 500-8 500, P4: 21 000-23 000 Hz) in order to facilitate calculations and clarify changes in frequency.

    Results

    There were significant (p<005) changes in the acoustic fingerprint when increasing the pump speed between 8 000 and 12 000 rpm. In 2/4 patients there were no significant changes in P1, otherwise there were significant changes in all regions and peaks. During the ramp test the power increased in mean 7 W, flow 3,1 L/min and the blood pressure measured with Doppler increased by ~15 mmHg. The left ventricular size decreased with ~2 cm.

    Conclusion

    The acoustic fingerprint changes with pump speed. This implies that when using sound check for detection of pump dysfunction, a new baseline should be set after every adjustment of speed.

  • 13.
    Hultman, Martin
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Järfälla-Stockholm, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Alvandpour, Atila
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    A 15.6 frames per second 1 megapixel Multiple Exposure Laser Speckle Contrast Imaging setup2017In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648Article in journal (Refereed)
    Abstract [en]

    A multiple exposure laser speckle contrast imaging (MELSCI) setup for visualizing blood perfusion was developed using a field programmable gate array (FPGA), connected to a 1000 frames per second (fps) 1-megapixel camera sensor. Multiple exposure time images at 1, 2, 4, 8, 16, 32 and 64 milliseconds were calculated by cumulative summation of 64 consecutive snapshot images. The local contrast was calculated for all exposure times using regions of 4 × 4 pixels. Averaging of multiple contrast images from the 64-millisecond acquisition was done to improve the signal-to-noise ratio. The results show that with an effective implementation of the algorithm on an FPGA, contrast images at all exposure times can be calculated in only 28 milliseconds. The algorithm was applied to data recorded during a 5 minutes finger occlusion. Expected contrast changes were found during occlusion and the following hyperemia in the occluded finger, while unprovoked fingers showed constant contrast during the experiment. The developed setup is capable of massive data processing on an FPGA that enables processing of MELSCI data in 15.6 fps (1000/64 milliseconds). It also leads to improved frame rates, enhanced image quality and enables the calculation of improved microcirculatory perfusion estimates compared to single exposure time systems.

    The full text will be freely available from 2018-08-07 12:43
  • 14.
    Olsson, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Eriksson, M
    Johnson, O
    Kjellström, T
    Lanke, J
    Lytken Larsen, M
    Pedersen, T
    Tikkanen, MJ
    Wiklund, O
    A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The Treat-to-Target (3T) Study2003In: Clinical Therapeutics, ISSN 0149-2918, Vol. 25, no 1, 119-138 p.Article in journal (Refereed)
    Abstract [en]

    Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C =2.6 mmol/L, TG =1.5 mmol/L, and both LDL-C =2.6 mmol/L and TG =1.5 mmol/L. Methods: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration =4.0 mmol/L (=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. Results: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation of the drugs' effects on YG. Patient demographic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001, 52 weeks: -49% vs -44%, P < 0.001) and in YG (8 weeks: -23% vs -14%, P < 0.001, 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%, P < 0.001). Fewer atorvastatin patients needed to have their dose doubled, nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%, P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. Conclusions: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d m reducing LDL-C and YG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statins were well tolerated.

  • 15.
    Persson, Ulf
    et al.
    Lund University, Sweden Lundby Hospital, Sweden .
    Gullstrand, Birgitta
    Lund University, Sweden .
    Pettersson, Asa
    Lund University, Sweden .
    Sturfelt, Gunnar
    Lund University, Sweden .
    Truedsson, Lennart
    Lund University, Sweden .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fc gamma-RIIa Genes2013In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 37, no 6, 641-648 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fc gamma-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegeners granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fc gamma-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.

  • 16.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindvall, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A case report of plasmapheresis treatment in a patient with paraneoplastic cerebellar degeneration and high anti-Yo antibody titers2008In: Therapeutic Apheresis and Dialysis, ISSN 1744-9979, Vol. 12, no 1, 82-85 p.Article in journal (Refereed)
    Abstract [en]

    A patient with paraneoplastic cerebellar degeneration due to anti-Purkinje cell antibodies (anti-Yo) arising from ovarian carcinoma with metastases was treated with three plasmapheresis (PP) series (a total of 22 PP treatments) over one year and was monitored by repeated otoneurological testing, balance tests and clinical investigations. Blood samples for antibody titers were checked on several occasions. Initially there was a weak clinical response and significantly improved test results regarding the caloric response, as well as a possible effect on visual suppression of the vestibulo-ocular reflex after caloric ear irrigation. After the first series of PP treatment, new metastases were found. A half year later there was a progressive course with increasing general symptoms. Serology tests showed continuously high titers of anti-Yo antibody, although somewhat lower after PP. We thus report a minor and short-lived effect of PP, possibly inhibited by the natural course of metastatic disease. © 2008 International Society for Apheresis.

  • 17.
    Olafsdottir, Arndis F.
    et al.
    NU Hospital Grp, Sweden; University of Gothenburg, Sweden.
    Attvall, Stig
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Sandgren, Ulrika
    Sahlgrens University Hospital, Sweden.
    Dahlqvist, Sofia
    NU Hospital Group, Uddevalla, Sweden.
    Pivodic, Aldina
    Statistiska Konsultgruppen, Sweden.
    Skrtic, Stanko
    University of Gothenburg, Sweden; AstraZeneca Rand D, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lind, Marcus
    NU Hospital Grp, Sweden; University of Gothenburg, Sweden.
    A Clinical Trial of the Accuracy and Treatment Experience of the Flash Glucose Monitor FreeStyle Libre in Adults with Type 1 Diabetes2017In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 19, no 3, 164-172 p.Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, FreeStyle Libre a flash glucose monitoring system came onto the market in 2014 as a complement to self-monitoring of blood glucose. The aim of this study was to evaluate the accuracy and treatment experience of the FreeStyle Libre system. Methods: Fifty-eight adults with type 1 diabetes used FreeStyle Libre for 10-14 days and measured capillary blood glucose levels with the HemoCue blood glucose measurement system at least six times a day simultaneously. Results: For the entire study period, the mean absolute relative difference (MARD) was 13.2% (95% confidence interval [CI] 12.0%-14.4%). MARD was 13.6% (95% CI 12.1%-15.4%) during week 1 and 12.7% (95% CI 11.5%-13.9%) during week 2. The mean absolute difference (MAD) for the whole study period was 19.8mg/dL (1.1mmol/L) (95% CI 17.8-21.8 mg/dL), including 20.5 mg/dL (1.14 mmol/L) during week 1 and 19.0 mg/dL (1.05 mmol/L) during week 2. The overall correlation coefficient was 0.96. For glucose values amp;lt; 72, 72-180, and amp;gt; 180mg/dL (amp;lt; 4, 4-10, and amp;gt; 10 mmol/L), the MARD was 20.3% (95% CI 17.7%-23.1%), 14.7% (95% CI 13.4%-16%), and 9.6% (95% CI 8.5%-10.8%), respectively, and respective MAD values were 12.3, 17.8, and 23.6 mg/dL (0.69, 0.99, and 1.31mmol/L). Using the 10-item visual analog scale, patients rated their experience with FreeStyle Libre as generally positive, with mean values ranging from 8.22 to 9.8. Conclusions: FreeStyle Libre had a similar overall MARD as continuous blood glucose monitoring systems in earlier studies when studied in similar at-home conditions. The overall patient satisfaction was high.

  • 18.
    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.
    Janzon, Magnus
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    A clinician’s experience of using the Cardiac Reader NT-proBNP point-of-care assay in a clinical setting2008In: European Journal of Heart Failure, ISSN 1388-9842, Vol. 10, no 3, 260-266 p.Article in journal (Refereed)
    Abstract [en]

    The evaluation of natriuretic peptides has become increasingly valuable in a clinical setting, where information is often needed promptly.

    Objectives: To compare the usefulness of the recently released Roche Cardiac Reader ® NT-proBNP assay against the Roche Elecsys® NT-proBNP laboratory system in a clinical setting.

    Design and Results: Blood samples from 440 patients admitted for acute coronary syndromes, worsening of heart failure, or as policlinic heart failure patients were evaluated. The relation between the assays was analysed and the diagnostic concordance calculated. A good correlation was found between the assays (r=0.96, 95% CI: 0.94-0.97) with a diagnostic concordance of 0.93. A separate analysis was performed in the range where most clinical decisions are made (60-3000 ng/L), with a diagnostic concordance of 88%. The usefulness in a clinical setting where time is important was high.

    Conclusion: The Roche Cardiac Reader® NT-proBNP assay has been evaluated in a clinical setting. The point-of-care method shows good results, although with a restricted analytical range compared with the reference.

  • 19.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Roman, Markus
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Dahlgren, Maria
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Thelander, Gunilla
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Wikström, Maria
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Druid, Henrik
    Department of Forensic Medicine, National Board of Forensic Medicine, Linköping and Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden.
    A Cluster of Deaths Involving 5-(2-Aminopropyl)Indole(5-IT)2013In: Journal of Analytical Toxicology, ISSN 0146-4760, Vol. 37, no 8, 542-546 p.Article in journal (Refereed)
    Abstract [en]

    During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 mg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.

  • 20.
    Druid, Henrik
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Holmgren, Per
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    A compilation of fatal and control concentrations of drugs in postmortem femoral blood1997In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 42, no 1, 79-87 p.Article in journal (Refereed)
    Abstract [en]

    A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Linkoping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.

  • 21. Sparring Björkstén, Karin
    et al.
    Ekberg, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Säfström, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Dige, N
    Granerus, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    A computerized human reference brain for rCBF/SPET technetium-99m exametazime (HMPAO) investigation of elderly2004In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, Vol. 24, no 4, 196-204 p.Article in journal (Refereed)
    Abstract [en]

    Using the bull's eye approach, a reference brain from the single photon emission tomography (SPET) images of 10 subjects aged 62-81 years with excellent mental and physical health was constructed. SPET images were acquired twice, 1 week apart, using a single detector rotating gamma camera collecting 64 planar images over a 360° orbit. The centre of each transaxial slice was first defined with an automatic edge detecting algorithm applied to an anterior-posterior and a side profile of the brain. Each slice was divided into 40 sectors. Maximum counts/pixel in each sector was picked. The 40 maximum count values from one transaxial slice were allowed to form a horizontal row in a new parametric image on the x-axis and slice number from the vertex to the basal parts of the brain on the y-axis. This new image was scaled to a 64 × 16 pixel matrix by interpolation, which meant a normalization of all studies to the same size. The parametric image in each subject was scaled with regard to intensity by a factor calculated by a normalization procedure using the least squares analysis. Mean and SD for each pixel were calculated, thereby constructing a 'mean parametric image', and a 'SD parametric image'. These two images are meant to be used as the reference brain for evaluation of patient studies. This method can be used for objective measurements of diffuse brain changes and for pattern recognition in larger groups of patients. Statistical multifactorial analysis of parameters used for acquisition and data processing is possible. © 2004 Blackwell Publishing Ltd.

  • 22.
    Petersson, Ulla
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Peter
    Department of Clinical Sciences, Lund University, University Hospital, Malmö , Sweden.
    A consultation-based method is equal to SCORE and an extensive laboratory-based method in predicting risk of future cardiovascular disease2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 5, 536-540 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As cardiovascular disease (CVD) is one of the most common causes of mortality worldwide, much interest has been focused on reliable methods to predict cardiovascular risk.

    DESIGN: A cross-sectional, population-based screening study with 17-year follow-up in Southern Sweden.

    METHODS: We compared a non-laboratory, consultation-based risk assessment method comprising age, sex, present smoking, prevalent diabetes or hypertension at baseline, blood pressure (systolic >/=140 or diastolic >/=90), waist/height ratio and family history of CVD to Systemic COronary Risk Evaluation (SCORE) and a third model including several laboratory analyses, respectively, in predicting CVD risk. The study included clinical baseline data on 689 participants aged 40-59 years without CVD. Blood samples were analyzed for blood glucose, serum lipids, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-1, C-reactive protein, asymmetric dimethyl arginine and symmetric dimethyl arginine. During 17 years, the incidence of total CVD (first event) and death was registered.

    RESULTS: A non-laboratory-based risk assessment model, including variables easily obtained during one consultation visit to a general practitioner, predicted cardiovascular events as accurately [hazard ratio (HR): 2.72; 95% confidence interval (CI): 2.18-3.39, P<0.001] as the established SCORE algorithm (HR: 2.73; 95% CI: 2.10-3.55, P<0.001), which requires laboratory testing. Furthermore, adding a combination of sophisticated laboratory measurements covering lipids, inflammation and endothelial dysfunction, did not confer any additional value to the prediction of CVD risk (HR: 2.72; 95% CI: 2.19-3.37, P<0.001). The c-statistics for the consultation model (0.794; 95% CI: 0.762-0.823) was not significantly different from SCORE (0.767; 95% CI: 0.733-0.798, P=0.12) or the extended model (0.806; 95% CI: 0.774-0.835, P=0.55).

    CONCLUSION: A risk algorithm based on non-laboratory data from a single primary care consultation predicted long-term cardiovascular risk as accurately as either SCORE or an elaborate laboratory-based method in a defined middle-aged population.

  • 23.
    Zhao, Juan
    et al.
    Peking University, Peoples R China.
    Han, Zhenhui
    Kaifeng Childrens Hospital, Peoples R China.
    Zhang, Xi
    Kaifeng Childrens Hospital, Peoples R China.
    Du, Shuxu
    Capital Medical University, Peoples R China.
    Dong Liu, Angie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Holmberg, Lukas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xueying
    Peking University, Peoples R China.
    Lin, Jing
    Peking University, Peoples R China.
    Xiong, Zhenyu
    Kaifeng Childrens Hospital, Peoples R China.
    Gai, Yong
    Kaifeng Childrens Hospital, Peoples R China.
    Yang, Jinyan
    Peking University, Peoples R China.
    Liu, Ping
    Peking University, Peoples R China.
    Tang, Chaoshu
    Peking University, Peoples R China.
    Du, Junbao
    Peking University, Peoples R China; Minist Educ, Peoples R China.
    Jin, Hongfang
    Peking University, Peoples R China.
    A cross-sectional study on upright heart rate and BP changing characteristics: basic data for establishing diagnosis of postural orthostatic tachycardia syndrome and orthostatic hypertension2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 6, e007356Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to determine upright heart rate and blood pressure (BP) changes to suggest diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) and orthostatic hypertension (OHT) in Chinese children. Methods: In this cross-sectional study, 1449 children and adolescents aged 6-18 years were randomly recruited from two cities in China, Kaifeng in Henan province and Anguo in Hebei province. They were divided into two groups: 844 children aged 6-12 years (group I) and 605 adolescents aged 13-18 years (group II). Heart rate and BP were recorded during an active standing test. Results: 95th percentile (P-95) of delta heart rate from supine to upright was 38 bpm, with a maximum upright heart rate of 130 and 124 bpm in group I and group II, respectively. P-95 of delta systolic blood pressure (SBP) increase was 18 mm Hg and P-95 of upright SBP was 132 mm Hg in group I and 138 mm Hg in group II. P-95 of delta diastolic blood pressure (DBP) increase was 24 mm Hg in group I and 21 mm Hg in group II, and P-95 of upright DBP was 89 mm Hg in group I and 91 mm Hg in group II. Conclusions: POTS is suggested when delta heart rate is greater than= 38 bpm (for easy memory, greater than= 40 bpm) from supine to upright, or maximum heart rate greater than= 130 bpm (children aged 6-12 years) and greater than= 125 bpm (adolescents aged 13-18 years), associated with orthostatic symptoms. OHT is suggested when delta SBP (increase) is greater than= 20 mm Hg, and/or delta DBP (increase) greater than= 25 mm Hg (in children aged 6-12 years) or greater than= 20 mm Hg (in adolescents aged 13-18 years) from supine to upright; or upright BP greater than= 130/90 mm Hg (in children aged 6-12 years) or greater than= 140/90 mm Hg (in adolescents aged 13-18 years).

  • 24.
    Lymer, Ulla-Britt
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Antonsson Schütz, A.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    A descriptive study of blood exposure incidents among healthcare workers in a university hospital in Sweden1997In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 35, no 3, 223-235 p.Article in journal (Refereed)
    Abstract [en]

    In an attempt to document blood exposure incidents and compliance with recommended serological investigations, universal precautions and incident reporting routines, data was collected from occupational injury reports during a two-year period. In addition, a sample of healthcare workers (HCWs) answered a questionnaire about blood tests and work routines. In a third part of the study some HCWs were asked about the type and actual frequency of incidents, together with the number of reported incidents during the two-year study period. Of a total of 473 reported occupational blood exposures, the majority came from nurses and the minority from physicians. Most reported incidents occurred on hospital wards. The most common incidents were needlestick injuries, and 35% occurred when the needle was recapped. Medical laboratory technicians (MLT) reported significantly more mucocutaneous incidents than other professionals (P < 0·01). In 10% of the incidents, the patient had a known blood-borne infection. Serological investigations post-exposure varied among professional groups, and 35% were not tested. No seroconversion was shown in the HCWs tested. In the third part of the study, respondents recalled 1180 incidents, although only 9% of these had been reported. The majority occurred in operating theatres, and in connection with anaesthesia. There was a significant difference (P < 0·001) between the different professional groups with regard to the frequency of incident reporting. Physicians reported only 3% and MLTs 36% of the incidents. Eighty-one percent believed that the accident could have been avoided. Despite knowledge of universal precautions, professionals continue to behave in a risky manner, which can result in blood exposure incidents.

  • 25.
    Shamsudin, Nebil
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A Device for Measurement of Capillary Refilling Time2012Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    The main objective of this project is to design, construct and validate a portable prototype of a device that is capable of performing a test to accurately measure Capillary Refilling Time (CRT), and to analyze the results with defined parameters; force, area, pressure (compression) and time. This prototype is dedicated to study and evaluate CRT readouts for different pressure values, collected from healthy subjects.The presented prototype of this study is capable of producing skin compressing and to measure the refilling time of capillaries following this compression. This prototype introduces accuracy, mechanical reproducibility and controlling options for the applied pressure and compression time. The presented prototype is non-invasive, portable and it can be used to conduct more CRT tests and other capillary refilling studies.CRT measurement is done by calculating time interval starting from the first point when the applied pressure is released; ending with the recording point at the time when the concentration of red blood cells has reached the level of its pre-occlusion values.Based on the calculated CRT values and the number of iterations of the test in CRT tables, one can observe that given the same applied pressure value, CRT values do not significantly vary when the test is repetitively conducted on the same subject and on the same site.

  • 26.
    Häggblad, Erik
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Petersson, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Ilias, Michail A.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A diffuse reflectance spectroscopic study of UV-induced erythematous reaction across well-defined borders in human skin2010In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 16, no 3, 283-290 p.Article in journal (Refereed)
    Abstract [en]

    Introduction The colour of tissue is often of clinicaluse in the diagnosis of tissue homeostasis andphysiological responses to various stimuli.Determining tissue colour changes and borders,however, often poses an intricate problem and visualexamination, constituting clinical praxis, does notallow them to be objectively characterized orquantified. Demands for increased inter- and intraobserverreproducibility have been incentives for theintroduction of objective methods and techniques fortissue colour (e.g. erythema) evaluation. The aim ofthe present paper was to study the border zone of anUVB provoked erythematous response of humanskin in terms of blood volume and oxygenationmeasured by means of diffuse reflectancespectroscopy using a commercial probe.

    Material and Methods A provocation model, basedon partial masking of irradiated skin areas, definestwo erythema edges at every skin site responding tothe UV irradiation. In every subject, 5 test sites wereexposed with a constant UV light irradiance (14mW/cm2), but with different exposures times (0, 3,6, 9, 12 seconds). An analysis of the spectral datameasured across the two edges was performed for every scan line. The oxygenized and deoxygenizedhemoglobin contents were estimated in everymeasurement point, using a modified Beer-Lambertmodel.

    Results The fit of the experimental data to the model derived by the modified Beer-Lambert law was excellent (R2>0.95). Analyzing data for the chromophore content showed that the erythematous response in provoked areas is dominated by the increase in oxyhemoglobin. The width for the left and right border zone was estimated to 1.81±0.93 mm and 1.90±0.88 mm respectively (M±SD). The unprovoked area between the two edges was estimated to 0.77±0.68 mm.

    Conclusion While the chosen data analysis performed satisfactory, the ability of the probe design to differentiate spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging are possible solutions.

  • 27.
    Svärd, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Sommarin, Yngve
    EuroDiagnostica AB, Malmö.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    A disease-modifying role for mucosal IgA antibodies to citrullinated antigens?2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no Issue suppl. 1, A38-A39 p.Article in journal (Refereed)
    Abstract [en]

    Objective

    The aim of this study was to investigate whether immunoglobulin A (IgA) antibodies to cyclic citrullinated peptides CCP) can be detected in saliva of patients with established heumatoid arthritis (RA) and if it relates to clinical manifestations.

    Methods

    Salivary samples were collected (by ‘passive drooling’) from 63 consecutive patients with established RA at a visit to the rheumatology outpatient clinic (Falun, Sweden), and from 20 healthy persons (hospital staff). The samples were centrifuged and kept frozen at −70°C until analysis. IgA-class anti-CCP antibodies in saliva were analysed by adaptation of commercial ELISA (Immunoscan RA, Euro-Diagnostica AB, Malmo, Sweden) using polyclonal rabbit antihuman α-chain specific antibodies conjugated with horseradish peroxidase(DakoCytomation, Glostrup, Denmark) as secondary antibody. To ensure specificity of the reaction, a corresponding ELISA was set up to analyse IgA antibodies to control antigen(cyclic arginine peptide, CAP), and anti-CCP/anti-CAP ratios were calculated. Also, inhibition studies were performed by preincubation of sera with soluble CCP or CAP. Clinical and laboratory data on disease activity, that is, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and 28-joint count disease activity score (DAS28) as well as radiological outcome (occurrence or absence of erosions as judged by a radiologist in diagnostic routine) were achieved retrospectively via the patients’ medical records.

    Results

    Background reactivity against CCP was found in virtually all patients and healthy subjects, whereas a positive anti-CCP/anti-CAP ratio (≥1.5) was found in 14 out of 63 RA patients (22%) and in one healthy subject (5%). Salivary IgA-reactivity with CCP was dose-dependently inhibited by soluble CCP (but not with CAP) in sera with anti-CCP/anti- CAP ratios ≥1.5. No IgG-reactivity to CCP was found in saliva, although all patients with salivary IgA anti-CCP tested IgG anti-CCP-positive in serum. Furthermore, less than half of those testing IgA-positive in saliva were IgA anti-CCP positive in serum, strongly arguing against passive leakage of anti-CCP antibodies from blood to saliva. The patients testing positive for salivary IgA antibodies had lower average disease activity measures (CRP, ESR, DAS28) at presentation and fewer developed bony erosions within 6 years after presentation (p=0.043, Fisher’s exact test).

    Conclusion

    Salivary IgA antibodies to citrullinated proteins were found in a subset of IgG anti-CCP positive RA patients. In contrast to their serum counterparts, salivary IgA antibodies may associate with a milder/less destructive disease course. This accords with the notion that secretory IgA antibodies exert anti-inflammatory actions, and that they may be associated with induction of systemic tolerance (oral tolerance). The possible disease-modifying role of mucosal immunity to citrullinated proteins needs further investigation!

                    

                                                                    

  • 28.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults2002In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 147, no 1, 49-57 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.

    DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.

    RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.

    CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

  • 29.
    Hadimeri, Henrik
    et al.
    Kärnsjukhuset, Skövde, Sweden.
    Frisenette-Fich, Carsten
    Ryhov, Jönköping, Sweden.
    Deurell, Sven-Ingemar
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Svensson, Lars
    Höglandssjukhuset, Eksjö, Sweden.
    Carlsson-Bjering, Lena
    Höglandssjukhuset, Eksjö, Sweden.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Almroth, Gabriel
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Melander, Stefan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Haarhaus, Mathias
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Andersson, Per-Olof
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Cassel, Agneta
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Mauritz, Nils-Johan
    Ryhov, Jönköping, Sweden.
    Ståhl-Nilsson, Agneta
    Ryhov, Jönköping, Sweden.
    Wilske, Jan
    Värnamo Sjukhus, Sweden .
    Nordström, Kataryna
    Värnamo Sjukhus, Sweden .
    Oruda, Pavel
    Värnamo Sjukhus, Sweden .
    Eriksson, Marie
    Umeå University, Sweden .
    Inghilesi Larsson, Annelie
    Umeå University, Sweden .
    Stegmayr, Bernd
    Umeå University, Sweden .
    A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure2013In: Renal failure, ISSN 0886-022X, E-ISSN 1525-6049, Vol. 35, no 6, 845-854 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome.

    METHODS:

    The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement.

    RESULTS:

    At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1.

    CONCLUSIONS:

    However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.

  • 30.
    Ramström, A Sofia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fagerberg, I.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A flow cytometric assay for the study of dense granule storage and release in human platelets1999In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 10, no 2-3, 153-158 p.Article in journal (Refereed)
    Abstract [en]

    The clinical manifestations of platelet dense (δ) granule defects are easy bruising, as well as epistaxis and bleeding after delivery, tooth extractions and surgical procedures. The observed symptoms may be explained either by a decreased number of granules or by a defect in the uptake/release of granule contents. We have developed a method to study platelet dense granule storage and release. The uptake of the fluorescent marker, mepacrine, into the platelet dense granule was measured using flow cytometry. The platelet population was identified by the size and binding of a phycoerythrin-conjugated antibody against GPIb. Cells within the discrimination frame were analysed for green (mepacrine) fluorescence. Both resting platelets and platelets previously stimulated with collagen and the thrombin receptor agonist peptide SFLLRN was analysed for mepacrine uptake. By subtracting the value for mepacrine uptake after stimulation from the value for uptake without stimulation for each individual, the platelet dense granule release capacity could be estimated. Whole blood samples from 22 healthy individuals were analysed. Mepacrine incubation without previous stimulation gave mean fluorescence intensity (MFI) values of 83±6 (mean ± 1 SD, range 69–91). The difference in MFI between resting and stimulated platelets was 28±7 (range 17–40). Six members of a family, of whom one had a known δ-storage pool disease, were analysed. The two members (mother and son) who had prolonged bleeding times also had MFI values disparate from the normal population in this analysis. The values of one daughter with mild bleeding problems but a normal bleeding time were in the lower part of the reference interval.

  • 31.
    Harris, L. F.
    et al.
    Dublin Institute Technology, Ireland.
    Rainey, P.
    Queens University of Belfast, North Ireland.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Killard, A. J.
    University of West England, England.
    A fully integrated microfluidic device for point of care monitoring of antithrombotics2016In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 8, no 35, 6500-6505 p.Article in journal (Refereed)
    Abstract [en]

    The simplicity and efficiency of point of care diagnostics have revolutionised patient care. Current methods for measuring hypercoagulability often require trained technicians, large blood volumes, and result in long turnaround times. Standard testing for hypercoagulable disorders is performed in the central laboratory using automated coagulation analysers. However the trend is moving towards the development and implementation of point of care testing, as a result of the ever increasing number of patients on antithrombotic therapy. We present a novel microfluidic device and assay for monitoring the effect of two anticoagulants, unfractionated heparin (UFH) and low molecular weight heparin (LMWH). The assay is based on the anti-Xa assay principle but uses fluorescence detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor (R), which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure both UFH and LMWH in human plasma samples from 0 to 1 U mL(-1), with a rapid result obtained within 30-60 seconds.

  • 32.
    Nordgren, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Kindberg, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    Department of Clinical Microbiology, Division of Laboratory Medicine, County Hospital Ryhov, Jönköping, Sweden/Department of Clinical Microbiology, Capio Diagnostik AB, Capio St Görans Hospital, Stockholm, Sweden.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    A FUT2 nonsense mutation (G428A) and Lewis-independent norovirus GI.3 outbreak2009Article in journal (Other academic)
    Abstract [en]

    Background: Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Previous studies have shown that histo-blood group antigens (HBGAs) and secretor status are associated with susceptibility to symptomatic NoV infection, with non-secretors being almost completely resistant to disease. Here we report on a food-borne GI.3 NoV outbreak affecting 33/83 (40%) individuals.

    Methods: Secretor status and HBGA expression in saliva were determined with pyrosequencing and ELISA. Virus characterization was performed by sequencing the N/S region and the complete capsid gene.

    Results: A novel observation was that homozygous carriers of the nonsense FUT2 G428A allele were more susceptible to symptomatic infection than secretors (odds ratio [OR] 1.41 vs 0.71). Consistent with this observation was that Lewis a positive b negative (Lea+b-) individuals showed the highest susceptibility (OR 2.42) compared with other Lewis phenotypes. Blood group B was associated with partial protection (OR 0.27). The capsid gene of the outbreak strain exhibits high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize non-secretor saliva.

    Conclusion: We describe for the first time a NoV outbreak with Lea+b- individuals homozygous for the G428A nonsense mutation in the FUT2 gene being more susceptible for disease than secretor-positive individuals.

  • 33.
    Satha, Ganarupan
    et al.
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Lindström, Stefan B.
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Klarbring, Anders
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    A goal function approach to remodeling of arteries uncovers mechanisms for growth instability2014In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 13, no 6, 1243-1259 p.Article in journal (Refereed)
    Abstract [en]

    A novel, goal function-based formulation for the growth dynamics of arteries is introduced, and used for investigating the development of growth instability in blood vessels. Such instabilities would lead to abnormal growth of the vessel, reminiscent of an aneurysm. The blood vessel  is modeled as a thin-walled cylindrical tube and the constituents that form the vessel wall are assumed to deform together as a constrained mixture. The growth dynamics of the composite material of the vessel wall is described by an evolution equation, where the effective area of each constituent changes in the direction of steepest descent of a goal function. This goal function is formulated in such way that the constituents grow toward a target potential energy and a target composition. The convergence of the simulated response of the evolution equation toward a target homeostatic state is investigated for a range of isotropic and orthotropic material models. These simulations suggest that elastin-deficient vessels are more prone to growth instability. Increased stiffness of the vessel wall, on the other hand, gives a more stable growth process. Another important finding is that an increased rate of degradation of materials impairs growth stability.

  • 34.
    Nyman, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Brännmark, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Palmér, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Brugård, Jan
    MathCore Engn.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Cedersund, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    A Hierarchical Whole-body Modeling Approach Elucidates the Link between in Vitro Insulin Signaling and in Vivo Glucose Homeostasis2011In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 29, 26028-26041 p.Article in journal (Refereed)
    Abstract [en]

    Type 2 diabetes is a metabolic disease that profoundly affects energy homeostasis. The disease involves failure at several levels and subsystems and is characterized by insulin resistance in target cells and tissues (i.e. by impaired intracellular insulin signaling). We have previously used an iterative experimental-theoretical approach to unravel the early insulin signaling events in primary human adipocytes. That study, like most insulin signaling studies, is based on in vitro experimental examination of cells, and the in vivo relevance of such studies for human beings has not been systematically examined. Herein, we develop a hierarchical model of the adipose tissue, which links intracellular insulin control of glucose transport in human primary adipocytes with whole-body glucose homeostasis. An iterative approach between experiments and minimal modeling allowed us to conclude that it is not possible to scale up the experimentally determined glucose uptake by the isolated adipocytes to match the glucose uptake profile of the adipose tissue in vivo. However, a model that additionally includes insulin effects on blood flow in the adipose tissue and GLUT4 translocation due to cell handling can explain all data, but neither of these additions is sufficient independently. We also extend the minimal model to include hierarchical dynamic links to more detailed models (both to our own models and to those by others), which act as submodules that can be turned on or off. The resulting multilevel hierarchical model can merge detailed results on different subsystems into a coherent understanding of whole-body glucose homeostasis. This hierarchical modeling can potentially create bridges between other experimental model systems and the in vivo human situation and offers a framework for systematic evaluation of the physiological relevance of in vitro obtained molecular/cellular experimental data.

  • 35.
    Berg, Kirsti
    et al.
    Norwegian University of Science and Technology, Trondheim, Norway.
    Ericsson, Madelene
    Umeå University, Sweden.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technology, Trondheim, Norway.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering.
    A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies2014In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 3Article in journal (Refereed)
    Abstract [en]

    Objective

    An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetr​amethylpyrrolidine(CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies.

    Materials and Methods

    Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP•) with known spin concentration.

    Results

    The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k = 1). The spin concentration of samples stored at −80°C could be reproduced after 6 months of storage well within the same error estimate.

    Conclusion

    The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

  • 36.
    Bach, Anders
    et al.
    University of Copenhagen.
    Clausen, Bettina H
    University of South Denmark.
    Moller, Magda
    University of Copenhagen.
    Vestergaard, Bente
    University of Copenhagen.
    Chi, Celestine N
    Uppsala University.
    Round, Adam
    European Molecular Biol Lab.
    Sorensen, Pernille L
    University of Copenhagen.
    Nissen, Klaus B
    University of Copenhagen.
    Kastrup, Jette S
    University of Copenhagen.
    Gajhede, Michael
    University of Copenhagen.
    Jemth, Per
    Uppsala University.
    Kristensen, Anders S
    University of Copenhagen.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Lambertsen, Kate L
    University of South Denmark.
    Stromgaard, Kristian
    University of Copenhagen.
    A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 9, 3317-3322 p.Article in journal (Refereed)
    Abstract [en]

    Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.

  • 37.
    Sekretaryova, Alina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Beni, Valerio
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Eriksson, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    Turner, Anthony
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Vagin, Mikhail Y
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    A highly sensitive and self-powered cholesterol biosensor2014In: 24th Anniversary World Congress on Biosensors – Biosensors 2014, Elsevier, 2014Conference paper (Other academic)
    Abstract [en]

    Blood cholesterol is a very important parameter for the assessment of atherosclerosis and other lipid disorders. The total cholesterol concentration in human blood should be less than 5.17 mM. Concentrations in the range 5.17 – 6.18 mM are considered borderline high risk and levels above 6.21 mM, high risk. Cholesterol determination with high accuracy is therefore necessary in order to differentiate these levels for medical screening or diagnosis. Several attempts to develop highly sensitive cholesterol biosensors have been described, but, to the best of our knowledge, this is the first report of a self-powered cholesterol biosensor, i.e. a device delivering the analytical information from the current output of the energy of the biocatalytic conversion of cholesterol, without any external power source. This is particularly relevant to the development of inexpensive screening devices based on printed electronics.

     

    We present two complementary bioelectrocatalytic platforms suitable for the fabrication of a self-powered biosensor. Both are based on cholesterol oxidase (ChOx) immobilisation in a sol-gel matrix, as illustrated in Fig. 1 [1]. Mediated biocatalytic cholesterol oxidation [2] was used as the anodic reaction and electrocatalytic reduction of hydrogen peroxide on Prussian Blue (PB) as the cathodic reaction. Due to a synergistic effect in the self-powered cholesterol biosensor, the analytical parameters of the overall device exceeded those of the individual component half-cells, yielding a sensitivity of 0.19 A M-1 cm-2 and a dynamic range that embraces the free cholesterol concentrations found in human blood.

     

    Thus, we have demonstrated the novel concept of highly sensitive cholesterol determination using the first self-powered cholesterol biosensor. This configuration is particularly promising for incorporation in emerging plastic- and paper-based analytical instruments for decentralised diagnostics and mobile health.

     

  • 38.
    Dizdar (Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, 33-42 p.Article in journal (Refereed)
    Abstract [en]

    A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.

  • 39. Thorven, Maria
    et al.
    Grahn, Ammi
    Hedlund, Kjell-Olof
    Johansson, Hugo
    Wahlfrid, Christer
    Larsson, Göran
    Svensson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    A homozygous nonsense mutation (428G→A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections2005In: Journal of Virology, ISSN 0022-538X, Vol. 79, no 24, 15351-15355 p.Article in journal (Refereed)
    Abstract [en]

    Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an a(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G→A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese428) secretors, and none were secretor negative (Se428Se428), in contrast to 20% nonsecretors (se 428se428) among Swedish blood donors (n = 104) (P < 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P < 0.00001). Furthermore, saliva from secretor-positive and symptomatic patients but not from secretor-negative and asymptomatic individuals bound the norovirus strain responsible for that particular outbreak. This is the first report showing that the FUT2 nonsecretor (se428se 428) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus. Copyright © 2005, American Society for Microbiology. All Rights Reserved.

  • 40.
    Folkesson, Tchou
    et al.
    Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden,.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dahlström, B.
    Berzelius Clinical Research Center, Linköping, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of noradrenaline and vasopressin in skin: in JOURNAL OF VASCULAR RESEARCH, vol 48, pp 320-3202011In: JOURNAL OF VASCULAR RESEARCH, Karger , 2011, 320-320 p.Conference paper (Refereed)
    Abstract [en]

    Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the Emax model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

  • 41.
    Tchou Folkesson, Kim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Dahlström, Bengt
    AB Biopharmacon, Uppsala.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    A Human Vascular Model Based on Microdialysis for the Assessment of the Vasoconstrictive Dose-Response Effects of Norepinephrine and Vasopressin in Skin2012In: Microcirculation, ISSN 1073-9688, Vol. 19, no 4, 352-359 p.Article in journal (Refereed)
    Abstract [en]

    Abstract Objective: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). Results: We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 +/- 1.7 to 10.9 +/- 0.9 mmol/L for the highest concentration of NE (p andlt; 0.001) and from 8.1 +/- 1.4 to 10.0 +/- 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 +/- 0.7 to 0.41 +/- 0.18 mmol/L for NE (p = 0.001) and from 2.7 +/- 0.6 to 1.3 +/- 0.5 mmol/L for VP (p andlt; 0.001). Lactate increased from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for NE (p = 0.005) and from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Conclusions: Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

  • 42.
    Wren, Joakim
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Mechanical Engineering, Applied Thermodynamics and Fluid Mechanics.
    Karlsson, Matts
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Modelling and Simulation .
    Loyd, Dan
    Linköping University, The Institute of Technology. Linköping University, Department of Mechanical Engineering, Applied Thermodynamics and Fluid Mechanics.
    A hybrid equation for simulation of perfused tissue during thermal treatment2001In: International Journal of Hyperthermia, ISSN 0265-6736, Vol. 17, no 6, 483-498 p.Article in journal (Refereed)
    Abstract [en]

    Bio-heat equations (BHEs) are necessary for predicting tissue temperature during thermal treatment. For some applications, however, existing BHEs describe the convective heat transfer by the blood perfusion in an unsatisfactory way. The two most frequently used equations, the BHE of Pennes and the keff equation, use for instance either a heat sink or an increased thermal conductivity in order to account for the blood perfusion. Both these methods introduce modelling inaccuracies when applied to an ordinary tissue continuum with a variety of vessel sizes. In this study, a hybrid equation that includes both an increased thermal conductivity and a heat sink is proposed. The equation relies on the different thermal characteristics associated with small, intermediate and large sized vessels together with the possibilities of modelling these vessels using an effective thermal conductivity in combination with a heat sink. The relative importance of these two terms is accounted for by a coefficient ▀. For ▀ = 0 and ▀ = 1, the hybrid equation coincides with the BHE of Pennes and the keff equation, respectively. The hybrid equation is used here in order to simulate temperature fields for two tissue models. The temperature field is greatly affected by ▀, and the effect is dependent on, e.g. the boundary conditions and the power supply. Since the BHE of Pennes and the keff equation are included in the hybrid equation, this equation can also be useful for evaluation of the included equations. Both these heat transfer modes are included in the proposed equation, which enables implementation in standard thermal simulation programmes.

  • 43.
    Rejmstad, Peter
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Åkesson, Gustav
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Åneman, Oscar
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A laser Doppler system for monitoring of cerebral microcirculation: implementation and evaluation during neurosurgery2016In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, ISSN 0140-0118, Vol. 54, no 1, 123-131 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to adapt and evaluate laser Doppler perfusion monitoring (LDPM) together with custom designed brain probes and software for continuous recording of cerebral microcirculation in patients undergoing neurosurgery. The LDPM system was used to record perfusion and backscattered light (TLI). These parameters were displayed together with the extracted heart rate (HR), pulsatility index (PI) and signal trends from adjustable time intervals. Technical evaluation was done on skin during thermal provocation. Clinical measurements were performed on ten patients undergoing brain tumour surgery. Data from 76 tissue sites were captured with a length varying between 10 s to 15 min. Statistical comparisons were done using Mann-Whitney tests. Grey and tumour tissue could be separated from white matter using the TLI-signal (p < 0.05). The perfusion was significantly higher in grey and tumour tissue compared to white matter (p < 0.005). LDPM was successfully used as an intraoperative tool for monitoring local blood flow and additional parameters linked to cerebral microcirculation (perfusion, TLI, heart rate and PI) during tumour resection. The systems stability opens up for studies in the postoperative care of patients with e.g. traumatic brain injury or subarachnoid haemorrhage.

  • 44.
    Arshamian, Artin
    et al.
    Karolinska Institute, Sweden; Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands; Stockholm University, Sweden.
    Laska, Matthias
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Gordon, Amy R.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA.
    Norberg, Matilda
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Lahger, Christian
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Porada, Danja K.
    Karolinska Institute, Sweden.
    Jelvez Serra, Nadia
    Lund University, Sweden.
    Johansson, Emilia
    Karolinska Institute, Sweden.
    Schaefer, Martin
    Karolinska Institute, Sweden.
    Amundin, Mats
    Kolmarden Wildlife Pk, Sweden.
    Melin, Harald
    Karolinska Institute, Sweden.
    Olsson, Andreas
    Karolinska Institute, Sweden.
    Olsson, Mats J.
    Karolinska Institute, Sweden.
    Stensmyr, Marcus
    Lund University, Sweden.
    Lundstrom, Johan N.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA; University of Penn, PA 19104 USA.
    A mammalian blood odor component serves as an approach-avoidance cue across phylum border - from flies to humans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 13635Article in journal (Refereed)
    Abstract [en]

    Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

  • 45.
    Budde, Kiran Kumar
    Linköping University, Department of Electrical Engineering, Computer Vision.
    A Matlab Toolbox for fMRI Data Analysis: Detection, Estimation and Brain Connectivity2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Functional Magnetic Resonance Imaging (fMRI) is one of the best techniques for neuroimaging and has revolutionized the way to understand the brain functions. It measures the changes in the blood oxygen level-dependent (BOLD) signal which is related to the neuronal activity. Complexity of the data, presence of different types of noises and the massive amount of data makes the fMRI data analysis a challenging one. It demands efficient signal processing and statistical analysis methods.  The inference of the analysis is used by the physicians, neurologists and researchers for better understanding of the brain functions.

         The purpose of this study is to design a toolbox for fMRI data analysis. It includes methods to detect the brain activity maps, estimation of the hemodynamic response (HDR) and the connectivity of the brain structures. This toolbox provides methods for detection of activated brain regions measured with Bayesian estimator. Results are compared with the conventional methods such as t-test, ordinary least squares (OLS) and weighted least squares (WLS). Brain activation and HDR are estimated with linear adaptive model and nonlinear method based on radial basis function (RBF) neural network. Nonlinear autoregressive with exogenous inputs (NARX) neural network is developed to model the dynamics of the fMRI data.  This toolbox also provides methods to brain connectivity such as functional connectivity and effective connectivity.  These methods are examined on simulated and real fMRI datasets.

  • 46.
    Lundengård, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A mechanistic model for blood flow regulation in response to neuronal activity2013Conference paper (Other academic)
  • 47.
    Stålhand, Jonas
    et al.
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Klarbring, Anders
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Holzapfel, Gerhard A
    Graz University of Technology, Institute of Biomechanics, Center of Biomedical Engineering / Royal Institute of Technology, Department of Solid Mechanics, School of Engineering Sciences.
    A mechanochemical 3D continuum model for smooth muscle contraction under finite strains2011In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 268, no 1, 120-130 p.Article in journal (Refereed)
    Abstract [en]

    This paper presents a modelling framework in which the mechanochemical properties of smooth muscle cells may be studied. The activation of smooth muscles is considered in a three-dimensional continuum model which is key to realistically capture the function of hollow organs such as blood vessels. On the basis of a general thermodynamical framework the mechanical and chemical phases are specialized in order to quantify the coupled mechanochemical process. A free-energy function is proposed as the sum of a mechanical energy stored in the passive tissue, a coupling between the mechanical and chemical kinetics and an energy related purely to the chemical kinetics and the calcium ion concentration. For the chemical phase it is shown that the cross-bridge model of Hai and Murphy [1988. Am. J. Physiol. Cell Physiol. 254, C99–C106] is included in the developed evolution law as a special case. In order to show the specific features and the potential of the proposed continuum model a uniaxial extension test of a tissue strip is analysed in detail and the related kinematics and stress–stretch relations are derived. Parameter studies point to coupling phenomena; in particular the tissue response is analysed in terms of the calcium ion level. The model for smooth muscle contraction may significantly contribute to current modelling efforts of smooth muscle tissue responses.

  • 48.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Johansson, Anders
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    A method for accurate localization of the first heart sound and possible applications2008In: Physiological Measurement, ISSN 0967-3334, Vol. 29, no 3, 417-428 p.Article in journal (Refereed)
    Abstract [en]

    We have previously developed a method for localization of the first heart sound (S1) using wavelet denoising and ECG-gated peak-picking. In this study, an additional enhancement step based on cross-correlation and ECG-gated ensemble averaging (EA) is presented. The main objective of the improved method was to localize S1 with very high temporal accuracy in (pseudo-) real time. The performance of S1 detection and localization, with and without EA enhancement, was evaluated on simulated as well as experimental data. The simulation study showed that EA enhancement reduced the localization error considerably and that S1 could be accurately localized at much lower signal-to-noise ratios. The experimental data were taken from ten healthy subjects at rest and during invoked hyper- and hypotension. For this material, the number of correct S1 detections increased from 91% to 98% when using EA enhancement. Improved performance was also demonstrated when EA enhancement was used for continuous tracking of blood pressure changes and for respiration monitoring via the electromechanical activation time. These are two typical applications where accurate localization of S1 is essential for the results.

  • 49.
    Augier, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S.
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA.
    Singley, Erick
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 119, e53305Article in journal (Refereed)
    Abstract [en]

    Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

  • 50.
    Rejmstad, Peter
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Johansson, Johannes D.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy2017In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 10, no 3, 446-455 p.Article in journal (Refereed)
    Abstract [en]

    Continuous measurement of local brain oxygen saturation (SO2) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the “gold standard” in measuring cerebral oxygen pressure (pO2), which is closely related to SO2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO2 for different blood concentrations. The P3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO2. The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5–2%) where pO2 and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile.

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