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  • 1.
    Aardal, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ann-Charlotté, Holm
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum1995In: European Journal of Clinical Chemistry and Clinical Biochemistry, ISSN 0939-4974, Vol. 33, p. 927-932Article in journal (Refereed)
    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.

  • 2.
    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
  • 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.
    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.

  • 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.
    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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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)
  • 8.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Karlberg, Bengt E.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests1998In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 36, no 4, p. 215-222Article in journal (Refereed)
    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.

  • 9.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Mobäck, Caroline
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jakobsson, Sandra
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Germany.
    Hoffmann, Johannes J. M. L.
    Abbott GmbH and Co KG, Germany.
    Iron depletion in blood donors - Have extended erythrocyte and reticulocyte parameters diagnostic utility?2015In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 53, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Background: Blood donation is associated with iron depletion, but donor iron status is not usually investigated, as such tests are cumbersome and costly. It would therefore be desirable to have simple, fast and inexpensive tests that give information on a donors risk of developing iron depletion. In a pilot study we investigated whether novel erythrocyte and reticulocyte parameters can serve this goal. Methods: In regular blood donors extended red cell parameters were measured using the Abbott CELL-DYN Sapphire hematology analyzer and conventional biochemical tests of iron status. Donors were compared with a regionally matched group of non-donating controls. Results: In the controls, the reference ranges of extended RBC parameters were well comparable to published data. Donors had significantly more microcytic RBC than controls (median 0.9 vs 0.6%), lower serum ferritin concentration (median 43 vs 91 mg/L) and higher soluble transferrin receptor/ferritin index (median 1.60 vs 1.27). Overall 18-28% of the donors were iron depleted. Moreover, 3.3% of donors had iron-restricted erythropoiesis. Microcytic RBC and reticulocyte mean cell hemoglobin content predicted iron depletion with 70% and 64% sensitivities and specificities of 72% and 78%, respectively. When combined these two parameters increased the sensitivity to 82%. Conclusions: Our results in Swedish blood donors confirm a high prevalence of iron depletion, despite iron supplementation used by about half of the donors. Microcytic RBC and MCHr appeared to be helpful in identifying iron-depleted donors, who might benefit from iron supplementation. We recommend larger prospective investigations in order to confirm and extend the findings of this pilot study. (C) 2015 Elsevier Ltd. All rights reserved.

  • 10.
    Backlund, Nils
    et al.
    Umea Univ, Sweden.
    Brattsand, Göran
    Umea Univ, Sweden.
    Lundstedt, Staffan
    Umea Univ, Sweden.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Arts and Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Bartuseviciene, Inga
    Karolinska Univ Hosp, Sweden.
    Berinder, Katarina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hoybye, Charlotte
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Burman, Pia
    Skane Univ Hosp, Sweden.
    Eden Engström, Britt
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Isaksson, Anders
    Lund Univ, Sweden.
    Blomgren, Anders
    Lund Univ, Sweden.
    Ragnarsson, Oskar
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ruetschi, Ulrika
    Sahlgrens Univ Hosp, Sweden.
    Wahlberg, Jeanette
    Orebro Univ, Sweden; Orebro Univ Hosp, Sweden.
    Olsson, Tommy
    Umea Univ, Sweden.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Salivary cortisol and cortisone in diagnosis of Cushings syndrome - a comparison of six different analytical methods2023In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, no 10, p. 1780-1791Article in journal (Refereed)
    Abstract [en]

    Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushings syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

  • 11.
    Imamovic, Marcus
    et al.
    Umea Univ, Sweden.
    Backlund, Nils
    Umea Univ, Sweden.
    Lundstedt, Staffan
    Umea Univ, Sweden.
    Brattsand, Goran
    Umea Univ, Sweden.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Tommy
    Umea Univ, Sweden.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone2023In: Endocrine Connections, E-ISSN 2049-3614, Vol. 12, no 1, article id e220324Article in journal (Refereed)
    Abstract [en]

    Objective: To determine the effects of liquorice consumption, topical hydro cortisone, and blood contamination on salivary cortisol and cortisone concentrations. Design and methods: Thirty healthy volunteers were randomized to a low, medium, or high dose of liquorice. Late-night saliva samples were collected using a Salivette (R) collection device at baseline, during 1 week of daily liquorice consumption, and during 4 weeks washout. Saliva sampling was also performed before and after the application of topical hydrocortisone on the skin. Furthermore, in a subgroup (n = 16), saliva and venous blood were collected from each individual and mixed to achieve graded blood contamination in saliva. Salivary cortisol and cortisone were a nalyzed with liquid chromatography-tandem mass spectrometry. Results: Significant increases in salivary cortisol concentrations were observed during medium- (+49%) and high-dose (+97%) liquorice intake, which returned to baseline 4 days after liquorice withdrawal. Topical hydrocortisone on fingers holding the collection swab increased salivary cortisol concentrations &gt;1000-fold with concomitant pronounced elevation of the cortisol:cortisone ratio. Salivary cortisol in creased significantly after contamination with blood &gt;= 0.5%. Visual examination could safely detect these samples. Salivary cortisone concentrations were unaffected by liquorice consumption and blood contamination, and only marginally affected by topical hydrocortisone. Conclusion: Liquorice, topical hydrocortisone, and blood contamination may all cause elevated salivary cortisol concentrations. Improved sampling instructions and visual examination of the sample may minimize these risks. Salivary cortisone is essentially unaffected by the different preanalytical confounders and may be used as a first-line screening test for Cushings syndrome.

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  • 12.
    Lood, Yvonne
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Aardal, Elisabeth
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Ärlemalm, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Carlsson, Björn
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Ekman, Bertil
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. National Forensic Centre, Linköping, Sweden.
    Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: An accurate and sensitive method applied on clinical and forensic samples2021In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 195, article id 113823Article in journal (Refereed)
    Abstract [en]

    A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC–MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4−1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99–101 % and 93–95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.

  • 13.
    Lood, Yvonne
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Aardal, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Gustavsson, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Prasolov, Ilya
    Swedish Doping Control Laboratory, Karolinska University Hospital, Stockholm, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Drug Unit Department, National Forensic Centre, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH2021In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. n/a, no n/aArticle in journal (Refereed)
    Abstract [en]

    At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio?≥?12 together with testosterone/luteinizing hormone (T/LH) in urine?>?400?nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio?>?4 are considered suspicious and shall be further analysed by gas chromatography?combustion?isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography?mass spectrometry (GC?MS), serum testosterone and LH?by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E?≥?12 combined with T/LH?>?400?nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%?50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

  • 14.
    Walter, Susanna A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Pre-experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions2006In: Neurogastroenterology and Motility, ISSN 1350-1925, Vol. 18, no 12, p. 1069-1077Article in journal (Refereed)
    Abstract [en]

    Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se. In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment (P = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls (P = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation (P = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.

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