Change search
Refine search result
1234567 101 - 150 of 18125
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 101.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Grindborg, Jan-Erik
    Statens Strålskyddsinstitut, Stockholm.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Response of Lithium Formate EPR Dosimeters at Photon Energies Relelvant to Brachytherapy2009In: IFMBE Proceedings, Heidelberg: Springer Berlin Heidelberg , 2009, 236-239 p.Conference paper (Other academic)
    Abstract [en]

    After development of sensitive dosimeter materials Electron Paramagnetic Resonance EPR dosimetry has been successfully used also in radiation therapy. The intensity of the EPR-signal is a measure of the amount of free radicals created by ionizing radiation which is proportional to the absorbed dose in the dosimeter. Lithium formate monohydrate is a dosimeter material with 2-6 times higher sensitivity than alanine, a linear dose response over a wide dose range and mass-energy absorption properties similar to water. These properties make lithium formate promising for verification of absorbed doses around high dose rate brachytherapy sources where the dose gradient is steep and the photon energy distribution changing with distance from the source. Calibration of the dosimeters is performed in 60Co or MV photon beams where high dosimetric accuracy is feasible. The use in brachytherapy field relies on the assumption that the production of free radicals per mean absorbed dose in the dosimeter is similar at the lower photon energies present there. The aim of this work was to test that assumption. The response of the dosimeters as a function of photon energy was determined by irradiations with four x-ray qualities in the range 100-250 kV and 137Cs, relative to the response when irradiated with 60Co, all photon beams with well-known air kerma rates at the Swedish Secondary Standards Dosimetry Laboratory. Monte Carlo simulations were used to convert air kerma free in air to mean absorbed dose to the dosimeter. The measured response relative 60Co as a function of photon energy was below unity for all qualities. The maximum deviation from unity was 2.5% (100 kV, 135 kV) with a relative standard deviation of 1.5% (k = 1).

  • 102.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Grindborg, Jan-Erik
    Swedish Radiation Safety Authority, Stockholm, Sweden .
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics. Swedish Radiation Safety Authority, Stockholm, Sweden .
    Response of lithium formate EPR dosimeters at photon energies relevant to the dosimetry of brachytherapy2010In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 37, no 9, 4946-4959 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To investigate experimentally the energy dependence of the detector response of lithium formate EPR dosimeters for photon energies below 1 MeV relative to that at 60Co energies. High energy photon beams are used in calibrating dosimeters for use in brachytherapy since the absorbed dose to water can be determined with high accuracy in such beams using calibrated ion chambers and standard dosimetry protocols. In addition to any differences in mass-energy absorption properties between water and detector, variations in radiation yield (detector response) with radiation quality, caused by differences in the density of ionization in the energy imparted (LET), may exist. Knowledge of an eventual deviation in detector response with photon energy is important for attaining high accuracy in measured brachytherapy dose distributions.

    METHODS:

    Lithium formate EPR dosimeters were irradiated to known levels of air kerma in 25-250 kV x-ray beams and in 137Cs and 60Co beams at the Swedish Secondary Standards Dosimetry Laboratory. Conversions from air kerma free in air into values of mean absorbed dose to the detectors were made using EGSnrc MC simulations and x-ray energy spectra measured or calculated for the actual beams. The signals from the detectors were measured using EPR spectrometry. Detector response (the EPR signal per mean absorbed dose to the detector) relative to that for 60Co was determined for each beam quality.

    RESULTS:

    Significant decreases in the relative response ranging from 5% to 6% were seen for x-ray beams at tube voltages < or = 180 kV. No significant reduction in the relative response was seen for 137Cs and 250 kV x rays.

    CONCLUSIONS:

    When calibrated in 60Co or MV photon beams, corrections for the photon energy dependence of detector response are needed to achieve the highest accuracy when using lithium formate EPR dosimeters for measuring absorbed doses around brachytherapy sources emitting photons in the energy range of 20-150 keV such as 169Yb and electronic sources.

  • 103.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Optimisation of an EPR dosimetry system for robust and high precision dosimetry2014In: Radiation Measurements, ISSN 1350-4487, E-ISSN 1879-0925, Vol. 70, 21-28 p.Article in journal (Refereed)
    Abstract [en]

    Clinical applications of electron paramagnetic resonance (EPR) dosimetry systems demand high accuracy causing time consuming analysis. The need for high spatial resolution dose measurements in regions with steep dose gradients demands small sized dosimeters. An optimization of the analysis was therefore needed to limit the time consumption. The aim of this work was to introduce a new smaller lithium formate dosimeter model (diameter reduced from standard diameter 4.5 mm to 3 mm and height from 4.8 mm to 3 mm). To compensate for reduced homogeneity in a batch of the smaller dosimeters, a method for individual sensitivity correction suitable for EPR dosimetry was tested. Sensitivity and repeatability was also tested for a standard EPR resonator and a super high Q (SHQE) one. The aim was also to optimize the performance of the dosimetry system for better efficiency regarding measurement time and precision. A systematic investigation of the relationship between measurement uncertainty and number of readouts per dosimeter was performed. The conclusions drawn from this work were that it is possible to decrease the dosimeter size with maintained measurement precision by using the SHQE resonator and introducing individual calibration factors for dosimeter batches. It was also shown that it is possible reduce the number of readouts per dosimeter without significantly decreasing the accuracy in measurements.

  • 104.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Olsson, Sara
    Medical Physics and Technology, Växjö Central Hospital, Växjö, Sweden.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    A system for remote dosimetry audit of 3D-CRT, IMRT and VMAT based on lithium formate dosimetry2014In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 113, no 2, 279-282 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to develop and test a remote end-to-end audit system using lithium formate EPR dosimeters. Four clinics were included in a pilot study, absorbed doses determined in the PTV agreed with TPS calculated doses within ±5% for 3D-CRT and ±7% (k=1) for IMRT/VMAT dose plans.

  • 105.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Karlsson, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Swedish Radiation Safety Authority, Stockholm, Sweden .
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Olsson, Sara
    Central Hospital Växjö, Sweden.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Investigation of signal fading in lithium formate EPR dosimeters using a new sensitive method2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 8, 2209-2217 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate signal fading in lithium formate electron paramagnetic resonance (EPR) dosimeters used for clinical applications in radiotherapy. A new experimental method for determination of signal fading, designed to resolve small changes in signal from slowly decaying unstable radicals, was used. Possible signal fading in lithium formate due to different storage temperatures was also tested. Air humidity was kept at a constant level of 33% throughout the experiments. The conclusion drawn from the investigations was that the EPR signal from lithium formate is stable during at least 1 month after irradiation and is not sensitive to variations in storage temperature andlt;40 degrees C when kept at a relative air humidity of 33%. This makes lithium formate a suitable dosimeter for transfer dosimetry in clinical audits.

  • 106.
    Adolfsson, Emelie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences.
    Smide, B.
    Dept. of Pub. Hlth. and Caring Sci., Uppsala University, Uppsala, Sweden.
    Gregeby, E.
    Köping Hospital, Köping, Sweden.
    Fernstrom, L.
    Fernström, L., Diabet. Educ. and Research Centre, Karolinska Hospital, Karolinska, Sweden.
    Wikblad, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Welfare and Care (IVV), Self-Care and Learning.
    Implementing empowerment group education in diabetes2004In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 53, no 3, 319-324 p.Article, review/survey (Refereed)
    Abstract [en]

    The overall aim was to gain insight into and understand how physicians and nurses view the implementation of empowerment group education (EGE) in diabetes. Prior to the study the physicians and nurses attended a 2-day empowerment workshop. Further, they had implemented the empowerment approach in two groups of patients with type II diabetes. Three to 9 months later they (five physicians and 11 nurses from six family practices) participated in focus group interviews to evaluate the implementation of the EGE. The interviews were audio-taped, transcribed and analysed using the constant comparative method. The main result showed a conflict in roles. The physicians and nurses knew their role in the traditional approach but not with respect to the empowerment approach, which they needed to grow into. At the same time as they started a new way of working, their role had changed from being an expert to being a facilitator. As experts they felt secure, as facilitators they needed support in their educational process. To implement EGE they required support both from the family practice and from a supervisor in direct connection with the EGE. © 2004 Elsevier Ireland Ltd. All rights reserved.

  • 107.
    Adolfsson, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    White, Shane
    Department of Radiation Oncology (MAASTRO), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.
    Landry, Guillaume
    Department of Radiation Oncology (MAASTRO), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering.
    Verhaegen, Frank
    Department of Radiation Oncology (MAASTRO), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.
    Reniers, Brigitte
    Department of Radiation Oncology (MAASTRO), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Alm Carlsson, Gudrun
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Measurement of absorbed dose to water around an electronic brachytherapy source: Comparison of two dosimetry systems: lithium formate EPR dosimeters and radiochromic EBT2 film2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 9, 3869-3882 p.Article in journal (Refereed)
    Abstract [en]

    Interest in high dose rate (HDR) electronic brachytherapy operating at 50 kV is increasing. For quality assurance it is important to identify dosimetry systems that can measure the absorbed doses in absolute terms which is difficult in this energy region. In this work a comparison is made between two dosimetry systems, EPR lithium formate dosimeters and radiochromic EBT2 film.

    Both types of dosimeters were irradiated simultaneously in a PMMA phantom using the Axxent EBS. Absorbed dose to water was determined at distances of 10 mm, 30 mm and 50 mm from the EBS. Results were traceable to different primary standards as regards to absorbed dose to water (EPR) and air kerma (EBT2). Monte Carlo simulations were used in absolute terms as a third estimate of absorbed dose to water.

    Agreement within the estimated expanded (k = 2) uncertainties (5% (EPR), 7% (EBT2)) was found between the results at 30 mm and 50 mm from the x-ray source. The same result was obtained in 4 repetitions of irradiation, indicating high precision in the measurements with both systems. At all distances, agreement between EPR and Monte Carlo simulations was shown as was also the case for the film measurements at 30mm and 50mm. At 10mm the geometry for the film measurements caused too large uncertainty in measured values depending on the exact position (within sub-mm distances) of the EBS and the 10 mm film results were exculded from comparison.

    This work has demonstrated good performance of the lithium formate EPR dosimetry system in accordance with earlier experiments at higher photon energies (192Ir HDR brachytherapy). It was also highlighted that there might be issues regarding the energy dependence and intrinsic efficiency of the EBT2 film that need to be considered for measurements using low energy sources.

  • 108. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Ahlgren, Göran
    Ahlstrand, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Andrén, Ove
    Bill-Axelson, Ann
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karinq
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Pettersson, Bill
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Törnblom, Magnus
    Widmark, Anders
    Stattin, Pär
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 20052007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 6, 456-477 p.Article in journal (Refereed)
    Abstract [en]

    Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer. © 2007 Taylor & Francis.

  • 109.
    Adolfsson, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Arthroscopic removal of os centrale carpi causing wrist pain.2000In: Arthroscopy: The Journal of Arthroscopy And Related, ISSN 0749-8063, E-ISSN 1526-3231, Vol. 16, 537-539 p.Article in journal (Refereed)
    Abstract [en]

    The Os centrale carpi is a relatively rare accessory carpal bone of the wrist that infrequently has been reported to cause symptoms. This report describes 2 cases where an apparently mobile Os centrale carpi caused painful clicking and crepitus and where the symptoms disappeared after arthroscopic removal of the ossicles.

  • 110.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Arthroscopic synovectomy in wrist arthritis2005In: Hand Clinics, ISSN 0749-0712, E-ISSN 1558-1969, Vol. 21, no 4, 527-530 p.Article, review/survey (Refereed)
    Abstract [en]

    Arthroscopic synovectomy is a safe outpatient procedure with minimal postoperative morbidity. In patients who have rheumatoid arthritis and possibly also in patients who have JRA, SLE, and postinfectious arthritis, a long period of increased comfort and improved function can be anticipated. The procedure may be considered in post-traumatic cases with joint contracture and as an adjunct to other measures for certain osteoarthritic disorders. In patients who have septic arthritis with insufficient clinical improvement after systemic antibiotics and lavage, arthroscopic synovectomy seems advantageous. © 2005 Elsevier Inc. All rights reserved.

  • 111.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Arthroscopic Synovectomy of the Wrist2011In: Hand Clinics, ISSN 0749-0712, E-ISSN 1558-1969, Vol. 27, no 3, 395-399 p.Article in journal (Refereed)
    Abstract [en]

    Arthroscopic synovectomy is safe and reliable, with mild postoperative morbidity. The rationale of a surgical synovectomy is to excise inflamed synovium and thereby, remove as much effusion and inflammatory substrate as possible. In most cases, arthroscopic synovectomy is performed as an outpatient procedure. The technique has also been used for other diagnoses causing wrist arthritis, but very few results have been reported and the indications remain to be defined. In rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and post-infectious monoarthritis, a long period of increased comfort and improved function can be anticipated.

  • 112.
    Adolfsson, Lars
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Arthroscopy in the upper extremity1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This stndy comprising six separate papers, is concerned with the techniques of, and bevaluation of arthroscopy as a diagnostic and therapeutic tool in different pathologic conditions in the upper extremity.

    Arthroscopy proved to increase diagnostic accuracy in 177 examined patients with anterior shoulder instability or shoulder pain. Previously not well described patterns of pathological morphology in the ventral joint capsule after anterior shoulder dislocations were disclosed. A new classification system of rotator cuff pathology to be used for arthroscopy in the subacromial impingement syndrome is suggested. Different stages of rotator cuff pathology were found to influence the clinical results after arthroscopic acromioplasty in 79 patients.

    An anatomical stndy on 16 cadaver elbows revealed the close proximity between commonly used arthroscopic portals and important neurovascular structures. The usefulness and potential risks of each portal were demonstrated and a preferred procedure for diagnostic elbow arthroscopy was suggested.

    Wrist arthroscopy was performed in 30 patients with long-standing post-traumatic pain and resulted in increased diagnostic accuracy. In patients where clinical examination and radiography had shown no abnormality, arthroscopy demonstrated serious carpal ligament injuries and related instability.

    A technique for arthroscopic wrist synovectomy was described in patients with rheumatoid arthritis. In 18 wrists of 16 patients, a reasonably radical synovectomy could be achieved with this atraumatic method. Primary results showed decreased pain and increased grip-strength in all patients and an increased range of motion in some.

  • 113.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Fractures of the Distal Humerus: Total Elbow Arthroplasty (Hemi-Arthroplasty)2014In: European Surgical Orthopaedics and Traumatology / [ed] George Bentley, Heidelberg: Springer Berlin/Heidelberg, 2014, 3, 1407-1422 p.Chapter in book (Other academic)
    Abstract [en]

    This important reference textbook covers the surgical management of all major orthopaedic and traumatological conditions. The book will act as the major source of education and guidance in surgical practice for surgeons and trainees, especially those preparing for higher surgical examinations and the Board of Orthopaedics and Traumatology examinations within and beyond Europe. The emphasis throughout is on the application of current knowledge and research to technical problems, how to avoid operative problems, and how to salvage complications if they occur. The didactic text is complemented by abundant illustrations that highlight the essentials of each clinical scenario. The authors are all recognized international authorities active at congresses and workshops as well as in universities and hospitals across the world. ​

  • 114.
    Adolfsson, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Open vs. arthroscopic synovectomy of the wrist2006In: Excerpta Medica: International Congress Series, ISSN 0531-5131, E-ISSN 1873-6157, Vol. 1295, 56-62 p.Article in journal (Refereed)
    Abstract [en]

    Synovectomy may be considered for the treatment of chronic wrist arthritis. The indications for wrist synovectomy are, however, not clearly defined. Open synovectomy has been reported to provide good pain relief for a relatively long time but can be associated with loss of mobility. Arthroscopic synovectomy seems equally reliable in terms of symptom reduction and no adverse effects have been reported. © 2006 Elsevier B.V. All rights reserved.

  • 115.
    Adolfsson, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Hammer, R.
    Orthopaedic Surgery, Central Hospital, SE-291 85 Kristianstad, Sweden.
    Elbow hemiarthroplasty for acute reconstruction of intraarticular distal humerus fractures: A preliminary report involving 4 patients2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 5, 785-787 p.Article in journal (Refereed)
    Abstract [en]

    We treated 4 female patients (mean age 80) with complex intraarticular acute fracture of the distal humerus with a Kudo humeral component, i.e. a hemiarthroplasty. All fractures were considered impossible to treat with open reduction and internal fixation. At mean 10 (3-14) months, 3 patients had an excellent result and 1 a good result according to the Mayo elbow performance score. We conclude that a hemiarthroplasty may be a valuable alternative in eldery patients with complex fractures of the distal humerus. Copyright© Taylor & Francis 2006.

  • 116.
    Adolfsson, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Lysholm, J
    Ortopedklin Boden.
    Nettelblad, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Adverse effects of extensive clavicular resections and a suggessted method of reconstruction.1999In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 8, 361-365 p.Article in journal (Refereed)
  • 117.
    Adolfsson, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Nestorson, Jens
    Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    The Kudo humeral component as primary hemiarthroplasty in distal humeral fractures2012In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 21, no 4, 451-455 p.Article in journal (Refereed)
    Abstract [en]

    Background: Treatment of intra-articular fractures of the distal humerus in the elderly is challenging. In patients with very distal fractures and severe comminution, primary arthroplasty has been advocated. Recently, a few reports have described promising results of hemiarthroplasty. This study describes the medium-term results of using the Kudo humeral implant (Biomet Ltd, Bridgend, U. K.) as replacement of the distal humerus. less thanbrgreater than less thanbrgreater thanMaterial and methods: Eight women (mean age, 79 years) were treated. Follow-up was conducted at a mean of 4 years after the procedure and consisted of the Mayo Elbow Performance Score (MEPS), radiographic images, and range of motion (ROM). less thanbrgreater than less thanbrgreater thanResults: All patients had a good or excellent outcome according to the MEPS. Mean ROM was 31 degrees to 126 degrees. Radiographic signs of attrition of the ulna were observed in 3 patients but did not correlate with the functional outcome. A periprosthetic fracture occurred in 1 patient 3 years after the index operation, and ROM was unsatisfactory in 1 patient. No other complications were observed. less thanbrgreater than less thanbrgreater thanConclusion: The use of the Kudo humeral implant as a hemiarthroplasty resulted in a reasonable functional outcome in the medium-term, but the radiographic signs of attrition suggest that the implant is not recommended as a hemiprosthesis.

  • 118.
    Adolfsson, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Povlsen, B
    Arthroscopic findings in wrists with severe post-traumatic pain despite normal standard radiographs2004In: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, E-ISSN 1532-2211, Vol. 29 B, no 3, 208-213 p.Article in journal (Refereed)
    Abstract [en]

    This study assessed the role of diagnostic arthroscopy following a wrist injury in patients with normal standard radiographs, an unclear clinical diagnosis and persistent severe pain at 4 to 12 weeks. Forty-three patients were included after conservative management had failed to improve their wrist pain so that a stability test could be performed satisfactorily and underwent arthroscopy within 12 weeks. Arthroscopy revealed recent pathology in 41 wrists, of which 17 had significant ligament lesions that might have benefited from acute repair. We conclude that patients with marked persistent post-traumatic symptoms despite conservative management are likely to have sustained ligament injuries despite normal radiographs. We therefore recommend that under these circumstances an arthroscopy is carried out within 4 weeks if the patient and surgeon wish to acutely repair significant ligament injuries.

  • 119. Adolfsson, L.E.
    et al.
    Nettelblad, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Radial nerve entrapment in the upper arm as a cause of lateral arm pain: A report of four cases2001In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 35, no 2, 217-220 p.Article in journal (Refereed)
    Abstract [en]

    Four patients with no history of trauma presented with lateral arm pain, local tenderness, and a tingling sensation at the distal end of the arm when the radial nerve was percussed in the mid-third of the upper arm (Tinel's sign), but no clinical or subjective signs of muscular weakness. They were treated by decompression of the radial nerve in the fibrous canal proximal to the lateral intermuscular septum. Three of the patients had a complete or pronounced reduction in pain, while the fourth had only a slight improvement. Non-traumatic radial nerve entrapment in the upper arm may be the cause of lateral arm pain without clinical signs of muscular weakness.

  • 120.
    Adolfsson, Per
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.

    This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).

    Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).

    In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.

    In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.

    In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.

    The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.

    In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.

  • 121.
    Adolfsson, Per
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlstrand, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition2002In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 51, no 1, 50-58 p.Article in journal (Refereed)
    Abstract [en]

    Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

    Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

    Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

    Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

  • 122.
    Adolfsson, Per
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Haug, Ingrid
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas2000In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, no 9, 835-842 p.Article in journal (Refereed)
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

  • 123.
    Adolfsson, Per I.
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlstrand, Christer
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Hultgren, Sitti
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel P. S.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cellsManuscript (preprint) (Other academic)
    Abstract [en]

    The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.

    In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.

    First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.

    The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

  • 124.
    Adolfsson, Per I
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, 704.e15-704.e19 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 125.
    Adolfsson, Per I.
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Dahle, Lars Olav
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel P. S.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium1998In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 45, no 3, 145-150 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

    In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.

  • 126.
    Aerts, Joel
    et al.
    University of Liege, Belgium; University of Paris 07, France.
    Ballinger, James R.
    Guy's and St Thomas' Hospital, London, UK.
    Behe, Martin
    ETH PSI USZ Paul Scherrer Institute, Villigen-PSI, Switzerland.
    Decristoforo, Clemens
    Innsbruck Medical University, Austria.
    Elsinga, Philip H.
    University of Groningen, Netherlands.
    Faivre-Chauvet, Alain
    CHU Nantes, France.
    Mindt, Thomas L.
    University Hospital Basel, Switzerland.
    Kolenc Peitl, Petra
    University Medical Centre Ljubljana, Slovenia.
    Todde, Sergio C.
    University of Milano-Bicocca, Italy.
    Koziorowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective2014In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, no 10, 615-620 p.Article in journal (Refereed)
    Abstract [en]

    This document is meant to complement Part B of the EANM Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.

  • 127.
    af Klercker, Tom
    Linköping University, Department of Department of Health and Society, General Practice. Linköping University, Faculty of Health Sciences.
    Method for inductive case-based decision support system over the Internet: exemplified by ear, nose and throat diagnostics in primary care1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is an example of an ear to loaf process:

    A Preliminary Essential Data Set (PEDS) for Ear, Nose and Throat (ENT) diagnostics in Primary Health Care (PHC) was established by infologic modelling of existing tractates, between the specialist organisations of ENT and PHC, and four contemporary text-books on the subject (I). The PEDS was then compared to the aggregated data from a sample of case-files from a Swedish PHC centre. The quality of the individual medical record was found to be poor and not sufficient for follow-up and Quality Management (QM) purposes (II). The aggregated data from the case-file sample was processed by an inductive "expert" computer program that generated a decision-tree, based on the total number of decisions (diagnoses) in the data-base. This was nearly identical to the PEDS and somewhat less complicated. Infological modelling of the PEDS and the decision-tree resulted in the proposed Essential Data Set (EDS) for ENT diagnostics in PHC. The decision tree was "pruned" to achieve simplicity and ease of use (III). It was converted into a Computer-aided Decision Support System (CDSS) and put on the Internet using World Wide Web (WWW) tools (IV). This system was then implemented in the Skänninge PHC centre where an Electronic Medical Record System (EMRS) was in everyday use. Due to technical difficulties no integration between the two systems was possible. The CDSS was run on a computer outside the centre and this raised the question of secrecy and security (V). Prior to the implementation, and after a study period of four months attitudes towards, and the acceptance of, new Information Technology (IT) was explored by using focus group methodology (VI). It is important that those who are to use the system are intimately involved in its development. The results showed, that participation of the end-users during implementation is crucial for its acceptance. The need for a uniform and agreed terminology was obvious to facilitate co-operation and QM. The importance of nurses and physicians using the same terminology for documentation, was paramount.

  • 128.
    Afoke, Anthony Okoro
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.

    A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.

    While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.

  • 129.
    Afrell, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Att leva med en kropp som värker: samtal med fysioterapeuten2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aim: Physiotherapists in primary care meet, assess and treat patients with long-standing benign musculoskeletal pain. As a clinical condition, long-standing pain is common but nonetheless it is quite complex. The aim of this thesis has been, from a bodily existential perspective, to investigate and conceptualise the experience of living with longstanding benign musculoskeletal pain, and from there, to work out a method for conversation and assessment within non-specialised physiotherapy.

    Methods: Our first study was an interview study where we applied a phenomenological approach and investigated the ways individuals suffering from long-standing pain experienced their body and their illness. Four aspects of body experience were described, and based on these aspects, four typologies of attitudes to pain were distinguished. In the second study, we made two group interviews with six physiotherapists about their experiences of using, in their clinical work, questions from the interview guide in study I that had given particularly rich responses. Transcripts were analysed using phenomenography. In the third study, patients’ verbal responses to the key questions, directed to them by physiotherapists in clinical situations, were investigated, and the four aspects of body experience from study I formed the concepts of a deductive analysis. In study IV, finally, the key questions and typologies were tried by a larger group (31), and their experiences and the possible applicability of the method were studied by qualitative content analysis combined with the counting of codes.

    Results: We created four typologies of attitudes to long-standing pain: “Surrendering to one’s fate”, “Accepting by an active process of change”, “Balancing between hope and resignation” and “Rejecting the body”. These typologies, in turn, were based on four aspects of body experience: “The body as an aspect of identity”. “Body reliance”, “Body awareness”, and “Ways of understanding pain”. In study II, by the aid of key questions,  patient and physiotherapist managed to have a conversation on bodily existential matters. The physiotherapist learnt to know the patient as a person, a process appeared to be initiated in the patient, and their relation changed. The patient was willing to talk about her body in pain, and had the words to do this. In study III, the key questions opened ways to reflections on body, existence, and biography. The four aspects of body experience were central to the patients’ descriptions. In study IV, the participating physiotherapists reported by large positive experiences from applying key questions and typologies. The patients reflected, emotions were evoked, and the relation and the communication often improved. The typologies helped in giving a comprehensive perspective of the patient’s problem, and to grasp where in the process of rehabilitation the patient was to be found.

    Conclusions: The method, seven key questions combined with the tentative frame of interpretation of the answers, seemed to be easily applied by interested physiotherapists in non-specialised practice. The application of the method addresses the need of developing the professional role of the physiotherapist. The challenge is to face the whole person, who is her lived body as well as her identity crisis, carried by emotions such as grief and anger. This may inspire the use of the full potential of the physiotherapist’s professional role in the clinical encounter.

  • 130.
    Afrell, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Samrehab, Kalmar County Council, Västervik Hospital, Sweden.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Clinical Physiology, Kalmar County Hospital, Kalmar, Sweden.
    Rudebeck, Carl Edvard
    Department of Community Medicine, University of Tromsö, Norway / The Research Unit, Kalmar County Council, Sweden.
    Improving the interaction between the physiotherapist and the patient with long-lasting pain2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: To investigate whether it would be possible to improve the understanding and communication between physiotherapists and patients with long-lasting pain by, in a systematic way, approaching their condition from a bodily existential perspective.

    Method: 31 physiotherapists answered written open questions about what happened when they in 90 encounters used key questions about living with pain together with a tentative frame for interpreting the answers - typologies of approaches to living with long-lasting pain. In the analysis, we combined qualitative content analysis with the counting of the numbers of codes.

    Results: According to the physiotherapists, patients were positive to answering the key questions, which also evoked emotional responses and reflection. The relation between the physiotherapists and their patients improved. The typologies helped the physiotherapists understand their patients better, as well as in assessing the patients’ problems and choosing treatment. In all, positive experience clearly dominated. Conclusion: When used by physiotherapists with an interest in patients with longlasting pain, the key questions and typologies seem to enrich the clinical interaction in many cases. To try the generalisability of our findings, we regard it an interesting possibility to conduct a larger, quantitative questionnaire study based on the experiences and results of the present one.

  • 131.
    Afrell, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Samrehab, Västerviks sjukhus, Kalmar County Council, Sweden.
    Rudebeck, Carl Edvard
    Department of Community Medicine, Tromsö University, Tromsö, Norway / The Research Unit, Kalmar County Council, Sweden.
    Telling about long-lasting pain – the role of key questions in physiotherapy encounters2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Aim: For a physiotherapist in primary care wishing to meet her/his patient in the entirety of possible causes of long-lasting pain, the ability to perceive its nuances and context is indispensable.

    The aim was to investigate the verbal responses of patients with long-lasting pain to key questions addressing their biography, identity and lived body.

    Methodology: Three Swedish physiotherapists asked eight patients with long-lasting pain seven questions regarding body experience at the introductory and concluding, tape-recorded, treatment sessions. A deductive, qualitative analysis was made through four concepts naming aspects of body experience: body reliance, body awareness, models for explaining pain and the body’s integration in the identity.

    Major findings: The key questions opened ways to bodily-existential reflections. The aspects of body experience were central to the patients’ descriptions. Appreciable differences emerged between the patients in how they described the experience of living with pain, and in some cases differences were seen between the conversations of the first and the last treatment session with the same patient.

    Conclusions: The questions addressed crucial issues of living with pain and seem to have a potential to capture changes in body experience. Physiotherapists may recognize their patients’ biographical disruptions, reconstruction and adapt their treatment accordingly.

  • 132.
    Afrell, Maria
    et al.
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Rudebeck, Carl Edvard
    University of Tromso.
    We got the whole story all at once: physiotherapists use of key questions when meeting patients with long-standing pain2010In: SCANDINAVIAN JOURNAL OF CARING SCIENCES, ISSN 0283-9318, Vol. 24, no 2, 281-289 p.Article in journal (Refereed)
    Abstract [en]

    Long-standing musculoskeletal pain has many dimensions. Physiotherapy lacks a tested method of dialogue with which physiotherapists and patients can together explore pain in all its complexity. The present aim was to find out how physiotherapists experienced the influence of systematically prepared key questioning on their relation to, and understanding of, patients with long-standing pain. A group of six physiotherapists with long experience of pain rehabilitation used such questions in their encounters with their patients. Two periods of work with the questions were followed by discussions in which the physiotherapists shared their experience in a joint focus group. Verbatim transcripts of the discussions constitute the data of the study. A phenomenographic method was used for the analysis. The responses to the key questions gave the physiotherapists an insight into the patient as a person. The questions started a process of change in the patient, and changed the physiotherapists relation to her or him. The patient expressed feelings and experience, and this also seemed to encourage a change in chosen coping strategies. This new content of the interaction challenged the physiotherapists role, thus raising questions about her professional mandate.

  • 133.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Wnt signaling and metaphyseal bone healing2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.

    Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.

    Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.

    Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.

    In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.

  • 134.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, P
    University of Gothenburg.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae2012In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 23, no 3, 743-752 p.Article in journal (Refereed)
    Abstract [en]

    Implant fixation in bone can be improved by a coating that delivers bisphosphonates locally, or by a hydroxyapatite (HA) coating. In this study, we compared these different types of coatings. For mechanical testing, 30 rats were assigned into three groups, and similar screws were implanted bilaterally in the proximal tibiae. The rats received screws that were either uncoated, coated with nano-crystalline hydroxyapatite or coated with a bisphosphonate releasing protein matrix. After 4 weeks, one screw was subjected to pull-out testing, and the contra-lateral one to torsion testing. For morphology, 30 rats were assigned to similar treatment groups, but received only one screw each. Bisphosphonates enhanced the pull-out force by 41% (P = 0.02) compared to controls, HA increased the pull-out force although not significantly. Conversely, HA increased the maximal torque by 64% (P = 0.02). Morphometry showed higher bone volume around bisphosphonate screws in comparison to HA-coated screws (P andlt; 0.001) and controls (P andlt; 0.001). The results suggest that bisphosphonates improve fixation by increasing the amount of surrounding bone, whereas HA mainly improves bone to implant attachment.

  • 135.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    University of Gothenburg.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    A win for bisphosphonates? Comparison between local bisphosphonate release and hydroxyapatite coating for screw fixation in rats in BONE, vol 46, issue , pp S67-S672010In: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, S67-S67 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 136.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Experimental results of combining bisphosphonates with allograft in a rat model2009In: Journal of Bone and Joint Surgery - Series B, ISSN 0301-620X, Vol. 91, no 5, 670-675 p.Article in journal (Refereed)
    Abstract [en]

    Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where nonimpacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

  • 137.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Reduced serum serotonin impairs metaphyseal repair in rats in BONE, vol 46, issue , pp S67-S672010In: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, S67-S67 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 138.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Wnt signaling and orthopedics, an overview2011In: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 82, no 2, 125-130 p.Article in journal (Refereed)
    Abstract [en]

    Wnt signaling is a ubiquitous system for intercellular communication, with multiple functions during development and in homeostasis of the body. It comprises several ligands, receptors, and inhibitors. Some molecules, such as sclerostin, appear to have bone-specific functions, and can be targeted by potential drugs. Now, ongoing clinical trials are testing these drugs as treatments for osteoporosis. Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing.

  • 139.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kuhstoss, Stuart
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions2011In: BONE, ISSN 8756-3282, Vol. 48, no 5, 988-996 p.Article in journal (Refereed)
    Abstract [en]

    The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, mu CT and histology were used for evaluation. The animals were injected with either 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.

  • 140.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Hanna
    Department of Applied physics, University of Eastern Finland, Kuopio, Finland.
    Li, Xiaodong
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Ke, Hua Zhu
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats2011In: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, no 5, 628-632 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Sclerostin is produced by osteocytes and is an inhibitor of bone formation. Thus, inhibition of sclerostin by a monoclonal antibody increases bone formation and improves fracture repair. Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model.

    Methods: 10-week-old male rats (n = 48) were divided into 4 groups, with 12 in each. In 24 rats, the right hind limb was unloaded by paralyzing the calf and thigh muscles with an injection of botulinum toxin A (Botox). 3 days later, all the animals had a steel screw inserted into the right proximal tibia. Starting 3 days after screw insertion, either anti-sclerostin antibody (Scl-Ab) or saline was given twice weekly. The other 24 rats did not receive Botox injections and they were treated with Scl-Ab or saline to serve as normal-loaded controls. Screw pull-out force was measured 4 weeks after insertion, as an indicator of the regenerative response of bone to trauma.

    Results: Unloading reduced the pull-out force. Scl-Ab treatment increased the pull-out force, with or without unloading. The response to the antibody was similar in both groups, and no statistically significant relationship was found between unloading and antibody treatment. The cancellous bone at a distance from the screw showed changes in bone volume fraction that followed the same pattern as the pull-out force.

    Interpretation: Scl-Ab increases bone formation and screwfixation to a similar degree in loaded and unloaded bone.

  • 141.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Li, Xiaodong
    Amgen Inc.
    Isaksson, Hanna
    University of Eastern Finland.
    Zhu Ke, Hua
    Amgen Inc.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats2010In: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, no 11, 2412-2418 p.Article in journal (Refereed)
    Abstract [en]

    Sclerostin is the product of the SOST gene Loss of-function mutations in the SOST gene result in a high bone-mass phenotype demonstrating that sclerostin is a negative regulator of bone mass Primarily expressed by osteocytes in bone sclerostin is reported to bind the LRP5/6 receptor thereby antagonizing canonical Wnt signaling and negatively regulating bone formation We therefore investigated whether systemic administration of a sclerostin neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks In four groups, the screws were tested for pull out strength At the time of euthanasia a similar screw also was inserted in the contralateral tibia and pull-out tested immediately Sclerostin antibody significantly increased the pull out force by almost 50% compared with controls after 2 and 4 weeks Also the screws inserted at the time of euthanasia showed increased pull out force Micro-computed tomography (mu CT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw There also was a general increase in trabecular thickness in cancellous bone Thus as measured by the amount of bone and its mechanical resistance the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone

  • 142.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Macias, Brandon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hamang, Matt
    Lilly Research Labs, IN USA .
    Lucchesi, Jonathan
    Lilly Research Labs, IN USA .
    Adrian, Mary D.
    Lilly Research Labs, IN USA .
    Kuhstoss, Stuart
    Lilly Research Labs, IN USA .
    Harvey, Anita
    Lilly Research Labs, IN USA .
    Sato, Masahiko
    Lilly Research Labs, IN USA .
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing2014In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 32, no 3, 471-476 p.Article in journal (Refereed)
    Abstract [en]

    We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25mg/kg, twice weekly) or PTH (5 mu g/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mu CT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p=0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mu CT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing.

  • 143.
    Agholme, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Wnt gene expression during metaphyseal bone healing under different load conditionsManuscript (preprint) (Other academic)
    Abstract [en]

    Bone Wnt signalling has been presented as one of the key pathways through which bone responds to mechanical load. This pathway is also active during the healing process after bone trauma. Bone healing can be improved by pharmacological modulation of Wnt signalling. We investigated how the expression of several Wntrelated genes changed due to trauma and unloading in metaphyseal bone.

    20 male rats had one hind limb unloaded by intramuscular Botox injections. In half of the animals a hole was drilled bilaterally in the proximal tibia. After 7 days, a cylindrical biopsy was taken from the bone surrounding the hole and at a corresponding site in animals without trauma. The biopsies were analyzed for the mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt5b, Sost, Dkk1, Dkk2, Sfrp1, Sfrp4, Lrp5, Lrp6, Wisp1, Wif1 and Wnt10b.

    Trauma led to upregulation of most of the studied genes. This effect was most evident in unloaded bone, where 8 genes were upregulated, among them Wnt receptors, ligands and inhibitors. Unloading increased the expression of Sost in untraumatized bone, but did not significantly influence the other genes.

  • 144.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.

    The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.

    Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.

    We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.

  • 145.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Getting rid of intracellular Aβ- loss of cellular degradation leads to transfer between connected neurons2014In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 20, no 15, 2458-2468 p.Article in journal (Refereed)
    Abstract [en]

    The sporadic, late onset form of Alzheimers disease (AD) shares pathological hallmarks with the familial form; however, no clear reason for increased beta-amyloid (A beta) generation has been found in the former. It has long been speculated that the late onset form of AD is caused by reduced degradation and/or clearance of A beta. Indeed, both intracellular degradation systems, the proteasomal and lysosomal systems, have been shown to be defective in AD. Reduced proteasome activity increases levels of intracellular and secreted A beta. Furthermore, accumulation of improperly degraded A beta in the lysosomes causes lysosomal disruption and cell death. We recently showed that oligomeric A beta can be transmitted from one neuron to another, which causes neurotoxicity. In both the donating and receiving cells, A beta accumulates in the endo-lysosomal compartment. It is possible that ineffective degradation of A beta causes its transfer to neighboring neurons, thereby spreading AD pathology. This review summarizes the data underlying the idea of reduced A beta clearance and subsequent A beta spread in AD, and also suggests new therapeutic methods, which are aimed at targeting the degradation systems and synaptic transfer. By enhancing degradation of intracellular accumulated A beta, it can be possible to remove it and avoid A beta-induced neurodegeneration without disturbing the endogenously important pool of secreted A beta. Additionally, drugs targeted to inhibit the spread of intracellular toxic A beta aggregates may also be useful in stopping the progression of pathology, without affecting the level of A beta that normally occurs in the brain.

  • 146.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Benedikz, Eirikur
    Department of Neurobiology, Division of Neurodegeneration, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy2012In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, no 2, 343-358 p.Article in journal (Refereed)
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

  • 147.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Lindström, Tobias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, 1069-1082 p.Article in journal (Refereed)
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

  • 148.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Geriatric Medicine in Norrköping.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Domert, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease2014In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, 29-39 p.Article in journal (Refereed)
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

  • 149.
    Agic, Haris
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Hope Rites: An Ethnographic Study of Mechanical Help-Heart Implantation Treatment2012Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis is about cultural aspects of advanced medical technology for treating end-stage heart failure. New medical technologies like mechanical help-hearts save lives, but they also bring new uncertainties, risks, and challenges. Based on nine months of ethnographic field work in a Swedish academic hospital, this study examines the ways of managing uncertainties of end-stage heart failure and of high-tech treatment, and also how these practices tie into the shared understandings of life-threatening chronic illness, the body, and medical technology’s role.

    This study draws on anthropological discussions of healing rituals as an analytical tool to make sense of social and cultural dimensions of mechanical help-heart implantation treatment. Viewed as a ritual, this treatment creates and maintains hope as a virtue through which possibilities of new medical technology are justified as culturally approved ways of handling the uncertainties of severe heart failure and mechanical help-heart treatment. Ultimately, even when treatment is regarded as successful, the patients may be saved but are never really ‘cured’ and remain, thus, permanently tied to the world of medicine. This new mode of existence is characterized by paradoxical permanent transit between uncertainty and hope.

  • 150.
    Agnafors, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences.
    Comasco, Erika
    Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dekeyser, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Oreland, Lars
    Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems - a longitudinal study.2013In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, no 1, 10- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS: Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS: Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS: Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

1234567 101 - 150 of 18125
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf