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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, E-ISSN 1476-3990, Vol. 139, no 1, p. 1-9Article, 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.
    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)
  • 3.
    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, p. 755-762Article 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.

  • 4.
    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, E-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.

  • 5.
    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, p. 1657-1666Article 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.

  • 6.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Holm, AC
    Eriksson, TE
    Lundin, T
    Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Ctr Clin Chem, S-58185 Linkoping, Sweden.
    Thorell, Lars-Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Salivary cortisol and posttraumatic stress reactions methodological and applied studies before and after trauma2002In: International Journal of Psychophysiology, ISSN 0167-8760, E-ISSN 1872-7697, Vol. 45, no 1-2, p. 89-89Conference paper (Other academic)
  • 7.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Mobäck, Caroline
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jakobsson, Sandra
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Germany.
    Hoffmann, Johannes J. M. L.
    Abbott GmbH and Co KG, Germany.
    Iron depletion in blood donors - Have extended erythrocyte and reticulocyte parameters diagnostic utility?2015In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 53, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

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

  • 8.
    Aase, Audun
    et al.
    Norwegian Institute Public Heatlh, Norway.
    Hajdusek, Ondrej
    Academic Science Czech Republic, Czech Republic.
    Oines, Oivind
    Norwegian Vet Institute, Norway.
    Quarsten, Hanne
    Sorlandet Hospital Health Enterprise, Norway.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Herstad, Tove K.
    Norwegian Institute Public Heatlh, Norway.
    Kjelland, Vivian
    University of Agder, Norway; Sorlandet Hospital Health Enterprise, Norway.
    Sima, Radek
    Academic Science Czech Republic, Czech Republic.
    Jalovecka, Marie
    Academic Science Czech Republic, Czech Republic.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Aaberge, Ingeborg S.
    Norwegian Institute Public Heatlh, Norway.
    Validate or falsify: Lessons learned from a microscopy method claimed to be useful for detecting Borrelia and Babesia organisms in human blood2016In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 48, no 6, p. 411-419Article in journal (Refereed)
    Abstract [en]

    Background A modified microscopy protocol (the LM-method) was used to demonstrate what was interpreted as Borrelia spirochetes and later also Babesia sp., in peripheral blood from patients. The method gained much publicity, but was not validated prior to publication, which became the purpose of this study using appropriate scientific methodology, including a control group. Methods Blood from 21 patients previously interpreted as positive for Borrelia and/or Babesia infection by the LM-method and 41 healthy controls without known history of tick bite were collected, blinded and analysed for these pathogens by microscopy in two laboratories by the LM-method and conventional method, respectively, by PCR methods in five laboratories and by serology in one laboratory. Results Microscopy by the LM-method identified structures claimed to be Borrelia- and/or Babesia in 66% of the blood samples of the patient group and in 85% in the healthy control group. Microscopy by the conventional method for Babesia only did not identify Babesia in any samples. PCR analysis detected Borrelia DNA in one sample of the patient group and in eight samples of the control group; whereas Babesia DNA was not detected in any of the blood samples using molecular methods. Conclusions The structures interpreted as Borrelia and Babesia by the LM-method could not be verified by PCR. The method was, thus, falsified. This study underlines the importance of doing proper test validation before new or modified assays are introduced.

  • 9.
    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, p. 133-140Article 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.

  • 10.
    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
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    2010 (English)In: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 42, no 9, p. 650-657Article 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.
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    2012 (English)In: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 44, no 11, p. 828-834Article 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, E-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: 2017-12-07
    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.

    Keywords
    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.

    Keywords
    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
  • 11.
    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, E-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.

  • 12.
    Abate, Ebba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. University of Gondar, Ethiopia.
    Belayneh, Meseret
    University of Addis Ababa, Ethiopia.
    Idh, Jonna
    Vastervik Hospital, Sweden.
    Diro, Ermias
    University of Gondar, Ethiopia.
    Elias, Daniel
    University of Southern Denmark, Denmark.
    Britton, Sven
    Karolinska Hospital, Sweden.
    Aseffa, Abraham
    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 Medicine and Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity2015In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 8, article id e0003994Article in journal (Refereed)
    Abstract [en]

    Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

    Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

    Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

    Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

  • 13.
    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.

  • 14.
    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.

  • 15.
    Abbas, Ashraf H.
    et al.
    Plastic Surgery Unit, Surgery Dept., Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Dept., Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Adly, Osama A.
    Plastic Surgery Unit, Surgery Dept., Suez Canal University, Ismailia, Egypt.
    Elbadawy, Mohamed A.
    Plastic Surgery Unit, Surgery Dept., Suez Canal University, Ismailia, Egypt.
    Moati, Taha Ali
    General Surgery department, Suez Canal University, Ismailia, Egypt.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Aesthetic Outcome After Reconstruction of Complex SoftTissue Defects with Free Antero-Lateral Thigh Flap UsingSimple Equipment2015In: Journal of surgery, ISSN 2330-0914, Vol. 3, no 2-1, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Aim: We aimed to assess the aesthetic outcome of surgical reconstruction by free ALT flap using binocular single-refraction magnifying glasses and a modified post- operative surveillance protocol. Methods: 16 patients were operated for free antero-lateral thigh flap to reconstruct complex soft tissue defects with a close clinical follow up protocol for post operative care depending on the attending personnel in the Plastic surgery unit, Suez Canal University hospital, Ismailia, Egypt. Aesthetic outcome was assessed using a questionnaire based on Posch et al. 2005, including the following items colour, contour, presence of hair, overall appearance and donor site scar. Results: The patients’ assessed aesthetic outcome was acceptable in majority of the cases; median score was 4 for all assessed items. Complete flap loss occurred in one case, other complications as arterial thrombosis and hematomas and infection were detected and managed accordingly with flap salvage in the 3 complicated cases. Conclusion: The result suggests that the proposed protocol is sufficient as an alternative. The aesthetic outcome assessed by the patient and the failure rate was in line with other studies.

  • 16.
    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, p. 191-197Article 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.

  • 17.
    Abdalla, Maie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Suez Canal University, Egypt.
    Landerholm, Kalle
    Ryhov County Hospital, Sweden.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 7, p. 1055-1060, article id e2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.

    METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.

    RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).

    CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.

  • 18.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Validation of the burn intervention score in a National Burn Centre2018In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, no 5, p. 1159-1166Article in journal (Refereed)
    Abstract [en]

    The Linköping burn score has been used for two decades to calculate the cost to the hospital of each burned patient. Our aim was to validate the Burn Score in a dedicated Burn Centre by analysing the associations with burn-specific factors: percentage of total body surface area burned (TBSA%), cause of injury, patients referred from other (non-specialist) centres, and survival, to find out which of these factors resulted in higher scores. Our second aim was to analyse the variation in scores of each category of care (surveillance, respiration, circulation, wound care, mobilisation, laboratory tests, infusions, and operation).

    We made a retrospective analysis of all burned patients admitted during the period 2000–15. Multivariable regression models were used to analyse predictive factors for an increased daily burn score, the cumulative burn score (the sum of the daily burn scores for each patient) and the total burn score (total sum of burn scores for the whole group throughout the study period) in addition to sub-analysis of the different categories of care that make up the burn score.

    We retrieved 22 301 daily recordings for inpatients. Mobilisation and care of the wound accounted for more than half of the total burn score during the study. Increased TBSA% and age over 45 years were associated with increased cumulative (model R2 0.43, p < 0.001) and daily (model R2 0.61, p < 0.001) burn scores. Patients who died had higher daily burn scores, while the cumulative burn score decreased with shorter duration of hospital stay (p < 0.001).

    To our knowledge this is the first long term analysis and validation of a system for scoring burn interventions in patients with burns that explores its association with the factors important for outcome. Calculations of costs are based on the score, and it provides an indicator of the nurses’ workload. It also gives important information about the different dimensions of the care provided from thorough investigation of the scores for each category.

  • 19.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Olofsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Division of overall duration of stay into operative stay and postoperative stay improves the overall estimate as a measure of quality of outcome in burn care.2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174579Article in journal (Refereed)
    Abstract [en]

    Patients and Methods: Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay.less thanbr /greater thanResults: Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, pless than0.01). The size of the burn, and the number of operations, were the independent factors that influenced operative stay (R2 0.65). Except for the size of the burn other factors were associated with duration of postoperative stay: wound related, psychological and other medical causes, advanced medical support, and accommodation arrangements before discharge, of which the two last were the most important with an increase of (mean) 12 and 17 days (pless than0.001, R2 0.51).less thanbr /greater thanConclusion: Adjusted operative stay showed less variation than total hospital stay and thus can be considered a more accurate outcome measure for surgically managed burns. The size of burn and number of operations are the factors affecting this outcome measure.

  • 20.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. a Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Improvement in mortality at a National Burn Centre since 2000: Was it the result of increased resources?2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 25, article id e6727Article in journal (Refereed)
    Abstract [en]

    Abstract The aim of this study was to find out whether the charging costs (calculated using interventional burn score) increased as mortality decreased. During the last 2 decades, mortality has declined significantly in the Linköping Burn Centre. The burn score that we use has been validated as a measure of workload and is used to calculate the charging costs of each burned patient. We compared the charging costs and mortality in 2 time periods (2000–2007 and 2008–2015). A total of 1363 admissions were included. We investigated the change in the burn score, as a surrogate for total costs per patient. Multivariable regression was used to analyze risk-adjusted mortality and burn score. The median total body surface area % (TBSA%) was 6.5% (10–90 centile 1.0–31.0), age 33 years (1.3–72.2), duration of stay/ TBSA% was 1.4 days (0.3–5.3), and 960 (70%) were males. Crude mortality declined from 7.5% in 2000–2007 to 3.4% in 2008–2015, whereas the cumulative burn score was not increased (P=.08). Regression analysis showed that risk-adjusted mortality decreased (odds ratio 0.42, P=.02), whereas the adjusted burn score did not change (P=.14, model R2 0.86). Mortality decreased but there was no increase in the daily use of resources as measured by the interventional burn score. The data suggest that the improvements in quality obtained have been achieved within present routines for care of patients (multidisciplinary/ orientated to patients’ safety).

    Abbreviation: TBSA% = total body surface area %.

  • 21.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal University, Egypt.
    Moghazy, Amr
    Suez Canal University, Egypt.
    Abbas, Ashraf
    Suez Canal University, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal University, Egypt.
    Adly, Osama
    Suez Canal University, Egypt.
    Elbadawy, Mohamed
    Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    A prospective randomized cost billing comparison of local fasciocutaneous perforator versus free Gracilis flap reconstruction for lower limb in a developing economy2016In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 69, no 8, p. 1121-1127Article in journal (Refereed)
    Abstract [en]

    Distal half leg complex wounds are usually a formidable problem that necessitates either local or free flap coverage. The aim of this study was to compare cost billing charges in free Gracilis flap (fGF) and local fasciocutaneous perforator flap (lFPF) in reconstructing complex soft tissue leg and foot defects. Patients and methods: Thirty consecutive adult (amp;gt; 15-year-old) patients with soft tissue defects in the leg and/or foot requiring tissue coverage with a flap in the period between 2012 and 2015 were randomly assigned (block randomization) to either an fGF or lFPF procedure. The outcome measures addressed were total billed charges costs, perioperative billed charges cost, partial or complete flap loss, length of hospital stay, inpatient postsurgical care duration, complications, operating time and number of operative scrub staff. Results: One patient suffered from complete flap loss in each group. Reconstruction with lFPF showed total lower billed charges costs by 62% (2509 USD) (p amp;lt; 0.001) and perioperative billed charges cost by 54% (779 USD) (p amp;lt; 0.001), and shorter total hospital stay (36.5 days; p amp;lt; 0.001), inpatient postsurgical care duration (6.4 days; p amp;lt; 0.001), operating time (4.3 h; p amp;lt; 0.001) and fewer scrub staff (2.2 persons; p amp;lt; 0.001). Conclusion: These results suggest that neither flap is totally superior to the other; the choice should instead be based on the outcome sought and logistics. lFPF requires lower billed charges cost and resource use and saves operative time and personnel and reduces length of hospital stay. Our approach changed towards using perforator flaps in medium-sized defects, keeping the free flap option for larger defects. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  • 22.
    Abdelrahman, Islam Mohamedy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Response to comments on: A prospective randomized cost billing comparison of local fasciocutaneous perforator versus free Gracilis flap reconstruction for lower limb in a developing economy2017In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 70, no 9, p. 1307-1308Article in journal (Other academic)
  • 23.
    Abdelrahman, Islam Mohamedy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal Univ, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Mossaad, Bassem
    Suez Canal Univ, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal Univ, Egypt.
    Male Breast Glandular Liposculpture Challenges2018In: Aesthetic Plastic Surgery, ISSN 0364-216X, E-ISSN 1432-5241, Vol. 42, no 5, p. 1437-1437Article in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Mossaad, Bassem
    Plastic Surgery Unit, Surgery Department Suez, Canal University, Ismailia, Egypt.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Evaluation of Glandular Liposculpture as a Single Treatment for Grades I and II Gynaecomastia2018In: Aesthetic Plastic Surgery, ISSN 0364-216X, E-ISSN 1432-5241, Vol. 42, no 2, p. 1222-1230Article in journal (Refereed)
    Abstract [en]

    Background

    Gynaecomastia is a benign enlargement of the male breast, of which the psychological burden on the patient can be considerable, with the increased risk of disorders such as depression, anxiety, and social phobia. Minimal scarring can be achieved by liposuction alone, though it is known to have a limited effect on the dense glandular and fibroconnective tissues. We know of few studies published on “liposuction alone”, so we designed this study to evaluate the outcome of combining liposuction with glandular liposculpturing through two axillary incisions as a single treatment for the management of grades I and II gynaecomastia.

    Methods

    We made a retrospective analysis of 18 patients with grade I or II gynaecomastia who were operated on by combined liposuction and glandular liposculpturing using a fat disruptor cannula, without glandular excision, during the period 2014–2016. Patient satisfaction was assessed using the Breast Evaluation Questionnaire (BEQ), which is a 5-point Likert scale (1 = very dissatisfied; 2 = dissatisfied; 3 = neither; 4 = satisfied; 5 = very satisfied). The post-operative aesthetic appearance of the chest was evaluated by five independent observers on a scale from 1 to 5 (5 = considerable improvement).

    Results

    The patient mean (SD) overall satisfaction score was 4.7 (0.7), in which 92% of the responders were “satisfied” to “very satisfied”. The mean (SD) BEQ for all questions answered increased from 2.1 (0.2) “dissatisfied” preoperatively to 4.1 (0.2) “satisfied” post-operatively. The observers’ mean (SD) rate for the improvement in the shape of the front chest wall was 4.1 (0.7). No haematomas were recorded, one patient developed a wound infection, and two patients complained of remnants of tissue. The median (IQR) body mass index was 27.4 (26.7–29.4), 11 patients had gynaecomastia grade I, and 7 patients grade II. The median (IQR) volume of aspirated fat was 700 ml (650–800), operating time was 67 (65–75) minutes, 14 patients had general anaesthesia, and hospital charges were US$ 538 (481–594).

    Conclusions

    Combined liposuction and liposculpturing using the fat disruptor cannula resulted in satisfied patients and acceptable outcomes according to the observers’ ratings. It could be a useful alternative with an outcome that corresponds to that of more expensive methods.

  • 25.
    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, p. 71-74Article 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.

  • 26.
    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, p. 823-830Article 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.

  • 27.
    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, p. 170-171Conference paper (Refereed)
    Abstract [en]

    n/a

  • 28.
    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, p. 82-88Article 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.

    Keywords
    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
    Show others...
    2011 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 5, p. 495-500Article 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.

    Keywords
    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: 2017-12-08
    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
    Show others...
    2014 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, p. 387-393Article 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
    Keywords
    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: 2017-12-05Bibliographically 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
  • 29.
    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, p. 100-109Article 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.

  • 30.
    Abelius, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jedenfalk, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Pregnancy modulates the allergen-induced cytokine production differently in allergic and non-allergic women2017In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 28, no 8, p. 818-824Article in journal (Refereed)
    Abstract [en]

    Background: The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. Methods: The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-gamma(IFN-gamma), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n=13) and 36 women without allergic symptoms (non-sensitized, n=30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12months post-partum. Results: Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-gamma secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. Conclusions: Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-gamma and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.

  • 31.
    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, p. 495-500Article 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.

  • 32.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Helsingborg Hospital, Helsingborg.
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart J
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, no 5, p. 445-459Article in journal (Refereed)
    Abstract [en]

    PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

    METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

    RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

    CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

  • 33.
    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.

  • 34.
    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, p. 387-393Article 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.

  • 35.
    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, p. 380-386Article 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.

  • 36.
    Abioye, Ajibola I.
    et al.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Park, Sangshin
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Ripp, Kelsey
    Brown Univ, RI 02912 USA.
    McDonald, Emily A.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Kurtis, Jonathan D.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Wu, Hannah
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Pond-Tor, Sunthorn
    Rhode Isl Hosp, RI USA.
    Sharma, Surendra
    Brown Univ, RI 02912 USA; Women and Infants Hosp Rhode Isl, RI 02908 USA.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Baltazar, Palmera
    Res Inst Trop Med, Philippines; Remedios Trinidad Romualdez Hosp, Philippines.
    Acosta, Luz P.
    Res Inst Trop Med, Philippines.
    Olveda, Remigio M.
    Res Inst Trop Med, Philippines.
    Tallo, Veronica
    Res Inst Trop Med, Philippines.
    Friedman, Jennifer F.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment2018In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 148, no 3, p. 427-436Article in journal (Refereed)
    Abstract [en]

    Background: To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. Objectives: The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. Methods: We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin amp;lt; 30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin amp;gt;= 30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. Results: Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 mu g/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 mu g/L; P = 0.042). Conclusions: Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy.

  • 37.
    Aboelnaga, Ahmed
    et al.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Adly, Osama A.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Elbadawy, Mohamed A.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Abbas, Ashraf H.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Abdelrahman, Islam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Salah, Omar
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Microbial cellulose dressing compared with silver sulphadiazine for the treatment of partial thickness burns: A prospective, randomised, clinical trial2018In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 44, no 8, p. 1982-1988Article in journal (Refereed)
    Abstract [en]

    Background

    The current treatment for partial thickness burns at the trial site is silver sulphadiazine, as it minimises bacterial colonisation of wounds. Its deleterious effect on wound healing, together with the need for repeated, often painful, procedures, has brought about the search for a better treatment. Microbial cellulose has shown promising results that avoid these disadvantages. The aim of this study was therefore to compare microbial cellulose with silver sulphadiazine as a dressing for partial thickness burns.

    Method

    All patients who presented with partial thickness (superficial and deep dermal) burns from October 2014 to October 2016 were screened for this randomised clinical trial. Twenty patients were included in each group: the cellulose group was treated with microbial cellulose sheets and the control group with silver sulphadiazine cream 10 mg/g. The wound was evaluated every third day. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC) scale during and after each procedure. Other variables recorded were age, sex, percentage total body surface area burned (TBSA%), clinical signs of infection, time for epithelialisation and hospital stay. Linear multivariable regression was used to analyse the significance of differences between the treatment groups by adjusting for the size and depth of the burn, and the patient’s age.

    Results

    Median TBSA% was 9% (IQR 5.5–12.5). The median number of dressing changes was 1 (IQR 1–2) in the cellulose group, which was lower than that in the control group (median 9.5, IQR 6–16) (p < 0.001). Multivariable regression analysis showed that the group treated with microbial cellulose spent 6.3 (95% CI 0.2–12.5) fewer days in hospital (p = 0.04), had a mean score that was 3.4 (95% CI 2.5–4.3) points lower during wound care (p < 0.001), and 2.2 (95% CI 1.6–2.7) afterwards (p < 0.001). Epithelialisation was quicker, but not significantly so.

    Conclusion

    These results suggest that the microbial cellulose dressing is a better first choice for treatment of partial thickness burns than silver sulphadiazine cream. Fewer dressings of the wound were done and, combined with the low pain scores, this is good for both the patients and the health care system. The differences in randomisation of the area of burns is, however, a concern that needs to be included in the interpretation of the results.

  • 38.
    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, p. 237-248Article 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.

    Keywords
    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, p. 480-486Article 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.

    Keywords
    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: 2017-12-13Bibliographically 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, E-ISSN 1083-351X, Vol. 281, no 17, p. 11446-11449Article 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: 2017-12-13Bibliographically 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, E-ISSN 1090-2104, Vol. 350, no 3, p. 657-661Article 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.

    Keywords
    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: 2017-12-13Bibliographically approved
  • 39.
    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, E-ISSN 1090-2104, Vol. 350, no 3, p. 657-661Article 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.

  • 40.
    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, p. 237-248Article 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.

  • 41.
    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, E-ISSN 1083-351X, Vol. 281, no 17, p. 11446-11449Article 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.

  • 42.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 54, p. 92134-92142Article in journal (Refereed)
    Abstract [en]

    Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.

  • 43.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tissue specific expression of extracellular microRNA in human breast cancers and normal human breast tissue in vivo2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 26, p. 22959-22969Article in journal (Refereed)
    Abstract [en]

    Extracellular circulating microRNAs (miRNAs) have been suggested to be biomarkers for disease monitoring but data are inconsistent, one reason being that blood miRNA is of heterogeneous origin. Here, we sampled extracellular microRNAs locally in situ using microdialysis. Three different cohorts of women were included; postmenopausal women with ongoing breast cancer investigated within the cancer and in normal adjacent breast tissue, postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy, premenopausal women during the menstrual cycle. Samples were initially screened using TaqMan array cards with subsequently absolute quantification. 124 miRNA were expressed in microdialysates. After absolute quantifications extracellular miRNA-21 was found to be significantly increased in breast cancer. In addition, the levels were significantly higher in pre-menopausal breast tissue compared with postmenopausal. In breast tissue of pre-menopausal women miRNA-21 exhibited a cyclic variation during the menstrual cycle and in postmenopausal women six weeks of tamoxifen treatment decreased miRNA-21 suggesting that this miRNA may be important for breast carcinogenesis. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed tissue specific changes of extracellular circulating miRNAs that would be otherwise unraveled using blood samples.

  • 44.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Morad, Vivian
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Saarinen, Niina M
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Dabrosin, Charlotta
    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 Oncology UHL.
    Estradiol, Tamoxifen, and Flaxseed Alter IL-1 beta and IL-1Ra Levels in Normal Human Breast Tissue in Vivo2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 11, p. E2044-E2054Article in journal (Refereed)
    Abstract [en]

    Introduction: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression. IL-1Ra is an endogenous inhibitor of the proinflammatory IL-1 alpha and IL-1 beta. less thanbrgreater than less thanbrgreater thanObjective: The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL-1 levels in normal human breast tissue. less thanbrgreater than less thanbrgreater thanDesign and Methods: Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. less thanbrgreater than less thanbrgreater thanResults: We show a significant positive correlation between estradiol and in vivo levels of IL-1 beta in breast tissue and abdominal sc fat, whereas IL-1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL-1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL-1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL-1 beta were significantly higher compared with normal adjacent breast tissue. less thanbrgreater than less thanbrgreater thanConclusion: IL-1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL-1 beta in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.

  • 45.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1994Article in journal (Refereed)
    Abstract [en]

    The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

  • 46.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42733Article in journal (Refereed)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

  • 47.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo2016In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, no 10, article id e1229723Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

  • 48.
    Abrahamsson, Thomas
    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 MH.
    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.

    Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.

    Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.

    Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.

    Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.

    Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.

    List of papers
    1. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Open this publication in new window or tab >>Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Show others...
    2007 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1174-1180Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants.

    OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri.

    METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens.

    RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected.

    CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.

    Keywords
    Children, eczema, IgE, Lactobacillus, prevention, probiotics, sensitization, skin prick test
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20580 (URN)10.1016/j.jaci.2007.01.007 (DOI)17349686 (PubMedID)
    Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2017-12-13Bibliographically approved
    2. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Open this publication in new window or tab >>Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Show others...
    2009 (English)In: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, no 3, p. 349-354Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

    MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

    RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

    CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

    Keywords
    Bifidobacteria, Clostridium, Faeces, Probiotics, Lactobacillus reuteri
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20622 (URN)10.1097/MPG.0b013e31818f091b (DOI)19525871 (PubMedID)
    Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2009-09-27Bibliographically approved
    3. Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Open this publication in new window or tab >>Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Show others...
    2008 (English)In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, no 6, p. 497-504Article in journal (Refereed) Published
    Abstract [en]

    The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast-fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF-beta1, TGF-beta2, IL-10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen-specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE-associated eczema. The levels of total IgA, SIgA, TGF-beta1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.

    Keywords
    Lactobacilli, breast milk, TGF-b, sensitization, infancy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20623 (URN)10.1111/j.1399-3038.2007.00687.x (DOI)18221472 (PubMedID)
    Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2009-09-27Bibliographically approved
    4. A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Open this publication in new window or tab >>A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Show others...
    2009 (English)In: in Allergy, vol 64, 2009, Vol. 64, p. 56-56Conference paper, Published paper (Refereed)
    Abstract [en]

    Background: Analyses of circulating chemokines offer novel tools to investigate the Th1/Th2 imbalance in allergic disease in vivo and explore the influence of pre- and postnatal factors in infancy.

    Objective: To relate circulating Th1- and Th2-associated chemokines to the development of allergic disease, pre- and postnatal factors and probiotic supplementation in infancy.

    Methods: Circulating levels of Th1-associated CXC-chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17, CCL18 and CCL22 were assessed with Luminex and ELISA at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 179 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding development of allergic disease and sensitization until two years of age.

    Results: The Th2-associated chemokines were as highest at birth and then decreased, whereas the Th1-associated chemokines increased with age. Low Th1- and high Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated CCL22 and reduced CXCL11 levels. High Th2-associated chemokine46 levels were associated with increased birth length and weight and long duration of breastfeeding, and high Th1-associated chemokine levels with day-care attendance. Presence of L. reuteri in stool the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months.

    Conclusion: Allergic disease in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels during the first year of life. The chemokine levels were affected by both pre and –postnatal factors.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19153 (URN)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-09-15Bibliographically approved
  • 49.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Editorial Material: Not all probiotic strains prevent necrotising enterocolitis in premature infants in LANCET, vol 387, issue 10019, pp 624-6252016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10019, p. 624-625Article in journal (Other academic)
    Abstract [en]

    n/a

  • 50.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Using probiotics to prevent necrotising enterocolitis2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 11, p. 1718-1719Article in journal (Other academic)
    Abstract [en]

    n/a

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