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  • 201.
    Ahlstrand, Inger
    et al.
    Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för rehabilitering.
    Björk, Mathilda
    Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för rehabilitering.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Börsbo, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Falkmer, Torbjörn
    Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för rehabilitering.
    Smärta och dagliga aktiviteter vid Reumatoid artrit ur ett patientperspektiv2011Conference paper (Other academic)
    Abstract [sv]

    Bakgrund: Smärta vid Reumatoid artrit (RA) ärett välkänt symtom som orsakar lidande ochaktivitetsbegränsning. Traditionellt mäts smärtainom reumatologin som smärtintensitet på enVisuell Analog Skala (VAS). Kunskapen kring hurpatienter med RA upplever smärta och dess konsekvenser är begränsad. Patientens egenbeskrivning behövs som underlag för behandlingsplanering och för att utveckla nya metoderför att beskriva problematiken.Syfte: Syftet med studien är att beskriva smärtavid RA ur ett patientperspektiv med fokus på hursmärtan påverkar dagliga aktiviteter.Metod: Patienter med diagnostiserad RA i syd-östra Sverige identifierades via Svenska Reumatologiregistret. Urvalet baserades på minst 5 årssjukdomsduration och minst 40 mm smärtintensitet på VAS vid de två senaste besöken på reumatologklinik. Sammanlagt 33 patienter, 7 män och26 kvinnor, deltog i sju fokusgrupper. Gruppernaformades utifrån kön och ålder. Intervjuguideninnehöll frågor som: Hur beskriver patienter medRA sin smärta? Vad påverkar smärtan? Vilkakonsekvenser har smärtan för aktivitetsutförande,aktivitetsbalans och undvikande av aktivitet? Enkvalitativ innehållsanalys görs.Resultat/förväntat resultat: Analyser hittills visar patienternas frustration över att inteklara det man vill eller behöver göra, beroendeav andra, minskade möjligheter till delaktigheti sociala sammanhang. Och närståendes betydelse. Analyserna visar att smärtan är relaterad till Göteborg6-8 april 201134trötthet, stress och sinnesstämning och att arbeteeller andra aktiviteter medverkar till att glömmabort smärtan och uppehålla förmåga. Analysenslutförs under hösten.Konklusion: Denna studie förväntas genererany angelägen kunskap om och förståelse försmärta.

  • 202.
    Ahlstrom, G.
    et al.
    Ahlström, G., Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    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.
    Wenneberg, S.
    Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    Gunnarsson, L.G.
    Department of Neurology and Neurophysiology, Örebro University Hospital, Örebro, Sweden.
    A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy2006In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 20, no 2, p. 132-141Article in journal (Refereed)
    Abstract [en]

    Objective: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. Design: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. Setting: Two different counties in Sweden, being either study or control setting. Subjects: The study group comprised 37 adults (21 women, 16 men, mean age 50 years), while the control group comprised 39 people (25 women, 14 men, mean age 46 years). Interventions: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. Main measures: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. Results: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P = 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P = 0.073) when being compared to the study group. Conclusions: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial. © 2006 Edward Arnold (Publishers) Ltd.

  • 203.
    Ahlström, Christer
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Nonlinear phonocardiographic Signal Processing2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis work has been to develop signal analysis methods for a computerized cardiac auscultation system, the intelligent stethoscope. In particular, the work focuses on classification and interpretation of features derived from the phonocardiographic (PCG) signal by using advanced signal processing techniques.

    The PCG signal is traditionally analyzed and characterized by morphological properties in the time domain, by spectral properties in the frequency domain or by nonstationary properties in a joint time-frequency domain. The main contribution of this thesis has been to introduce nonlinear analysis techniques based on dynamical systems theory to extract more information from the PCG signal. Especially, Takens' delay embedding theorem has been used to reconstruct the underlying system's state space based on the measured PCG signal. This processing step provides a geometrical interpretation of the dynamics of the signal, whose structure can be utilized for both system characterization and classification as well as for signal processing tasks such as detection and prediction. In this thesis, the PCG signal's structure in state space has been exploited in several applications. Change detection based on recurrence time statistics was used in combination with nonlinear prediction to remove obscuring heart sounds from lung sound recordings in healthy test subjects. Sample entropy and mutual information were used to assess the severity of aortic stenosis (AS) as well as mitral insufficiency (MI) in dogs. A large number of, partly nonlinear, features was extracted and used for distinguishing innocent murmurs from murmurs caused by AS or MI in patients with probable valve disease. Finally, novel work related to very accurate localization of the first heart sound by means of ECG-gated ensemble averaging was conducted. In general, the presented nonlinear processing techniques have shown considerably improved results in comparison with other PCG based techniques.

    In modern health care, auscultation has found its main role in primary or in home health care, when deciding if special care and more extensive examinations are required. Making a decision based on auscultation is however difficult, why a simple tool able to screen and assess murmurs would be both time- and cost-saving while relieving many patients from needless anxiety. In the emerging field of telemedicine and home care, an intelligent stethoscope with decision support abilities would be of great value.

    List of papers
    1. A method for accurate localization of the first heart sound and possible applications
    Open this publication in new window or tab >>A method for accurate localization of the first heart sound and possible applications
    2008 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 29, no 3, p. 417-428Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Institutionen för medicinsk teknik, 2008
    Keywords
    ensemble averaging, detection, localization, heart sound, bioacoustics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-11856 (URN)10.1088/0967-3334/29/3/011 (DOI)
    Note
    Original publication: C Ahlstrom, T Länne, P Ask and A Johansson, A method for accurate localization of the first heart sound and possible applications, 2008, Physiological Measurement, (29), 3, 417-428. http://dx.doi.org/10.1088/0967-3334/29/3/011. Copyright: Institute of Physics and IOP Publishing Limited, http://www.iop.org/EJ/journal/PMAvailable from: 2008-05-20 Created: 2008-05-20 Last updated: 2017-12-13
    2. Assessing Aortic Stenosis using Sample Entropy of the Phonocardiographic Signal in Dogs
    Open this publication in new window or tab >>Assessing Aortic Stenosis using Sample Entropy of the Phonocardiographic Signal in Dogs
    Show others...
    2008 (English)In: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 55, no 8, p. 2107-2109Article in journal (Refereed) Published
    Abstract [en]

    In aortic valve stenosis (AS), heart murmurs arise as an effect of turbulent blood flow distal to the obstructed valves. With increasing AS severity, the flow becomes more unstable, and the ensuing murmur becomes more complex. We hypothesize that these hemodynamic flow changes can be quantified based on the complexity of the phonocardiographic (PCG) signal. In this study, sample entropy (SampEn) was investigated as a measure of complexity using a dog model. Twenty-seven boxer dogs with various degrees of AS were examined with Doppler echocardiography, and the peak aortic flow velocity (Vmax) was used as a reference of AS severity. SampEn correlated to Vmax with R = 0.70 using logarithmic regression. In a separate analysis, significant differences were found between physiologic murmurs and murmurs caused by AS (p < 0.05), and the area under a receiver operating characteristic curve was calculated to 0.96. Comparison with previously presented PCG measures for AS assessment showed improved performance when using SampEn, especially for differentiation between physiological murmurs and murmurs caused by mild AS. Studies in patients will be needed to properly assess the technique in humans.

    Keywords
    Aortic stenosis (AS), bioacoustics, heart sound, murmur, sample entropy (SampEn)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13042 (URN)10.1109/TBME.2008.923767 (DOI)
    Available from: 2008-03-20 Created: 2008-03-20 Last updated: 2017-12-13
    3. Assessing mitral regurgitation attributable to myxomatous mitral valve disease in dogs using signal analysis of heart sounds and murmurs
    Open this publication in new window or tab >>Assessing mitral regurgitation attributable to myxomatous mitral valve disease in dogs using signal analysis of heart sounds and murmurs
    Show others...
    2008 (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13043 (URN)
    Available from: 2008-03-20 Created: 2008-03-20 Last updated: 2009-03-26
    4. Feature Extraction for Systolic Heart Murmur Classification
    Open this publication in new window or tab >>Feature Extraction for Systolic Heart Murmur Classification
    Show others...
    2006 (English)In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 34, no 11, p. 1666-1677Article in journal (Refereed) Published
    Abstract [en]

    Heart murmurs are often the first signs of pathological changes of the heart valves, and they are usually found during auscultation in the primary health care. Distinguishing a pathological murmur from a physiological murmur is however difficult, why an “intelligent stethoscope” with decision support abilities would be of great value. Phonocardiographic signals were acquired from 36 patients with aortic valve stenosis, mitral insufficiency or physiological murmurs, and the data were analyzed with the aim to find a suitable feature subset for automatic classification of heart murmurs. Techniques such as Shannon energy, wavelets, fractal dimensions and recurrence quantification analysis were used to extract 207 features. 157 of these features have not previously been used in heart murmur classification. A multi-domain subset consisting of 14, both old and new, features was derived using Pudil’s sequential floating forward selection (SFFS) method. This subset was compared with several single domain feature sets. Using neural network classification, the selected multi-domain subset gave the best results; 86% correct classifications compared to 68% for the first runner-up. In conclusion, the derived feature set was superior to the comparative sets, and seems rather robust to noisy data.

    Keywords
    Auscultation, Bioacoustics, Feature selection, Heart sounds, Valvular disease
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-13044 (URN)10.1007/s10439-006-9187-4 (DOI)
    Available from: 2008-03-20 Created: 2008-03-20 Last updated: 2017-12-13
    5. Heart sound cancellation from lung sound recordings using recurrence time statistics and nonlinear prediction
    Open this publication in new window or tab >>Heart sound cancellation from lung sound recordings using recurrence time statistics and nonlinear prediction
    2005 (English)In: IEEE Signal Processing Letters, ISSN 1070-9908, E-ISSN 1558-2361, Vol. 12, no 12, p. 812-815Article in journal (Refereed) Published
    Abstract [en]

    Heart sounds (HS) obscure the interpretation of lung sounds (LS). This letter presents a new method to detect and remove this undesired disturbance. The HS detection algorithm is based on a recurrence time statistic that is sensitive to changes in a reconstructed state space. Signal segments that are found to contain HS are removed, and the arising missing parts are replaced with predicted LS using a nonlinear prediction scheme. The prediction operates in the reconstructed state space and uses an iterated integrated nearest trajectory algorithm. The HS detection algorithm detects HS with an error rate of 4% false positives and 8% false negatives. The spectral difference between the reconstructed LS signal and an LS signal with removed HS was 0.34/spl plusmn/0.25, 0.50/spl plusmn/0.33, 0.46/spl plusmn/0.35, and 0.94/spl plusmn/0.64 dB/Hz in the frequency bands 20-40, 40-70, 70-150, and 150-300 Hz, respectively. The cross-correlation index was found to be 99.7%, indicating excellent similarity between actual LS and predicted LS. Listening tests performed by a skilled physician showed high-quality auditory results.

    Place, publisher, year, edition, pages
    Institutionen för medicinsk teknik, 2005
    Keywords
    Bioacoustics, heart sound (HS), lung sound (LS), nonlinear prediction, recurrence time statistics
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-11857 (URN)10.1109/LSP.2005.859528 (DOI)
    Note
    Original publication: Ahlstrom, C., Liljefeldt, O., Hult, P. and Ask, P., Heart sound cancellation from lung sound recordings using recurrence time statistics and nonlinear prediction, 2005, IEEE Signal Processing Letters, (12), 12, 812-815. http://dx.doi.org/10.1109/LSP.2005.859528. Copyright: IEEE, http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=97Available from: 2008-05-20 Created: 2008-05-20 Last updated: 2017-12-13
  • 204.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Rask, Peter
    University Hospital, Örebro, Sweden .
    Karlsson, Jan-Erik
    County Hospital Ryhov, Jönköping, Sweden.
    Nylander, Eva
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Assessment of Suspected Aortic Stenosis by Auto Mutual Information Analysis of Murmurs2007In: Engineering in Medicine and Biology Society, 2007. EMBS 2007, 2007, p. 1945-1948Conference paper (Refereed)
    Abstract [en]

    Mild sclerotic thickening of the aortic valve affects 25% of the population, and the condition causes aortic valve stenosis (AS) in 2% of adults above 65 years. Echocardiography is today the clinical standard for assessing AS. However, a cost effective and uncomplicated technique that can be used for decision support in the primary health care would be of great value. In this study, recorded phonocardiographic signals were analyzed using the first local minimum of the auto mutual information (AMI) function. The AMI method measures the complexity in the sound signal, which is related to the amount of turbulence in the blood flow and thus to the severity of the stenosis. Two previously developed phonocardiographic methods for assessing AS severity were used for comparison, the murmur energy ratio and the sound spectral averaging technique. Twenty-nine patients with suspected AS were examined with Doppler echocardiography. The aortic jet velocity was used as a reference of AS severity, and it was found to correlate with the AMI method, the murmur energy ratio and the sound spectral averaging technique with the correlation coefficient R = 0.82, R = 0.73 and R = 0.76, respectively.

  • 205.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Rask, P
    Karlsson, J-E
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Using the intelligent stethoscope for extraction of features for systolic heart murmur classification2006In: World Congress on Medical Physics and Biomedical Engineering WC2006,2006, 2006Conference paper (Other academic)
  • 206.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Rask, Peter
    Örebro university.
    Karlsson, Jan-Erik
    Nylander, Eva
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Feature Extraction for Systolic Heart Murmur Classification2006In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 34, no 11, p. 1666-1677Article in journal (Refereed)
    Abstract [en]

    Heart murmurs are often the first signs of pathological changes of the heart valves, and they are usually found during auscultation in the primary health care. Distinguishing a pathological murmur from a physiological murmur is however difficult, why an “intelligent stethoscope” with decision support abilities would be of great value. Phonocardiographic signals were acquired from 36 patients with aortic valve stenosis, mitral insufficiency or physiological murmurs, and the data were analyzed with the aim to find a suitable feature subset for automatic classification of heart murmurs. Techniques such as Shannon energy, wavelets, fractal dimensions and recurrence quantification analysis were used to extract 207 features. 157 of these features have not previously been used in heart murmur classification. A multi-domain subset consisting of 14, both old and new, features was derived using Pudil’s sequential floating forward selection (SFFS) method. This subset was compared with several single domain feature sets. Using neural network classification, the selected multi-domain subset gave the best results; 86% correct classifications compared to 68% for the first runner-up. In conclusion, the derived feature set was superior to the comparative sets, and seems rather robust to noisy data.

  • 207.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Schmekel, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Automatisk detektering av ronki med icke-linjära metoder2004In: Svenska Läkaresällskapets riksstämma,2004, 2004, p. 66-66Conference paper (Other academic)
  • 208.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Schmekel, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Wheeze detection with nonlinear statespace embedding2004In: International Lung Sound Association,2004, 2004, p. 38-39Conference paper (Other academic)
  • 209.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Höglund, Katja
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Häggström, Jens
    Kvart, Clarence
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Assessing Aortic Stenosis using Sample Entropy of the Phonocardiographic Signal in Dogs2008In: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 55, no 8, p. 2107-2109Article in journal (Refereed)
    Abstract [en]

    In aortic valve stenosis (AS), heart murmurs arise as an effect of turbulent blood flow distal to the obstructed valves. With increasing AS severity, the flow becomes more unstable, and the ensuing murmur becomes more complex. We hypothesize that these hemodynamic flow changes can be quantified based on the complexity of the phonocardiographic (PCG) signal. In this study, sample entropy (SampEn) was investigated as a measure of complexity using a dog model. Twenty-seven boxer dogs with various degrees of AS were examined with Doppler echocardiography, and the peak aortic flow velocity (Vmax) was used as a reference of AS severity. SampEn correlated to Vmax with R = 0.70 using logarithmic regression. In a separate analysis, significant differences were found between physiologic murmurs and murmurs caused by AS (p < 0.05), and the area under a receiver operating characteristic curve was calculated to 0.96. Comparison with previously presented PCG measures for AS assessment showed improved performance when using SampEn, especially for differentiation between physiological murmurs and murmurs caused by mild AS. Studies in patients will be needed to properly assess the technique in humans.

  • 210.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    A respiration monitor based on electrocardiographic and photoplethysmographic sensor fusion2004In: IEEE Engineering in Medical and Biological Society,2004, Piscataway, N.J. USA: IEEEEMBS , 2004, p. 2311-Conference paper (Refereed)
  • 211.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Monitorering av andning and blodtrycksförändringar baserat på EKG och hjärtljud2007In: Medicinteknik dagarna,2007, 2007Conference paper (Other academic)
  • 212.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Uhlin, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Noninvasive investigation of blood pressure changes using the pulse wave transit time: A novel approach in the monitoring of hemodialysis patients2005In: Journal of Artificial Organs, ISSN 1434-7229, E-ISSN 1619-0904, Vol. 8, no 3, p. 192-197Article in journal (Refereed)
    Abstract [en]

    Severe blood pressure changes are well known in hemodialysis. Detection and prediction of these are important for the well-being of the patient and for optimizing treatment. New noninvasive methods for this purpose are required. The pulse wave transit time technique is an indirect estimation of blood pressure, and our intention is to investigate whether this technique is applicable for hemodialysis treatment. A measurement setup utilizing lower body negative pressure and isometric contraction was used to simulate dialysis-related blood pressure changes in normal test subjects. Systolic blood pressure levels were compared to different pulse wave transit times, including and excluding the cardiac preejection period. Based on the results of these investigations, a pulse wave transit time technique adapted for dialysis treatment was developed and tried out on patients. To determine systolic blood pressure in the normal group, the total pulse wave transit time was found most suitable (including the cardiac preejection period). Correlation coefficients were r = 0.80 ± 0.06 (mean ± SD) overall and r = 0.81 ± 0.16 and r = 0.09 ± 0.62 for the hypotension and hypertension phases, respectively. When applying the adapted technique in dialysis patients, large blood pressure variations could easily be detected when present. Pulse wave transit time is correlated to systolic blood pressure within the acceptable range for a trend-indicating system. The method's applicability for dialysis treatment requires further studies. The results indicate that large sudden pressure drops, like those seen in sudden hypovolemia, can be detected. © The Japanese Society for Artificial Organs 2005.

  • 213.
    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, E-ISSN 1361-6579, Vol. 29, no 3, p. 417-428Article 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.

  • 214.
    Ahlström, Gerd
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Carlsson, C
    Att visa upp sin värld: Hur personer med stora varaktiga funktionshinder uppfattar sin livssituation relaterat till de etiska principerna i LSS2002Report (Other academic)
  • 215.
    Ahlström, Gerd
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Wennberg, S
    Coping with illness-related problems in persons with progressive muscular diseases: the Swedish version of the Ways of Coping Questionnaire2002In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 16, p. 368-375Article in journal (Refereed)
  • 216.
    Ahmad, Faiyaz
    et al.
    NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA .
    Lindh, Rebecka
    Lund University, Department Expt Med Science, S-22184 Lund, Sweden .
    Tang, Yan
    NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA .
    Ruishalme, Iida
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Sahachartsiri, Bobby
    NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA .
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Degerman, Eva
    Lund University, Department Expt Med Science, S-22184 Lund, Sweden .
    C Manganiello, Vincent
    NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA .
    Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta(3)-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes2009In: BIOCHEMICAL JOURNAL, ISSN 0264-6021, Vol. 424, no 3, p. 399-410Article in journal (Refereed)
    Abstract [en]

    In adipocytes, PDE3B (phosphodiesterase 3B) is an important regulatory effector in signalling pathways controlled by insulin and cAMP-increasing hormones. Stimulation of 3T3-L1 adipocytes with insulin or the beta(3)-adrenergic receptor agonist CL316243 (termed CL) indicated that insulin preferentially phosphorylated/activated PDE3B associated with internal membranes (endoplasmic reticulum/Golgi), whereas CL preferentially phosphorylated/activated PDE3B associated with caveolae. siRNA (small interfering RNA)-mediated KD (knockdown) of CAV-1 (caveolin-1) in 3T3-L1 adipocytes resulted in down-regulation of expression of membrane-associated PDE3B. Insulin-induced activation of PDE3B was reduced, whereas CL-mediated activation was almost totally abolished. Similar results were obtained in adipocytes from Cav-1-deficient mice. siRNA-mediated KID of CAV-1 in 3T3-L1 adipocytes also resulted in inhibition of CL-stimulated phosphorylation of HSL (hormone-sensitive lipase) and perilipin A, and of lipolysis. Superose 6 gel-filtration chromatography of solubilized membrane proteins from adipocytes stimulated with insulin or CL demonstrated the reversible assembly of distinct macromolecular complexes that contained P-32-phosphorylated PDE3B and signalling molecules thought to be involved in its activation. Insulin- and CL-induced macromolecular complexes were enriched in cholesterol, and contained certain common signalling proteins [14-3-3, PP2A (protein phosphatase 2A) and cav-1]. The complexes present in insulin-stimulated cells contained tyrosine-phosphorylated IRS-1 (insulin receptor substrate 1) and its downstream signalling proteins, whereas CL-activated complexes contained beta(3)-adrenergic receptor, PKA-RII [PKA (cAMP-dependent protein kinase)-regulatory subunit] and HSL. Insulin- and CL-mediated macromolecular complex formation was significantly inhibited by CAV-1 KID. These results suggest that cav-1 acts as a molecular chaperone or scaffolding molecule in cholesterol-rich lipid rafts that may be necessary for the proper stabilization and activation of PDE3B in response to CL and insulin.

  • 217.
    Ahmadi, Ahmad
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Genetic predisposition and risk factors for neurodegenerative diseases2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.

    An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).

    Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.

    Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.

    An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.

    Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.

    List of papers
    1. GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset
    Open this publication in new window or tab >>GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset
    Show others...
    2000 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, no 3, p. 676-680Article in journal (Refereed) Published
    Abstract [en]

    Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24837 (URN)10.1006/bbrc.2000.2338 (DOI)9235 (Local ID)9235 (Archive number)9235 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Monoamine oxidase A and B genes polymorphisms in Parkinson's disease
    Open this publication in new window or tab >>Monoamine oxidase A and B genes polymorphisms in Parkinson's disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by degeneration of nig:rostriatal dopaminergic neurons including the loss of cell bodies in the pars compacta of substantia nigra (SN). The mechanism for neurodegeneration is unknown, but the pathogenesis is considered to be multifactorial involving exposure for toxins, genetic inheritance, age, oxidative stress and mitochondrial electron transport chain defects. This study has been focused on polymorphisms in the genes for the enzymes monoamine oxidase A and B (MAO-A, MAO-B) and relation to smoking for the development of idiopathic Parkinson's disease. MAO enzymes are important in the dopamine metabolism and in the detoxification of neurotoxins. During metabolism of dopamine, MAO generates large amounts of free radicals and hydrogen peroxide, and may damage the neurons in substantia nigra, which has been suggested as a pathologic mechanism for PD.

    Blood samples were collected from 256 PD patients, age 30-80 years, and 582 unrelated control individuals, age 31 - 78 years, from southeastern Sweden.

    Two polymorphisms (exon 8 and exon 14) located in the MAO-A gene and one polymorphism located in the MA O-B gene were examined, with denatming HPLC, PCR-RFLP or DNA sequencing. Genotype and allele frequencies were determined for patients and controls. No statistical significant difference was revealed between any of the polymorphisms in the MAO-A and MAO-B genes and Parkinson's disease. Smoking displayed an enviromnental exposure with a strong decreased risk for both male (OR=0.40, 95% CI 0.25 - 0.63) and female (OR=0.48, 95% CI 0.25-0.89) PD without any interaction with MAO genotype.

    The polymorphisms in MAO genes might therefore not be acting as modifiers of risk for developing of PD either by itself or by interacting with smoking. With respect to the size of the study (256 PD patients and 582 controls) MAO polymorphisms do not represent any predisposing factor or a weak PD susceptibility factor.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84799 (URN)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2012-10-22Bibliographically approved
    3. Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's disease
    Open this publication in new window or tab >>Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Mitochondrial dysfunction has been hypothesized to contribute to the pathogenesis of Parkinson's disease (PD). Oxidative stress and production of oxygen radicals is produced in mitochondria. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals. Oxidative stress has also an important role to decrease Complex I activity in the mitochondria. In addition, Complex I contains several subunits, where one, NDUFV2, plays a major role in the electron transport pathway of Complex I in substantia nigra.

    The aim of this project was to study polymorphisms in MTS-SOD2 and the Complex I subunit, NDUFV2 as predisposing factors for the development of idiopathic PD.

    Blood samples from 200 PD and 404 population controls were collected from the Southeastern part of Sweden. DNA was isolated and the polymorphisms were analyzed by pyrosequencing and direct dideoxy termination sequencing.

    Genotypes and allele frequencies were compared for the patient and control groups with Χ2 statistics. No statistical significant difference was evident for any of the polymorphisms neither in MTS-SOD2 (OR=0<85, 95% CI, 0<52-1.38) nor NDUFV2 (OR=0.64, 95% CI, 0.24-1.64) genes and PD.

    These results indicate that the MTS-SOD2 and NDUFV2 gene variants do not contribute to PD pathogenesis.

    Keywords
    SOD2, NDUFV2, polymorphisms, Parkinson's disease
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84800 (URN)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2012-10-22Bibliographically approved
    4. Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy
    Open this publication in new window or tab >>Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy
    Show others...
    1996 (English)In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 22, no 5, p. 360-363Article in journal (Refereed) Published
    Abstract [en]

    Objectives Exposure to organic solvents increases the risk of neuropsychiatric disability or chronic toxic encephalopathy (CTE). Polymorphisms in the biotransformation of xenobiotics and solvents may influence individual susceptibility to develop toxic effects. In this study the problem of whether there could be any association between the glutathione S-transferase M1 (GSTM1) null genotype and the risk for CTE, with regard to solvent exposure, was investigated.

    Methods Sixty patients referred to a clinic because of some degree of some degrees of psychiatric or neurological symptoms, as well as exposure to solvents, were examined by means of a validated questionnaire and psychometric testing. The degree of exposure to solvents was assessed by a thorough interview. According to clinical findings, the patients were classified into three categories as those with solvent-induced CTE, those with incipient CTE, and those who were non-CTE patients. Afterwards, leukocyte DNA (deoxyribonucleic acid) was isolated and the GSTM1 null genotype was determined by an assay based on polymerase chain reaction, blindly with regard to both exposure and disease status.

    Results The relative proportion (RP) of GSTM1 null genotypes was significantly increased for patients with a diagnosed CTE when they were compared with non-CTE patients (RP 2.55, 95% confidence interval 1.0--6.2). Dichotomizing the patients by high and low exposure revealed an increased risk for both GSTM1 gene carriers and the GSTM1 null genotype in the high-exposure group, the relative risks (RR) being 4.5 and 7.9, respectively. The chi-square for the Mantel extension for trend was 6.2 (P=0.025).

    Conclusion The GSTM1 null genotype acts as a risk modifier for CTE among patients occupationally exposed to solvents. The risk seems to increase in a dose-dependent fashion.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84801 (URN)10.5271/sjweh.154 (DOI)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2017-12-07Bibliographically approved
    5. Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy
    Open this publication in new window or tab >>Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy
    2002 (English)In: Toxicology and industrial health, ISSN 0748-2337, E-ISSN 1477-0393, Vol. 18, no 6, p. 289-296Article in journal (Refereed) Published
    Abstract [en]

    Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM 1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

    Keywords
    chronic toxic encephalopathy, molecular epidemiology, polymorphism, smoking, solvent exposure
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46280 (URN)10.1191/0748233702th152oa (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
  • 218.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Monoamine oxidase A and B genes polymorphisms in Parkinson's diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by degeneration of nig:rostriatal dopaminergic neurons including the loss of cell bodies in the pars compacta of substantia nigra (SN). The mechanism for neurodegeneration is unknown, but the pathogenesis is considered to be multifactorial involving exposure for toxins, genetic inheritance, age, oxidative stress and mitochondrial electron transport chain defects. This study has been focused on polymorphisms in the genes for the enzymes monoamine oxidase A and B (MAO-A, MAO-B) and relation to smoking for the development of idiopathic Parkinson's disease. MAO enzymes are important in the dopamine metabolism and in the detoxification of neurotoxins. During metabolism of dopamine, MAO generates large amounts of free radicals and hydrogen peroxide, and may damage the neurons in substantia nigra, which has been suggested as a pathologic mechanism for PD.

    Blood samples were collected from 256 PD patients, age 30-80 years, and 582 unrelated control individuals, age 31 - 78 years, from southeastern Sweden.

    Two polymorphisms (exon 8 and exon 14) located in the MAO-A gene and one polymorphism located in the MA O-B gene were examined, with denatming HPLC, PCR-RFLP or DNA sequencing. Genotype and allele frequencies were determined for patients and controls. No statistical significant difference was revealed between any of the polymorphisms in the MAO-A and MAO-B genes and Parkinson's disease. Smoking displayed an enviromnental exposure with a strong decreased risk for both male (OR=0.40, 95% CI 0.25 - 0.63) and female (OR=0.48, 95% CI 0.25-0.89) PD without any interaction with MAO genotype.

    The polymorphisms in MAO genes might therefore not be acting as modifiers of risk for developing of PD either by itself or by interacting with smoking. With respect to the size of the study (256 PD patients and 582 controls) MAO polymorphisms do not represent any predisposing factor or a weak PD susceptibility factor.

  • 219.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fredriksson, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Jerregård, H.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Åkerbäck, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fall, Per-Arne
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rannug, A.
    National Institute for Working Life, Solna and Inst. of Environ. Medicine, Karolinska Institutet, Stockholm, Sweden.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset2000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, no 3, p. 676-680Article in journal (Refereed)
    Abstract [en]

    Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

  • 220.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Johansson, Sofia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Mitochondrial dysfunction has been hypothesized to contribute to the pathogenesis of Parkinson's disease (PD). Oxidative stress and production of oxygen radicals is produced in mitochondria. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals. Oxidative stress has also an important role to decrease Complex I activity in the mitochondria. In addition, Complex I contains several subunits, where one, NDUFV2, plays a major role in the electron transport pathway of Complex I in substantia nigra.

    The aim of this project was to study polymorphisms in MTS-SOD2 and the Complex I subunit, NDUFV2 as predisposing factors for the development of idiopathic PD.

    Blood samples from 200 PD and 404 population controls were collected from the Southeastern part of Sweden. DNA was isolated and the polymorphisms were analyzed by pyrosequencing and direct dideoxy termination sequencing.

    Genotypes and allele frequencies were compared for the patient and control groups with Χ2 statistics. No statistical significant difference was evident for any of the polymorphisms neither in MTS-SOD2 (OR=0<85, 95% CI, 0<52-1.38) nor NDUFV2 (OR=0.64, 95% CI, 0.24-1.64) genes and PD.

    These results indicate that the MTS-SOD2 and NDUFV2 gene variants do not contribute to PD pathogenesis.

  • 221.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Jonsson, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Flodin, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy2002In: Toxicology and industrial health, ISSN 0748-2337, E-ISSN 1477-0393, Vol. 18, no 6, p. 289-296Article in journal (Refereed)
    Abstract [en]

    Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM 1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

  • 222.
    Ahn, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Baranowski, Jacek
    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.
    Dahlin, Lars-Göran
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Nielsen, Niels-Erik
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Nylander, Eva
    Linköping University, Center for Medical Image Science and Visualization, CMIV. 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.
    Wallby, Lars
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
    TAVI without concomitant balloon dilatation2012Conference paper (Other academic)
  • 223.
    Ahn, Henrik
    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 Thoracic and Vascular Surgery.
    Baranowski, Jacek
    Myasnikova, Irina
    Rahgozar, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine.
    Delshad, Baz
    First in man: wireless pressure sensors in left heart rooms'2014Conference paper (Refereed)
  • 224.
    Ahn, Henrik Casimir
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Mitral valve surgery - current results and future development to catheter based approaches2006In: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Conference paper (Other academic)
  • 225.
    Ahn, Henrik Casimir
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The Impella temporary assist device, the Swedish experience2006In: International Society of Extracorporeal Circulation - Cardiac Surgery beyond 2006,2006, 2006Conference paper (Other academic)
  • 226.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Baranowski, J
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nielsen, Nils Erik
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Nylander, Eva
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Tamas, Eva
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Wallby, Lars
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Transcatheter aortic valve implantation in high-risk surgical candidates with low risk-scores1984Conference paper (Other academic)
  • 227.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Jodal, M.
    Lindhagen, J
    Lundgren, O.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Bestämning av tunntarmsblodflödet med laser Doppler teknik1984In: Läkarsällskapets Riksstämma,1984, 1984Conference paper (Other academic)
  • 228.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johansson, K.
    Lindhagen, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Förändringar av blodflödet i ventrikeln i samband med mätt med laser Dopplerteknik1984In: Läkarsällskapets Riksstämma,1984, 1984Conference paper (Other academic)
  • 229.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johansson, K.
    Lindhagen, J.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Laser Doppler flowmetry in the assessment of gastric blood flow1984In: man. Scand J of Gastroenterology,1984, 1984, p. 98:33-98:33Conference paper (Other academic)
  • 230.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lindhagen, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Jodal, M.
    Lundgren, O.
    Evaluation of Laser Doppler Flowmetry in the assessment of blood flow in the small intestine1984In: Third World Congress of Microcirculation,1984, 1984Conference paper (Other academic)
  • 231.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lindhagen, J
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Jodal, M
    Lundgren, O
    Evaluation of Laser Doppler Flowmetry in the assessment of intestinal blood flow1985In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 4, no 88, p. 951-957Article in journal (Refereed)
    Abstract [en]

      

  • 232.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lönn, Urban
    IMV/Thoraxkirurgi/Hjärtcentrum LiU/HU.
    Peterzén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alternatives to circulatory support during coronary artery surgery1999In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 16 suppl 2, p. 143-150Article in journal (Refereed)
  • 233.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Baranowski, Jacek
    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.
    Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study2016In: Journal of Cardiothoracic Surgery, ISSN 1749-8090, E-ISSN 1749-8090, Vol. 11, no 124Article in journal (Refereed)
    Abstract [en]

    Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.

  • 234.
    Ahn, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Granfeldt, Hans
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Hübbert, Laila
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Peterzén, Bengt
    Linköping University, Department of Medical and Health Sciences, Cardiothoracic Anaesthesia and Intensive care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Long-term mechanical circulatory support in patients with a prosthetic aortic valve2012Conference paper (Other academic)
  • 235.
    Ahn, Jae-Il
    et al.
    Ottawa Hospital, Canada .
    Kuffova, Lucia
    University of Aberdeen, Scotland .
    Merrett, Kimberley
    Ottawa Hospital, Canada .
    Mitra, Debbie
    Ottawa Hospital, Canada .
    Forrester, John V.
    University of Aberdeen, Scotland .
    Li, Fengfu
    Ottawa Hospital, Canada .
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Ottawa Hospital, Canada .
    Crosslinked collagen hydrogels as corneal implants: Effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 8, p. 7796-7805Article in journal (Refereed)
    Abstract [en]

    We have previously shown that recombinant human collagen can be crosslinked with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) to fabricate transparent hydrogels possessing the shape and dimensions of the human cornea. These corneal implants have been tested in a Phase I human clinical study. Although these hydrogels successfully promoted corneal tissue and nerve regeneration, the gelling kinetics were difficult to control during the manufacture of the implants. An alternative carbodiimide capable of producing hydrogels of similar characteristics as EDC in terms of strength and biocompatibility, but with a longer gelation time would be a desirable alternative. Here, we compared the crosslinking kinetics and properties of hydrogels crosslinked with a sterically bulky carbodiimide, N-Cyclohexyl-N-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (CMC), with that of EDC. CMC crosslinking was possible at ambient temperature whereas the EDC reaction was too rapid to control and had to be carried out at low temperatures. The highest tensile strength obtained using optimized formulations were equivalent, although CMC crosslinked hydrogels were found to be stiffer. The collagenase resistance of CMC crosslinked hydrogels was superior to that of EDC crosslinked hydrogels while biocompatibility was similar. We are also able to substitute porcine collagen with recombinant human collagen and show that the in vivo performance of both resulting hydrogels as full-thickness corneal implants is comparable in a mouse model of an orthotopic corneal graft. In conclusion, CMC is a viable alternative to EDC as a crosslinker for collagen-based biomaterials for use as corneal implants, and potentially for use in other tissue engineering applications.

  • 236.
    Ahn, Song Ee
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences.
    Rimpilainen, Sanna
    University of Stirling, UK.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Fenwick, Tara
    University of Stirling, UK.
    Interprofessional training in technology-enhanced medical simulation: Locations and knowings2013In: Conference Programme Book: 8th International Conference on Researching Work and Learning 2013, 2013, p. 15-16Conference paper (Other academic)
    Abstract [en]

    This paper take an actor-network theory perspective on the use of medical simulators in professional education as a means of training students in medical education and nursing in handling acute emergency situations in health care.  The main aim of the study is to investigate what activities are performed in what material arrangements in a full cycle of simulation, i.e  the briefing, the simulation in the emergency room, the observations in the control room and the debriefing and what knowing is produced as an effect of these arrangements.

     The use of simulators has become a common teaching strategy in medical education. An ageing population, declining financial resources and lack of trained health care personnel are global trends that call for changing the system of health care practice as well as for professional education in the sector.  To build more effective health services, professionals are required to work more collaboratively and in partnership with health care consumers (WHO 2008; 2010). Recently, leading medical experts have also criticised the training of health personnel for not adequately preparing for cooperation and inter-professional communication (Frenk et al, 2010). In health care, this concern situations demanding effective communication for making prompt decisions that are of critical importance in emergency situations. Training of students and professionals by means of full-scale simulators is a response to accommodate for these needs.  Education in simulation-based environments is seen to offer opportunities to address the needs for training interprofessional collaboration by focusing on communication, situation awareness, decision making and coping with stress (Arafeh et al 2010; Östergaard et al,2011). Cook et al has shown in a meta analysis of more than 600 research articles, that in comparison with no intervention, technology-enhanced simulation is consistently associated with large effects for outcomes of knowledge, skills, and behaviors but moderate effects for patient-related outcomes (Cook et al 2011). A majority of the studies are effect studies with quantitative designs. The authors argue that there is a need for rigorous, theory based qualitative studies in order to clarify how and when to effectively use technology enhanced simulations in the training of health care professionals.

     The present study draws upon Actor-network theory (Latour, 2005).  This perspective which situates materiality as a part of the social practices, provides theoretical tools for observation and discussion of the relation between the material assemblages and human actors. Observations of full-scale simulations of acute trauma handling in the emergency room with ten groups of medical and nursing students make up the data for analysis. Preliminary findings indicate that the different locations and material arrangements of the simulation cycle produce different kinds of knowing and learning than the intended curriculum objectives. The findings can contribute to the theoretical knowledge of how to design simulation-based medical education.

     

     

     

     

     

  • 237.
    Ahn, Song Ee
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences.
    Rimpiläinen, Sanna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Three locations of technology enhanced medical simulation training and their effect on learning and knowing2014In: Professional Matters: Materialities and virtualities of professional learning, 2014Conference paper (Refereed)
    Abstract [en]

    This qualitative study aims to address the identified gap in literature concerning  the lack of rigorous, theory-based, qualitative studies to clarify how and when to effectively use simulations to train health care professionals (Cook, et al, 2011). By drawing upon actor-network theory (ANT) (Latour, 2005) an approach that situates materiality as a part of the social practices, and provides theoretical tools for observation and discussion of the relation between the material assemblages and human actors, we have investigated how learning takes place during a simulation-based medical training. Knowing and learning, according to ANT, are not simply cognitive or social phenomena, but are seen as emerging as effects of the socio-material networks gathered together and being performed into being in particular locations (Law, 2004; Rimpiläinen, 2011).  In this study we have focussed on observing the socio-material arrangements that emerged in three locations involved in the simulation – the simulation room, the observation room and the reflection room - and analysing what kinds of knowing and learning they have produced through which socio-material arrangements. Data for analysis consists of observations of full-scale simulations of acute trauma handling in the emergency room with ten groups of medical and nursing students.  Preliminary findings indicate that the different locations and material arrangements of the simulation cycle produce different kinds of knowing and learning from the intended curriculum objectives. The findings can contribute to the theoretical knowledge of how to design simulation-based medical education.

  • 238.
    Ahnström, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Askmalm Stenmark, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Fornander, Tommy
    Karolinska University Hospital.
    Skoog, Lambert
    Karolinska University Hospital.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer2009In: International Journal of Oncology, ISSN 1019-6439, Vol. 34, no 2, p. 441-448Article in journal (Refereed)
    Abstract [en]

    Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G(1) phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.93) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).

  • 239.
    Ahnström Waltersson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Cell cycle alterations and 11q13 amplification in breast cancer: prediction of adjuvant treatment response2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.

    List of papers
    1. Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.
    Open this publication in new window or tab >>Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.
    Show others...
    2005 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 91, no 2, p. 145-151Article in journal (Refereed) Published
    Abstract [en]

    Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.

    Keywords
    Beta, fonder, prediction, OLS, LAD, WLS
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17431 (URN)10.1007/s10549-004-6457-4 (DOI)15868442 (PubMedID)
    Available from: 2009-03-25 Created: 2009-03-24 Last updated: 2017-12-13Bibliographically approved
    2. Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer
    Open this publication in new window or tab >>Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer
    Show others...
    2009 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 34, no 2, p. 441-448Article in journal (Refereed) Published
    Abstract [en]

    Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G(1) phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.93) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).

    Keywords
    cell cycle, radiotherapy, chemotherapy, overexpression, Rb, p53
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-16619 (URN)10.3892/ijo_00000168 (DOI)
    Available from: 2009-02-07 Created: 2009-02-06 Last updated: 2017-12-14Bibliographically approved
    3. Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.
    Open this publication in new window or tab >>Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.
    Show others...
    2007 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 26, no 49, p. 6997-7005Article in journal (Refereed) Published
    Abstract [en]

    The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (P<0.001). In ER-positive patients, amplification of at least one of the genes indicated a reduced recurrence-free survival (P=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47-5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32-0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.

    Keywords
    Cyclin D1, pak1, drug resistance, breast cancer, real-time PCR
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17456 (URN)10.1038/sj.onc.1210506 (DOI)17486065 (PubMedID)
    Available from: 2009-03-25 Created: 2009-03-25 Last updated: 2017-12-13Bibliographically approved
    4. miR-206 expression is downregulated in cyclin D1 amplified breast tumours
    Open this publication in new window or tab >>miR-206 expression is downregulated in cyclin D1 amplified breast tumours
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Amplification in the 11q13 region has been found in around 15% of all breast cancers and is strongly correlated with oestrogen receptor (ER) positive tumours. We have previously found that amplification of at least one of the genes PAK1 or CCND1 is associated with decreased recurrencefree survival among ER+ patients. Other genes in the amplicon might also contribute to this effect and situated close to CCND1 are the FGF-3, -4 and - 19 genes. The FGF-4 protein has been shown to inhibit the expression of the ERα regulator miR-206 in chicken embryo. In this study we analysed 23 tumours with and 27 tumours without previously detected 11q13 amplification to explore if 11q13 amplification is associated with decreased levels of miR-206 and if miR-206 is associated with ER expression. Using real-time PCR, we found that miR-206 expression was inversely correlated to CCND1 and 11q13 amplification (P=0.016 and P=0.022 respectively). Tumours with low miR-206 expression had higher levels of ERα than tumours with intermediate and high expression (P=0.043). We conclude that miR-206 might be an important regulator of the ERα. Our finding that low mir-206 is associated with CCND1 amplification and thereby also FGF-4 amplification points towards the possibility of a miR-206 regulator, FGF-4 or another FGF, present in the amplicon.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17457 (URN)
    Available from: 2009-03-25 Created: 2009-03-25 Last updated: 2010-01-14Bibliographically approved
  • 240.
    Ahnström Waltersson, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Fornander, Tommy
    Department of Cytology, Karolinska University Hospital, SE-104 01 Stockholm, Sweden.
    Skoog, Lambert
    Department of Cytology, Karolinska University Hospital, SE-104 01 Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    miR-206 expression is downregulated in cyclin D1 amplified breast tumoursManuscript (preprint) (Other academic)
    Abstract [en]

    Amplification in the 11q13 region has been found in around 15% of all breast cancers and is strongly correlated with oestrogen receptor (ER) positive tumours. We have previously found that amplification of at least one of the genes PAK1 or CCND1 is associated with decreased recurrencefree survival among ER+ patients. Other genes in the amplicon might also contribute to this effect and situated close to CCND1 are the FGF-3, -4 and - 19 genes. The FGF-4 protein has been shown to inhibit the expression of the ERα regulator miR-206 in chicken embryo. In this study we analysed 23 tumours with and 27 tumours without previously detected 11q13 amplification to explore if 11q13 amplification is associated with decreased levels of miR-206 and if miR-206 is associated with ER expression. Using real-time PCR, we found that miR-206 expression was inversely correlated to CCND1 and 11q13 amplification (P=0.016 and P=0.022 respectively). Tumours with low miR-206 expression had higher levels of ERα than tumours with intermediate and high expression (P=0.043). We conclude that miR-206 might be an important regulator of the ERα. Our finding that low mir-206 is associated with CCND1 amplification and thereby also FGF-4 amplification points towards the possibility of a miR-206 regulator, FGF-4 or another FGF, present in the amplicon.

  • 241.
    Ahnström Waltersson, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Rutqvist, Lars Erik
    Department of Oncology, Huddinge University Hospital, Stockholm, Sweden.
    Skoog, Lambert
    Department of Cytology, Karolinska Hospital, Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.2005In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 91, no 2, p. 145-151Article in journal (Refereed)
    Abstract [en]

    Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.

  • 242.
    Aho, Anna Carin
    et al.
    Linnaeus Univ, Dept Hlth & Caring Sci, Vaxjo, Sweden.
    Hultsjö, Sally
    Cty Hosp, Psychiat Clin, Jonkoping, Sweden.
    Hjelm, Katarina
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Young adults' experiences of living with recessive limb-girdle muscular dystrophy from a salutogenic orientation: an interview study.2015In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 37, no 22, p. 2083-2091Article in journal (Refereed)
    Abstract [en]

    To describe young adults' experiences of living with recessive limb-girdle muscular dystrophy (LGMD2) from a salutogenic orientation. Methods: A qualitative explorative interview study, including 14 participants aged 20-30 years, was performed focusing on comprehensibility, manageability and meaningfulness in daily life. Content analysis was used for data analysis. Result: Living with LGMD2 not only implies learning to live with the disease and the variations between good and bad periods but also means trying to make sense of a progressive disease that brings uncertainty about future health, by striving to make the best of the situation. Disease progression involves practical and mental struggle, trying to maintain control over one's life despite vanished physical functions that require continual adjustments to the body. Restrictions in a double sense were described, not only due to the disease but also due to poor comprehension of the disease in society. Lack of knowledge about LGMD2 among professionals often results in having to fight for the support needed. Conclusion: In order to manage daily life, it is important to be seen and understood as an individual in contacts with professionals and in society in general, to have informal social support and meaningful activities as well as access to personal assistance if necessary. Implications for Rehabilitation Recessive limb-girdle muscular dystrophy (LGMD2) is a group of progressive disorders, which manifest in physical and psychological consequences for the individual. According to the salutogenic orientation, people need to find life comprehensible, manageable and meaningful, i.e. to achieve a sense of coherence (SOC), but living with LGMD2 may recurrently challenge the individual's SOC. Through the holistic view of the individual's situation that the salutogenic orientation provides, professionals may support the individual to strengthen SOC and thereby facilitate the movement towards health.

  • 243.
    Ahrén, Maria
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics .
    Olsson, Petter
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Söderlind, Fredrik
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Klasson, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Petoral, Rodrigo Jr
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics .
    Engström, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Käll, Per-Olov
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Physical Chemistry .
    Uvdal, Kajsa
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics .
    Rare earth nanoparticles as contrast agent in MRI: Nanomaterial design and biofunctionalization2007In: IVC-17/ICSS-13 ICNT,2007, 2007Conference paper (Other academic)
  • 244.
    Ahrén, Maria
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Selegård, Linnéa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Klasson, Anna
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Abrikossova, Natalia
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, The Institute of Technology.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Käll, Per-Olov
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement2010In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 26, no 8, p. 5753-5762Article in journal (Refereed)
    Abstract [en]

    Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study, we report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in MRI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3−5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r1 and r2 values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is, an extremely high MR signal at the cellular and molecular level.

  • 245.
    Aifa, Sami
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Aydin, J
    Nordvall, G
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Svensson, Samuel
    Hermanson, O
    A basic peptide within the juxtamembrane region is required for EGF receptor dimerization2005In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 302, no 1, p. 108-114Article in journal (Refereed)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is fundamental for normal cell growth and organ development, but has also been implicated in various pathologies, notably tumors of epithelial origin. We have previously shown that the initial 13 amino acids (P13) within the intracellular juxtamembrane region (R645-R657) are involved in the interaction with calmodulin, thus indicating an important role for this region in EGFR function. Here we show that P13 is required for proper dimerization of the receptor. We expressed either the intracellular domain of EGFR (TKJM) or the intracellular domain lacking P13 (ΔTKJM) in COS-7 cells that express endogenous EGFR. Only TKJM was immunoprecipitated with an antibody directed against the extracellular part of EGFR, and only TKJM was tyrosine phosphorylated by endogenous EGFR. Using SK-N-MC cells, which do not express endogenous EGFR, that were stably transfected with either wild-type EGFR or recombinant full-length EGFR lacking P13 demonstrated that P13 is required for appropriate receptor dimerization. Furthermore, mutant EGFR lacking P13 failed to be autophosphorylated. P13 is rich in basic amino acids and in silico modeling of the EGFR in conjunction with our results suggests a novel role for the juxtamembrane domain (JM) of EGFR in mediating intracellular dimerization and thus receptor kinase activation and function. © 2004 Elsevier Inc. All rights reserved.

  • 246. Aifa, Sami
    et al.
    Johansen, Knut
    Nilsson, Ulrica K
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance2002In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 14, no 12, p. 1005-1013Article in journal (Refereed)
    Abstract [en]

    One early response to epidermal growth factor receptor (EGFR) activation is an increase in intracellular calcium. We have used surface plasmon resonance (SPR) to study real-time interactions between the intracellular juxtamembrane (JM) region of EGFR and calmodulin. The EGFR-JM (Met644-Phe688) was expressed as a GST fusion protein and immobilised on a sensor chip surface. Calmodulin specifically interacts with EGFR-JM in a calcium-dependent manner with a high on and high off rate. Chemical modification of EGFR-JM by using arginine-selective phenylglyoxal or deletion of the basic segment Arg645-Arg657 inhibits the interaction. Phosphorylation of EGFR-JM by protein kinase C (PKC) or glutamate substitution of Thr654 inhibits the interaction, suggesting that PKC phosphorylation electrostatically interferes with calmodulin binding to basic arginine residues. Calmodulin binding was also inhibited by suramin. Our results suggest that EGFR-JM is essential for epidermal growth factor (EGF)-mediated calcium-calmodulin signalling and for signal integration between other signalling pathways.

  • 247.
    Aifa, Sami
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Miled, N
    Frikha, F
    Aniba, MR
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Rebai, A
    Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation2006In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 62, no 4, p. 1036-1043Article in journal (Refereed)
    Abstract [en]

    The mechanism by which ligand-activated EGFR induces autophosphorylation via dimerization is not fully understood. Structural studies have revealed an extracellular loop mediated receptor dimerization. We have previously presented experimental data showing the involvement of a positive 13 amino acid peptide (R645-R657, P13+) from the intracellular juxtamembrane domain (JM) of EGFR important for intracellular dimerization and autophosphorylation. A model was presented that suggest that P13+ interacts with a negative peptide (D979-E991, P13-) positioned distal to the tyrosine kinase domain in the opposite EGFR monomer. The present work shows additional data strengthening this model. In fact, by analyzing protein sequences of 21 annotated ErbB proteins from 9 vertebrate genomes, we reveal the high conservation of peptides P13+ and P13- with regard to their sequence as well as their position relative to the tyrosine kinase (TK) domain. Moreover in silico structure modeling of these ErbB intracellular domains supports a general electrostatic P13+/P13- interaction, implying that the C-terminal of one receptor monomer is facing the TK domain of the other monomer in the receptor dimer and vice versa. This model provides new insights into the molecular mechanism of ErbB receptor activation and suggests a new strategy to pharmacologically interfering with ErbB receptor activity. © 2005 Wiley-Liss, Inc.

  • 248.
    Aili Fagerholm, Siri
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Insulin signaling in primary adipocytes in insulin sensitive and insulin resistant states2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Increasing numbers of people world-wide develops the disease type 2 diabetes. Development of type 2 diabetes is characterized by a shift from an insulin sensitive state to an insulin resistant state in peripheral insulin responding organs, which originates from the development of insulin resistance in the adipose tissue. Insulin resistance in combination with reduced pancreatic insulin secretion lead to overt type 2 diabetes.

    In this thesis, the insulin signaling network in primary adipocytes was analyzed. Key proteins and mechanisms were studied to gain deeper knowledge of signaling both in the insulin sensitive state and in the insulin resistant state produced by rapid weight gain as well as in type 2 diabetes.

    The surface of the adipocyte is dotted with invaginations in the cell membrane called caveolae that act as important metabolic and signaling platforms in adipocytes, and also harbor the insulin receptor. In paper I we show that insulin stimulation of primary adipocytes results in a rapid phosphorylation of the insulin receptor and caveolin-1, and that internalization of the proteins is mediated by endocytosis of caveolae.

    Weight gain due to overfeeding and obesity has been associated with the development of insulin resistance in insulin sensitive tissues such as the adipose tissue. In paper II we show that short-term overfeeding for one month of lean subjects results in an insulin resistant state. At the end of the study, the subjects had developed a mild systemic insulin resistance. Moreover, in isolated subcutaneous adipocytes we found several alterations of the insulin signaling pathway that mimicked alterations found in isolated subcutaneous adipocytes from subjects with type 2 diabetes.

    In paper III we present a first dynamic mathematical model of the insulin signaling network in human adipocytes that are based on experimental data acquired in a consistent fashion. The model takes account of insulin signaling in both the healthy, insulin sensitive state and in the insulin resistant state of type 2 diabetes. We show that attenuated mTORC1-mediated positive feedback to control of phosphorylation of IRS1 at Ser307 is an essential component of the insulin resistant state of type 2 diabetes. A future application of the model is the identification and evaluation of drug targets for the treatment of insulin resistance and type 2 diabetes.

    In paper IV we examine the protein kinase that catalyzes the insulin stimulated mTORC1- mediated feedback to IRS1. We find that the phosphorylation of IRS1 at Ser307 is not likely to be catalyzed by the kinases S6K1, mTOR or PKB. However, a catalyzing protein kinase for the in vitro phosphorylation of IRS1 at Ser307 was found to be associated with the complex mTORC1.

    In conclusion, this thesis provide new insights and characterize mechanisms of the intrinsically complex insulin signaling network of primary adipocytes, both in insulin sensitive and insulin resistant states.

    List of papers
    1. Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
    Open this publication in new window or tab >>Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
    Show others...
    2009 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 4, no 6, p. e5985-Article in journal (Refereed) Published
    Abstract [en]

    Background: The insulin receptor is localized in caveolae and is dependent on caveolae or cholesterol for signaling in adipocytes. When stimulated with insulin, the receptor is internalized. Methodology/Principal Findings: We examined primary rat adipocytes by subcellular fractionation to examine if the insulin receptor was internalized in a caveolae-mediated process. Insulin induced a rapid, t1/2 less than3 min, endocytosis of the insulin receptor in parallel with receptor tyrosine autophosphorylation. Concomitantly, caveolin-1 was phosphorylated at tyrosine(14) and endocytosed. Vanadate increased the phosphorylation of caveolin-1 without affecting insulin receptor phosphorylation or endocytosis. Immunocapture of endosomal vesicles with antibodies against the insulin receptor co-captured caveolin-1 and immunocapture with antibodies against tyrosine(14)-phosphorylated caveolin-1 co-captured the insulin receptor, demonstrating that the insulin receptor was endocytosed together with tyrosine(14)-phosphorylated caveolin-1. By immunogold electron microscopy the insulin receptor and caveolin-1 were colocalized in endosome vesicles that resembled caveosomes. Clathrin was not endocytosed with the insulin receptor and the inhibitor of clathrin-coated pit-mediated endocytosis, chlorpromazine, did not inhibit internalization of the insulin receptor, while transferrin receptor internalization was inhibited. Conclusion: It is concluded that in response to insulin stimulation the autophosphorylated insulin receptor in primary adipocytes is rapidly endocytosed in a caveolae-mediated process, involving tyrosine phosphorylation of caveolin-1.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21319 (URN)10.1371/journal.pone.0005985 (DOI)
    Note
    Original Publication: Siri Fagerholm, Unn Örtegren Kugelberg, M. Karlsson, I. Ruishalme and Peter Strålfors, Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes, 2009, PLoS ONE, (4), 6, e5985. http://dx.doi.org/10.1371/journal.pone.0005985 Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2013-07-08
    2. Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
    Open this publication in new window or tab >>Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
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    2009 (English)In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 15, no 7-8, p. 228-234Article in journal (Refereed) Published
    Abstract [en]

    Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20893 (URN)10.2119/molmed.2009.00037 (DOI)000276043800004 ()
    Available from: 2009-09-24 Created: 2009-09-24 Last updated: 2019-06-28
    3. Insulin Signaling in Type 2 Diabetes: Experimental and Modeling Analyses Reveal Mechanisms of Insulin Resistance in Human Adipocytes
    Open this publication in new window or tab >>Insulin Signaling in Type 2 Diabetes: Experimental and Modeling Analyses Reveal Mechanisms of Insulin Resistance in Human Adipocytes
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    2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 14, p. 9867-9880Article in journal (Refereed) Published
    Abstract [en]

    Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems-level mechanistic understanding of insulin resistance in humans. We developed a dynamic mathematical model of insulin signaling – normally and in diabetes – based on quantitative steady-state and dynamic time-course data on signaling intermediaries in human mature adipocytes. At the core of insulin resistance is attenuation of a positive feedback from mammalian target of rapamycin in complex with raptor (mTORC1) to the insulin receptor substrate-1 (IRS1), which explains reduced sensitivity and signal strength throughout the signaling network. We demonstrate the potential of the model for identification of drug targets, e.g. increasing the feedback restores insulin signaling. Our findings suggest that insulin resistance in an expanded adipose tissue results from cell growth restriction to prevent cell necrosis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84999 (URN)10.1074/jbc.M112.432062 (DOI)000317114000027 ()
    Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2017-12-07Bibliographically approved
    4. Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
    Open this publication in new window or tab >>Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
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    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4Article in journal (Refereed) Published
    Abstract [en]

    The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 phosphorylation on tyrosine residues by the insulin receptor. This in turn directly affects downstream signaling and is in human adipocytes implicated in the pathogenesis of insulin resistance and type 2 diabetes. The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). The mTORC1-downstream p70 ribosomal protein S6 kinase (S6K1), which is activated by insulin, can phosphorylate IRS1 at serine 307 in vitro and is considered the physiological protein kinase. Because the IRS1 serine 307-kinase catalyzes a critical step in the control of insulin signaling and constitutes a potential target for treatment of insulin resistance, it is important to know whether S6K1 is the physiological serine 307-kinase or not. We report that, by several criteria, S6K1 does not phosphorylate IRS1 at serine 307 in response to insulin in intact human primary adipocytes: (i) The time-courses for phosphorylation of S6K1 and its phosphorylation of S6 are not compatible with the phosphorylation of IRS1 at serine 307; (ii) A dominant-negative construct of S6K1 inhibits the phosphorylation of S6, without effect on the phosphorylation of IRS1 at serine 307; (iii) The specific inhibitor of S6K1 PF-4708671 inhibits the phosphorylation of S6, without effect on phosphorylation of IRS1 at serine 307. mTOR-immunoprecipitates from insulin-stimulated adipocytes contains an unidentified protein kinase specific for phosphorylation of IRS1 at serine 307, but it is not mTOR or S6K1.

    Place, publisher, year, edition, pages
    Public Library of Science, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-93257 (URN)10.1371/journal.pone.0059725 (DOI)000317717300032 ()
    Note

    Funding Agencies|Swedish Diabetes Fund||Novo Nordic Foundation||University of Linkoping||Swedish Research Council||

    Available from: 2013-05-28 Created: 2013-05-28 Last updated: 2019-06-28
  • 249.
    Aittomaki, K.
    et al.
    Aittomäki, K., Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland, Department of Clinical Genetics, Helsinki University Central Hospital, POB 140, FI-00029 HUS Helsinki, Finland.
    Bergh, C.
    Department of Obstetrics, Institute of Women and Children's Health, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hazekamp, J.
    Department of Reproductive Medicine, Volvat Medical Center, Oslo, Norway.
    Nygren, K.-G.
    IVF Clinic, Sophiahemmet, Stockholm, Sweden.
    Selbing, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Soderstrom-Anttila, V.
    Söderström-Anttila, V., Infertility Clinic, Family Federation of Finland, Helsinki, Finland.
    Wennerholm, U.-B.
    Department of Obstetrics, Institute of Women and Children's Health, Sahlgrenska University Hospital, Göteborg, Sweden.
    Genetics and assisted reproduction technology2005In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, no 5, p. 463-473Article, review/survey (Refereed)