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  • 51.
    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.

  • 52.
    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.

  • 53.
    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.

  • 54.
    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.

  • 55.
    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.

  • 56.
    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.

  • 57.
    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
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    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
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    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
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    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
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    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
  • 58.
    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

  • 59.
    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

  • 60.
    Abrahamsson, Thomas
    et al.
    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 Paediatrics in Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 61.
    Abrahamsson, Thomas
    et al.
    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.
    Jakobsson, Hedvig E.
    Karolinska Institute, Sweden .
    Andersson, Anders F.
    KTH Royal Institute Technology, Sweden .
    Bjorksten, Bengt
    University of Örebro, Sweden .
    Engstrand, Lars
    KTH Royal Institute Technology, Sweden .
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Reply: Gut microbiota diversity and atopic disease: Does breast-feeding play a role?2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal (Refereed)
    Abstract [en]

    n/a

  • 62.
    Abrahamsson, Thomas
    et al.
    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.
    Jakobsson, Hedvig E
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Andersson, Anders F
    Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and the School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Engstrand, Lars
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Low diversity of the gut microbiota in infants with atopic eczema2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 434-440Article in journal (Refereed)
    Abstract [en]

    Background

    It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts.

    Objective

    We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development.

    Methods

    Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830).

    Results

    Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02).

    Conclusion

    Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.

  • 63.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jakobsson, Ted
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Oldaeus, Göran
    County Hospital Ryhov, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 6, p. 556-561Article in journal (Refereed)
    Abstract [en]

    Background

    Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective

    To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods

    A randomized, placebo-controlled trial with oral supplementation with Lreuteri ATCC 55730 (1 × 108 CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.gov ID NCT01285830).

    Results

    The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion

    The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect of L. reuteri on the immune system seems to be transient. Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 64.
    Abrahamsson, Thomas R
    et al.
    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.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Böttcher, Malin Fagerås
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    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.
    Oldaeus, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1174-1180Article in journal (Refereed)
    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.

  • 65.
    Abrahamsson, Thomas R
    et al.
    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.
    Sinkiewicz, Gabriela
    Department of Biomedical Lab Science, Malmö University, Malmö, Sweden.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    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.
    Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life2009In: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, no 3, p. 349-354Article in journal (Refereed)
    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.

  • 66.
    Abrahamsson, Thomas
    et al.
    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 Paediatrics in Linköping.
    Rautava, Samuli
    University of Turku, Finland; Turku University Hospital, Finland.
    Moore, Aideen M.
    University of Toronto, Canada.
    Neu, Josef
    University of Florida, FL USA.
    Sherman, Philip M.
    University of Toronto, Canada.
    Editorial Material: The Time for a Confirmative Necrotizing Enterocolitis Probiotics Prevention Trial in the Extremely Low Birth Weight Infant in North America Is Now! in JOURNAL OF PEDIATRICS, vol 165, issue 2, pp 389-3942014In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, no 2, p. 389-394Article in journal (Other academic)
    Abstract [en]

    n/a

  • 67.
    Abrahamsson, Thomas
    et al.
    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.
    Sandberg, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Forsberg, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 12, p. 1729-1739Article in journal (Refereed)
    Abstract [en]

    Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo. less thanbrgreater than less thanbrgreater thanObjective To relate circulating Th1- and Th2-associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation. less thanbrgreater than less thanbrgreater thanMethods Circulating levels of Th1-associated CXC-chemokine ligand (CXCL) 9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17 and CCL22 were assessed with Luminex and CCL18 with enzyme-linked immunosorbent assay at birth (n = 109), 6 (n = 104), 12 (n = 116) and 24 months (n = 123) in 161 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 the development of allergic disease and sensitization until 2 years of age. less thanbrgreater than less thanbrgreater thanResults The Th2-associated chemokines CCL17 and CCL22 were the highest at birth and then decreased, whereas CCL18 and the Th1-associated chemokines increased with age. High Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated levels of the Th2-associated CCL22 and reduced levels of the Th1-associated CXCL11 already at birth. The Th2-associated CCL17 was also elevated at birth in infants developing recurrent wheeze. A high Th2/Th1 ratio (CCL22/CXCL10) at birth associated with both sensitization and eczema development. The presence of L. reuteri in stool in the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months of age. High Th1-associated chemokine levels were associated with day-care. less thanbrgreater than less thanbrgreater thanConclusion and Clinical Relevance Allergic disease and sensitization in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels already from birth. Circulating chemokines are useful for investigating the Th1/Th2 imbalance in allergic disease in vivo. Elucidation of the role of chemokines in allergic diseases may lead to future treatments.

  • 68.
    Abrahamsson, Thomas
    et al.
    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.
    Sandberg, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Forsberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics2009In: in Allergy, vol 64, 2009, Vol. 64, p. 56-56Conference 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.

  • 69.
    Abrahamsson, Thomas
    et al.
    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 Paediatrics in Linköping.
    Sherman, Philip M.
    University of Toronto, Canada .
    Editorial Material: Multifaceted Effects of Human Milk Oligosaccharides2014In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, no 3, p. 323-324Article in journal (Other academic)
    Abstract [en]

    n/a

  • 70.
    Abrahamsson, Thomas
    et al.
    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.
    Wu, Richard Y.
    University of Toronto, Canada.
    Sherman, Philip M.
    University of Toronto, Canada.
    Microbiota in Functional Gastrointestinal Disorders in Infancy: Implications for Management2017In: INTESTINAL MICROBIOME: FUNCTIONAL ASPECTS IN HEALTH AND DISEASE, KARGER , 2017, Vol. 88, p. 107-115Conference paper (Refereed)
    Abstract [en]

    The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel

  • 71.
    Abrahamsson, Thomas
    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 of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. University of Toronto, Canada.
    You Wu, Richard
    University of Toronto, Canada.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gut microbiota and allergy: the importance of the pregnancy period2015In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, no 1, p. 214-219Article, review/survey (Refereed)
    Abstract [en]

    Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

  • 72.
    Abrandt Dahlgren, Madeleine
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences.
    Dahlberg, Johanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Foreman, Dawn
    Curtin University, Perth, Australia.
    Emerging criteria for assessment of interprofessional conference. Straddling the contexts of professional education and clinical practice2011Conference paper (Other academic)
  • 73.
    Abrandt Dahlgren, Madeleine
    et al.
    Linköping University, Department of Medical and Health Sciences, Medical Pedagogics. Linköping University, Faculty of Health Sciences.
    Dahlgren, Lars Owe
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Educational Sciences.
    Dahlberg, Johanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Learning professional practice through education2012In: Practice, Learning and Change: Practice-theory perspectives on professional learning. / [ed] Paul Hager, Ann Reich & Alison Lee, Dordrecht: Springer Publishing Company, 2012, 1Chapter in book (Other academic)
    Abstract [en]

    The three concepts central to this volume--practice, learning and change--have received very different treatments in the educational literature, an oversight directly confronted here. While learning and change have been extensively theorised, their various contexts articulated and analysed, practice is notably underrepresented. Where much of the literature on learning and change takes the notion of 'practice' as an unexamined given, its co-location as a term with various classifiers, as in 'legal practice' and 'teaching practice', render it curiously devoid of semantic force. In this book, 'practice' is the super-ordinate organising idea. Drawing on what has been termed the 'practice turn in contemporary theory', the work develops a conceptual framework for researching learning in, and on, practice. It challenges received notions of practice, questioning the assumptions, elisions, conflations and silences on the subject. In so doing, it offers fresh insights into learning and change, and how they relate to practice. In tandem with this conceptual work, the book details site-ontological studies of practice and learning in diverse professional and workplace contexts, examining the work of occupations as various as doctors, chefs and orchestral musicians. It demonstrates the value of theorising practice, learning and change, as well as exploring the connections between them amid our evolving social and institutional structures.

  • 74.
    Abrouk, Michael
    et al.
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Balcarkova, Barbora
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Simkova, Hana
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Kominkova, Eva
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Martis, Mihaela-Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Institute for Bioinformatics and Systems Biology, Helmholtz Center Munich, Neuherberg, Germany.
    Jakobson, Irena
    Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 19086, Estonia.
    Timofejeva, Ljudmilla
    Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 19086, Estonia.
    Rey, Elodie
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Vrana, Jan
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Kilian, Andrzej
    Diversity Arrays Technology Pty Ltd, Yarralumla, ACT2600, Australia.
    Järve, Kadri
    Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 19086, Estonia.
    Dolezel, Jaroslav
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    Valarik, Miroslav
    Institute of Experimental Botany, Centre of the Region Hana for Biotechnological and Agricultural Research, Olomouc, Czech Republic.
    The in silico identification and characterization of a bread wheat/Triticum militinae introgression line: Characterization of alien introgression in wheat2017In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 15, no 2, p. 249-256Article in journal (Refereed)
    Abstract [en]

    The capacity of the bread wheat (Triticum aestivum) genome to tolerate introgression from related genomes can be exploited for wheat improvement. A resistance to powdery mildew expressed by a derivative of the cross bread wheat cv. Tähti ⨯ T. militinae (Tm) is known to be due to the incorporation of a Tm segment into the long arm of chromosome 4A. Here, a newly developed in silico method termed RICh (rearrangement identification and characterization) has been applied to characterize the introgression. A virtual gene order, assembled using the GenomeZipper approach, was obtained for the native copy of chromosome 4A; it incorporated 570 4A DArTseq markers to produce a zipper comprising 2,132 loci. A comparison between the native and introgressed forms of the 4AL chromosome arm showed that the introgressed region is located at the distal part of the arm. The Tm segment, derived from chromosome 7G, harbors 131 homoeologs out of the 357 genes present on the corresponding region of Chinese Spring 4AL. The estimated number of Tm genes transferred along with the disease resistance gene was 169. Characterizing the introgression's position, gene content and internal gene order should facilitate not only gene isolation, but may also be informative with respect to chromatin structure and behavior studies.

  • 75.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Bisphosphonates and implants in the jaw bone2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.

    The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?

    In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.

    In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.

    List of papers
    1. Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
    Open this publication in new window or tab >>Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
    2010 (English)In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, no 7, p. 673-677Article in journal (Refereed) Published
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

    Place, publisher, year, edition, pages
    Elsevier Science B.V., Amsterdam, 2010
    Keywords
    bisphosphonate coating; dental implants; fixation
    National Category
    Orthopaedics Other Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-58193 (URN)10.1016/j.ijom.2010.04.002 (DOI)000279972500007 ()
    Available from: 2010-08-11 Created: 2010-08-09 Last updated: 2018-01-12
    2. A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
    Open this publication in new window or tab >>A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
    2012 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 5, p. 1148-1151Article in journal (Refereed) Published
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Bone healing, Dental implant, Drug delivery, Mechanical test, Osseointegration bisphosphonates
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-77527 (URN)10.1016/j.bone.2012.02.001 (DOI)000303274400018 ()
    Note

    Funding Agencies|Swedish Research Council|VR 2009-6725|

    Available from: 2012-05-28 Created: 2012-05-22 Last updated: 2017-12-07
    3. Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
    Open this publication in new window or tab >>Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
    2012 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, no 6, p. 494-499Article in journal (Refereed) Published
    Abstract [en]

    J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

    Place, publisher, year, edition, pages
    John Wiley and Sons, 2012
    Keywords
    bisphosphonates; bisphosphonate associated osteonecrosis of the jaw; osteonecrosis; rat
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-79679 (URN)10.1111/j.1600-0714.2011.01125.x (DOI)000305961100010 ()
    Available from: 2012-08-14 Created: 2012-08-13 Last updated: 2017-12-07
    4. Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw
    Open this publication in new window or tab >>Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw
    2013 (English)In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 92, no 3, p. 279-283Article in journal (Refereed) Published
    Abstract [en]

    Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

    Place, publisher, year, edition, pages
    Sage Publications, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-89667 (URN)10.1177/0022034512472335 (DOI)000314914100013 ()23264610 (PubMedID)
    Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2017-12-06Bibliographically approved
    5. Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model
    Open this publication in new window or tab >>Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model
    2013 (English)In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 42, no 5, p. 632-636Article in journal (Refereed) Published
    Abstract [en]

    There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

    Keywords
    Bisphosphonates, osteonecrosis, jaw, rat, mucoperiosteal flap, antibiotics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-89668 (URN)10.1016/j.ijom.2013.02.007 (DOI)000318132600014 ()
    Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2017-12-06Bibliographically approved
  • 76.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model2013In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 42, no 5, p. 632-636Article in journal (Refereed)
    Abstract [en]

    There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

  • 77.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone2012In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, no 6, p. 494-499Article in journal (Refereed)
    Abstract [en]

    J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

  • 78.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw2013In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 92, no 3, p. 279-283Article in journal (Refereed)
    Abstract [en]

    Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

  • 79.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Ajan, Aida
    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, Maxillofacial Unit.
    Malignant Transformation of Ossifying Fibroma into Parosteal Osteosarcoma with High-grade Component: Presentation of an Unusual Case and Review of the Literature2018In: The Open Dentistry Journal, E-ISSN 1874-2106, Vol. 12, p. 1059-1068Article in journal (Refereed)
    Abstract [en]

    Background: Parosteal Osteosarcoma of the Jaw (POSJ) is a rare entity that is associated with a high survival rate. Several case reports and case series of POSJ have been published in the literature, but few authors have described development of this tumor by possible transformation from a fibro-osseous neoplasm. Objective: We present a rare occurrence of parosteal osteosarcoma with involvement of the posterior maxilla, orbit floor, and infra-temporal fossa in a 20-year-old man. Furthermore, we performed a literature review regarding clinical, radiological, and histological features; treatment strategies; and etiology/pathophysiology. Methods: A PubMed search yielded a total of 74 articles and the articles were sorted according to their corresponding key area of focus. Results: This was a case of POSJ with high-grade component in the maxillofacial region of a 20-year old male. Co-expression of MDM2 and CDK4 was confirmed. At 2.5-year follow-up, the patient had died. The literature review revealed 18 articles including 20 cases of POSJ. Four cases represent the possible development of this tumor by transformation from a fibro-osseous neoplasm: Two cases of fibrous dysplasia, one case of cemento-ossifying fibroma, and the case of Ossifying Fibroma (OF) in the present study. Conclusion: In conclusion, we found an unusual case of POSJ of the midface in a patient with a previous diagnosis of OF in the same region. To our knowledge, there have been no previous reports of development of POSJ in OF. Furthermore, this is the first described case of high-grade surface osteosarcoma in the craniofacial region.

  • 80.
    Abtahi, Jahan
    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, Maxillofacial Unit.
    Henefalk, G.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Aspenberg, Per
    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 Orthopaedics in Linköping.
    Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading2016In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 45, no 12, p. 1564-1569Article in journal (Refereed)
    Abstract [en]

    The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.

  • 81.
    Abtahi, Jahan
    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, Maxillofacial Unit.
    Henefalk, Gustav
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Aspenberg, Per
    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 Orthopaedics in Linköping.
    Impact of a zoledronate coating on early post-surgical implant stability and marginal bone resorption in the maxilla-A split-mouth randomized clinical trial.2019In: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 30, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The objective of this clinical study was to evaluate the effect of a bisphosphonate coating on a titanium implant on the implant stability quotient (ISQ) and the radiographic marginal bone levels at implants during early healing (2-8 weeks).

    MATERIALS AND METHODS: In a randomized double-blind trial with internal controls, 16 patients received a dental implant coated with zoledronate and one uncoated implant as a control. The coated and uncoated implants which were visually indistinguishable were bone level titanium implants with a moderately rough surface and a microthreaded neck. ISQ values were obtained at insertion and at 2, 4, 6, and 8 weeks. Radiographs were obtained at insertion and at 8 weeks. The primary outcome was the difference in ISQ values between the coated implants and the control implants at 4 and 6 weeks, corrected for insertion values. The secondary outcome was loss of marginal bone level from insertion to 8 weeks.

    RESULTS: Implant stability quotient values remained largely constant over the 8 weeks, and there was no significant difference between coated and uncoated implants at any time point. There was 0.12 (SD 0.10) mm marginal bone loss at the control implants and 0.04 (SD 0.08) mm at the coated implants. The difference was 0.17 mm; SD 0.14; p < 0.006). On blind qualitative scoring, 13 of the 15 control implants and two of 15 coated implants showed small marginal bone defects (p = 0.003).

    CONCLUSIONS: There were no statistically significant differences observed in ISQ values between the coated and uncoated implants during the early healing. There was less marginal bone loss at the coated implants.

  • 82.
    Abtahi, Jahan
    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, Maxillofacial Unit.
    Malakuti, Iman
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Ajan, Aida
    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, Maxillofacial Unit.
    Surgical Management of Granular Cell Tumor of the Orbit: Case Report and Literature Review2019In: Open Dentistry Journal, ISSN 1874-2106, E-ISSN 1874-2106, Vol. 13, p. 33-40Article in journal (Refereed)
    Abstract [en]

    Introduction: Granular Cell Tumors (GCTs) of the orbit are rare-entity soft-tissue tumors, and few reports have been published in the literature. The treatment of the choice is total excision. Early diagnosis prior to surgery is valuable for the distinction of malignant from benign tumor.

    Case presentation: We report a case of a 55-year-old woman with a solitary slow-growing mass in the right orbit with the involvement of the rectus inferior muscle, and present a review of the recent literature. The lesion had a diameter of 1 cm and was noticed 2 years before the examination. Excisional biopsy confirmed the diagnosis of GCT. The tumor was resected through a retroseptal transconjunctival approach. The final histological examination revealed findings characteristic of GCT, including positive reaction for protein S-100, SOX10, and calcitonin and negative reaction for desmin, myogenin, Smooth Muscle Antigen (SMA), Melan-A, and HMB-45. There were no signs of malignancy in this sample. Disturbance of motility was not noted by the patient after surgery.

    Conclusion: GCT should be included in the differential diagnosis of intraorbital lesions, particularly those that involve the orbit muscles. A biopsy is recommended before surgical resection, to exclude malignancy and prevent radical resection.

  • 83.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Tengvall, Pentti
    Gothenburg University.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 5, p. 1148-1151Article in journal (Refereed)
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

  • 84.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study2010In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, no 7, p. 673-677Article in journal (Refereed)
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

  • 85. Abu-Elyazeed, R R
    et al.
    Heineman, T
    Dubin, G
    Fourneau, M
    Leroux-Roels, I
    Leroux-Roels, G
    Richardus, J H
    Ostergaard, L
    Diez-Domingo, J
    Poder, A
    Van Damme, P
    Romanowski, B
    Blatter, M
    Silfverdal, S A
    Berglund, J
    Josefsson, Ann
    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.
    Cunningham, A L
    Flodmark, C E
    Tragiannidis, A
    Dobson, S
    Olafsson, J
    Puig-Barbera, J
    Mendez, M
    Barton, S
    Bernstein, D
    Mares, J
    Ratner, P
    Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial.2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 51, p. 6136-6043Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

    METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

    RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

    CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

  • 86.
    Abuzeid, Nadir
    et al.
    Medical and Aromat Plants Research Institute, Sudan; Omdurman Islamic University, Sudan.
    Kalsum, Sadaf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Koshy, Richin John
    Larsson, Marie C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Glader, Mikaela
    Andersson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Pienaar, Elsje
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Alhassan, Muddathir S.
    Medical and Aromat Plants Research Institute, Sudan.
    AlGadir, Haidar A.
    Medical and Aromat Plants Research Institute, Sudan.
    Koko, Waleed S.
    Medical and Aromat Plants Research Institute, Sudan.
    Schon, Thomas
    Kalmar County Hospital, Sweden.
    Ahmed Mesaik, M.
    University of Kebangsaan Malaysia, Malaysia; University of Karachi, Pakistan.
    Abdalla, Omer M.
    University of Karachi, Pakistan.
    Khalid, Asaad
    Medical and Aromat Plants Research Institute, Sudan.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases2014In: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 157, p. 134-139Article in journal (Refereed)
    Abstract [en]

    Ethnopharmacological relevance: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases. Materials and methods: Plants were harvested and ethanolic extracts were prepared. For selected extracts, fractionation with hydrophilic and hydrophobic solvents was undertaken. A luminometry-based assay was used for determination of mycobacterial growth in broth cultures and inside primary human macrophages in the presence or absence of plant extracts and fractions of extracts. Cytotoxicity was also assessed for active fractions of plant extracts. Results: Of the tested extracts, three exhibited a significant inhibitory effect on an avirulent strain of Mycobacterium tubercluosis (H37Ra) at the initial screening doses (125 and 6.25 mu g/ml). These were bark and leaf extracts of Khaya senegalensis and the leaf extract of Rosmarinus officinalis L. Further fractions of these plant extracts were prepared with n-hexane, chloroform, ethyl acetate, n-butanol, ethanol and water, and the activity of these extracts was retained in hydrophobic fractions. Cytotoxicity assays revealed that the chloroform fraction of Khaya senegalensis bark was non-toxic to human monocyte-derived macrophages and other cell types at the concentrations used and hence, further analysis, including assessment of IC50 and intracellular activity was done with this fraction. Conclusion: These results encourage further investigations to identify the active compound(s) within the chloroform fraction of Khaya senegalensis bark. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

  • 87. Abu-Zidan, FM
    et al.
    Siosteen, AK
    Wang, Jianpu
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery.
    Al-Ayoubi, Fawzi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Lennquist, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology.
    Establishment of a teaching animal model for sonographic diagnosis of trauma2004In: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 56, no 1, p. 99-104Article in journal (Refereed)
    Abstract [en]

    Background: Ultrasound is widely accepted as a valuable diagnostic tool for detecting intra-abdominal and intrathoracic bleeding in trauma patients. Nevertheless, many doctors are reluctant to use it because they do not have sufficient training. This study aimed to define intraabdominal and intrathoracic fluid volumes that can be detected by sonography and their relation to fluid width in pigs to establish a clinically relevant animal model for teaching and training. Methods: Different volumes of normal saline were infused into the abdomen (50-2,000 mL) and chest (25-250 mL) in five anesthetized pigs. The maximum width of fluid as detected by ultrasound was recorded. The right upper quadrant, left upper quadrant, pelvis, and right paracolic section of the abdomen and right pleural cavity were studied. An experienced radiologist performed the studies. The effects on respiratory and cardiovascular functions were evaluated. Results: The sonographic findings in the pig were similar to those in humans. Up to 50 mL of intra-abdominal fluid and up to 25 mL of intrathoracic fluid could be detected by ultrasound. There was a significant correlation between the volume infused and the fluid width detected. The respiratory and cardiovascular monitoring of the animals showed that the infused intrathoracic volumes mimicked a survivable hemothorax. Conclusion: The pig may serve as an excellent clinically relevant model with which to teach surgeons detection of different volumes of intra-abdominal and intrathoracic fluids. The value of this model as an educational tool has yet to be tested.

  • 88.
    Acerini, Carlo L.
    et al.
    University of Cambridge, England.
    Wac, Katarzyna
    University of Geneva, Switzerland.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lehwalder, Dagmar
    Merck KGaA, Germany.
    Optimizing Patient Management and Adherence for children receiving Growth Hormone2017In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 8, article id 313Article in journal (Refereed)
    Abstract [en]

    Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

  • 89.
    Ackerley, R
    et al.
    Institute of Neuroscience and Physiology, University of Gothenburg, Sweden / SDS Clinic, ESRS accredited Sleep Research Laboratory, Gothenburg, Sweden.
    Badre, G
    Institute of Neuroscience and Physiology, University of Gothenburg, Sweden / SDS Clinic, ESRS accredited Sleep Research Laboratory, Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Institute of Neuroscience and Physiology, University of Gothenburg, Sweden / SDS Clinic, ESRS accredited Sleep Research Laboratory, Gothenburg, Sweden.
    Positive Effects of a Weighted Blanket on Insomnia2015In: Journal of Sleep Medicine & Disorders, ISSN 2379-0822, Vol. 2, no 3, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Insomnia is a common occurrence and can have a negative impact on physiological, psychological and social well-being. There is a need for simple, effective solutions to increase sleep quality. It has been suggested that weighted blankets and vests can provide a beneficial calming effect, especially in clinical disorders. Hence, we aimed to investigate the effects of a chain weighted blanket on insomnia, using objective and subjective measures. Objectively, we found that sleep bout time increased, as well as a decrease in movements of the participants, during weighted blanket use. Subjectively, the participants liked sleeping with the blanket, found it easier to settle down to sleep and had an improved sleep, where they felt more refreshed in the morning. Overall, we found that when the participants used the weighted blanket, they had a calmer night’s sleep. A weighted blanket may aid in reducing insomnia through altered tactile inputs, thus may provide an innovative, non-pharmacological approach and complementary tool to improve sleep quality.

  • 90.
    Adell, Gunnar
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Boeryd, B.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Frånlund, B.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Håkansson, L.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes' B colorectal carcinoma: an immunohistochemical study1996In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 162, no 8, p. 637-642Article in journal (Refereed)
    Abstract [en]

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

    DESIGN: Retrospective study.

    SETTING: University hospital, Sweden.

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

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

    OUTCOME MEASURES: Incidence and prognostic importance of micrometastases.

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

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

  • 91.
    Adil, Mohammed Yasin
    et al.
    Univ Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Xiao, Jiaxin
    Univ Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Olafsson, Jonatan
    Univ Oslo, Norway.
    Chen, Xiangjun
    Univ Oslo, Norway; Norwegian Dry Eye Clin, Norway; Arendal Hosp, Norway; Vestre Viken Hosp Trust, Norway; Univ Coll Southeast Norway, Norway.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Utheim, Oygunn A.
    Oslo Univ Hosp, Norway.
    Dartt, Darlene A.
    Harvard Med Sch, MA 02115 USA.
    Utheim, Tor P.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Oslo, Norway; Vestre Viken Hosp Trust, Norway; Univ Coll Southeast Norway, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Meibomian Gland Morphology Is a Sensitive Early Indicator of Meibomian Gland Dysfunction2019In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 200, p. 16-25Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the relationship between meibomian gland (MG) morphology and clinical dry eye tests in patients with meibomian gland dysfunction (MGD). DESIGN: Cross-sectional study. SUBJECTS: Total 538 MGD patients and 21 healthy controls. METHODS: MG loss on meibography images of upper (UL) and lower lids (LL) was graded on a scale of 0 (lowest degree of MG loss) to 3. MG length, thickness, and interglandular space in the UL were measured. Clinical tests included meibum expression and quality, tear film break-up time, ocular staining, osmolarity, Schirmer I, blink interval timing, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Mean UL and LL meibogrades were significantly higher in MGD patients compared to controls (P amp;lt; .001 for UL and LL). The sensitivity and specificity of the meibograde as a diagnostic parameter for MGD was 96.7% and 85%, respectively. Schirmer I was significantly increased in MGD patients with meibograde 1 compared to patients with meibograde 0, 2, and 3 in the UL (P amp;lt; .05 ). MG thickness increased with higher meibograde (P amp;lt; .001). MG morphology correlated significantly but weakly with several clinical parameters (P amp;lt; .05). OSDI did not correlate with any MG morphologic parameter. CONCLUSIONS: Grading of MG loss using meibograde effectively diagnoses MGD. Compensatory mechanisms such as increased aqueous tear production and dilation of MGs make early detection of MGD difficult by standard clinical measures of dry eye, whereas morphologic analysis of MGs reveals an early stage of MGD, and therefore represents a complementary clinical parameter with diagnostic potential. (C) 2018 Elsevier Inc. All rights reserved.

  • 92.
    Adini, B.
    et al.
    Tel Aviv University, Israel.
    Bodas, M.
    Tel Aviv University, Israel.
    Nilsson, Heléne
    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 Disaster Medicine and Traumatology.
    Peleg, K.
    Tel Aviv University, Israel; Gertner Institute Health Policy and Epidemiol, Israel.
    Policies for managing emergency medical services in mass casualty incidents2017In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 48, no 9, p. 1878-1883Article in journal (Refereed)
    Abstract [en]

    Introduction: Diverse decision-making is needed in managing mass casualty incidents (MCIs), by emergency medical services (EMS). The aim of the study was to review consensus among international experts concerning policies of EMS management during MCIs. Methods: Applicability of 21 EMS policies was tested through a 2-cycle modified e-Delphi process, in which 38 multi-disciplinary experts from 10 countries participated. Threshold for approving proposed solutions was defined as consensus of amp;gt;80%. Policies that did not achieve the targeted consensus were reviewed to detect variability according to respondents origin country. Results: 16 policies were endorsed in the first cycle including collaboration between ambulance service providers; implementing a unified mode of operation; preparing criteria for ground versus aerial evacuation; and, developing support systems for caregivers exposed to violence. An additional policy which proposed that senior EMS officers should not necessarily act as on-site MCI commanders was endorsed in the second cycle. Demographic breakdown of views concerning non-consensual policies revealed differences according to countries of origin. Assigning ambulances to off-duty team members was highly endorsed by experts from Israel and South Africa and strongly rejected by European respondents. Avoiding entry to risk areas until declared safe was endorsed by European, Asian and Oceanic experts, but rejected by Israeli, South African and North American experts. Conclusions: Despite uniqueness of countries and EMS agencies, solutions to most dilemmas were applicable to all organizations, regardless of location or affiliation. Cultural diversity was found concerning readiness to implement military-civilian collaboration in MCIs and a rigid separation between work-leisure responsibilities. (C) 2017 Elsevier Ltd. All rights reserved.

  • 93.
    Adolfsson, Ann-Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Miscarriage: Women’s Experience and its Cumulative Incidence2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many women experience miscarriage every year. Every fourth woman who has given birth reports that she has previous experience of miscarriage. In a study of all women in the Swedish Medical Birth Register 1983-2003, we found that the number of cases of self reported miscarriage had increased in Sweden during this 21 year period. This increase can be explained by the introduction of sensitive pregnancy tests around 1990, as well as an increase in the mean age of the mothers, by approximately 3 years, during the observation period. The risk of miscarriage is 13% with the first child. With subsequent pregnancies, the risk of miscarriage is 8%, 6% and 4% with the second, third and fourth child, respectively.

    Thirteen of these women who had suffered a recent miscarriage were interviewed four months later, and their feelings of guilt and emptiness were explored. Their experience was that they wanted their questions to be answered, and that they wanted others to treat them as the mothers to be that they felt themselves to be. They also experienced the need for time to grieve their loss.

    Measurement of grief by means of the Perinatal Grief Scale (PGS) is used in research but has also been proposed for clinical use. We have translated this psychological instrument to Swedish, back-translated and tested it in a small pilot study. In a randomized controlled study, women with early miscarriage were allocated, either to a structured visit (study group) or a regular visit (control group) to a midwife. The structured visit was conducted according to the Swanson caring theory. We could conclude that the structured visit had no significant effect on grief compared to the regular visit, as measured using the PGS. However, women with the sub-diagnosis missed abortion have significantly more grief four months after early miscarriage, regardless of visit type.

    We also performed a content analysis of the tape-recorded structured follow-up visit. The code-key used was Bonanno and Kaltman’s general grief categorization. Women’s expression of grief after miscarriage was found to be very similar to the grief experienced following the death of a relative. Furthermore, the grief was found to be independent of number of children, women’s age, or earlier experience of miscarriage.

    Conclusions: Every fourth woman who gives birth reports that she has also experienced early miscarriage. The experience of these women is that they have suffered a substantial loss and their reaction is grief similar to that experienced following the death of a relative.

    List of papers
    1. Cumulative incidence of previous spontaneous abortion in Sweden 1983-2003: A register study
    Open this publication in new window or tab >>Cumulative incidence of previous spontaneous abortion in Sweden 1983-2003: A register study
    2006 (English)In: Acta obstetricia et gynecologica Scandinavica, ISSN 0001-6349, Vol. 85, no 6, p. 741-747Article in journal (Refereed) Published
    Abstract [en]

    Aim. The aim of this study is to find out how common miscarriages are among women who have delivered a child.

    Methods. The numbers of deliveries and miscarriages were extracted from the Swedish Medical Birth Register between 1983 and 2003. Linear regression was performed in order to investigate whether the increasing mean age of mothers or differences in pregnancy identification methods could explain the increased frequency of miscarriage.

    Results. The reported number of miscarriages increased each year during the 21-year period, with a marked increase between 1991 and 1993 and only a slight increase during the final 10 years. For primiparous women, the frequency of reported miscarriages per delivery increased from 8.6% in 1983 to 13.9% in 2003. The corresponding figures for 2-parous women showed an increase from 14.5% to 21.3% respectively. Women aged 30-34 years had an odds ratio of 1.43 (95% CI 1.40-1.45) to suffer spontaneous abortion compared to the age group 25-29 years. Linear regression showed that an increase in mean age at delivery could only partly explain the increase in the frequency of reported miscarriages. A possible explanation could be differences in methods of identifying early pregnancy.

    Conclusion. Of all women who deliver a child, nearly 20% have experienced previous miscarriage. The increased mean age of women could only explain a small portion of the seen increase in miscarriage. The marked increase from 1991 to 1993 is interesting. Possible reasons for the increase are discussed.

    Keywords
    Miscarriage; register study; retrospective study; spontaneous abortion; Medical Birth Register
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13806 (URN)10.1080/00016340600627022 (DOI)
    Available from: 2006-04-03 Created: 2006-04-03
    2. Guilt and emptiness: Women’s experiences of miscarriage
    Open this publication in new window or tab >>Guilt and emptiness: Women’s experiences of miscarriage
    2004 (English)In: Health Care for Women International, ISSN 0739-9332, Vol. 25, no 6, p. 543-560Article in journal (Refereed) Published
    Abstract [en]

    Women who lose an early pregnancy are shocked when they are first given the information that they have miscarried. Later they feel guilt and emptiness. Heideggerian interpretive phenomenology has been used with 13 women from southwest Sweden to uncover their lived experience of miscarriage. Women plan their future with a child during early pregnancy. When miscarriage occurs it is not a gore, an embryo, or a fetus they lose, it is their child. They feel that they are the cause of the miscarriage through something they have done, eaten, or thought. They feel abandonment and they grieve for their profound loss; they are actually in bereavement.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13807 (URN)10.1080/07399330490444821 (DOI)
    Available from: 2006-04-03 Created: 2006-04-03 Last updated: 2018-11-15
    3. Translation of the short version of the Perinatal Grief Scale into Swedish
    Open this publication in new window or tab >>Translation of the short version of the Perinatal Grief Scale into Swedish
    2006 (English)In: Scandinavian journal of caring sciences, ISSN 1471-6712, Vol. 20, no 3, p. 269-273Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Women's emotions and grief after miscarriage are influenced not only by the context in which the miscarriage occurred but also by their past experience, the circumstances around the miscarriage and their future prospects. Their emotions therefore express a specific form of grief. Normally the time needed to work through the loss varies. A number of different scales, measuring women's emotions and grief after miscarriage have been published. One instrument that measures the specific grief, such as the grief after miscarriage is the Perinatal Grief Scale (PGS) that was designed to measure grief after perinatal loss and has good reliability and validity.

    Aims: The purpose of this study was to translate the PGS into Swedish and to use the translation in a small pilot study.

    Material and method: The original short version of the PGS was first translated from English into Swedish and then back-translated into English, using different translators. During translation and back-translation, not only the linguistic and grammatical aspects were considered but also cultural differences. The Likert 5-point and a 10-point scale were tested in a pilot study where 12 volunteers anonymously answered the PGS twice. The intra-personal correlations were compared and analysed with weighted κ-coefficient.

    Findings: In all, five different versions were tested before the final Swedish version was established. The weighted κ-coefficient for the volunteers was 0.58, which is regarded as representing good reproducibility.

    Conclusion: The PGS was translated successfully into Swedish and could be used in a Swedish population. As this work is rather time-consuming we therefore wish to publish the Swedish version so that it may be used by other researchers.

    Keywords
    translation, Perinatal Grief Scale, miscarriage, grief, spontaneous abortion
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13808 (URN)10.1111/j.1471-6712.2006.00404.x (DOI)
    Available from: 2006-04-03 Created: 2006-04-03 Last updated: 2010-05-17
    4. Effect of a structured follow-up visit to a midwife on women with early miscarriage: A randomized study
    Open this publication in new window or tab >>Effect of a structured follow-up visit to a midwife on women with early miscarriage: A randomized study
    2006 (English)In: Acta obstetricia et gynecologica Scandinavica, ISSN 0001-6349, Vol. 85, no 3, p. 330-335Article in journal (Refereed) Published
    Abstract [en]

    Background. Women's grief after miscarriage is substantial and important. Women who experience early miscarriage do not constitute a homogenous group. The aim of this study is to measure whether a structured follow-up visit to a midwife (group 1) at 21-28 days after early miscarriage could reduce the women's grief, measured using the perinatal grief scale Swedish short version (PGS) after a further 3 months (i.e. 4 months after the miscarriage), compared to a regular follow-up visit to a midwife (group 2). Methods. We performed an open randomized study of women who experienced early miscarriage (n = 88). The midwife's attitude in group 1 came from Swanson science theory of midwifery. In group 2, the women were offered only the ordinary type of consultation at a regular visit. A questionnaire with the PGS was used in both groups. Four months after the miscarriage, a second questionnaire with the same perinatal grief scale was sent by post. Results. There was a 30% greater reduction in grief in group 1 than that in group 2, when comparing the first and second measurements (not significant). The biggest differences were in the subscales active grief and difficulty in coping. Women with the subdiagnosis missed abortions had, as a group, significantly higher PGS scores at both visits, especially in active grief and difficulty in coping, regardless of the type of follow-up visit. Conclusions. A structured follow-up visit did not, in comparison with a regular follow-up visit, imply any significant reduction in grief as measured using the PGS scale. However, the subgroup missed abortion had more extensive grief than the other women with miscarriage. Structured follow-up visits are not imperative for all women with early miscarriage.

    Keywords
    Early miscarriage; grief; midwife; support; treatment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13809 (URN)10.1080/00016340500539376 (DOI)
    Available from: 2006-04-03 Created: 2006-04-03 Last updated: 2013-09-12
    5. Applicability of general grief theory to Swedish women’s experiences after early miscarriage, with factor analysis of Bonanno´s taxonomy, using the Perinatal Grief Scale.
    Open this publication in new window or tab >>Applicability of general grief theory to Swedish women’s experiences after early miscarriage, with factor analysis of Bonanno´s taxonomy, using the Perinatal Grief Scale.
    2010 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, Vol. 115, no 3, p. 201-209Article in journal (Refereed) Published
    Abstract [en]

    Background. Grief is a normal phenomenon but showing great variation depending on cultural and personal features. Bonanno and Kaltman have nonetheless proposed five aspects of normal grief. The aim of this study was to investigate if women with miscarriage experience normal grief.

    Material and methods. Content analyses of 25 transcribed conversations with women 4 weeks after their early miscarriages were classified depending on the meaning-bearing units according to Bonanno and Kaltman's categories. In the factor analyses, these categories were compared with the Perinatal Grief Scale and women's age, number of children and number of miscarriages, and gestational weeks.

    Results. Women with miscarriage fulfill the criteria for having normal grief according to Bonanno and Kaltman. All of the 25 women had meaning-bearing units that were classified as cognitive disorganization, dysphoria, and health deficits, whereas disrupted social and occupational functioning and positive aspects of bereavement were represented in 22 of 25 women. From the factor analysis, there are no differences in the expression of the intensity of the grief, irrespective of whether or not the women were primiparous, younger, or had suffered a first miscarriage.

    Conclusion. Women's experience of grief after miscarriage is similar to general grief after death. After her loss, the woman must have the possibility of expressing and working through her grief before she can finish her pregnancy emotionally. The care-giver must facilitate this process and accept that the intensity of the grief is not dependent on the woman's age, or her number of earlier miscarriages.

    Keywords
    Content analysis, factor analysis, general grief theory, miscarriage, perinatal grief scale, women
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13810 (URN)10.3109/03009731003739851 (DOI)000281013000008 ()
    Note
    On the day of the defence day the status of this article was Submitted.Available from: 2006-04-03 Created: 2006-04-03 Last updated: 2010-09-03
  • 94.
    Adolfsson, Annsofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Larsson, Per-Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Effect of a structured follow-up visit to a midwife on women with early miscarriage: A randomized study2006In: Acta obstetricia et gynecologica Scandinavica, ISSN 0001-6349, Vol. 85, no 3, p. 330-335Article in journal (Refereed)
    Abstract [en]

    Background. Women's grief after miscarriage is substantial and important. Women who experience early miscarriage do not constitute a homogenous group. The aim of this study is to measure whether a structured follow-up visit to a midwife (group 1) at 21-28 days after early miscarriage could reduce the women's grief, measured using the perinatal grief scale Swedish short version (PGS) after a further 3 months (i.e. 4 months after the miscarriage), compared to a regular follow-up visit to a midwife (group 2). Methods. We performed an open randomized study of women who experienced early miscarriage (n = 88). The midwife's attitude in group 1 came from Swanson science theory of midwifery. In group 2, the women were offered only the ordinary type of consultation at a regular visit. A questionnaire with the PGS was used in both groups. Four months after the miscarriage, a second questionnaire with the same perinatal grief scale was sent by post. Results. There was a 30% greater reduction in grief in group 1 than that in group 2, when comparing the first and second measurements (not significant). The biggest differences were in the subscales active grief and difficulty in coping. Women with the subdiagnosis missed abortions had, as a group, significantly higher PGS scores at both visits, especially in active grief and difficulty in coping, regardless of the type of follow-up visit. Conclusions. A structured follow-up visit did not, in comparison with a regular follow-up visit, imply any significant reduction in grief as measured using the PGS scale. However, the subgroup missed abortion had more extensive grief than the other women with miscarriage. Structured follow-up visits are not imperative for all women with early miscarriage.

  • 95.
    Adolfsson, Ann-Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Larsson, Per-Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Applicability of general grief theory to Swedish women’s experiences after early miscarriage, with factor analysis of Bonanno´s taxonomy, using the Perinatal Grief Scale.2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, Vol. 115, no 3, p. 201-209Article in journal (Refereed)
    Abstract [en]

    Background. Grief is a normal phenomenon but showing great variation depending on cultural and personal features. Bonanno and Kaltman have nonetheless proposed five aspects of normal grief. The aim of this study was to investigate if women with miscarriage experience normal grief.

    Material and methods. Content analyses of 25 transcribed conversations with women 4 weeks after their early miscarriages were classified depending on the meaning-bearing units according to Bonanno and Kaltman's categories. In the factor analyses, these categories were compared with the Perinatal Grief Scale and women's age, number of children and number of miscarriages, and gestational weeks.

    Results. Women with miscarriage fulfill the criteria for having normal grief according to Bonanno and Kaltman. All of the 25 women had meaning-bearing units that were classified as cognitive disorganization, dysphoria, and health deficits, whereas disrupted social and occupational functioning and positive aspects of bereavement were represented in 22 of 25 women. From the factor analysis, there are no differences in the expression of the intensity of the grief, irrespective of whether or not the women were primiparous, younger, or had suffered a first miscarriage.

    Conclusion. Women's experience of grief after miscarriage is similar to general grief after death. After her loss, the woman must have the possibility of expressing and working through her grief before she can finish her pregnancy emotionally. The care-giver must facilitate this process and accept that the intensity of the grief is not dependent on the woman's age, or her number of earlier miscarriages.

  • 96.
    Adolfsson, Ann-Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Larsson, Per-Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine . Linköping University, Faculty of Health Sciences.
    Cumulative incidence of previous spontaneous abortion in Sweden 1983-2003: A register study2006In: Acta obstetricia et gynecologica Scandinavica, ISSN 0001-6349, Vol. 85, no 6, p. 741-747Article in journal (Refereed)
    Abstract [en]

    Aim. The aim of this study is to find out how common miscarriages are among women who have delivered a child.

    Methods. The numbers of deliveries and miscarriages were extracted from the Swedish Medical Birth Register between 1983 and 2003. Linear regression was performed in order to investigate whether the increasing mean age of mothers or differences in pregnancy identification methods could explain the increased frequency of miscarriage.

    Results. The reported number of miscarriages increased each year during the 21-year period, with a marked increase between 1991 and 1993 and only a slight increase during the final 10 years. For primiparous women, the frequency of reported miscarriages per delivery increased from 8.6% in 1983 to 13.9% in 2003. The corresponding figures for 2-parous women showed an increase from 14.5% to 21.3% respectively. Women aged 30-34 years had an odds ratio of 1.43 (95% CI 1.40-1.45) to suffer spontaneous abortion compared to the age group 25-29 years. Linear regression showed that an increase in mean age at delivery could only partly explain the increase in the frequency of reported miscarriages. A possible explanation could be differences in methods of identifying early pregnancy.

    Conclusion. Of all women who deliver a child, nearly 20% have experienced previous miscarriage. The increased mean age of women could only explain a small portion of the seen increase in miscarriage. The marked increase from 1991 to 1993 is interesting. Possible reasons for the increase are discussed.

  • 97.
    Adolfsson, Ann-Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine. Linköping University, Faculty of Health Sciences.
    Larsson, Per-Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Guilt and emptiness: Women’s experiences of miscarriage2004In: Health Care for Women International, ISSN 0739-9332, Vol. 25, no 6, p. 543-560Article in journal (Refereed)
    Abstract [en]

    Women who lose an early pregnancy are shocked when they are first given the information that they have miscarried. Later they feel guilt and emptiness. Heideggerian interpretive phenomenology has been used with 13 women from southwest Sweden to uncover their lived experience of miscarriage. Women plan their future with a child during early pregnancy. When miscarriage occurs it is not a gore, an embryo, or a fetus they lose, it is their child. They feel that they are the cause of the miscarriage through something they have done, eaten, or thought. They feel abandonment and they grieve for their profound loss; they are actually in bereavement.

  • 98.
    Adolfsson, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology .
    Persson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology .
    Prosodiska aspekter av nonordsproduktion hos barn med cochleaimplantat och barn med språkstörning2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]