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  • 1.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol and posttraumatic stress reactions: methodological and applied studies before and after trauma2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.

    The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.

    Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.

    The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.

    List of papers
    1. Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum
    Open this publication in new window or tab >>Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum
    1995 (English)In: European Journal of Clinical Chemistry and Clinical Biochemistry, ISSN 0939-4974, Vol. 33, p. 927-932Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to establish morning and evening reference ranges for cortisol in saliva. Another objective was to compare the concentrations of the mainly free cortisol in saliva to those of total cortisol in serum as determined with a commercial radioimmunoassay. The concentrations were determined in matched samples of saliva and serum collected at 8am and 10pm from 197 healthy volunteers. The saliva samples were stable for at least 7 days at room temperature and for 9 months at —20 °C. Reference ranges, the central 95%, were estimated to 3.5—27.0 nmol/1 at 8 am and < 6.0 nmol/1 at 10 pm. The intra-assay coefficient of variation (CV) was below 5% and total CV below 10%. The relation between the cortisol concentrations in serum and saliva was nonlinear with r = 0.86 for serum concentrations < 450 nmol/1 and r = 0.44 for serum concentrations ^ 450 nmol/1. In conclusion, the satisfactory precision of the analysis and the simple non-invasive sampling procedure suggest that saliva may be used for cortisol measurements in situations where blood sampling is difficult to perform.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80129 (URN)10.1515/cclm.1995.33.12.927 (DOI)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
    2. Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests
    Open this publication in new window or tab >>Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests
    1998 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 36, no 4, p. 215-222Article in journal (Refereed) Published
    Abstract [en]

    Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80133 (URN)10.1515/CCLM.1998.037 (DOI)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2017-12-07Bibliographically approved
    3. Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
    Open this publication in new window or tab >>Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
    1999 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 46, no 6, p. 850-855Article in journal (Refereed) Published
    Abstract [en]

    Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.

    Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.

    Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.

    Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24816 (URN)10.1016/S0006-3223(98)00381-3 (DOI)9214 (Local ID)9214 (Archive number)9214 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
    Open this publication in new window or tab >>Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
    2001 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 50, no 12, p. 986-993Article in journal (Refereed) Published
    Abstract [en]

    Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.

    Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.

    Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.

    Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24817 (URN)10.1016/S0006-3223(01)01253-7 (DOI)9215 (Local ID)9215 (Archive number)9215 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in Bosnia
    Open this publication in new window or tab >>Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in Bosnia
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The psychobiology of post-traumatic distress is known to some extent, however the pre-trauma psychobiology is not. The aims of the present study were to relate pre- and post-trauma salivary cortisol levels and general health to post-traumatic distress in a Swedish UN-battalion in Bosnia.

    Methods: Salivary 8 AM and I 0 PM cortisol levels and "General Health Questionnaire" ratings were collected from 145 subjects before the six months' mission, at return and two and six months after mission. During follow-up, the ratings were extended by the "Impact of Events Scale" (IES) and "Post Traumatic Symptom Scale".

    Results: Low pre-trauma morning and evening salivary cortisol levels were statistically significantly related to high scores in all rating scales six months after mission and to increasing IES scores during follow-up. Low morning and high evening post-trauma salivary cortisol levels were related to high ratings of psychological distress six months after mission

    Conclusions: Pre-trauma salivary cortisol levels seem to be related to posttrauma psychological distress, however not to the extent that salivary cortisol levels in a simple way could be used for predictive screening.

    Keywords
    Saliva, cortisol, relation to, rating scales, traumatic stress, UN-soldiers
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80134 (URN)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
    6. Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in Bosnia
    Open this publication in new window or tab >>Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in Bosnia
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Our group has presented evidence of relationships between salivary cortisol levels and psychological distress before, during and after trauma-related stress. The aim of the present study was to confirm the part of evidence of relationships between salivary cortisol and posttraumatic distress and their change over time.

    Methods: Salivary cortisol levels at 8 AM and 10 PM and self-ratings were collected from 106 subjects six and twelve months after a six months UNmission in Bosnia. The rating instruments were the "Impact of Event Scale" (IES), the "Post Traumatic Symptom Scale" and the "General Health Questionnaire".

    Results: Significant statistical interactions were found between changes in mean cortisol levels and IES scores over time. Decreasing evening cortisol levels over time were significantly related to decreasing IES scores and vice versa. Morning cortisol levels showed negative, and evening cortisol positive correlations with all rating scores.

    Conclusions: The evidence from previous studies on trauma related stress, that salivary cortisol is related to the development of posttraumatic stress reactions, the morning cortisol in reverse (negative) direction to that (positive) of evening cortisol, were confirmed.

    Keywords
    Saliva, cortisol, follow-up, relation to, rating scales, traumatic stress, UN-soldiers
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80136 (URN)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
  • 2.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in BosniaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The psychobiology of post-traumatic distress is known to some extent, however the pre-trauma psychobiology is not. The aims of the present study were to relate pre- and post-trauma salivary cortisol levels and general health to post-traumatic distress in a Swedish UN-battalion in Bosnia.

    Methods: Salivary 8 AM and I 0 PM cortisol levels and "General Health Questionnaire" ratings were collected from 145 subjects before the six months' mission, at return and two and six months after mission. During follow-up, the ratings were extended by the "Impact of Events Scale" (IES) and "Post Traumatic Symptom Scale".

    Results: Low pre-trauma morning and evening salivary cortisol levels were statistically significantly related to high scores in all rating scales six months after mission and to increasing IES scores during follow-up. Low morning and high evening post-trauma salivary cortisol levels were related to high ratings of psychological distress six months after mission

    Conclusions: Pre-trauma salivary cortisol levels seem to be related to posttrauma psychological distress, however not to the extent that salivary cortisol levels in a simple way could be used for predictive screening.

  • 3.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up2001In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 50, no 12, p. 986-993Article in journal (Refereed)
    Abstract [en]

    Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.

    Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.

    Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.

    Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.

  • 4.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in BosniaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Our group has presented evidence of relationships between salivary cortisol levels and psychological distress before, during and after trauma-related stress. The aim of the present study was to confirm the part of evidence of relationships between salivary cortisol and posttraumatic distress and their change over time.

    Methods: Salivary cortisol levels at 8 AM and 10 PM and self-ratings were collected from 106 subjects six and twelve months after a six months UNmission in Bosnia. The rating instruments were the "Impact of Event Scale" (IES), the "Post Traumatic Symptom Scale" and the "General Health Questionnaire".

    Results: Significant statistical interactions were found between changes in mean cortisol levels and IES scores over time. Decreasing evening cortisol levels over time were significantly related to decreasing IES scores and vice versa. Morning cortisol levels showed negative, and evening cortisol positive correlations with all rating scores.

    Conclusions: The evidence from previous studies on trauma related stress, that salivary cortisol is related to the development of posttraumatic stress reactions, the morning cortisol in reverse (negative) direction to that (positive) of evening cortisol, were confirmed.

  • 5.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lundin, Tom
    Department of Psychiatry, Uppsala Academic Hospital, Uppsala University, Uppsala (TL), Sweden.
    Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers1999In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 46, no 6, p. 850-855Article in journal (Refereed)
    Abstract [en]

    Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.

    Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.

    Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.

    Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.

  • 6.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Holm, AC
    Eriksson, TE
    Lundin, T
    Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Ctr Clin Chem, S-58185 Linkoping, Sweden.
    Thorell, Lars-Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Salivary cortisol and posttraumatic stress reactions methodological and applied studies before and after trauma2002In: International Journal of Psychophysiology, ISSN 0167-8760, E-ISSN 1872-7697, Vol. 45, no 1-2, p. 89-89Conference paper (Other academic)
  • 7.
    Abdiu, Avni
    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.
    Larsson, Sven-Erik
    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.
    Wasteson, Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Walz, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Suramin blocks growth-stimulatory effects of platelet-derived growth factor on malignant fibrous histiocytomas in vitro.1999In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 146, p. 189-194Article in journal (Refereed)
  • 8.
    Abdiu, Avni
    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.
    Wingren, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Larsson, S-E
    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.
    Wasteson, Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Walz, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Effects of human platelet-derived growth factor-AB on sarcoma growth in vitro and in vivo.1999In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 141, p. 39-45Article in journal (Refereed)
  • 9.
    Abildgaard, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Aaro, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine.
    Lisander, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Limited effectiveness of intraoperative autotransfusion in major back surgery2001In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 18, no 12, p. 823-828Article in journal (Refereed)
    Abstract [en]

    Background and objective: The efficiency of intraoperative autotransfusion in scoliosis surgery is poorly known but needs to be evaluated, not least because of the large blood losses in these patients. This is a retrospective analysis of transfusion requirements of 43 such patients. Methods: Records from 43 patients were studied. During surgery, the shed blood was salvaged and washed in an autotransfusion device (AT1000 Auto-transfusion Unit«) and a suspension of red cells was reinfused. Results: Fifty-eight per cent of the intraoperative blood loss was salvaged. The total blood loss during the patients' hospital stay was calculated from the haemoglobin balance, 24% of this loss was salvaged by the device. Moreover, 36 of the patients needed allogeneic blood transfusion. Conclusion: The efficiency of the autotransfusion device was relatively low in relation to the total extravasation, mainly because the postoperative blood loss is substantial.

  • 10.
    Adell, Gunnar
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Boeryd, B.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Frånlund, B.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Håkansson, L.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes' B colorectal carcinoma: an immunohistochemical study1996In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 162, no 8, p. 637-642Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the incidence and prognostic importance of micrometastatic disease in regional lymph nodes from Dukes' B colorectal carcinomas.

    DESIGN: Retrospective study.

    SETTING: University hospital, Sweden.

    SUBJECTS: 100 patients operated on for primary colorectal carcinoma, classified as Dukes' B lesions.

    INTERVENTIONS: The regional lymph nodes were re-examined immunohistochemically using monoclonal antibodies against cytokeratin.

    OUTCOME MEASURES: Incidence and prognostic importance of micrometastases.

    RESULTS: Micrometastases were found in 39% (39/100) of the patients. The number of positive cells in the lymph nodes examined varied from 1 to over 100. They appeared as single cells or small clusters of cells located within the capsule or in the peripheral sinus of the lymph node. At least three sections from each of three lymph nodes had to be examined to identify 95% of the patients with lymph node micrometastases. The outcome of the patients with micrometastases was not significantly different from that of patients with no epithelial cells in the lymph nodes.

    CONCLUSION: Micrometastases in regional lymph nodes are a interesting phenomenon but clinically seem to be of only weak prognostic value.

  • 11.
    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, p. 208-213Article 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.

  • 12.
    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, p. 1069-1082Article 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.

  • 13.
    Agrup, Måns
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Olsen, Karen
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    C-erbB-2 overexpression and survival in early onset breast cancer2000In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 63, no 1, p. 23-29Article in journal (Refereed)
    Abstract [en]

    Young breast cancer patients have a decreased survival rate and it has been demonstrated that young age is an independent predictor of adverse prognosis. Overexpression of c-erbB-2 protein (also known as HER-2/neu) has been shown to be a prognostic indicator in breast cancer in general and especially among patients with axillary nodal metastases. The present study was initiated to determine the prognostic significance of c-erbB-2 protein overexpression in early onset breast cancer.

    A population consisting of 110 young breast cancer patients, ≤ 36-year-old at diagnosis, was analyzed with immunohistochemical staining for c-erbB-2 protein.

    Thirty patients (27%) were found to overexpress the c-erbB-2 protein. C-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (P = 0.002) and for patients with axillary nodal metastases (P = 0.0007). No such association was found for node-negative patients. Furthermore, the difference in prognosis in relation to c-erbB-2 among node-positive patients was maintained, when these were stratified in groups treated or not treated with adjuvant chemotherapy.

    The study indicates that overexpression of c-erbB-2 protein is a strong prognostic factor in young breast cancer patients with axillary nodal metastases. Moreover, the adverse prognosis associated with c-erbB-2 overexpression in node-positive patients was observed whether or not the patients had received adjuvant chemotherapy.

  • 14.
    Ahlgren, Ewa
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Lundqvist, Anna
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Nordlund, Anders
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Arén, Claes
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Rutberg, Hans
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Neurocognitive impairment and driving performance after coronary artery bypass surgery2003In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 23, no 3, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Objective: Neurocognitive impairment is common after cardiac surgery but few studies have examined the relationship between postoperative neuropsychological test performance and everyday behavior. The influence of postoperative cognitive impairment on car driving has previously not been investigated. The purpose of this study was to evaluate neurocognitive function and driving performance after coronary artery bypass grafting (CABG).

    Methods: Twenty-seven patients who underwent coronary artery bypass grafting with standard cardiopulmonary bypass technique and 20 patients scheduled for percutaneous coronary intervention (PCI) under local anesthesia (control group) were enrolled in this prospective study conducted from April 1999 to September 2000. Complete data were obtained in 23 and 19 patients, respectively. The patients underwent neuropsychological examination with a test battery including 12 tests, a standardized on-road driving test and a test in an advanced driving simulator before and 4–6 weeks after intervention.

    Results: More patients in the coronary artery bypass grafting group (n=11, 48%) than in the percutaneous coronary intervention group (n=2, 10%) showed a cognitive decline after intervention (P=0.01). In the on-road driving test, patients who underwent coronary artery bypass grafting deteriorated after surgery in the cognitive demanding parts like traffic behavior (P=0.01) and attention (P=0.04). Patients who underwent percutaneous intervention deteriorated in maneuvering of the vehicle (P=0.04). No deterioration was detected in the simulator in any of the groups after intervention. Patients with a cognitive decline after intervention also tended to drop in the on-road driving scores to a larger extent than did patients without a cognitive decline.

    Conclusion: This study indicates that cognitive functions important for safe driving may be influenced after cardiac surgery.

  • 15.
    Ahlgren, Ewa
    et al.
    Östergötlands Läns Landsting, Heart Centre.
    Lundqvist, Anna
    Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Nordlund, Anders
    Linköping University, Department of Department of Health and Society. Linköping University, Faculty of Health Sciences.
    Rutberg, Hans
    Östergötlands Läns Landsting, Heart Centre.
    Driving performance of patients with coronary artery diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives To compare patients with coronary artery disease and healthy controls with respect to cognitive function and driving performance.

    Design and setting A controlled study conducted between April 1999 and January 2001.

    Subjects Forty-four patients with stable coronary artery disease scheduled for cardiac intervention with coronary artery bypass surgery or percutaneous coronary intervention. Forty volunteers of similar age without symptoms of coronary artery disease served as controls.

    Main outcome measures On-road driving scores in five specific test areas with a rating scale from 1 to 5. Neuropsychological test scores, including 12 tests.

    Results Compared with controls, patients with coronary artery disease had lower scores in all areas of the on-road driving test (p<0.05) and in the neuropsychological tests assessing psychomotor speed, visual and verbal memory, focused attention and simultaneous capacity (p<0.05). The difference between the groups in the on-road driving test appeared to be more pronounced among those above 65 years-of-age. Both patients and controls rated their performance significantly higher than the traffic inspector (p<0.05).

    Conclusions Cognitive function and driving performance may be impaired in patients with coronary artery disease.

  • 16.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fredriksson, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Jerregård, H.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Åkerbäck, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fall, Per-Arne
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rannug, A.
    National Institute for Working Life, Solna and Inst. of Environ. Medicine, Karolinska Institutet, Stockholm, Sweden.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset2000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, no 3, p. 676-680Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Albertsson, Pontus
    et al.
    Umeå Universitet.
    Björnstig, Ulf
    Umeå Universitet.
    Petzäll, Jan
    Vägverket.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Näsman, Yvonne
    Räddningsverket, Sandö.
    Utrymningsförsök av passagerare ur buss vid brand och brandtillbud samt antalet bränder och brandtillbud i bussar i Sverige2006In: Akuttjournalen: Tidsskrift for avansert akuttmedisin, ISSN 0805-6129, E-ISSN 1500-7480, Vol. 14, p. 85-91Article in journal (Refereed)
    Abstract [sv]

       

  • 18.
    Albertsson, Pontus
    et al.
    Umeå Universitetet.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Is there a pattern in European bus and coach incidents? A literature analysis with special focus on injury causation and injury mechanisms2005In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 37, no 2, p. 225-233Article in journal (Refereed)
    Abstract [en]

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

  • 19.
    Albertsson, Pontus
    et al.
    Umeå Universitet.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Kirk, Alan
    Loughborough University, UK.
    Mayrhofer, Erich
    University of Technology, Graz, Austria.
    Björnstig, Ulf
    Umeå Universitet.
    Case study: 128 Injured in rollover coach crashes in Sweden - Injury outcome, mechanisms and possible effects of seat belts2006In: Safety Science, ISSN 0925-7535, E-ISSN 1879-1042, Vol. 44, no 2, p. 87-109Article in journal (Refereed)
    Abstract [en]

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

  • 20.
    Algvere, Peep
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Gouras, P.
    Dafgård Kopp, E.
    Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD.1999In: European Journal of Ophthalmology, ISSN 1120-6721, E-ISSN 1724-6016, Vol. 9, p. 217-230Article in journal (Refereed)
  • 21.
    Algvere, Peep
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Jahnberg, P.
    Textorius, Ola
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    The swedish retinal detachment register. I. A database for epidemiological and clinical studies.1999In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 237, p. 137-144Article in journal (Refereed)
  • 22. Allard, P
    et al.
    Englund, E
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Caudate nucleus dopamine D2 receptors in vascular dementia2002In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 14, no 1, p. 22-25Article in journal (Refereed)
    Abstract [en]

    Caudate nucleus dopamine (DA) D2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [3H]raclopride as a radioligand. There was no significant difference in the number of DA D2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D2 receptors in Alzheimer's disease and Parkinson's disease. Copyright ⌐ 2002 S. Karger AG, Basel.

  • 23. Allgulander, Christer
    et al.
    Mangano, Richard
    Zhang, Jun
    Dahl, Alv A
    Lepola, Ulla
    Sjödin, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Emilien, Gerard
    Efficacy of venlafaxine ER in patients with social anxiety disorder: A double-blind, placebo-controlled, parallel-group comparison with paroxetine2004In: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 19, no 6, p. 387-396Article in journal (Refereed)
    Abstract [en]

    This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n=434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p<0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.

  • 24. Allum, JHJ
    et al.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Recovery of vestibulo-ocular reflex-function in subjects with an acute unilateral peripheral vestibular deficit.1999In: Journal of Vestibular Research-Equilibrium & Orientation, ISSN 0957-4271, E-ISSN 1878-6464, Vol. 9, p. 135-144Article in journal (Refereed)
  • 25.
    Alm, Tina
    et al.
    Linköping University, Department of Neuroscience and Locomotion.
    Franzén, Daniel
    Linköping University, Department of Neuroscience and Locomotion.
    Arbetssökandes upplevelser av utredningsperioden på Arbetsförmedlingen Rehabilitering2005Independent thesis Basic level (degree of Bachelor), 10 points / 15 hpStudent thesis
    Abstract [en]

    Work has a great influence on most of individuals in society. It influences both identity as well as the structure of the day. Unemployed people are often affected in a negative way through economic and psychological problems. In order to help people with reduced work capacity back to the labour market and decrease unemployment, the Labour Market Board works with vocational rehabilitation. The aim of this study is to investigate experiences of vocational rehabilitation within the Labour Market Board among unemployed people. A qualitative method was used by which interviews were made with 11 unemployed persons who participated in an investigation as a part of vocational rehabilitation within the Labour Market Board. The result shows both positive and negative experiences of the investigation period. The identified experiences were sorted into code groups: Support, Insight, Confidence in the investigation and result, Belief in the future, Motivation, and Participation. Both the actions of the personnel and the presence of the group members influenced the experiences. The support given by the personnel and how it is experienced is of great importance for the future of the unemployed. When the investigation was pursued during a short period of time, there was a lack of confidence in the investigation and result. A suggestions for future studies is to design a questionnaire that can be used in a larger study including a large number of individuals who are participating in vocational rehabilitation within the Labour Market Board.

  • 26.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Nephrology.
    Eneström, S.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Hed, J.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Samuelsson, I.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Sjöström, P.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Autoantibodies to leucocyte antigens in hydralazine-associated nephritis1992In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 231, no 1, p. 37-42Article in journal (Refereed)
    Abstract [en]

    Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

  • 27. Ameur, Safia
    et al.
    Carlander, Kristina
    Grundström, Kristin
    Hallberg, Pernilla
    Lundgren, Kristin
    Lundquist, Per-Gotthard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery.
    Wikström, Thore
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Disaster Medicine and Traumatology. Östergötlands Läns Landsting, Centre for Teaching and Research in Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology.
    Att lära bronkoskopi i simulator gav mer fingerfärdighet än omdöme2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, p. 2694-2699Article in journal (Other academic)
  • 28.
    Andersson, Eva
    et al.
    Linköping University, Department of Neuroscience and Locomotion. Linköping University, Faculty of Health Sciences.
    Arlinger, Stig
    Linköping University, Department of Neuroscience and Locomotion. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Jacobsson, Stellan
    ENT-Clinic, Sahlgrens University Hospital Mölndal, Sweden.
    Evaluation of OAE-recording as a complementary test method for adults with moderate to profound mental retardation2000In: Scandinavian Audiology, ISSN 0105-0397, E-ISSN 1940-2872, Vol. 29, no 2, p. 120-126Article in journal (Refereed)
    Abstract [en]

    The recording of otoacoustic emissions (OAE) was evaluated as a complementary test method for adults with moderate to profound mental retardation (MR). A portable apparatus, ILO 288 Echoport linked to a Compaq LTE 5100 notebook with software ILO 88 V 4.2, was used. Otoscopy and tympanometry were also performed. Criteria for emissions were S/N 3 dB or more and reproducibility 60% or more for at least three frequency-bands. The criteria for partial emissions were the same, but for only one or two frequencies. Two examiners were needed: one to keep the tested person calm and quiet and the other to handle the keyboard. Thirty-eight people with different degrees of MR in connection with other disabilities were included. They had all exhibited incomplete results in a previous hearing screening of more than 1000 adults with MR. Reproducible transiently evoked OAEs (TEOAE) were recorded from II ears (7 people), partial TEOAEs from 6 ears (4 people) and no emissions from 15 ears (10 people). Registration from 24 ears (13 people) could not be evaluated because of too much external and internal noise. Eight people rejected the examination. Only four people showed emissions in both ears. Accordingly, 34 people (89.5%) had to be re-tested or referred for further investigation, 21 of them (55%) because of noisy recordings or no co-operation. It is concluded that the TEOAE-test in its present form cannot fulfil the demands for a functioning test method for this population. In single cases, however, TEOAE-recording can complement other audiological tests.

  • 29.
    Andersson, Susanna
    et al.
    Linköping University, Department of Neuroscience and Locomotion.
    Thuresson Muhrman, Eva
    Linköping University, Department of Neuroscience and Locomotion.
    Arbetsminne och receptivt lexikon hos barn med cochleaimplantat: en undersökning med SIPS och PPVT2007Independent thesis Advanced level (degree of Magister), 20 points / 30 hpStudent thesis
    Abstract [en]

    Cochlear implants (CI) are one of the most important medical innovations in the last 20 years. A CI can enable hearing and spoken language in children with severe hearing impairment or deafness. However, many children with CIs do not reach the expected level of language. The reasons for this are not yet fully understood and further research is therefore necessary. In the present study 9 children, 6;7-12;4 years old with CIs participated. The purpose of this study was to investigate cognitive and language abilities with focus on working memory and receptive lexicon in children with CI. For this purpose selected parts of the computer based test battery SIPS (Sound Information Processing System) and PPVT (Peabody Picture Vocabulary Test) were used. The test results were analysed on group level and on individual level. In addition the results were compared to results from a control group of children with normal hearing.

    The children with CIs achieved lower results than the control group did, measured on a group level. A few individuals though performed at the same level as the children in the control group which implies that it is possible for children with CIs to reach good results on the examined aspects. The results of this study also indicate that late implantation is not necessarily an obstacle for good language development. Correlations between working memory and lexicon were found both in the children with CIs and in the control group. No correlation between the investigated demographic factors and test results was found.

  • 30.
    Andersson, Thomas
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Johansson, Anders G.
    Kliniskt Mikrobiologiska Laboratoriet, Akademiska Sjukhuset, Uppsala.
    Westermark, Per
    Avdelningen för Genetik och Patologi, Enheten för Patologi, Akademiska Sjukhuset, Uppsala.
    Lundmark, Katarzyna
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Vanlig svamp gav ovanlig hudinfektion: Fallbeskrivning1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 45, p. 4926-4927Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Vid opportunistisk svampinfektion i huden är diagnosen sällan självklar. Ett samarbete mellan dermatolog, patolog och mykolog kan behövas, som i detta fall av kutan alternarios. Denna typ av svampinfektion innefattas i begreppet feohyfomykos.

  • 31.
    Andersson-Engels, Stefan
    et al.
    Inst för fysik Lunds Tekniska Högskola.
    Pålsson, S
    Backlund, Erik Olof
    IMT LiU.
    Sturnegk, Patrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Lundberg, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Svanberg, K
    Eriksson, Ola
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    ALA-PpIX Fluorescence and spectroscopy in connection with stereotactic biopsy of human glioblastomas2005In: European Conference on Biomedical Optics,2005, 2005Conference paper (Refereed)
  • 32.
    Andin, Josefine
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Pharmacological and environmental modulations of the rat glutamatergic system2006Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glutamate is the principal excitatory neurotransmitter in the central nervous system and it is implicated in neural transmission, learning, memory processes and neuronal plasticity. In the glutamatergic synapse two main components are present; the glutamate receptors and the glutamate transporters. The receptors, the NMDA, AMPA, kainite and the metabotroptic receptors, are responsible for conveying neural transmission, including long term potentiation (LTP), synaptic strengthening and modification. The transporters, located to the neuronal membrane and to the membranes of surrounding astrocytes, regulates the extracellular concentration of glutamate and thereby the duration of the synaptic signal.

    Alterations in both receptor and transporter systems have been suggested to be important in the pathogenesis of several acute and chronic nervous system diseases, such as psychosis, mood disorders, epilepsy, Parkinson's disease and Alzheimer's disease. The pathophysiology of these disorders is not yet completely understood and the involvement of glutamate is unclear. In this thesis we have sought to investigate the role of the glutamatergic system in the treatment of mood disorders and dementia. The antidepressant drug amitriptyline exerts its main effects on the serotonergic and noradrenergic systems and the antidementia drug rivastigmine acts mainly on the cholinergic system. However, given the close relationship between different neurotransmitter systems we have investigated the influence of amitriptyline and rivastigmine on the mRNA expression of the neuronal transporter, EAAC1, in rats. The results showed for the first time an involvement of EAAC1 in amitriptyline and rivastigmine treatment. Amitriptyline induced an acute increase in EAAC1 mRNA expression, which 24 hour after administration returned to baseline levels. Chronic treatment, on the other hand, induces a significant decrease in cortical areas, which we suggest results in enhanced neuronal transmission. Rivastigmine treatment, acute as well as chronic, induced increases in the mRNA expression in hippocampus. We hypothesize that this counteracts the excitotoxic glutamate levels seen in Alzheimer's disease.

    Further, environmental enrichment has been shown to have beneficial effects on capillary supply, the number of glial cells and dendritic spines, the thickness and weight of cortex, the concentration of cholinesterase, LTP and synaptic strength in animals. It has also been reported that humans that lead an active life have a reduced risk of developing Alzheimer's disease. This suggests that an active and stimulated life may have a protective effect against dementia in man, by creating a cognitive reserve which provides a buffer against brain pathology or age-related changes. We investigated the influence of environmental enrichment on the mRNA expression of NMDA and AMPA receptors and on EAACl and showed for the first time that EAAC1 mRNA is decreased after environmental enrichment. This is probably followed by an increase of glutamate in the synapse, which in turn leads to enhanced neuronal transmission including enhanced memory formation and learning. Furthermore, we confirmed in greater detail previous findings on the upregulation of NMDA mRNA and show that the regulation is regionally and hemisphere specific. We also confirm that AMPA mRNA is not per se changed by environmental enrichment in adult animals.

    This work provides further evidence about the involvement of the glutamatergic system in affective and cognitive disorders. Improved knowledge of the glutamatergic system will contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

    List of papers
    1. Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline
    Open this publication in new window or tab >>Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline
    2004 (English)In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 126, no 1, p. 74-77Article in journal (Refereed) Published
    Abstract [en]

    Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24088 (URN)10.1016/j.molbrainres.2004.03.023 (DOI)000222569100009 ()3654 (Local ID)3654 (Archive number)3654 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    2. Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
    Open this publication in new window or tab >>Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
    2005 (English)In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 19, no 1, p. 18-23Article in journal (Refereed) Published
    Abstract [en]

    Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-42255 (URN)10.1159/000080966 (DOI)000226012200004 ()62059 (Local ID)62059 (Archive number)62059 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    3. Environmental enrichment induces changes in the mRNA expression of rat EAAC1 and NMDA but not in AMPA
    Open this publication in new window or tab >>Environmental enrichment induces changes in the mRNA expression of rat EAAC1 and NMDA but not in AMPA
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment has been shown on neuronal strucrure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g. Alzheimer's disease. Glutamatergic corticocortical pathways are imperative for cognitive functions, such as memory and learning, and long term porenriation relies on the AMPA and NMDAglutamate rcceptors. The glutamate signalling is also dependent on a fine-runed transport system, in the hippocampus primarily by theglutamate transporter EAACl. In this study we show how environmental enrichment modulates these parts of the glutamarergic system using in siru hybridization. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly decreased in hippocampal and cortical areas. We also provide further evidence about the upregulation of NMDA mRNA after environmental enrichement, and show it to have a regionally and hemisphere specific regulation. The current work also confirms that AMPA mRNA is nor per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-97633 (URN)
    Available from: 2013-09-18 Created: 2013-09-18 Last updated: 2013-09-18
  • 33.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Enz, Albert
    Neuroscience Research, The Novartis Institutes for BioMedical Research, Basel, Switzerland.
    Gentsch, Conrad
    Neuroscience Research, The Novartis Institutes for BioMedical Research, Basel, Switzerland.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression2005In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 19, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.

  • 34.
    Andin, Josefine
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics.
    Hallbeck, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Mohammed, Abdul H
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1174, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.

  • 35.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Mohammed, Abdul
    Division of Geriatric Medicine, Neurontec, Karolinska Institutet, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Environmental enrichment induces changes in the mRNA expression of rat EAAC1 and NMDA but not in AMPAManuscript (preprint) (Other academic)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment has been shown on neuronal strucrure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g. Alzheimer's disease. Glutamatergic corticocortical pathways are imperative for cognitive functions, such as memory and learning, and long term porenriation relies on the AMPA and NMDAglutamate rcceptors. The glutamate signalling is also dependent on a fine-runed transport system, in the hippocampus primarily by theglutamate transporter EAACl. In this study we show how environmental enrichment modulates these parts of the glutamarergic system using in siru hybridization. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly decreased in hippocampal and cortical areas. We also provide further evidence about the upregulation of NMDA mRNA after environmental enrichement, and show it to have a regionally and hemisphere specific regulation. The current work also confirms that AMPA mRNA is nor per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

  • 36.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Stenfors, Carina
    Bioscience, Local Discovery, AstraZeneca R&D, Södertälje, Sweden.
    Ross, Svante B
    Bioscience, Local Discovery, AstraZeneca R&D, Södertälje, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline2004In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 126, no 1, p. 74-77Article in journal (Refereed)
    Abstract [en]

    Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

  • 37. Andreasson, Sten
    et al.
    Breuer, Debra K
    Eksandh, Louise
    Ponjavic, Vesna
    Frennesson, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Hiriyanna, Suja
    Filippova, Elena
    Yashar, Beverly M
    Swaroop, Anand
    Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes2003In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 24, no 4, p. 215-223Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.

  • 38.
    Antepohl, Wolfram
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Domeij, Erica
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    A follow-up of medical graduates of a problem-based learning curriculum2003In: Medical Education, ISSN 0308-0110, E-ISSN 1365-2923, Vol. 37, no 2, p. 155-162Article in journal (Refereed)
    Abstract [en]

    Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.

  • 39.
    Antepohl, Wolfram
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine/Pain Clinic. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Herzig, S
    Problem-based learning versus lecture-based learning i a course of basic pharmacology: A controlled, randomized study.1999In: Medical Education, ISSN 0308-0110, E-ISSN 1365-2923, Vol. 33, p. 103-113Article in journal (Refereed)
  • 40.
    Antepohl, Wolfram
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kiviloog, Liisa
    Andersson, Jan
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Cognitive impairment in patients with chronic whiplash-associated disorder - A matched control study2003In: NeuroRehabilitation (Reading, MA), ISSN 1053-8135, E-ISSN 1878-6448, Vol. 18, no 4, p. 307-315Article in journal (Refereed)
    Abstract [en]

    Aim: To verify the occurrence of cognitive impairment in patients with chronic whiplash-associated disorder (WAD) and to provide a more detailed description of the impairment's character and context. Methods: Thirty (30) patients with chronic WAD and 30 matched healthy controls completed a cognitive test battery. Four computerised tests were used: a) two different types of cognitive tasks (reaction time vs. working memory) and b) two types of information processing (verbal vs. spatial). Before testing and after every randomised subtest, subjects rated their pain level on a visual analogue scale. Results: A worse overall performance among patients with WAD and, specifically, worse results concerning working memory tasks were found. Post-hoc testing revealed a statistically significant difference concerning the single variable "verbal reaction time". Pain intensity among patients increased significantly during testing. Pain intensity after the subtest for verbal mental reaction time (independent of test sequence) was significantly correlated with results in this subtest, the more pain, the more time was needed. Conclusion: Compared to healthy controls, patients performed worse overall. Concerning verbal reaction time, the impairment was correlated with pain intensity. The findings support the hypothesis that pain might be one important factor leading to cognitive impairment in patients with chronic WAD.

  • 41. Antunes, Fernando
    et al.
    Cadenas, Enrique
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Apoptosis, induced by exposure to a low and steady-state concentration of H2O2, is a consequence of lysosomal rupture2001In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 356, p. 549-555Article in journal (Refereed)
  • 42.
    Anund, Anna
    et al.
    VTI.
    Kronqvist, Linda
    VTI.
    Falkmer, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Paediatric Habilitation Community Service.
    Är kraven på utmärkning av skolskjutsfordon utmärkta2005Report (Other academic)
  • 43. Apelqvist, G
    et al.
    Wikell, C
    Carlsson, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hjorth, S
    Bergqvist, P B F
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Dynamic and kinetic effects of chronic citalopram treatment in experimental hepatic encephalopathy2000In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 23, no 6, p. 304-317Article in journal (Refereed)
    Abstract [en]

    Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg ╖ kg-1 ╖ day-1), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCl-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or "normalized" behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.

  • 44. Apelqvist, G
    et al.
    Wikell, C.
    Hindfeldt, B
    Bergqvist, PBF
    Andersson, G.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Altered open-field behavior in experimental chronic hepatic encephalopathy after single venlafaxine and citalopram challenges.1999In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 143, p. 408-416Article in journal (Refereed)
  • 45.
    Appelqvist, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Nilsson, Cathrine
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Garner, Brett
    University of Wollongong.
    Brown, Andrew J
    University of New South Wales.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Öllinger, Karin
    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.
    Attenuation of the Lysosomal Death Pathway by Lysosomal Cholesterol Accumulation2011In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 178, no 2, p. 629-639Article in journal (Refereed)
    Abstract [en]

    In the past decade, lysosomal membrane permeabilization (LMP) has emerged as a significant component of cell death signaling. The mechanisms by which lysosomal stability is regulated are not yet fully understood, but changes in the lysosomal membrane lipid composition have been suggested to be involved. Our aim was to investigate the importance of cholesterol in the regulation of lysosomal membrane permeability and its potential impact on apoptosis. Treatment of normal human fibroblasts with U18666A, an amphiphilic drug that inhibits cholesterol transport and causes accumulation of cholesterol in lysosomes, rescued cells from lysosome-dependent cell death induced by the lysosomotropic detergent 0-methyl-serine dodecylamide hydrochloride (MSDH), staurosporine (STS), or cisplatin. LMP was decreased by pretreating cells with U18666A, and there was a linear relationship between the cholesterol content of lysosomes and their resistance to permeabilization induced by MSDH. U18666A did not induce changes in expression or localization of 70-kDa heat shock proteins (Hsp70) or antiapoptotic Bcl-2 proteins known to protect the lysosomal membrane. Induction of autophagy also was excluded as a contributor to the protective mechanism. By using Chinese hamster ovary (CHO) cells with lysosomal cholesterol overload due to a mutation in the cholesterol transporting protein Niemann-Pick type C1 (NPC1), the relationship between lysosomal cholesterol accumulation and protection from lysosome-dependent cell death was confirmed. Cholesterol accumulation in lysosomes attenuates apoptosis by increasing lysosomal membrane stability.

  • 46.
    Appelqvist, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Intensive Care.
    Saftig, Paul
    Biochemical Institute, Christian-Albrechts-University Kiel, Kiel, Germany.
    Garner, Brett
    Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
    Öllinger, Karin
    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.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Sensitivity to Lysosome-Dependent Cell Death is Directly Regulated by Lysosomal Cholesterol Content2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 11Article in journal (Refereed)
    Abstract [en]

    Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2), which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determined the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

  • 47.
    Arendt Nielsen, Lars
    et al.
    Laboratory for Experimental Pain Resarch Ahlborg, Denmark.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition2007In: Baillière's Best Practice & Research: Clinical Rheumatology, ISSN 1521-6942, E-ISSN 1532-1770, Vol. 21, no 3, p. 465-480Article in journal (Refereed)
    Abstract [en]

    Chronic musculoskeletal pain has biological, psychological and social components. This review deals with the biological factors, with emphasis on the fibromyalgia syndrome (FMS). Studies on central sensitization of pain-transmitting neurons, changes in endogenous pain modulation that give rise to pain disinhibition, referred pain, pain-related decrease in muscle strength and endurance, and pain generators in deep tissues are reviewed. In FMS there is strong scientific support for the statement that the biological part of the syndrome is a longstanding or permanent change in the function of the nociceptive nervous system that can be equated with a disease. Further research is necessary in order to determine which methods are best for diagnosis of the pain hypersensitivity in clinical practice. FMS may be the far end of a continuum that starts with chronic localized/regional musculoskeletal pain and ends with widespread chronic disabling pain. © 2007 Elsevier Ltd. All rights reserved.

  • 48.
    Arlinger, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Technical Audiology.
    A survey of public health policy on bilateral fittings and comparison with market trends: The evidence-base required to frame policy2006In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 45, no SUPPL. 1Article in journal (Refereed)
    Abstract [en]

    This report presents a review of the situation in a number of countries with respect to public health policy for funding of hearing aid services in general and support to bilateral fittings in particular. The data show considerable variations among the countries studied in number of hearing aids fitted per 1000 inhabitants, differing by a factor of 6 between the extremes. Also the percentage of bilateral fittings differs with an average estimated to be of the order of 50%. For hearing-impaired children, bilateral fittings are given full financial support in most countries studied. The data presented indicate the need for a reliable, scientifically valid evidence-base regarding bilateral hearing aid fitting. © 2006 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.

  • 49.
    Arlinger, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Technical Audiology. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Audiologic diagnosis of infants2000In: Seminars in Hearing, ISSN 0734-0451, E-ISSN 1098-8955, Vol. 21, p. 379-387Article in journal (Refereed)
  • 50.
    Arlinger, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Technical Audiology. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Can we establish internationally equivalent outcome measures in audiological rehabilitation?2000In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 21, no 4 SUPPL.Article in journal (Refereed)
    Abstract [en]

    Objective: This paper intends to discuss issues related to cultural, ethnic, and other nonaudiological variables that may affect the response when trying to determine outcome of audiological rehabilitation in different countries. Design: The ideal measure for the determination of outcome of audiological rehabilitation would be sensitive to changes in disability as well as handicap. Further, it would allow unforeseen effects to be identified and not be limited by language borders or cultural and ethnic differences. A variety of critical factors are discussed that are related to culture, social traditions, ethnic factors, etc. that may affect outcome measures and thus make international equivalence difficult. Conclusions: With careful consideration of the factors discussed, a basic set of questions could be formulated and agreed on, calibrated on suitable populations in different countries, and thereafter used as a bridge across borders to allow comparison of different procedures or meta-analyses of studies performed by different laboratories.

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