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  • 1.
    A Hulten, Maj
    et al.
    University Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands England .
    Patel, Suketu
    University Warwick, Department Biol Science, Coventry CV4 7AL, W Midlands England .
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Iwarsson, Erik
    Karolinska University Hospital, Karolinska Institute, Department Mol Med and Surg, Clin Genet Unit, S-17176 Stockholm, Sweden .
    On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model2010In: Reproduction, ISSN 1470-1626, Vol. 139, no 1, 1-9 p.Article, review/survey (Refereed)
    Abstract [en]

    We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. in particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.

  • 2.
    Aagaard, Lise
    et al.
    University of So Denmark, Denmark FKL Research Centre Qual Medical Use, Denmark Danish Pharmacovigilance Research Project DANPREP, Denmark .
    Strandell, Johanna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Melskens, Lars
    University of Copenhagen, Denmark .
    Petersen, Paw S. G.
    University of Copenhagen, Denmark .
    Holme Hansen, Ebba
    FKL Research Centre Qual Medical Use, Denmark Danish Pharmacovigilance Research Project DANPREP, Denmark University of Copenhagen, Denmark .
    Global Patterns of Adverse Drug Reactions Over a Decade Analyses of Spontaneous Reports to VigiBase (TM)2012In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 35, no 12, 1171-1182 p.Article in journal (Refereed)
    Abstract [en]

    Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase (TM), and to relate data to national income. Methods: We analysed ADR reports submitted to VigiBase (TM) from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1 359 067 ADR reports including 3 013 074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. Conclusion: This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type skin and subcutaneous tissue disorders and for the therapeutic groups antiinfectives for systemic use and antineoplastic and immunomodulation agents. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.

  • 3.
    Aalto, Anne
    et al.
    Linköping University, Department of Medicine and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Jaworski, M
    Gustavsson, M
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Effects of Betainterferon treatment in Multiple Sclerosis Studied by Quantitative 1H MRS2009Conference paper (Other academic)
  • 4.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, 755-762 p.Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 5.
    Aaltonen, Kristina E.
    et al.
    Lund University, Sweden.
    Rosendahl, Ann H.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Malmstrom, Per
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Hartman, Linda
    Lund University, Sweden; Regional Cancer Centre South, Sweden.
    Ferno, Marten
    Lund University, Sweden.
    Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer2014In: BMC Cancer, ISSN 1471-2407, Vol. 14, no 794Article in journal (Refereed)
    Abstract [en]

    Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.

  • 6.
    Aamand Grabau, Dorthe
    et al.
    Skåne University Hospital, Sweden .
    Bendahl, Par-Ola
    Lund University, Sweden .
    Ryden, Lisa
    Lund University, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ferno, Marten
    Lund University, Sweden .
    The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, 1657-1666 p.Article in journal (Refereed)
    Abstract [en]

    Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.

  • 7.
    Aanaes, K
    et al.
    Rigshosp, Denmark .
    Rasmussen, N
    Rigshosp, Denmark Statens Serum Institute, Denmark .
    Pressler, T
    Rigshosp, Denmark Rigshosp, Denmark .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Johansen, H K
    Rigshosp, Denmark .
    Lindberg, U
    Lund University, Sweden .
    Hoiby, N
    Rigshosp, Denmark .
    Carlsson, M
    Lund University, Sweden .
    Wieslander, J
    EuroDiagnostica AB, Sweden .
    Buchwald, C
    Rigshosp, Denmark .
    Extensive Endoscopic Image-Guided Sinus Surgery Decreases BPI-ANCA in Patients with Cystic Fibrosis2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 6, 573-579 p.Article in journal (Refereed)
    Abstract [en]

    Antineutrophil cytoplasm autoantibodies (ANCA) directed against bactericidal/permeability-increasing protein (BPI) are common in patients with cystic fibrosis (CF), and serum levels are correlated with lung colonization by Pseudomonas aeruginosa and the severity of lung damage. The production of BPI-ANCA may be due to the costimulation of BPI when mounting an immune response against P. aeruginosa. The effect of surgery aiming to eradicate bacteria and infected tissue on BPI-ANCA levels is sparsely described. A cohort of patients with CF were included: 53 patients having extensive image-guided sinus surgery (EIGSS) with topical postoperative antibiotic treatment, 131 non-operated controls and 36 who had double lung transplantation (LTX). In all 219 patients, serum samples before and after surgery or at similar intervals were analysed for IgG and IgA BPI-ANCA. The EIGSS group showed a highly significant decrease in both IgA and IgG BPI-ANCA levels compared with their own preoperative values and control group values (P andlt; 0.0010.02). The LTX patients also showed a highly significant decrease in both IgA and IgG BPI-ANCA levels (P andlt; 0.001). EIGSS and LTX decrease IgA and IgG BPI-ANCA levels in patients with CF, indicating that extensive removal of infected tissue influences the pathogenic process of autoantibody production. The results shown herein are in favour of applying EIGSS in selected patients with CF and for using BPI-ANCA as a surrogate marker for guiding further therapeutic interventions.

  • 8.
    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, 927-932 p.Article 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.

  • 9.
    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, 927-932 p.Article 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, Vol. 36, no 4, 215-222 p.Article 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: 2012-10-24Bibliographically 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, 850-855 p.Article 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: 2012-08-21Bibliographically 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, 986-993 p.Article 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: 2012-08-21Bibliographically 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.

    Keyword
    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.

    Keyword
    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
  • 10.
    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.

  • 11.
    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, 986-993 p.Article 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.

  • 12.
    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.

  • 13.
    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, 850-855 p.Article 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.

  • 14.
    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, Vol. 45, no 1-2, 89-89 p.Conference paper (Other academic)
  • 15.
    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, Vol. 36, no 4, 215-222 p.Article 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.

  • 16.
    Aasa, Agneta
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hovbäck, Malin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Det preoperativa informationssamtalets betydelse för patientens delaktighet i sin vård inom kolorektalkirurgi2011Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: ERAS (Enhanced Recovery After Surgery) är ett standardiserat multimodalt vårdprogram vid elektiv kolorektalkirurgi, som syftar till snabbare återhämtning och kortare vårdtider genom ett tvärprofessionellt samarbete.  En vecka innan planerad operation träffar sjuksköterskan patienten för ett samtal om vårdförloppet.

     

    Syfte: Att identifiera och beskriva patientens upplevelse av sjuksköterskans ERAS- samtal och dess betydelse för patientens delaktighet i sin vård. 

     

    Metod: Datainsamlingen skedde genom kvalitativa intervjuer. Tolv patienter, nio män och tre kvinnor har intervjuats. De ljudinspelade samtalen har transkriberats ordagrant och analyserats med hjälp av tolkande fenomenologisk analys (Interpretative Phenomenological Analysis).

     

    Resultat: Analysarbetet resulterade i fem olika teman; bli sedd, trygghet, tillit, ansvar samt delaktighet. Alla teman relaterar till varandra och illustrerar en positiv och en negativ sida av den upplevda erfarenheten. Tillsammans bildar en helhet av upplevelsen; ERAS- samtalet och dess betydelse för patientens delaktighet.

     

    Konklusion: Resultatet visar att patienterna känner sig sedda under informationssamtalet. Det är viktigt att bekräfta patienten och knyta an mer till informationssamtalet under vårdtiden för att patienterna ska vara delaktiga och ta eget ansvar. Tilliten till vårdpersonalen har betydelse för att patienterna ska känna trygghet. Studien visar att ERAS- samtalet upplevs strukturerat och individuellt men informationen måste följa patienterna under hela vårdtillfället.

  • 17.
    Aasa, Agneta
    et al.
    Kirurgmottagningen, Ryhovs Länssjukhus, Jönköping, Sweden.
    Hovbäck, Malin
    Kirurgmottagningen, Ryhovs Länssjukhus, Jönköping, Sweden.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    The importance of preoperative information for patient participation in colorectal surgery care2013In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 22, no 11-12, 1604-1612 p.Article in journal (Refereed)
    Abstract [en]

    Aims and objectives

    To identify and describe patients' experiences of a preoperative information session with a nurse, as part of the enhanced recovery after surgery (ERAS) concept, and its impact on patient participation in their own care.

    Background

    Enhanced recovery after surgery is a standardised, multimodal treatment programme for elective colorectal surgery, leading to faster recovery and shorter hospital stays via interprofessional collaboration. The ERAS concept is initiated for patients a week before surgery when the patient receives detailed information about the care process during a meeting with a nurse.

    Design

    The study is a qualitative interpretive study based on interviews.

    Methods

    Twelve patients, nine men and three women, were interviewed. The interviews were transcribed verbatim and analysed using interpretive phenomenological analysis (IPA).

    Results

    The analysis identified and formulated five themes: being seen, security, trust, responsibility and participation. All themes are closely related and illustrate positive and negative sides of the patient's experience. They hang together and form a complete set of experiences: ERAS conversation and its impact on patients' participation.

    Conclusions

    The results show that patients feel confirmed in the ERAS conversation. Healthcare professionals need to be bonding more information call during hospitalisation. It is important to confirm the patient in order for them to participate and take responsibility. Reliance on caregivers is important for patients to feel safe and to participate in their own care. This study shows that the ERAS conversation was experienced as being structured and individually tailored, but the information must apply to the patients throughout the period of care.

    Relevance to clinical practice

    Some shortcomings have been revealed, which should enable improvement in the care of patients. Healthcare professionals need to raise awareness of patients' responsibilities for participation in their own recovery and care. Healthcare professionals and patients need to be aware of each other's responsibilities.

  • 18.
    Aasa, Mikael
    et al.
    Karolinska Institute.
    Henriksson, Martin
    Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Dellborg, Mikael
    Gothenburg University.
    Grip, Lars
    Gothenburg University.
    Herlitz, Johan
    Gothenburg University.
    Levin, Lars-Åke
    Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Svensson, Leif
    Stockholm Prehospital Centre.
    Janzon, Magnus
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial2010In: AMERICAN HEART JOURNAL, ISSN 0002-8703, Vol. 160, no 2, 322-328 p.Article in journal (Refereed)
    Abstract [en]

    Background In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis. Methods Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach. Results Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be andlt;$0, $50,000, and $100,000 respectively. Conclusion In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.

  • 19.
    Aasland, Olaf G.
    et al.
    University of Oslo, Norway.
    Nygaard, Peter
    Norwegian Institute for Alcohol and Drug Research, Oslo, Norway.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    The long and winding road to widespread implementation of screening and brief intervention for alcohol problems: A historical overview with special attention to the WHO initiatives2008In: Nordic Studies on Alcohol and Drugs, ISSN 1458-6126, Vol. 25, no 6, 469-476 p.Article in journal (Refereed)
    Abstract [en]

    Before 1970, special institutions, often prison-like, were built for the severely dependent. The effect of this type of treatment, often lasting for months or even years, was hard to document scientifically. During the 1970s several steps were taken towards a more preventive strategy that involved delivery of alcohol interventions in general health care settings, particularly within primary health care. The World Health Organization's (WHO) introduction of the concepts of hazardous and harmful drinking represented a shift from the traditional dichotomous view of individuals being alcoholic-or-not to a continuum where, in line with Rose's "prevention paradox", a large number of people with low risk may give rise to more cases of disease than the small number with high risk. The need for efficient methods to detect persons with various degrees of alcohol risk was evident, and a WHO multinational project that resulted in the publication of AUDIT (Alcohol Use Disorders identification Test) was carried out in the mid 1980s. The usefulness of this principle of case finding was then investigated in a subsequent multinational WHO project of brief intervention, as well as in several other similar projects. Many of these projects have proven quite efficient, but screening and brief intervention for alcohol problems is still not standard procedure in primary health care. The paper discusses some of the reasons why.

  • 20.
    Abate, E.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. University of Gondar, Ethiopia.
    Elias, D.
    University of Southern Denmark, Denmark.
    Getachew, A.
    University of Gondar, Ethiopia.
    Alemu, S.
    University of Gondar, Ethiopia.
    Diro, E.
    University of Gondar, Ethiopia.
    Britton, S.
    Karolinska Hospital, Sweden.
    Aseffa, A.
    Armauer Hansen Research Institute, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Kalmar County Hospital, Sweden.
    Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial2015In: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, no 2-3, 133-140 p.Article in journal (Refereed)
    Abstract [en]

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  • 21.
    Abate, Ebba
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    The impact of helminth infection in patients with active tuberculosis2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The geographic distribution of helminth infection and tuberculosis (TB) overlap substantially. Experimental animal models and limited data from humans have shown that intestinal helminths could subvert the host immune response towards a T-helper 2 (Th2)-type immune response and an increased regulatory T-cell activity (Tregs). This in turn affects the host's ability to mount an effective Th1 immune-mediated protection against Mycobacterium tuberculosis. However, evidence for this hypothesis in the human setting from helminth infected TB patients is limited. This thesis primarily focuses on the immunological and clinical impact of helminth infection on pulmonary TB. The kinetics of the Quantiferon-Gold (QFN) assay, which measures IFN-³ response to TB-specific antigens in whole blood was assessed and showed a modest decline during TB treatment to the level observed for healthy blood donors. We further assessed another clinical monitoring tool, the-TB-score, composed of clinical signs and symptoms of TB, and found an early decline two weeks after initiation of TB- treatment where a failure of decline correlated with increased mortality. Overall, the helminth co-infection rate was significantly higher in TB patients compared to healthy controls. Helminth co-infection was associated to a significantly higher rate of eosinophilia and IgE-levels in healthy controls and patients with tuberculosis. During the first weeks of anti-TB treatment, a marked decrease in the rate of helminth infection was observed in HIV co-infected compared to HIV-negative TB patients. However, helminth co-infection was more common in HIV negative than HIV positive TB patients. There was no detectable impact of helminth infection on the clinical presentation of pulmonary tuberculosis. At baseline, helminth co-infected TB patients showed an increased frequency of Tregs compared to helminth negative TB patients and healthy controls. This was accompanied by an increased rate of PPD stimulated IL-5 and spontaneous production of IL-10 by peripheral blood mononuclear cells among helminth co-infected TB patients. A placebo controlled randomized trial was conducted in order to test the hypothesis that albendazole treatment of helminth positive TB patients may improve the clinical response of TB by reducing the immunmodulatory effect of helminthes on TB immunity. A total of 140 helminth co-infected TB patients were randomized to albendazole (400 mg per os for three consecutive days) or placebo. No significant difference was observed between the albendazole and placebo group in terms of the primary outcome (TB score change between baseline and week 8). Among the secondary outcomes, a significant decline of peripheral eosinophil cells was observed in the albendazole treated group, but no effect on other outcome variables (changes in chest x-ray findings, IgE level and sputum smear conversion). Regarding the immunological assessment no significant difference was observed for changes in Tregs, and PPD-induced production of IFN- ³ or IL-5 although a non-significant trend of a decrease in IL-10 expressing PBMCs were observed in the albendazole group. Taken together, the burden of helminth infection was higher in TB patients than in a healthy control group. Helminth co-infection during pulmonary TB in the human setting induces an immune response characterized by increased IgE production, eosinophilia as well as increased levels of Tregs and spontaneous IL-10 production. Thus, the immunological impact of helminth infection on the outcome and risk for developing TB merits further investigation.

    List of papers
    1. Kinetics of the QuantiFERON((R))-TB Gold In-Tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease
    Open this publication in new window or tab >>Kinetics of the QuantiFERON((R))-TB Gold In-Tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease
    Show others...
    2010 (English)In: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 42, no 9, 650-657 p.Article in journal (Refereed) Published
    Abstract [en]

    Abstract The QuantiFERON((R))-TB Gold In-Tube test (QFN) measures interferon-gamma production in response to Mycobacterium tuberculosis antigens. Our aim was to assess the kinetics of the QFN and initial tuberculin skin test (TST) result in relation to severity of disease in a tuberculosis (TB) endemic area. Smear-positive TB patients (n = 71) were recruited at Gondar University Hospital, Ethiopia. The TST, QFN, CD4+ cell count and clinical symptoms (TB score) were assessed and followed up during treatment. From baseline to 7 months after treatment, there was a significant decrease in QFN reactivity (93.8% to 62.5% in HIV-negative/TB; 70.3% to 33.3% in HIV-positive/TB patients) down to a level comparable to a control group of blood donors (51.2%). The agreement between TST and QFN was poor in TB patients compared to healthy controls. A negative TST correlated to more advanced TB in contrast to a negative QFN test. We conclude that the QFN reactivity is significantly reduced at the end of treatment against active TB to the background level of healthy blood donors, and that the agreement between TST and QFN is poor including correlation to the severity of disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-58804 (URN)10.3109/00365548.2010.482942 (DOI)000282716000002 ()20465490 (PubMedID)
    Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2013-05-02
    2. Early treatment response evaluated by a clinical scoring system correlates with the prognosis of pulmonary tuberculosis patients in Ethiopia: A prospective follow-up study.
    Open this publication in new window or tab >>Early treatment response evaluated by a clinical scoring system correlates with the prognosis of pulmonary tuberculosis patients in Ethiopia: A prospective follow-up study.
    Show others...
    2012 (English)In: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 44, no 11, 828-834 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: In resource-limited settings the monitoring of tuberculosis (TB) patients is challenging, and early identification of TB patients with a high mortality risk is important. The aim of this study was to investigate prospectively whether early changes in a clinical scoring system (TB score) can predict treatment outcome in Ethiopian patients with pulmonary tuberculosis. Method: TB patients (n = 250) and blood donors (n = 82) were recruited prospectively at Gondar University Hospital, Ethiopia. Clinical scoring was performed using an interview-based questionnaire and clinical examination. Results: Among TB patients (53.6% of whom were HIV co-infected) the median TB score declined from week 0 to week 2 (8 (interquartile range (IQR) 6-9) vs 4 (IQR 2-6)) and dropped to a low level at week 8, which was still significantly higher than that found in blood donors (2 (IQR 1-4) vs 0 (IQR 0-1), p < 0.0001). Patients who died had a significantly higher TB score at week 0, week 2, and week 8 than survivors. Mortality was associated with a failure to achieve a decrease greater than 25% in the TB score at 2 weeks. Baseline CD4 + cell counts (< 200 cells/mm(3)) were associated with mortality but not with initial TB score results. Conclusions: The TB score was increased during the first 2 months of treatment among patients who died. Failure to achieve a greater than 25% decrease in TB score after 2 weeks of treatment was associated with increased mortality. Repeated clinical scoring during the intensive phase of TB treatment could be useful to identify high-risk patients.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85315 (URN)10.3109/00365548.2012.694468 (DOI)000310008900004 ()22812387 (PubMedID)
    Note

    funding agencies|Swedish Heart and Lung Foundation||EU/EDCTP project|JP 2009.10800.006|Swedish heart and lung Foundation (King Oscar II Jubilee Foundation)||EU/EDCP|JP.10800.006|

    Available from: 2012-11-15 Created: 2012-11-15 Last updated: 2013-05-02
    3. The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia
    Open this publication in new window or tab >>The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia
    Show others...
    2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 8Article in journal (Refereed) Published
    Abstract [en]

    Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.

    Place, publisher, year, edition, pages
    Public Library of Science, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84349 (URN)10.1371/journal.pone.0042901 (DOI)000308206000014 ()
    Note

    Funding Agencies|Swedish Agency for Research Cooperation with Developing Countries||Swedish International Development Cooperation Agency (SAREC/SIDA)||European-Developing Countries Clinical Trials Partnership (EU/EDCTP)|JP 10800.006|Swedish Research Council||Swedish Heart and Lung Foundation (Oscar II Jubilee Foundation)||

    Available from: 2012-10-05 Created: 2012-10-05 Last updated: 2013-05-02
    4. Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis
    Open this publication in new window or tab >>Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis
    Show others...
    2013 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The effects of helminth infection on chronic infectious diseases such as HIV and tuberculosis (TB) merit further characterization. Thus, we assessed the baseline clinical characteristics of helminth infection in patients with active TB in a high endemic area.

    Methodology: Consecutive, newly diagnosed TB patients were recruited from three health institutions in the north Gondar administrative zone, Ethiopia. Structured questionnaires were used to collect socio-demographic and clinical characteristics. Additionally, the TB score, mid upper arm circumference, body mass index (BMI), BCG vaccination status, stool and sputum microscopy as well as HIV serology and CD4+T cells counts were evaluated.

    Results: A total of 377 pulmonary TB patients were included in the study. The helminth co infection rate was 33% (123/377) and the most prevalent parasite was Ascaris lumbricoides (53%, 65/123). The HIV co-infection rate was 29% (110/377). Seventy percent (77/110) of the HIV co-infected patients were on anti- retroviral therapy at the time of TB diagnosis. Helminth infection was more prevalent in HIV-negative TB patients compared to HIV-positive TB patients (p=0.025). Smoking and walking bare foot were independently associated to helminth infection in TB patients after adjusting for the influence of HIV. Other than increased eosinophilia, no other significant differences were observed between helminth positive and helminth negative TB patients in the clinical presentation including the TB score, CD4+T-cells, BMI or bacterial load.

    Conclusion: The clinical presentation of active pulmonary tuberculosis was not affected by helminth infection. Helminth infection was less frequent among HIV-positive TB patients and this finding merits further investigation.

    Keyword
    Tuberculosis, HIV, helminth, TB score, CD4, Ethiopia
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-91825 (URN)
    Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2013-05-02Bibliographically approved
    5. Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis: a randomized clinical trial
    Open this publication in new window or tab >>Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis: a randomized clinical trial
    Show others...
    2013 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The impact of helminth infection on the host immune response to tuberculosis (TB) has been characterized in experimental models but less so in the clinical setting. The objective of this study was to investigate the impact of deworming on the clinical outcome and cell mediated immune response in active TB.

    Methods: Newly diagnosed pulmonary TB patients in Gondar, Ethiopia were examined for helminth infection. Helminth-positive TB patients (W+/TB) were randomized to albendazole (400mg X III per os) or placebo. The primary outcome was change in TB-score after 2 months, and secondary outcomes were sputum smear conversion at the 2nd month, and changes in chest x-ray pattern, CD4+ T-cell count, eosinophil count, IgE-levels and immunological responses after 3 months. In a subset of W+/TB, W-/TB patients and healthy controls, flow cytometry and ELISPOT assays were used to characterize the regulatory T-cell population (Tregs) and the frequency of PPD- stimulated IFN-γ, IL-5 and IL-10 producing peripheral blood mononuclear cells (PBMCs).

    Results: A total of 140 helminth co-infected TB patients were included with an HIV coinfection rate of 22.8 %. Following albendazole treatment of the W+/TB patients, there was a significant decrease in helminth infection compared to placebo (8% (4/49) vs. 48 % (22/46), p<0.001). No significant effect was observed for albendazole compared to placebo on the primary outcome as evaluated by the TB-score (5.6 ±2.87 vs. 5.87 ±2.54, p=0.59). Eosinophil counts decreased significantly in the albendazole group. In a subgroup analysis of helminthnegative patients following albendazole treatment versus placebo, the albendazole group showed a trend for lower levels of IL-10 producing cells at month three (p=0.08). At baseline, W+/TB patients had a significantly higher mean level of Tregs (% Tregs/CD4+) compared to W-/TB patients and helminth-positive community controls. Additionally, the frequency of IFN-γ, IL-5 and spontaneous IL-10 levels was increased in helminth-positive compared to helminth-negative TB patients.

    Conclusions: No significant effects on the clinical outcome as measured with the TB-score was detected after albendazole treatment of helminth-positive TB patients compared to placebo. However, significant changes were observed in specific immunological responses such as reduced eosinophil counts and a trend towards lower levels of IL-10 producing cells. At baseline, helminth co-infected TB patients exhibited an increased Treg response as well as an increased IL-5 and spontaneous IL-10 production.

    Keyword
    Regulatory T-cells, helminth, tuberculosis, albendazole, deworming, Ethiopia, HIV
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-91827 (URN)
    Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2013-05-02Bibliographically approved
  • 22.
    Abate, Ebba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Belayneh, Meseret
    University of Addis Ababa, Ethiopia .
    Gelaw, Aschalew
    University of Gondar, Ethiopia .
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Getachew, Assefa
    University of Gondar, Ethiopia .
    Alemu, Shitaye
    University of Gondar, Ethiopia .
    Diro, Ermias
    University of Gondar, Ethiopia .
    Fikre, Nigussu
    University of Addis Ababa, Ethiopia .
    Britton, Sven
    Karolinska Hospital, Sweden .
    Elias, Daniel
    University of So Denmark, Denmark .
    Aseffa, Abraham
    Armauer Hansen Research Institute, Ethiopia .
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia2012In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 8Article in journal (Refereed)
    Abstract [en]

    Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.

  • 23.
    Abate, Ebba
    et al.
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia; Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Elias, Daniel
    University of Southern Denmark, Institute of Molecular Medicine, Department of cancer and inflammation, Odense, Denmark.
    Getachew, Assefa
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia.
    Alemu, Shitaye
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia.
    Diro, Ermias
    Department of Radiology, University of Gondar, Gondar, Ethiopia.
    Britton, Sven
    Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
    Aseffa, Abraham
    Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis: a randomized clinical trial2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The impact of helminth infection on the host immune response to tuberculosis (TB) has been characterized in experimental models but less so in the clinical setting. The objective of this study was to investigate the impact of deworming on the clinical outcome and cell mediated immune response in active TB.

    Methods: Newly diagnosed pulmonary TB patients in Gondar, Ethiopia were examined for helminth infection. Helminth-positive TB patients (W+/TB) were randomized to albendazole (400mg X III per os) or placebo. The primary outcome was change in TB-score after 2 months, and secondary outcomes were sputum smear conversion at the 2nd month, and changes in chest x-ray pattern, CD4+ T-cell count, eosinophil count, IgE-levels and immunological responses after 3 months. In a subset of W+/TB, W-/TB patients and healthy controls, flow cytometry and ELISPOT assays were used to characterize the regulatory T-cell population (Tregs) and the frequency of PPD- stimulated IFN-γ, IL-5 and IL-10 producing peripheral blood mononuclear cells (PBMCs).

    Results: A total of 140 helminth co-infected TB patients were included with an HIV coinfection rate of 22.8 %. Following albendazole treatment of the W+/TB patients, there was a significant decrease in helminth infection compared to placebo (8% (4/49) vs. 48 % (22/46), p<0.001). No significant effect was observed for albendazole compared to placebo on the primary outcome as evaluated by the TB-score (5.6 ±2.87 vs. 5.87 ±2.54, p=0.59). Eosinophil counts decreased significantly in the albendazole group. In a subgroup analysis of helminthnegative patients following albendazole treatment versus placebo, the albendazole group showed a trend for lower levels of IL-10 producing cells at month three (p=0.08). At baseline, W+/TB patients had a significantly higher mean level of Tregs (% Tregs/CD4+) compared to W-/TB patients and helminth-positive community controls. Additionally, the frequency of IFN-γ, IL-5 and spontaneous IL-10 levels was increased in helminth-positive compared to helminth-negative TB patients.

    Conclusions: No significant effects on the clinical outcome as measured with the TB-score was detected after albendazole treatment of helminth-positive TB patients compared to placebo. However, significant changes were observed in specific immunological responses such as reduced eosinophil counts and a trend towards lower levels of IL-10 producing cells. At baseline, helminth co-infected TB patients exhibited an increased Treg response as well as an increased IL-5 and spontaneous IL-10 production.

  • 24.
    Abate, Ebba
    et al.
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia; Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Belayneh, Meseret
    School of Medical Laboratory Sciences, Medical Faculty, Addis Ababa University, Addis Ababa.
    Getachew, Assefa
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia.
    Alemu, Shitaye
    Gondar College of Medical and Health Sciences, Gondar University, Gondar, Ethiopia.
    Diro, Ermias
    Department of Radiology, University of Gondar, Gondar, Ethiopia.
    Britton, Sven
    Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
    Elias, Daniel
    University of Southern Denmark, Institute of Molecular Medicine, Department of cancer and inflammation, Odense, Denmark.
    Aseffa, Abraham
    Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The effects of helminth infection on chronic infectious diseases such as HIV and tuberculosis (TB) merit further characterization. Thus, we assessed the baseline clinical characteristics of helminth infection in patients with active TB in a high endemic area.

    Methodology: Consecutive, newly diagnosed TB patients were recruited from three health institutions in the north Gondar administrative zone, Ethiopia. Structured questionnaires were used to collect socio-demographic and clinical characteristics. Additionally, the TB score, mid upper arm circumference, body mass index (BMI), BCG vaccination status, stool and sputum microscopy as well as HIV serology and CD4+T cells counts were evaluated.

    Results: A total of 377 pulmonary TB patients were included in the study. The helminth co infection rate was 33% (123/377) and the most prevalent parasite was Ascaris lumbricoides (53%, 65/123). The HIV co-infection rate was 29% (110/377). Seventy percent (77/110) of the HIV co-infected patients were on anti- retroviral therapy at the time of TB diagnosis. Helminth infection was more prevalent in HIV-negative TB patients compared to HIV-positive TB patients (p=0.025). Smoking and walking bare foot were independently associated to helminth infection in TB patients after adjusting for the influence of HIV. Other than increased eosinophilia, no other significant differences were observed between helminth positive and helminth negative TB patients in the clinical presentation including the TB score, CD4+T-cells, BMI or bacterial load.

    Conclusion: The clinical presentation of active pulmonary tuberculosis was not affected by helminth infection. Helminth infection was less frequent among HIV-positive TB patients and this finding merits further investigation.

  • 25.
    Abbott, Allan
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Bond University, Australia.
    Kjellman, Görel
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Multidimensional assessment of pain related disability after surgery for cervical disc disease2013In: APA Conference 2013: New moves, Australian Physiotherapy Association , 2013, 2-2 p.Conference paper (Other academic)
    Abstract [en]

    Questions: Given only 25% of patients, 10 year post-surgery for cervical disc disease report clinically meaningful improvements in functional disability, what are the biopsychosocial factors associated with continued long-term disability? What are the implications for physiotherapy practice?

    Design: Cross-sectional observational study.

    Participants: Ninety patients who had undergone anterior discectomy and fusion (ACDF) surgery 10-13 years prior.

    Outcome Measures: The Neck Disability Index (NDI), ACDF surgery type, surgical fusion status, patient age and Part 1 of the West Haven-Yale multidimensional pain inventory Swedish version (MPI-S) were entered into a statistical model. Part 1 of the MPI-S contains 5 subscales: pain severity, interference, life control, affective distress and support.

    Results: Seventy-three patients answered the questionnaires. Non-linear categorical regression modeling (CATREG) of the selected predictive variables explained 76.1% of the variance in NDI outcomes 10-13 years post ACDF. Of these predictors, MPI-S affective distress subscale (β = 0.635, p = <0.001) and pain severity subscale (β = 0.354, p = <0.001) were significant individual predictors of NDI ratings.

    Conclusion: This is the first study to investigate potential factors associated with prolonged functional disability greater than 10 years post-surgery for cervical disc disease. The results suggest the importance of not only pain severity but also screening affective distress as a potential barrier to physical functioning in patients previously operated for cervical disc disease. Future research on the utility of affect-focused body awareness therapy and pain coping strategies for post-surgical patients with continuing pain and physical disability is indicated.

    Key Practice Points:

    •  The screening of pain severity and affective distress is of importance for patients presenting with continuing physical disability after previous surgery for cervical disc disorders

    •  Affect-focused body awareness therapies and pain coping strategies may be a potential treatment alternative for patients with continuing pain and physical disability.

  • 26.
    Abbott, Allan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Department of Physical Therapy, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Division of Orthopaedics, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Tyni-Lenné, Raija
    Department of Physical Therapy, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Hedlund, Rune
    Department for Orthopaedics, Institute for Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Leg pain and psychological variables predict outcome 2-3 years after lumber fusion surgery2011In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 20, no 10, 1626-1634 p.Article in journal (Refereed)
    Abstract [en]

    Prediction studies testing a thorough range of psychological variables in addition to demographic, work-related and clinical variables are lacking in lumbar fusion surgery research. This prospective cohort study aimed at examining predictions of functional disability, back pain and health-related quality of life (HRQOL) 2-3 years after lumbar fusion by regressing nonlinear relations in a multivariate predictive model of pre-surgical variables. Before and 2-3 years after lumbar fusion surgery, patients completed measures investigating demographics, work-related variables, clinical variables, functional self-efficacy, outcome expectancy, fear of movement/(re)injury, mental health and pain coping. Categorical regression with optimal scaling transformation, elastic net regularization and bootstrapping were used to investigate predictor variables and address predictive model validity. The most parsimonious and stable subset of pre-surgical predictor variables explained 41.6, 36.0 and 25.6% of the variance in functional disability, back pain intensity and HRQOL 2-3 years after lumbar fusion. Pre-surgical control over pain significantly predicted functional disability and HRQOL. Pre-surgical catastrophizing and leg pain intensity significantly predicted functional disability and back pain while the pre-surgical straight leg raise significantly predicted back pain. Post-operative psychomotor therapy also significantly predicted functional disability while pre-surgical outcome expectations significantly predicted HRQOL. For the median dichotomised classification of functional disability, back pain intensity and HRQOL levels 2-3 years post-surgery, the discriminative ability of the prediction models was of good quality. The results demonstrate the importance of pre-surgical psychological factors, leg pain intensity, straight leg raise and post-operative psychomotor therapy in the predictions of functional disability, back pain and HRQOL-related outcomes.

  • 27.
    Abdalla, Hana
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Diab, Asim
    Department of Neurology, University of Texas Southwestern Medical Center, Dallas, USA.
    Forslund, Tony
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Bakhiet, Moiz
    Department of Medicine, Divisions of lnfectious Diseases, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Expression of inducible nitric oxide synthases and nitrotyrosine during the course of Haemophilus influenzae type b meningitis in ratManuscript (preprint) (Other academic)
    Abstract [en]

    Bacterial meningitis continues to be a major health problem and despite great advances in antimicrobial therapy the fatality rate remains high. There is increasing evidence that leukocyte-endothelial interactions are involved in CNS damage during bacterial meningitis. Once leukocytes have entered the CSF they cause injury by releasing toxic molecules such as nitric oxide (NO) and reactive oxygen species (ROS). The induction of iNOS was examined by assessing intracerebral mRNA expression and protein production during the course of Haemophilus influenzae type b (Hib) meningitis in the rat. Induction of iNOS mRNA was detected 12h postinoculation (pi), followed by a gradual reduction. The increased number of intracerebral iN OS expressing cells was detected at 12h pi. followed by further elevation to peak expression at 72h pi. The iNOS positive tissue also bound antibodies specific for nitrotyrosine. The expression of iNOS and NO production, as shown by nitrotyrosine expression, correlated with disease severity, suggesting that activation of iNOS may play an important role in Haemophilus irifluenzae type b meningitis.

  • 28.
    Abdalla, Hana
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Effects of CNI-1493 on human granulocyte functions2006In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 211, no 3, 191-197 p.Article in journal (Refereed)
    Abstract [en]

    During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNγ) had decreased NO production measured as NO2/NO3 levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNγ-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.

  • 29.
    Abdgawad, Mohamed
    et al.
    Lund University.
    Pettersson, Asa
    Lund University.
    Gunnarsson, Lena
    Lund University.
    Bengtsson, Anders A
    Lund University.
    Geborek, Pierre
    Lund University.
    Nilsson, Lars
    Lund University.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Hellmark, Thomas
    Lund University.
    Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis2012In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 3Article in journal (Refereed)
    Abstract [en]

    Background: ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. less thanbrgreater than less thanbrgreater thanMethods: Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. less thanbrgreater than less thanbrgreater thanResults: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p andlt; 0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. less thanbrgreater than less thanbrgreater thanConclusion: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.

  • 30.
    Abdiu, Avni
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Growth regulation in sarcomas: studies in vivo and in cell culture1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sarcomas are malignant tumors of mesenchymal origin, and can arise in soft-tissue and in bones. It has been suggested that the abnormal growth regulation in sarcoma cells may be due to an autocrine mechanism, in which the cells are stimulated by an endogenous production of growth factors. Platelet-derived growth factor (PDGF) has been detected in sarcomas, and may be one of the growth factors important for sarcoma growth.

    PDGF, originally discovered in platelets, is produced by, and binds to, a variety of cells. PDGF plays several roles both in normal conditions and in disease.

    Suramin is a polyanionic drug with antineoplastic activities, and is known to dissociate growth factors from their receptors. Suramin has been shown to inhibit growth in several tumors and tumor cell lines; however, some tumor cells have been unaffected, or even stimulated, by suramin.

    The present work was performed in order to a) examine the effects of suramin on sarcoma growth in vivo; b) investigate the kinetics of extravascularly administered PDGF in vivo; c) establish and characterize human sarcoma cells in vitro, including their relation to PDGF; d) evaluate the effects of suramin on sarcoma growth in vitro; e) compare the effects of PDGF on sarcoma growth in vivo and in vitro.

    Suramin was shown to inhibit growth of two different human osteosarcoma xenografts grown in nude mice. The action is believed to be mainly cytostatic, as the tumors continued to grow, albeit at a lower pace: the tumors of the suramin treated mice had a volume of one-third or less than the untreated ones. The percentage of cells in S and G2-M cell cycle phases was increased by suramin treatment, suggesting a selective effect of the drug in the S and G2 period.

    Blood and serum levels of 125I, after extravascular administration of 125I-PDGF-AB by intraperitoneal, intramuscular or subcutaneous injection in mice, were found to rise to a maximum 2-4 hours after injection. The levels of radioactivity persisted over several hours. Precipitiation of serum with 10% trichloracetic acid revealed that more than 50% of the radioactivity was in a macromolecular form. Gel chromatography of the serum showed that a major portion of the radioactive material in the circulation had the same molecular size as the original 125I-PDGF-AB.

    Eight cell lines derived from malignant fibrous histiocytomas (MFH) were established and characterized. A heterogeneity in the morphology of the MFH cell lines was noted. This heterogeneity was also reflected in the expression of mRNA for PDGF, transforming growth factor-alpha (TGF-/alpha/) and their receptors, ability to grow in serumfree media and secretion of PDGF into growth media. Two cell lines, able to grow in serum-free medium, coexpressed MRNA for PDGF, TGF-/aplpha/ and their receptors, suggesting that they may be regulated in an autocrine manner. However, other cell lines, unable to grow in a serum-free medium, also displayed this coexpression of mRNA. The simultaneous expression of a growth factor and its receptor is therefore not generally indicative of an autocrine mechanism.

    All cell lines, unable to grow in a serum-free medium, were growth inhibited by high-dose suramin (200 ug/ml). The two cell lines, previously noted to grow under serum-free conditions, were not affected by the high-dose suramin treatment. The finding that only serum-dependent human MFH cell lines were inhibited by high doses of suramin indicates that serum dependence in vitro may predict sensitivity of sarcoma cells to suramin.

    Two human sarcoma xenografts, one osteosarcoma and one malignant fibrous histiocytoma, were treated with human PDGF-AB when grown in nude mice. No effects on tumor growth were noted, although immunohistochemical studies revealed an expression of PDGF receptors. Furthermore, both sarcomas were markedly stimulated by PDGF-AB in vitro. It is concluded that mechanisms or factors other than available PDGF were limiting the growth of the examined tumors in vivo.

  • 31.
    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, Vol. 146, 189-194 p.Article in journal (Refereed)
  • 32.
    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.
    Nakamura, Hajime
    Sahaf, Bita
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Yodoi, Junji
    Holmgren, Arne
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Thioredoxin blood level increases after severe burn injury2000In: Antioxidants and Redox Signaling, ISSN 1523-0864, Vol. 2, no 4, 707-716 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post-bum days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 ▒ 19.5 ng/ml (mean ▒ SD) and on post-burn day one 122.6 ▒ 66.9 ng/ml, compared to control blood donor levels of 22.7 ▒ 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet.

  • 33.
    Abdiu, Avni
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Ohannessian, Peter
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Oral Surgery UHL.
    Berggren, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    The nasal alar elevator: A new device that may reduce the need for primary operation of the nose in patients with cleft lip2009In: SCANDINAVIAN JOURNAL OF PLASTIC AND RECONSTRUCTIVE SURGERY AND HAND SURGERY, ISSN 0284-4311, Vol. 43, no 2, 71-74 p.Article in journal (Refereed)
    Abstract [en]

    To improve the shape of the cleft lip nose preoperatively, we have developed the nasal alar elevator. This has been used routinely since 1996 on all our cleft lip patients who have an asymmetrical nose, from the first week after birth until the date of primary lip surgery. We present our 11-year-long experience of using the device on patients born with complete, unilateral cleft lip. In this study 56 children, born between 1996 and 2006 inclusive, with complete unilateral cleft lip, had preoperative treatment with the elevator. During this 11-year period, continuous evaluation during the preoperative period, and its effects on the cleft lip nose, were evaluated, both preoperatively and postoperatively. Our results show that the preoperative use of the device has led to less need for primary nasal surgery. Instead of having to have a primary rhinoplasty (McComb) together with a lip plasty, as a routine, now only about 30% of the patients need primary surgical correction of the nose. If nasal correction is needed, a rather limited undermining of skin over the ala on the cleft side will often be sufficient. The use of a nasal elevator reduces both the length and the extent of the primary intervention, without compromising the final result.

  • 34.
    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, Vol. 141, 39-45 p.Article in journal (Refereed)
  • 35.
    Abednazari, Hossein
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junyang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Millinger, Eva
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia2006In: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 52, no 5, 260-263 p.Article in journal (Refereed)
    Abstract [en]

    Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).

  • 36.
    Abednazari, Hossin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. PEAS Institute, Linköping.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nilsson, Ingela
    Kalmar County Hospital, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor is a reliable marker for efficient anti-bacterial therapy within the first day of treatment2014In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 5, no 10, 823-830 p.Article in journal (Refereed)
    Abstract [en]

    Rapid diagnosis and choice of appropriate antibiotic treatment might be life-saving in serious infectious diseases. Still the available markers that can evaluate and monitor the diagnosis and treatment are few. Hepatocyte growth factor (HGF) has been studied as a potent regenerative factor produced and released during injuries such as infectious diseases. Monitoring of HGF levels might predict therapy results better than C-reactive protein (CRP) within the first day of treatment in pneumonia. For further investigation of previous observations we aimed to study HGF as a first-day marker in over-representing infectious diseases in comparison to procalcitonin (PCT), CRP and body temperature. Fifty-one patients with community acquired infectious diseases were included consequently at admittance and the serum samples were collected before and within 18 - 24 hours of treatment. HGF levels decreased significantly in case of efficient antibiotic therapy and HGF was shown to be better than PCT, CRP and body temperature to evaluate treatment. In patients with pneumonia, monitoring of HGF was most reasonable. HGF might be used as a therapeutic marker within the first day of empiric antibiotic treatment during infection.

  • 37.
    Abelius, M
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nilsson, L J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Immunological interactions between mother and child: a characterisation of Th1-and Th2-like chemokines during pregnancy, postpartum and childhood in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 170-1712011In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, 170-171 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 38.
    Abelius, Martina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Pregnancy and allergic disease have both been postulated as T-helper 2 (Th2) phenomena. Thus, the increased propensity of allergic mothers to mount Th2-responses might generate favourable effects on the maintenance of pregnancy, but might also be unfavorable, as fetal exposure to a strong Th2 environment could influence the immune development in the offspring to a Th2-like phenotype, favouring IgE production and possibly allergy development later in life. The influence of the intrauterine environment on the immunity and allergy development in the offspring needs to be further investigated.

    Aim: The aim of this thesis was to explore the Th1/Th2 balance in allergic and non-allergic women during pregnancy and its influence on the shaping of the Th1/Th2 profile in the neonate and the development of allergic diseases in the offspring.

    Material and methods: The study group included 20 women with and 36 women without allergic symptoms followed during pregnancy (gestational week 10-12, 15-16, 25, 35, 39) and 2 and 12 months postpartum, and their children followed from birth to 6 years of age. The circulating Th1-like chemokines CXCL9, CXCL10, CXCL11, Th2-like chemokines CCL17, CCL18 and CCL22, and the allergen-induced secretion of interleukin-4 (IL-4), IL-5, IL-10, IL-13, Interferon-γ (IFN-γ), CXCL10 and CCL17 were measured by Luminex and ELISA. The allergen-specific and total IgE levels were quantified using ImmunoCAP Technology. mRNA expression of Th1-, Th2-, Treg- and Th17-associated genes were measured by PCR arrays and real-time PCR.

    Results: We found that sensitised women with allergic symptoms had increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy as compared with postpartum. The non-sensitised women without allergic symptoms had elevated cat-induced IL-5 and IL-13 responses and lower birch- and cat-induced IFN-γ during pregnancy, but similar IgE levels as compared with postpartum.

    Maternal total IgE levels during and after pregnancy correlated with cord blood (CB) IgE and CCL22 levels (regardless of maternal allergy status). Circulating CXCL11, CCL18 and CCL22 levels during pregnancy and postpartum correlated with the corresponding chemokine levels in the offspring at various time points during childhood. Maternal IL-5 expression in peripheral blood mononuclear cells (PBMC) was associated with neonatal Galectin-1, and placental p35 expression was negatively associated with neonatal Tbx21 expression. Increased mRNA expression of CCL22 in cord blood mononuclear cells (CBMC), and increased CCL17 and CCL22 levels in CB were observed in children later developing allergic symptoms and sensitisation as compared with children who did not. Development of allergic symptoms and sensitisation were associated with increased total IgE, CCL17, CCL18 and CCL22 levels during childhood.

    Conclusions: Maternal allergy was associated with a pronounced Th2 deviation during pregnancy, shown as increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy, possibly exposing their fetuses to a particular strong Th2 environment during gestation.

    Correlations were shown between the maternal immunity during pregnancy and the offspring’s immunity at birth and later during childhood, indicating an interplay between the maternal and fetal immunity.

    Allergy development during the first 6 years of life was associated with a marked Th2 deviation at birth and a delayed down-regulation of this Th2-skewed immunity during childhood.

    List of papers
    1. Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy
    Open this publication in new window or tab >>Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy
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    2009 (English)In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 0165-0378, Vol. 81, no 1, 82-88 p.Article in journal (Refereed) Published
    Abstract [en]

    Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (pandlt;0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.

    Keyword
    Allergy, IgE, Phadiatop, Pregnancy, Th2
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19894 (URN)10.1016/j.jri.2009.04.003 (DOI)
    Note

    Original Publication: Martina Sandberg, Anne Frykman, Yvonne Jonsson, Marie Persson, Jan Ernerudh, Göran Berg, Leif Matthiesen, Christina Ekerfelt and Maria Jenmalm, Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 1, 82-88. http://dx.doi.org/10.1016/j.jri.2009.04.003 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/

    Available from: 2009-09-09 Created: 2009-08-14 Last updated: 2014-04-29Bibliographically approved
    2. High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life
    Open this publication in new window or tab >>High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life
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    2011 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 5, 495-500 p.Article in journal (Refereed) Published
    Abstract [en]

    Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.

    Keyword
    AD, atopic dermatitis, ARC, allergic rhinoconjunctivitis, CB, cord blood, SPT, skin prick test, Th, T-helper
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74499 (URN)10.1203/PDR.0b013e31822f2411 (DOI)000296121100010 ()21796021 (PubMedID)
    Available from: 2012-01-30 Created: 2012-01-30 Last updated: 2014-04-29
    3. Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy
    Open this publication in new window or tab >>Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy
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    2014 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, 387-393 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

    Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

    Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

    Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2014
    Keyword
    Allergy; CCL17; CCL22; chemokines; pregnancy; Th2
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106218 (URN)10.1111/pai.12235 (DOI)000338037100013 ()
    Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2015-03-25Bibliographically approved
    4. Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women
    Open this publication in new window or tab >>Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

    Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

    Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

    Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

    Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106219 (URN)
    Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2015-03-25Bibliographically approved
  • 39.
    Abelius, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Enke, Uta
    University Hospital Jena, Germany.
    Varosi, Frauke
    University Hospital Jena, Germany.
    Hoyer, Heike
    University Hospital Jena, Germany.
    Schleussner, Ekkehard
    University Hospital Jena, Germany.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Markert, Udo R.
    University Hospital Jena, Germany.
    Placental immune response to apple allergen in allergic mothers2014In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 106, 100-109 p.Article in journal (Refereed)
    Abstract [en]

    The immunological milieu in the placenta may be crucial for priming the developing foetal immune system. Early imbalances may promote the establishment of immune-mediated diseases in later life, including allergies. The initial exposure to allergens seems to occur in utero, but little is known about allergen-induced placental cytokine and chemokine release. The release of several cytokines and chemokines from placenta tissue after exposure to mast cell degranulator compound 48/80 or apple allergen in placentas from allergic and healthy mothers was to be analysed. Four placentas from women with apple allergy and three controls were applied in a placental perfusion model with two separate cotyledons simultaneously perfused with and without apple allergen (Mal d 1). Two control placentas were perfused with compound 48/80. In outflow, histamine was quantified spectrophotofluorometrically, IL-2, IL-4, IL-6, IL-10, TNF and IFN-gamma by a cytometric multiplex bead array and IL-13 and CXCL10, CXCL11, CCL17 and CCL22 with an in-house multiplex Luminex assay. Compound 48/80 induced a rapid release of histamine, CXCL10, CXCL11, CCL17 and CCL22, but not of the other factors. Apple allergen induced a time-dependent release of IL-6 and TNF, but not of histamine, in placentas of women with apple allergy compared with the unstimulated cotyledon. CCL17 levels were slightly increased after allergen stimulation in control placentas. Allergens can induce placental cytokines and chemokines distinctly in allergic and healthy mothers. These mediators may affect the prenatal development of the immune system and modify the risk of diseases related to immune disorders in childhood such as allergies.

  • 40.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life2011In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 5, 495-500 p.Article in journal (Refereed)
    Abstract [en]

    Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.

  • 41.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

    Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

    Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

    Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

    Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

  • 42.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lempinen, Esma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lindblad, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy2014In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, 387-393 p.Article in journal (Refereed)
    Abstract [en]

    Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

    Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

    Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

    Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

  • 43.
    Abelsson, J.
    et al.
    NU Hospital Organization, Uddevalla.
    Merup, M.
    Karolinska Universitetssjukhuset, Huddinge.
    Birgegård, G.
    Uppsala University.
    WeisBjerrum, O.
    Rigshospitalet, University of Copenhagen.
    Brinch, L.
    Rikshospitalet, Oslo University Hospital.
    Brune, M.
    Sahlgrenska Universitetssjukhuset, Göteborg.
    Johansson, P.
    NU Hospital Organization, Uddevalla.
    Kauppila, M.
    Turku University Hospital, Finland.
    Lenhoff, S.
    Skåne University Hospital.
    Liljeholm, M.
    Norrlands Universitetssjukhus, Umeå.
    Malm, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology UHL.
    Remes, K.
    Turku University Hospital, Finland.
    Vindelöv, L.
    Rigshospitalet, University of Copenhagen.
    Andréasson, Björn
    NU Hospital Organization, Uddevalla.
    The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries2012In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 47, no 3, 380-386 p.Article in journal (Refereed)
    Abstract [en]

    Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.Bone Marrow Transplantation advance online publication, 9 May 2011; doi:10.1038/bmt.2011.91.

  • 44.
    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, Vol. 18, no 12, 823-828 p.Article 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.

  • 45.
    Aboulaich, Nabila
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The primary function of adipose tissue is to store energy in the form of triacylglycerol, which is hydrolyzed to fatty acids to supply other tissues with energy. While insulin promotes the storage of triacylglycerol, catecholamines stimulate its hydrolysis. The development of type II diabetes is strongly associated with obesity, indicating a role of triacylglycerol metabolism in the pathogenesis of diabetes. Caveolae are plasma membrane invaginations found in most cells but are highly abundant in adipocytes. Insulin receptors are localized in caveolae and their function depends on intact caveolae structures. In the present thesis work, mass spectrometry-based methodology allowed identification of a number of new proteins and their posttranslational modifications in caveolae of human adipocytes. Variable N-terminal acetylation and phosphorylation of caveolin-1α and caveolin-1β were identified, which might regulate the function of caveolae. The transcription regulator protein PTRF was identified as the major caveolae associated protein. Specific proteolytic modifications of PTRF at the cytosolic surface of caveolae and phosphorylation on nine serine and one threonine residues were identified. Moreover, insulin induced translocation of PTRF from the plasma membrane to the nucleus. PTRF was previously shown to regulate the activity of both RNA polymerase I and polymerase II, thus a role of PTRF in mediating the anabolic action of insulin on protein synthesis and gene transcription is proposed.

    PTRF was also involved in an extranuclear function in the hormonal regulation of triacylglycerol metabolism in caveolae. PTRF was colocalized with the triacylglycerol regulator proteins perilipin and hormone-sensitive lipase (HSL) in the triacylglycerol-synthesizing caveolae subclass. We showed that, while perilipin was translocated to the plasma membrane, both PTRF and HSL were translocated from the plasma membrane to the cytosol as a complex in response to insulin. The perilipin recruited to the plasma membrane was highly threonine phosphorylated. By mass spectrometry, three phosphorylated threonine residues were identified and were located in an acidic domain in the lipid droplet targeting domain of perilipin. The insulin-induced recruitment of perilipin to the plasma membrane might, therefore be phosphorylation-dependent. Isoproterenol, which stimulates hydrolysis of triacylglycerol, induced a complete depletion of perilipin B from the plasma membrane, suggesting a function of perilipin B to protect newly synthesized triacylglycerol in caveolae from being hydrolyzed by HSL. The location of PTRF and HSL was not affected by isoproterenol, indicating that insulin is acting against a default presence of PTRF and HSL in caveolae.

    Taken together, this thesis expands our knowledge about caveolae and provided valuable information about their involvement in novel roles, particularly in the hormonal regulation of triacylglycerol metabolism.

    List of papers
    1. Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes
    Open this publication in new window or tab >>Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes
    2004 (English)In: The Biochemical journal, ISSN 1470-8728, Vol. 383, no Pt 2, 237-248 p.Article in journal (Refereed) Published
    Abstract [en]

    Caveolae, the specialized invaginations of plasma membranes, formed sealed vesicles with outwards-orientated cytosolic surface after isolation from primary human adipocytes. This morphology allowed differential, vectorial identification of proteins at the opposite membrane surfaces by proteolysis and MS. Extracellular-exposed caveolae-specific proteins CD36 and copper-containing amine oxidase were concealed inside the vesicles and resisted trypsin treatment. The cytosol-orientated caveolins were efficiently digested by trypsin, producing peptides amenable to direct MS sequencing. Isolation of peripheral proteins associated with the cytosolic surface of caveolae revealed a set of proteins that contained nuclear localization signals, leucine-zipper domains and PEST (amino acid sequence enriched in proline, glutamic acid, serine and threonine) domains implicated in regulation by proteolysis. In particular, PTRF (polymerase I and transcript release factor) was found as a major caveolae-associated protein and its co-localization with caveolin was confirmed by immunofluorescence confocal microscopy. PTRF was present at the surface of caveolae in the intact form and in five different truncated forms. Peptides (44 and 45 amino acids long) comprising both the PEST domains were sequenced by nanospray-quadrupole-time-of-flight MS from the full-length PTRF, but were not found in the truncated forms of the protein. Two endogenous cleavage sites corresponding to calpain specificity were identified in PTRF; one of them was in a PEST domain. Both cleavage sites were flanked by mono- or diphosphorylated sequences. The phosphorylation sites were localized to Ser-36, Ser-40, Ser-365 and Ser-366 in PTRF. Caveolae of human adipocytes are proposed to function in targeting, relocation and proteolytic control of PTRF and other PEST-domain-containing signalling proteins.

    Keyword
    Caveolae, human adipocyte, MS, PEST sequence, polymerase I and transcript release factor (PTRF), proteolysis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19145 (URN)10.1042/BJ20040647 (DOI)15242332 (PubMedID)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-06-12Bibliographically approved
    2. N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes
    Open this publication in new window or tab >>N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes
    Show others...
    2004 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 320, no 2, 480-486 p.Article in journal (Refereed) Published
    Abstract [en]

    Caveolin, the principal structural protein of caveolae membrane domains, has a cytosol-exposed N-terminal part that was cleaved off by trypsin treatment of caveolae vesicles isolated from primary human adipocytes. Sequencing of the released tryptic peptides by nanospray quadrupole time-of-flight mass spectrometry revealed that both caveolin-1alpha and caveolin-1beta were processed by excision of the starting methionines. The N-terminus of the mature caveolin-1alpha was acetylated, while caveolin-1beta was found in acetylated as well as in non-acetylated forms. Fractional phosphorylation of serine-36 in the mature caveolin-1alpha and of the homologous serine-5 in caveolin-1beta was identified. This is the first experimental evidence for in vivo phosphorylation of caveolin-1 at the consensus site for phosphorylation by protein kinase C. The phosphorylation was found in both the acetylated and non-acetylated variants of caveolin-1beta. This variability in modifications is consistent with critical involvement of the N-terminal domain of caveolin in the regulation of caveolae.

    Keyword
    Human adipocyte, Caveolin-1; Caveolae, Protein phosphorylation, N-terminal acetylation, Mass spectrometry
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19146 (URN)10.1016/j.bbrc.2004.05.196 (DOI)15219854 (PubMedID)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2016-03-09Bibliographically approved
    3. Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes
    Open this publication in new window or tab >>Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes
    2006 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 281, no 17, 11446-11449 p.Article in journal (Refereed) Published
    Abstract [en]

    In adipocytes, perilipin coats and protects the central lipid droplet, which stores triacylglycerol. Alternative mRNA splicing gives rise to perilipin A and B. Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A. It was recently shown that perilipin was also located in triacylglycerol-synthesizing caveolae of the plasma membrane. We now report that perilipin at the plasma membrane of primary human adipocytes was phosphorylated on a cluster of threonine residues (299, 301, and 306) within an acidic domain that forms part of the lipid targeting domain. Perilipin B comprised <10% of total perilipin but was the major isoform associated with the plasma membrane of human adipocytes. This association was controlled by insulin and catecholamine: perilipin B was specifically depleted from the plasma membrane in response to the catecholamine isoproterenol, while insulin increased the amount of threonine phosphorylated perilipin at the plasma membrane. The reversible translocation of perilipin B to and from the plasma membrane in response to insulin and isoproterenol, respectively, suggests a specific function for perilipin B to protect newly synthesized triacylglycerol in the plasma membrane.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19147 (URN)10.1074/jbc.C500461200 (DOI)16527823 (PubMedID)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-06-12Bibliographically approved
    4. Association and insulin regulated translocation of hormone-sensitive lipase with PTRF
    Open this publication in new window or tab >>Association and insulin regulated translocation of hormone-sensitive lipase with PTRF
    2006 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 350, no 3, 657-661 p.Article in journal (Refereed) Published
    Abstract [en]

    Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly localized at the plasma membrane. This localization was under control of insulin, which translocated PTRF to the cytosol and nucleus, indicating a novel role for PTRF in insulin transcriptional control. In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). In response to insulin PTRF was translocated to the cytosol in parallel with HSL. PTRF and HSL were quantitatively immunoprecipitated from the cytosol by antibodies against either PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis.

    Keyword
    Hormone-sensitive lipase, Polymerase I and transcript release factor, Adipocyte, Human, Insulin, Translocation, Protein complex, Caveolae, Lipid metabolism, Transcriptional control
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19148 (URN)10.1016/j.bbrc.2006.09.094 (DOI)17026959 (PubMedID)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-07-06Bibliographically approved
  • 46.
    Aboulaich, Nabila
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ortegren, Unn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vener, Alexander V
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Association and insulin regulated translocation of hormone-sensitive lipase with PTRF2006In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 350, no 3, 657-661 p.Article in journal (Refereed)
    Abstract [en]

    Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly localized at the plasma membrane. This localization was under control of insulin, which translocated PTRF to the cytosol and nucleus, indicating a novel role for PTRF in insulin transcriptional control. In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). In response to insulin PTRF was translocated to the cytosol in parallel with HSL. PTRF and HSL were quantitatively immunoprecipitated from the cytosol by antibodies against either PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis.

  • 47.
    Aboulaich, Nabila
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vainonen, Julia P
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vener, Alexander V
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes2004In: The Biochemical journal, ISSN 1470-8728, Vol. 383, no Pt 2, 237-248 p.Article in journal (Refereed)
    Abstract [en]

    Caveolae, the specialized invaginations of plasma membranes, formed sealed vesicles with outwards-orientated cytosolic surface after isolation from primary human adipocytes. This morphology allowed differential, vectorial identification of proteins at the opposite membrane surfaces by proteolysis and MS. Extracellular-exposed caveolae-specific proteins CD36 and copper-containing amine oxidase were concealed inside the vesicles and resisted trypsin treatment. The cytosol-orientated caveolins were efficiently digested by trypsin, producing peptides amenable to direct MS sequencing. Isolation of peripheral proteins associated with the cytosolic surface of caveolae revealed a set of proteins that contained nuclear localization signals, leucine-zipper domains and PEST (amino acid sequence enriched in proline, glutamic acid, serine and threonine) domains implicated in regulation by proteolysis. In particular, PTRF (polymerase I and transcript release factor) was found as a major caveolae-associated protein and its co-localization with caveolin was confirmed by immunofluorescence confocal microscopy. PTRF was present at the surface of caveolae in the intact form and in five different truncated forms. Peptides (44 and 45 amino acids long) comprising both the PEST domains were sequenced by nanospray-quadrupole-time-of-flight MS from the full-length PTRF, but were not found in the truncated forms of the protein. Two endogenous cleavage sites corresponding to calpain specificity were identified in PTRF; one of them was in a PEST domain. Both cleavage sites were flanked by mono- or diphosphorylated sequences. The phosphorylation sites were localized to Ser-36, Ser-40, Ser-365 and Ser-366 in PTRF. Caveolae of human adipocytes are proposed to function in targeting, relocation and proteolytic control of PTRF and other PEST-domain-containing signalling proteins.

  • 48.
    Aboulaich, Nabila
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vener, Alexander V
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes2006In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 281, no 17, 11446-11449 p.Article in journal (Refereed)
    Abstract [en]

    In adipocytes, perilipin coats and protects the central lipid droplet, which stores triacylglycerol. Alternative mRNA splicing gives rise to perilipin A and B. Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A. It was recently shown that perilipin was also located in triacylglycerol-synthesizing caveolae of the plasma membrane. We now report that perilipin at the plasma membrane of primary human adipocytes was phosphorylated on a cluster of threonine residues (299, 301, and 306) within an acidic domain that forms part of the lipid targeting domain. Perilipin B comprised <10% of total perilipin but was the major isoform associated with the plasma membrane of human adipocytes. This association was controlled by insulin and catecholamine: perilipin B was specifically depleted from the plasma membrane in response to the catecholamine isoproterenol, while insulin increased the amount of threonine phosphorylated perilipin at the plasma membrane. The reversible translocation of perilipin B to and from the plasma membrane in response to insulin and isoproterenol, respectively, suggests a specific function for perilipin B to protect newly synthesized triacylglycerol in the plasma membrane.

  • 49.
    Aboyans, Victor
    et al.
    Dupuytren University Hospital.
    Criqui, Michael
    University of California, USA.
    Abraham, Pierre
    University Hospital of Angers, France.
    Allison, Matthew
    University of California, USA.
    Creager, Mark
    Brigham and Women’s Hospital, USA.
    Diehm, Curt
    Karlsbad Clinic/University of Heidelberg, Germany.
    Fowkes, Gerry
    University of Edinburgh, UK.
    Hiatt, William
    University of Colorado, USA.
    Jönsson, Björn
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Lacroix, Philippe
    Limoges University, France.
    Marin, Benoit
    Limoges Teaching Hospital, France.
    McDermott, Mary
    Northwestern University,USA.
    Norgren, Lars
    University Hospital, Örebro, Sweden.
    Pande, Reena
    Brigham and Women’s Hospital, USA.
    Preux, Pierre-Marie
    University of Limoges, France.
    Stoffers, H.E.
    Maastricht University, Netherlands.
    Treat-Jacobsson, Diane
    University of Minnesota, USA.
    Measurement and interpretation of the ankle-brachial index: a scientific statement from the Ammerican Heart Association2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539Article in journal (Refereed)
  • 50.
    Abrahams, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology.
    Eriksson, H
    Björnström, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Effects of propofol on extracellular acidification rates in primary cortical cell cultures: application of silicon microphysiometry to anaesthesia.1999In: British Journal of Anaesthesia, ISSN 0007-0912, Vol. 83, 567-569 p.Article in journal (Refereed)
1234567 1 - 50 of 18121
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