liu.seSearch for publications in DiVA
Change search
Refine search result
1234567 1 - 50 of 495
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Abelius, M
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nilsson, L J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Immunological interactions between mother and child: a characterisation of Th1-and Th2-like chemokines during pregnancy, postpartum and childhood in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 170-1712011In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 170-171Conference paper (Refereed)
    Abstract [en]

    n/a

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

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

  • 3.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19153 (URN)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-09-15Bibliographically approved
  • 4.
    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

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    Ahlberg, K
    et al.
    Barn- och ungdomshabiliteringen, Karlstad .
    Åhsgren,
    Barn- och ungdomshabiliteringen, Sundsvall.
    Gladh Mattsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mattsson, Sven
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Toilet training, incontinence and learning disability2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 37, p. 2164-2168Article in journal (Other academic)
  • 12.
    Ahlberg, Karin
    et al.
    Karlstad.
    Åhsgren, Ingegerd
    Sundsvall.
    Glad Mattsson, Gunilla
    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.
    Mattsson, Sven
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Toaletträning lönar sig även vid svår utvecklingsstörning: Råd och anvisningar vid inkontinens2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 37, p. 2164-2168Article in journal (Other academic)
    Abstract [sv]

    Råd och anvisningar för toaletträning vid utvecklingsstörning har efterlysts av föräldrar och vårdpersonal.

    Evidensbaserade riktlinjer enligt SBU:s rekommendationer för handläggning av toaletträning vid utvecklingsstörning har tagits fram efter granskning av befintlig forskning, som nästan uteslutande berör toaletträning vid måttlig, svår eller grav utvecklingsstörning.

    Barnorienterade råd för toaletträning av normalutvecklade barn kan eller ska som regel tillämpas för barn med utvecklingsstörning utan tilläggsproblematik.

    Intensiv strukturerad beteendeträning är sannolikt den bästa metoden för barn och ungdomar med svårare grad av utvecklingsstörning och för individer med neuropsy­kiatriska funktionsnedsättningar.

    Medicinsk bedömning ska alltid föregå toaletträning vid utvecklingsstörning, då neurogena och anatomiska avvikelser är vanligare hos barn och ungdomar med utvecklingsstörning.

  • 13.
    Aittoniemi, J
    et al.
    Klin mikro Tampere, Finland.
    Turpeinen, H
    Virologen Turku, Finland.
    Tiitanen, M
    National Public Health Institute Helsinki, Finland.
    Knip, M
    Hospital for Children and Adolescents Helsinki, Finland.
    Simell, O
    Paediatrics Turku, Finland.
    Ilonen, J
    Virologen Turku, Finland.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children2008In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 69, no 2, p. 108-111Article in journal (Refereed)
    Abstract [en]

    Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of β-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for ≥3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28, p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency. © 2008 American Society for Histocompatibility and Immunogenetics.

  • 14.
    Akefeldt, Selma O
    et al.
    Karolinska University Hospital Solna, Sweden .
    Finnström, Orvar
    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.
    Gavhed, Desiree
    Karolinska University Hospital Solna, Sweden .
    Henter, Jan-Inge
    Karolinska University Hospital Solna, Sweden .
    Langerhans cell histiocytosis in children born 1982-2005 after in vitro fertilization2012In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 101, no 11, p. 1151-1155Article in journal (Refereed)
    Abstract [en]

    Aim: In a recent Swedish study, comparing data from the Swedish Cancer Register with the Medical Birth Register including data on IVF, an increased risk of Langerhans cell histiocytosis (LCH) was found in children born 19822005 after IVF. Here, we aimed to verify the LCH diagnoses and examine whether any special forms of the disease were overrepresented in this population. Methods: Medical records for all children with LCH conceived by IVF were acquired and the diagnosis confirmed or discarded. Disease characteristics were compared with data from children diagnosed with LCH 19922001 in the Stockholm County. Results: We verified LCH in seven children born after IVF, all born prior to 2002. These children did not have milder disease forms. The odds ratio (OR) to develop LCH for the whole group born after IVF was 3.2 [95% confidence interval (CI), 1.47.3] and for children born before 2002, 5.2 [95% CI, 2.311.9], compared with children in Stockholm County 19922001. Conclusion: LCH was overrepresented in children born after IVF prior to 2002. Affected children did not have milder disease forms. These findings may be valuable to understand LCH aetiology. Additional studies on a putative correlation between IVF and LCH in the offspring are encouraged.

  • 15.
    Akerblom, H.K.
    et al.
    Åkerblom, H.K., Biomedicum Helsinki Institute, B.P. 700, Haartmaninkatu 8, FIN-00029 HUS, Finland, Department of Pediatrics, University of Helsinki.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Hyoty, H.
    Hyöty, H., Department of Virology, University of Tampere, Finland.
    Ilonen, J.
    Institute of Microbiology and Pathology, University of Turku.
    Knip, M.
    Department of Pediatrics, University of Helsinki.
    Environmental factors in the etiology of type 1 diabetes2002In: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 115, no 1, p. 18-29Article, review/survey (Refereed)
    Abstract [en]

    Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes. © 2002 Wiley-Liss, Inc.

  • 16.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    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.
    Hermansson, Göran
    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.
    Somasunduram, Konduri
    Centre for Social Medicine, Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Bangal, Vidyadhar
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Patil, Ashok
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Chandekar, Pratibha
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Nurse-based antenatal and child health care in rural India, implementation and effects - an Indian-Swedish collaboration2012In: Rural and remote health, ISSN 1445-6354, Vol. 12, no 3Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Improving maternal and child health care are two of the Millennium Development Goals of the World Health Organization. India is one of the countries worldwide most burdened by maternal and child deaths. The aim of the study was to describe how families participate in nurse-based antenatal and child health care, and the effect of this in relation to referrals to specialist care, institutional deliveries and mortality.

    METHODS:

    The intervention took place in a remote rural area in India and was influenced by Swedish nurse-based health care. A baseline survey was performed before the intervention commenced. The intervention included education program for staff members with a model called Training of Trainers and the establishment of clinics as both primary health centers and mobile clinics. Health records and manuals, and informational and educational materials were produced and the clinics were equipped with easily handled instruments. The study period was between 2006 and 2009. Data were collected from antenatal care and child healthcare records. The Chi-square test was used to analyze mortality differences between years. A focus group discussion and a content analysis were performed.

    RESULTS:

    Families' participation increased which led to more check-ups of pregnant women and small children. Antenatal visits before 16 weeks among pregnant women increased from 32 to 62% during the period. Women having at least three check-ups during pregnancy increased from 30 to 60%. Maternal mortality decreased from 478 to 121 per 100 000 live births. The total numbers of children examined in the project increased from approximately 6000 to 18 500 children. Infant mortality decreased from 80 to 43 per 1000 live births. Women and children referred to specialist care increased considerably and institutional deliveries increased from 47 to 74%.

    CONCLUSION:

    These results suggest that it is possible in a rural and remote area to influence peoples' awareness of the value of preventive health care. The results also indicate that this might decrease maternal and child mortality. The education led to a more patient-friendly encounter between health professionals and patients.

  • 17.
    Alstrand, N
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    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.
    Hyllienmark, L
    Karolinska Institute.
    Wahlberg, J
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Symptomatic neuropathy in type 1 diabetes is preceded by subclinical electrophysiological abnormalities - a prospective study in DIABETOLOGIA, vol 53, issue , pp2010In: DIABETOLOGIA, Springer Science Business Media , 2010, Vol. 53Conference paper (Refereed)
    Abstract [en]

    n/a

  • 18.
    Andersson, C
    et al.
    Lund University, Sweden .
    Vaziri-Sani, F
    Lund University, Sweden .
    Delli, A J.
    Lund University, Sweden .
    Lindblad, B
    Queen Silvia Childrens Hospital, Sweden .
    Carlsson, A
    Lund University, Sweden .
    Forsander, G
    Queen Silvia Childrens Hospital, Sweden .
    Ludvigsson, Johnny
    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.
    Marcus, C
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    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.
    Ivarsson, S A.
    Lund University, Sweden .
    Lernmark, A
    Lund University, Sweden .
    Elding Larsson, H
    Lund University, Sweden .
    Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes2013In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 2, p. 97-105Article in journal (Refereed)
    Abstract [en]

    Andersson C, Vaziri-Sani F, Delli AJ, Lindblad B, Carlsson A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ivarsson SA, Lernmark A, Elding Larsson H, the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatric Diabetes 2013: 14: 97-105. Objective To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA). Methods We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA). Results ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 13 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (pandlt;0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2). Conclusions Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.

  • 19.
    Angeby, K A
    et al.
    Karolinska University Hospital.
    Jureen, P
    Swedish Institute for Infectious Disease Control.
    Giske, C G
    Karolinska University Hospital.
    Chryssanthou, E
    Karolinska University Hospital.
    Sturegard, E
    Malmo University Hospital.
    Nordvall, Maria
    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.
    Johansson, A G
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Werngren, J
    Swedish Institute for Infectious Disease Control.
    Kahlmeter, G
    Växjö Hospital.
    Hoffner, S E
    Swedish Institute for Infectious Disease Control.
    Schon, T
    Kalmar County Hospital.
    Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data2010In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, ISSN 0305-7453, Vol. 65, no 5, p. 946-952Article in journal (Refereed)
    Abstract [en]

    To describe wild-type distributions of the MIC of fluoroquinolones for Mycobacterium tuberculosis in relation to current critical concentrations used for drug susceptibility testing and pharmacokinetic/pharmacodynamic (PK/PD) data. A 96-stick replicator on Middlebrook 7H10 medium was used to define the MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin for 90 consecutive clinical strains and 24 drug-resistant strains. The MICs were compared with routine BACTEC 460 susceptibility results and with MIC determinations in the BACTEC MGIT 960 system in a subset of strains using ofloxacin as a class representative. PK/PD data for each drug were reviewed in relation to the wild-type MIC distribution. The wild-type MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin were distributed from 0.125 to 1, 0.25 to 1, 0.032 to 0.5 and 0.125 to 0.5 mg/L, respectively. The MIC data correlated well with the BACTEC 960 MGIT and BACTEC 460 results. PD indices were the most favourable for levofloxacin, followed by moxifloxacin, ofloxacin and ciprofloxacin. We propose S (susceptible) andlt; 1.0 mg/L as the tentative epidemiological cut-off (ECOFF) for ofloxacin and ciprofloxacin, and S andlt; 0.5 mg/L for levofloxacin and moxifloxacin, although it is possible that adding more MIC data could shift the ECOFFs for ofloxacin and levofloxacin one dilution upwards. The proposed ECOFFs may be more appropriate if used as clinical breakpoints on Middlebrook 7H10 agar than the current critical concentrations of S andlt; 2.0 mg/L for ciprofloxacin, ofloxacin and levofloxacin, and S andlt; 0.5 mg/L could be considered as a clinical breakpoint for moxifloxacin, provided other investigators can confirm our findings.

  • 20.
    Asad, Samina
    et al.
    Karolinska Institute, Sweden .
    Nikamo, Pernilla
    Karolinska Institute, Sweden .
    Gyllenberg, Alexandra
    Karolinska Institute, Sweden .
    Bennet, Hedvig
    Lund University, Sweden Lund University, Sweden .
    Hansson, Ola
    Lund University, Sweden .
    Wierup, Nils
    Lund University, Sweden .
    Carlsson, Annelie
    University of Lund Hospital, Sweden .
    Forsander, Gun
    Queen Silvia Childrens Hospital, Sweden .
    Ivarsson, Sten-Anders
    Lund University, Sweden .
    Larsson, Helena
    Lund University, Sweden .
    Lernmark, Ake
    Lund University, Sweden .
    Lindblad, Bengt
    Queen Silvia Childrens Hospital, Sweden .
    Ludvigsson, Johnny
    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.
    Marcus, Claude
    Karolinska Institute, Sweden .
    Ronningen, Kjersti S.
    University of Oslo, Norway .
    Nerup, Jan
    Steno Diabet Centre, Denmark .
    Pociot, Flemming
    Lund University, Sweden University Hospital Glostrup, Denmark .
    Luthman, Holger
    Lund University, Sweden Lund University, Sweden .
    Fex, Malin
    Lund University, Sweden Lund University, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden .
    HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q132012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5Article in journal (Refereed)
    Abstract [en]

    Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.

  • 21.
    Austeng, Dordi
    et al.
    Uppsala University.
    Blennow, Mats
    Karolinska University Hospital .
    Ewald, Uwe
    Uppsala University.
    Fellman, Vineta
    Lund University.
    Fritz, Thomas
    Sahlgrens University Hospital.
    Hellstrom-Westas, Lena
    Uppsala University.
    Hellstrom, Ann
    University Gothenburg.
    Holmgren, Per Åke
    Umea University Hospital.
    Holmstrom, Gerd
    Uppsala University.
    Jakobsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Jeppsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Johansson, Kent
    Umeå University.
    Kallen, Karin
    Lund University.
    Lagercrantz, Hugo
    Astrid Lindgren Childrens Hospital.
    Laurini, Ricardo
    Bodo Central Hospital.
    Lindberg, Eva
    University of Örebro.
    Lundqvist, Anita
    Lund University.
    Marsal, Karel
    Lund University.
    Nilstun, Tore
    Lund University.
    Norden-Lindeberg, Solveig
    Uppsala University.
    Norman, Mikael
    Karolinska Institute.
    Olhager, Elisabeth
    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.
    Oestlund, Ingrid
    University of Örebro.
    Serenius, Fredrik
    Umeå University Hospital.
    Simic, Marija
    Karolinska University Hospital .
    Sjors, Gunnar
    Uppsala University.
    Stigson, Lennart
    Sahlgrens University Hospital.
    Stjernqvist, Karin
    Lund University.
    Stromberg, Bo
    Uppsala University.
    Tornqvist, Kristina
    Lund University.
    Wennergren, Margareta
    Sahlgrens University Hospital.
    Wallin, Agneta
    Karolinska University.
    Westgren, Magnus
    Karolinska University Hospital.
    Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)2010In: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 99, no 7, p. 978-992Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage andgt;= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

  • 22.
    Axelsson, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    GAD65 An Immunomodulator in Type 1 Diabetes2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is caused by a deficiency of insulin as a result of an autoimmune destruction of the pancreatic ² -cells. A possibility to preserve remaining ² -cells in children with newly diagnosed T1D is of great importance since sustained ² -cell function is recognized to result in reduced end-organ complications. Glutamic acid decarboxylase 65 (GAD65) is one of the major antigens targeted by self-reactive T cells in T1D, and immunomodulation with GAD65 formulated in aluminum (GAD-alum) has been considered both in prevention and treatment of T1D. Results from a Phase II trial have shown clinical effect of subcutaneous injections with GAD-alum, this was unfortunately not fully confirmed in the following larger Phase III trial which therefore was closed after 15 months. The general aim of this thesis was to study the immunomodulatory effect of GAD-alum-treatment in children with T1D participating in the Phase II and Phase III trials. We hypothesized that treatment with GAD-alum contributes to the preservation of residual insulin secretion through deviation of the GAD65-specific immune response from a destructive to a protective process, accompanied by a shift from T helper (Th) 1 towards a predominant Th2 profile. In the Phase II trial, GAD-alum-treated patients responded with an early GAD65-specific Th2 skewed cytokine secretion, with highest IL-5 and IL-13 secretion in clinical responders. Also, the CCR4/CCR5 ratio indicating balance between Th2/Tc2 and Th1/Tc1 responses, increased in treated patients. The recall response to GAD65 was characterized by a wide range of cytokines, but the relative contribution of each cytokine suggests a shift towards a more pronounced Th2-associated profile over time. Induction of a CD4+ cell subset upon GAD65-stimulation 4 years after treatment, suggesting clonal expansion of the memory T-cell compartment upon antigen re-challenge, was seen in parallel to a persistent GAD65-specific cytokine response. Finally, even if the phase III trial failed to reach the primary endpoint at 15 months, a subgroup analysis showed that the treatment had an effect on preservation of residual insulin secretion, but the effect was not seen until after 30 months. Taken together, these results suggest that GAD-alum treatment might exert its effect through induction of an early Th2 skewed immune response which tends to deviate away from a destructive Th1/Tc1 response upon GAD65 re-challenge, and generation of GAD65-specific memory T cells that produce cytokines and exert effector responses which may be important for regulating GAD65 immunity. Continued research to better understand how immunomodulation with autoantigen modifies T-cell responses and also which patients are suitable for treatment, is crucial for optimizing future intervention trials using ² -cell antigens.

    List of papers
    1. Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65)
    Open this publication in new window or tab >>Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65)
    Show others...
    2010 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 26, no 7, p. 559-568Article in journal (Refereed) Published
    Abstract [en]

    Background We have previously shown that two injections of 20 mu g alum-formulated glutamic acid decarboxylase 65 (GAD(65)) (GAD-alum; Diamyd (R)) in children with recent-onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months follow-up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow-ups, to investigate whether the immunomodulatory effect of GAD-alum was apparent earlier after treatment, preceding the changes previously reported at 15 months.<p>Methods Peripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD-alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD(65), tyrosine phosphatase-like protein IA-2 peptide, insulin peptide, GAD-alum, alum formulation or phytohaemagglutinin. Interleukin (IL)-5, -6, -10, -12, -13, -17, tumour necrosis factor and interferon-gamma were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor-beta was determined by real-time reverse transcription polymerase chain reaction.</p><p>Results Already 1 month after the first injection, GAD(65)-induced IL-5 and IL-13 together with FOXP3 were enhanced in GAD-alum-treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T-helper 2-associated cytokines IL-5 and IL-13 together with FOXP3 increased continuously over time.</p><p>Conclusions Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months. Copyright (C) 2010 John Wiley &amp; Sons, Ltd.</p>

    Place, publisher, year, edition, pages
    John Wiley and Sons, 2010
    Keywords
    GAD65, Immunotherapy, Th1/Th2 Immune Response, Immunomodulation, Cytokines
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-52141 (URN)10.1002/dmrr.1126 (DOI)000283399000007 ()
    Available from: 2009-12-07 Created: 2009-12-07 Last updated: 2017-12-12
    2. Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.
    Open this publication in new window or tab >>Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.
    2012 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 10, p. 1272-1278Article in journal (Refereed) Published
    Abstract [en]

    Aim  The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. Methods  Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results  Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion  Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2012
    Keywords
    Type 1 diabetes, GAD(65), immunomodulation, chemokines, chemokine receptors
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-77745 (URN)10.1111/j.1464-5491.2012.03710.x (DOI)000308960400014 ()22587593 (PubMedID)
    Note

    funding agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden) Diamyd Medical||Medical Research Council of Southeast Sweden||

    Available from: 2012-05-28 Created: 2012-05-28 Last updated: 2017-12-07
    3. Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
    Open this publication in new window or tab >>Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
    Show others...
    2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 12Article in journal (Refereed) Published
    Abstract [en]

    A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.

    Place, publisher, year, edition, pages
    Public Library of Science, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74156 (URN)10.1371/journal.pone.0029008 (DOI)000298366600057 ()
    Note
    Funding Agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden)||Medical Research Council of Southeast Sweden||Juvenile Diabetes Research Foundation (JDRF)|1-2008-106|Ile-de-France CODDIM||Inserm Avenir Program||Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
    4. Preserved C-peptide 30 months after GAD-alum treatment of children and adolescents with recent-onset type 1 diabetes, and its relation to immune markers
    Open this publication in new window or tab >>Preserved C-peptide 30 months after GAD-alum treatment of children and adolescents with recent-onset type 1 diabetes, and its relation to immune markers
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Glutamic acid decarboxylase 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes (T1D). Although alum-formulated GAD65 (GAD-alum) induced preservation of residual insulin secretion in a previous clinical Phase II trial, recent Phase II and Phase III trials failed to reach their primary end-points. The European Phase III trial was therefore closed after 15 months, and the 30 months follow-up period was completed only for a minority of the patients. This study aimed to assess whether GAD-alum preserved β-cell function in those recent-onset T1D patients who completed their 30 months visit in the European Phase III trial, and to characterize their GAD65-induced cytokine secretion and proliferation. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and after 1, 3, 9, 15 and 21 months from the 148 Swedish subjects included in the Phase III GAD-alum trial, and also at 30 months from 45 patients who had reached the final visit before the trial was closed. Patients had been randomly assigned into three arms: 4 doses of GAD-alum (4D), 2 doses of GAD-alum followed by two doses of placebo (2D), or 4 doses of placebo. Cytokine secretion was detected in cell culture supernatants by Luminex, after 7 days of in vitro culture. Cell proliferation was determined by 3H thymidine incorporation assay. Fasting and stimulated C-peptide was analysed in serum.

    Patients treated with 2 doses of GAD-alum had less decline of both fasting (p=0.040) and stimulated C-peptide (p=0.012) after 30 months, and a larger proportion of these patients preserved >25% of their initial stimulated C-peptide AUC compared to placebo (p=0.012). Both 2D and 4D patients showed increased PBMC proliferation to GAD65 and a cytokine profile that tended to switch towards a more predominant Th2 associated profile over time.

    The results support the concept of GAD-alum treatment, but no specific immune markers have been identified.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-77746 (URN)
    Available from: 2012-05-28 Created: 2012-05-28 Last updated: 2012-05-28Bibliographically approved
  • 23.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Martinuzzi, Emanuela
    St Vincent de Paul Hospital.
    Mallone, Roberto
    St Vincent de Paul Hospital.
    Ludvigsson, Johnny
    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.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 12Article in journal (Refereed)
    Abstract [en]

    A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.

  • 24.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    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.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Preserved C-peptide 30 months after GAD-alum treatment of children and adolescents with recent-onset type 1 diabetes, and its relation to immune markersManuscript (preprint) (Other academic)
    Abstract [en]

    Glutamic acid decarboxylase 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes (T1D). Although alum-formulated GAD65 (GAD-alum) induced preservation of residual insulin secretion in a previous clinical Phase II trial, recent Phase II and Phase III trials failed to reach their primary end-points. The European Phase III trial was therefore closed after 15 months, and the 30 months follow-up period was completed only for a minority of the patients. This study aimed to assess whether GAD-alum preserved β-cell function in those recent-onset T1D patients who completed their 30 months visit in the European Phase III trial, and to characterize their GAD65-induced cytokine secretion and proliferation. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and after 1, 3, 9, 15 and 21 months from the 148 Swedish subjects included in the Phase III GAD-alum trial, and also at 30 months from 45 patients who had reached the final visit before the trial was closed. Patients had been randomly assigned into three arms: 4 doses of GAD-alum (4D), 2 doses of GAD-alum followed by two doses of placebo (2D), or 4 doses of placebo. Cytokine secretion was detected in cell culture supernatants by Luminex, after 7 days of in vitro culture. Cell proliferation was determined by 3H thymidine incorporation assay. Fasting and stimulated C-peptide was analysed in serum.

    Patients treated with 2 doses of GAD-alum had less decline of both fasting (p=0.040) and stimulated C-peptide (p=0.012) after 30 months, and a larger proportion of these patients preserved >25% of their initial stimulated C-peptide AUC compared to placebo (p=0.012). Both 2D and 4D patients showed increased PBMC proliferation to GAD65 and a cytokine profile that tended to switch towards a more predominant Th2 associated profile over time.

    The results support the concept of GAD-alum treatment, but no specific immune markers have been identified.

  • 25.
    Axelsson, Stina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Faresjö, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Hedman, Maria
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Cryopreserved peripheral blood mononuclear cells are suitable for the assessment of immunological markers in type 1 diabetic children2008In: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 57, no 3, p. 201-208Article in journal (Refereed)
    Abstract [en]

    Cryopreserved peripheral blood mononuclear cells (PBMC) are commonly used when assessing immune responses in clinical trials, both for practical reasons and to minimize interassay variation, as samples are often collected and studied over time. This study investigated the effect of cryopreservation on cytokine and chemokine secretion, and on expression of regulatory T-cell associated markers, in samples from children with type 1 diabetes. PBMC were cultured before and after cryopreservation either with GAD(65) or PHA. Secretion of cytokines (IL-5, -6, -10, -12, -13 -17, IFN-gamma and TNF-alpha) and chemokines (IP-10, MCP-1, MIP-1 alpha, MIP-1 beta and RANTES) was analysed in cell supernatants using multiplex fluorochrome technique (Luminex). Expression of FOXP3 and TGF-beta mRNA was detected by multiplex real-time RT-PCR. Increased spontaneous secretion of IL-6, -10, -12, -13, IFN-gamma and MCP-1, and mRNA expression of FOXP3 and TGF-beta, was detected after cryopreservation. Stimulation with GAD65 induced higher levels of IL-6, IFN-gamma, TNF-alpha and MIP-1 alpha, whereas lower secretion was found for IL-10 and IL-13 in cryopreserved PBMC. Stimulation with PHA induced lower secretion of IP-10, MCPA and RANTES and FOXP3 mRNA expression after cryopreservation. Thus, cryopreserved PBMC were suitable to assess the immunological markers included in this study, even though their expression could differ from freshly handled cells.

  • 26.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Akerman, L
    Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    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.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Treatment with alum-formulated GAD65 in type 1 diabetic children results in early induction of Th2 responses2009In: in DIABETOLOGIA, vol 52, 2009, Vol. 52, p. S193-S193Conference paper (Refereed)
    Abstract [en]

    n/a

  • 27.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    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.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 10, p. 1272-1278Article in journal (Refereed)
    Abstract [en]

    Aim  The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. Methods  Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results  Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion  Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  • 28.
    Axelsson, Stina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65)2010In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 26, no 7, p. 559-568Article in journal (Refereed)
    Abstract [en]

    Background We have previously shown that two injections of 20 mu g alum-formulated glutamic acid decarboxylase 65 (GAD(65)) (GAD-alum; Diamyd (R)) in children with recent-onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months follow-up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow-ups, to investigate whether the immunomodulatory effect of GAD-alum was apparent earlier after treatment, preceding the changes previously reported at 15 months.<p>Methods Peripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD-alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD(65), tyrosine phosphatase-like protein IA-2 peptide, insulin peptide, GAD-alum, alum formulation or phytohaemagglutinin. Interleukin (IL)-5, -6, -10, -12, -13, -17, tumour necrosis factor and interferon-gamma were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor-beta was determined by real-time reverse transcription polymerase chain reaction.</p><p>Results Already 1 month after the first injection, GAD(65)-induced IL-5 and IL-13 together with FOXP3 were enhanced in GAD-alum-treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T-helper 2-associated cytokines IL-5 and IL-13 together with FOXP3 increased continuously over time.</p><p>Conclusions Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months. Copyright (C) 2010 John Wiley &amp; Sons, Ltd.</p>

  • 29.
    Bang, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Ahmed, S. Faisal
    University of Glasgow, Scotland .
    Argente, Jesus
    Hospital Infantil University of Nino Jesus, Spain University of Autonoma Madrid, Spain Institute Salud Carlos III, Spain .
    Backeljauw, Philippe
    University of Cincinnati, USA .
    Bettendorf, Markus
    University Hospital Children and Adolescents, Germany .
    Bona, Gianni
    University of Piemonte Orientale Amedeo Avogadro, Italy .
    Coutant, Regis
    Angers University Hospital, France .
    Rosenfeld, Ron G.
    Oregon Health and Science University, USA .
    Walenkamp, Marie-Jose
    Vrije University of Amsterdam, Netherlands .
    Savage, Martin O.
    Barts and London Queen Marys School Medical and Dent, England .
    Identification and management of poor response to growth-promoting therapy in children with short stature2012In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 2, p. 169-181Article, review/survey (Refereed)
    Abstract [en]

    Growth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin-like growth factor-1 (rhIGF-1) therapy is approved for severe primary IGF-I deficiency a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth-promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF-1 therapy so that a diagnosis-based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first-year management with GH and IGF-1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth-promoting therapy will lead to better patient care, greater cost-effectiveness and increased opportunities for clinical benefit.

  • 30.
    Bengt Kallen, A. J.
    et al.
    Lund University.
    Finnström, Orvar
    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.
    Lindam, Anna P.
    National Board for Health and Welfare, Stockholm.
    Nilsson, Emma M. E.
    National Board for Health and Welfare, Stockholm.
    Nygren, Karl-Gosta
    IVF and Fertility Clinic, Stockholm.
    Otterblad Olausson, Petra M.
    National Board for Health and Welfare, Stockholm.
    Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?2010In: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 14, no 6, p. 526-530Article in journal (Refereed)
    Abstract [en]

    Background: Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. Aims: To follow up children conceived by IVF with respect to risk for CP. Methods: Infants born after IVF were identified from all IVF clinics in Sweden 1982-2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. Results: The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52-2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004-2007) when the twinning rate after IVF was less than10%, the odds ratio for CP was 0.97 (95% CI 0.57-1.66). Conclusions: The moderately increased risk for CP was most likely a consequence of an increased risk of neonatal morbidity, notably associated with multiple births.

  • 31.
    Berg, Göran
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Special Issue: Marcus Wallenberg International Symposium in Comparative Reproductive Immunology, "Immunology at the fetal maternal interface: Basic science and clinical applications", July 7-8th, 2011, Linkoping University, Sweden2011In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 66, no Issue supplement 1, p. 1-1Article in journal (Other academic)
  • 32.
    Besser, Rachel E J
    et al.
    University of Exeter.
    Ludvigsson, Johnny
    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.
    Jones, Angus G
    University of Exeter.
    McDonald, Timothy J
    University of Exeter.
    Shields, Beverley M
    University of Exeter.
    Knight, Bridget A
    University of Exeter.
    Hattersley, Andrew T
    University of Exeter.
    Urine C-Peptide Creatinine Ratio Is a Noninvasive Alternative to the Mixed-Meal Tolerance Test in Children and Adults With Type 1 Diabetes2011In: DIABETES CARE, ISSN 0149-5992, Vol. 34, no 3, p. 607-609Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Stimulated serum C-peptide (sCP) during a mixed-meal tolerance test (MMTT) is the gold standard measure of endogenous insulin secretion, but practical issues limit its use. We assessed urine C-peptide creatinine ratio (UCPCR) as an alternative. RESEARCH DESIGN AND METHODS-Seventy-two type 1 diabetic patients (age of diagnosis median 14 years [interquartile range 10-22]; diabetes duration 6.5[2.3-32.7]) had an MMTT. sCP was collected at 90 min. Urine for UCPCR was collected at 120 min and following a home evening meal. RESULTS-MMTT 120-min UCPCR was highly correlated to 90-min sCP (r = 0.97; P andlt; 0.0001). UCPCR andgt;= 0.53 nmol/mmol had 94% sensitivity/100% specificity for significant endogenous insulin secretion (90-min sCP andgt;= 0.2 nmol/L). The 120-min postprandial evening meal UCPCR was highly correlated to 90-min sCP (r = 0.91; P andlt; 0.0001). UCPCR andgt;= 0.37 nmol/mmol had 84% sensitivity/97% specificity for sCP andgt;= 0.2 nmol/L. CONCLUSIONS-UCPCR testing is a sensitive and specific method for detecting insulin secretion. UCPCR may be a practical alternative to serum C-peptide testing, avoiding the need for inpatient investigation.

  • 33.
    Besser, Rachel E J
    et al.
    University of Exeter, England .
    Shields, Beverley M
    University of Exeter, England .
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hattersley, Andrew T.
    University of Exeter, England .
    Ludvigsson, Johnny
    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.
    Lessons From the Mixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-minMMTT-stimulated CP andgt;= 0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP andgt;= 0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged, 18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP andgt;= 0.2 nmol/L and FCP andgt;= 0.1 nmol/L to detect peak CP andgt;= 0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration. less thanbrgreater than less thanbrgreater thanRESULTS-AUC CP was highly correlated to 90CP (r(s) = 0.96; P andlt; 0.0001) and strongly correlated to FCP (r(s) = 0.84; P andlt; 0.0001). AUC CP andgt;= 23 nmol/L/150 min was the equivalent cutoff for peak CP andgt;= 0.2 nmol/L (98% sensitivity/97% specificity). A 90CP andgt;= 0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP andgt;= 0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase). less thanbrgreater than less thanbrgreater thanCONCLUSIONS-90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT. Diabetes Care 36:195-201, 2013

  • 34.
    Beyer, K.
    et al.
    Division of Pediatric Allergy and Immunology, Mount Sinai Medical Center, New York, NY, United States, Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States, Department of Pediatrics, Humboldt University, Berlin, Germany.
    Nickel, R.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States, Department of Pediatrics, Humboldt University, Berlin, Germany.
    Freidhoff, L.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Huang, S.-K.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Barnes, K.C.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    MacDonald, S.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Forster, J.
    Department of Pediatrics, University Hospitals, Freiburg, Germany.
    Zepp, F.
    Department of Pediatrics, University Hospitals, Mainz, Germany.
    Wahn, V.
    Department of Pediatrics, University Hospitals, Düsseldorf, Germany.
    Beaty, T.H.
    Department of Epidemiology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, United States.
    Marsh, D.G.
    Division of Pediatric Allergy and Immunology, Mount Sinai Medical Center, New York, NY, United States, Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Wahn, U.
    Department of Pediatrics, Humboldt University, Berlin, Germany.
    Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers2000In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 115, no 5, p. 906-908Article in journal (Refereed)
    Abstract [en]

    Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS '90), parental DNA was tested in 77 of 192 children with atopic dermatitis, (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.

  • 35.
    Bhai Mehta, Ratnesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mirrasekhian, E
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Svensson, J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Freland, Sofia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Sharma, S
    Brown University.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Trophoblast cells in immune regulation: modulation of macrophage polarization and production of IL-35 in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 165-1652011In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 165-165Conference paper (Refereed)
    Abstract [en]

    n/a

  • 36.
    Birberg Thornberg, Ulrika
    et al.
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry.
    Silfverdal, Sven-Arne
    Division of Paediatrics, Department of Clinical Sciences, Umeå University.
    Duchén, Karel
    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.
    A Placebo controlled, randomized study of PUFA (Poly Unsaturated Fatty Acids) as treatment for neurodevelopmental problems in 7-year-old children and cognitive performance in relation to an age-matched control groupManuscript (preprint) (Other academic)
    Abstract [en]

    OBJECTIVE: The goal of the present randomized placebo controlled double-blind study was to investigate the potential effect of PUFA supplementation on cognitive and behavioural performance in children with neurodevelopmental problems at 7 years of age (n = 28) and to compare findings with an age matched healthy control group (n = 20).

    METHODS: Children were screened with parent and teacher rating scales (Conner’s and SNAP-IV), and were included if they showed a range of neurodevelopmental problems that reached ADHD criteria. The group with neurodevelopmental difficulties was randomized to treatment with an EPA rich formula (n = 13) or to placebo (n = 15). Cognitive performance was determined at baseline and after 15 weeks of supplementation with a cognitive test battery including executive function and theory of mind tasks.

    RESULTS: Children with neurodevelopmental problems differed from the control group regarding working memory, inhibition and language ability, but not on an advanced theory of mind task. Regarding the treatment with EPA supplement there were no significant advantages in the active treatment group compared to placebo in any of the cognitive measures or in parents or teacher rating scales.

    CONCLUSION: The significant differences in cognitive performance and rating scales between the group with neurodevelopmental problems and the healthy control group at baseline indicate problems at a clinical level and suitability for treatment. However we found no significant effects of PUFA supplementation. The study is small and limited by a number of drop-outs.

  • 37.
    Birberg Thornberg, Ulrika
    et al.
    Linköping University, Department of Behavioural Sciences. Linköping University, Faculty of Arts and Sciences.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Gustafsson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry.
    Duchén, Karel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nutrition and theory of mind: The role of polyunsaturated fatty acids (PUFA) in the development of theory of mind2006In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 75, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    Breast-milk provides nutrients required for the development of the brain. n-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been suggested to be particularly involved. In this study levels of fatty acids in breast-milk were examined in relation to theory of mind (ToM) (n=13) and WISC-III (n=22) in six-year-old children. ToM tasks comprised four illustrated stories with questions about emotional (sad) events. Single polyunsaturated fatty acids (PUFA) were estimated as well as ratios between different fatty acids in order to describe putative associations between PUFA and psychological measures. Results show correlations between both ToM and WISC-III with single n-6 PUFA and the ratios DHA/AA and DHA/DPA. The correlations remained when socio-demographic factors were statistically controlled for. The positive findings related to the n-6 and n-3 LCPUFAs corroborate previous findings related to child cognitive development. © 2006 Elsevier Ltd. All rights reserved.

  • 38.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The intrauterine and postnatal environments1999In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 104, no 6, p. 1119-1127Article, review/survey (Refereed)
    Abstract [en]

    Pregnancy is associated with a strong skewing toward T(H)2 cytokine pattern, which enables the survival of the fetus, including fetal allergen-specific immune responses, The postnatal maturation of the immune system which is characterized by the development of a balanced T(H)1/T(H)2 immunity is genetically determined and modified by the environment. The process seems to proceed at a slower rate in atopic than in nonatopic infants. There is a close immunologic interaction between the mother and her offspring through the breast milk. Individual variations in the composition of human milk may el,plain the controversy with regard to the possible allergy-preventive effects of breast-feeding. Recurrent respiratory infections have been suggested to enhance immune deviation. The microbial flora are a more likely source, however, because they are a major driving force in the maturation of the immune system. Changes in its composition, as a consequence of an altered lifestyle and diet, may play a role in the higher prevalence of allergy. So far, primary prevention of allergy has failed. Future studies should therefore focus on factors enhancing immune deviation (ie, "success" factors) rather than on "risk" factors. The intestinal microflora is one of these factors that deserves closer analysis.

  • 39.
    Björkstén, Bengt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Sepp, E
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Julge, K
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Voor, T
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Mikelsaar, M
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Allergy development and the intestinal microflora during the first year of life2001In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 108, no 4, p. 516-520Article in journal (Refereed)
    Abstract [en]

    Background: The intestinal microflora is a likely source for the induction of immune deviation in infancy. Objective: The purpose of this study was to prospectively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases. Methods: Newborn infants were followed prospectively through the first 2 years of life in Estonia (n = 24) and Sweden (n = 20). By that age, 9 Estonian and 9 Swedish infants had developed atopic dermatitis and/or positive skin prick test results. Stool samples were obtained at 5 to 6 days and at 1, 3, 6, and 12 months, and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of standard methods. Results: In comparison with healthy infants, babies who developed allergy were less often colonized with enterococci during the first month of life (72 % vs 96 %, P < .05) and with bifidobacteria during the first year of life (17 % to 39 % vs 42 % to 69 %, P < .05). Furthermore, allergic infants had higher counts of clostridia at 3 months (median value, 10.3 vs 7.2 log(10), P < .05). The prevalence of colonization with Staphylococcus aureus was also higher at 6 months (61 % vs 23 %, P < .05), whereas the counts of Bacteroides were lower at 12 months (9.9 vs 10.6 log(10), P < .05). Conclusion: Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy. Because the observations were made in 2 countries with different standards of living, we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy.

  • 40.
    Bladh, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Finnström, Orvar
    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.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hospitalization in Adolescence and Young Adulthood Among Twins and Singletons: A Swedish Cohort Study of Subjects Born Between 1973 and 19832013In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 16, no 3, p. 707-715Article in journal (Refereed)
    Abstract [en]

    Children born with non-optimal birth characteristics — that is, are small for gestational age and/or preterm — have an increased risk for several long-term effects such as neurological sequelae and chronic disease. The purpose of this study was to examine whether twins exhibited a different outcome, compared with singletons, in terms of hospitalization during adolescence and early adulthood, and to what extent differences remain when considering the divergence in birth characteristics between singletons and twins. Persons born between 1973 and 1983 in Sweden and surviving until age 13 were included and followed until the end of 2006. Data on birth characteristics, parental socio-demographic factors, and hospitalizations were collected from national registers. Adjusting for parental socio-demographic factors, twins had a higher risk of being hospitalized than singletons (odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10–1.25) and more often due to ‘Congenital anomalies’ (OR = 1.18, 95% CI = 1.06–1.28), ‘Infections’ (OR = 1.14; 95% CI = 1.08–1.20), ‘External causes of illness’ (OR = 1.10, 95% CI = 1.06–1.15), and ‘Diseases of the nervous system’ (OR = 1.18, 95% CI = 1.10–1.26). Stratifying for birth characteristics, this difference diminishes, and for some diagnoses non-optimal twins seem to do slightly better than non-optimal singletons. Thus, twins with non-optimal birth characteristics had a lower risk of hospitalization than non-optimal singletons on, for example, ‘Congenital anomalies’ and ‘Diseases of the nervous system’ (OR = 0.86, 95% CI = 0.77–0.96; OR = 0.88, 95% CI = 0.81–0.97, respectively) and Total (any) hospitalization (OR = 0.87, 95% CI = 0.83–0.92). Among those with optimal birth characteristics, twins had an increased hospitalization due to ‘External causes of illness’ (OR = 1.07, 95% CI = 1.02–1.13) compared with optimal singletons. Twins have higher hospitalization rates than singletons. In stratifying for birth characteristics, this difference diminishes, and for some diagnoses, non-optimal twins seem to do less poorly than non-optimal singletons.

  • 41.
    Bladh, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    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.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Reproductive patterns among twins: a Swedish register study of men and women born 1973-19832013In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 13Article in journal (Refereed)
    Abstract [en]

    Background

    During the last decades there has been a steady increase of twin births. A combination of improved medical treatment of preterm and small-for-gestational age children has contributed to a higher number of surviving twins. Prematurity is known to affect reproduction in a negative way. Few studies have focused on the potential effect twinning may have on future reproduction. Thus, the aim of this study was to investigate the effect of being born a twin compared to being born a singleton have on future reproduction.

    Methods

    In a national population-based register study, all individuals born between 1973–1983 who were alive and living in Sweden at 13 years of age (n = 1 016 908) constituted the sample. Data on each study subject’s own birth as well as the birth of their first offspring, and parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios and corresponding 95% CI was calculated using Cox proportional hazards model.

    Results

    Twins, both men and women, had a reduced likelihood of reproducing compared to singletons (women: HR = 0.89, 95% CI = 0.86-0.93; men: HR = 0.92, 95% CI = 0.87-0.97). This difference in birth rates can only partly be explained by diverging birth characteristics. Amongst men and women born very preterm, twins had an increased likelihood of reproducing compared to singletons (women: HR = 1.25, 95% CI = 1.02-1.62; men: HR = 1.34, 95% CI = 1.01-1.78).

    Conclusions

    Twins have lower reproduction rates compared to singletons, which only to a certain degree can be explained by diverging birth characteristics.

  • 42.
    Blennow, M
    et al.
    Karolinska Institute.
    Ewald, U
    Uppsala University.
    Fritz, T
    Sahlgrens University Hospital.
    Fellman, V
    Lund University.
    Hellstrorm-Westas, L
    Uppsala University.
    Holmgren, P A
    Norrland University.
    Holmstrom, G
    Uppsala University.
    Jeppsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Kallen, K
    Lund University.
    Lagercrantz, H
    Karolinska Institute.
    Laurini, R
    Bodo Central Hospital.
    Lindberg, E
    University of Örebro.
    Lundqvist, A
    Lund University.
    Marsal, K
    Lund University.
    Nilstun, T
    Lund University.
    Norden-Lindeberg, S
    Uppsala University.
    Norman, M
    Karolinska Institute.
    Olhager, Elisabeth
    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.
    Otterblad Olausson, P
    Natl Board Hlth & Welf, Epidemiol Centre, Stockholm.
    Ostlund, I
    University of Örebro.
    Serenius, F
    Norrland University.
    Simic, M
    Karolinska University Hospital.
    Sjors, G
    Uppsala University.
    Stigsson, L
    Sahlgrens University Hospital.
    Stjernqvist, K
    Lund University.
    Stromberg, B
    Uppsala University.
    Wennergren, M
    Sahlgrens University Hospital.
    Westgren, M
    Karolinska University Hospital.
    HIGH ONE-YEAR SURVIVAL AFTER ACTIVE PERINATAL CARE: EXTREMELY PRETERM INFANTS IN SWEDEN (EXPRESS)2009In: in ACTA PAEDIATRICA, vol 98, 2009, Vol. 98, p. 8-8Conference paper (Refereed)
    Abstract [en]

    n/a

  • 43.
    Blennow, Mats
    et al.
    Karolinska University Hospital.
    Ewald, Uwe
    Uppsala University.
    Fritz, Tomas
    Sahlgrens University Hospital.
    Ake Holmgren, Per
    Umeå University.
    Jeppsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Lindberg, Eva
    University of Örebro.
    Lundqvist, Anita
    Lund University.
    Norden Lindeberg, Solveig
    Uppsala University.
    Olhager, Elisabeth
    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.
    Ostlund, Ingrid
    Örebro University Hospital.
    Simic, Marija
    Karolinska University Hospital.
    Sjoers, Gunnar
    Uppsala University.
    Stigson, Lennart
    Sahlgrens University Hospital.
    Fellman, Vineta
    Lund University.
    Hellstrom-Westas, Lena
    Uppsala University.
    Norman, Mikael
    Karolinska University Hospital.
    Westgren, Magnus
    Karolinska University Hospital.
    Holmstrom, Gerd
    Uppsala University.
    Laurini, Ricardo
    Nordland Hospital.
    Stjernqvist, Karin
    Lund University.
    Kallen, Karin
    Lund University.
    Lagercrantz, Hugo
    Karolinska Institute.
    Marsal, Karel
    Lund University.
    Serenius, Fredrik
    Umeå University.
    Wennergren, Margareta
    Sahlgrens University Hospital.
    Nilstun, Tore
    Lund University.
    Otterblad Olausson, Petra
    National Board of Health & Welfare.
    Stromberg, Bo
    Uppsala University.
    One-Year Survival of Extremely Preterm Infants After Active Perinatal Care in Sweden2009In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, ISSN 0098-7484, Vol. 301, no 21, p. 2225-2233Article in journal (Refereed)
    Abstract [en]

    Context Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling. Objective To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007. Design, Setting, and Patients Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007. Main Outcome Measures Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade andgt; 2, retinopathy of prematurity stage andgt; 2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival. Results The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% ( 95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% ( 95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [ OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth ( OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity. Conclusion During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.

  • 44.
    Boij, R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nilsson-Ekdahl, K
    Uppsala University.
    Svensson, J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandholm, K
    Linneus University.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Palonek, E
    Karolinska University.
    Jarle, M
    Karolinska University.
    Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-1092012In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, no 1, p. 109-109Conference paper (Refereed)
    Abstract [en]

    n/a

  • 45.
    Boij, Roland
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Nilsson-Ekdahl, Kristina
    Uppsala University, Sweden Linneaus University, Sweden .
    Sandholm, Kerstin
    Linneaus University, Sweden .
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Palonek, Elzbieta
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Garle, Mats
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia2012In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, no 3, p. 258-270Article in journal (Refereed)
    Abstract [en]

    Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

  • 46.
    Borres, Magnus P.
    et al.
    Department of Pediatrics, Sahlgrenska Academy of Göteborg University, Göteborg, Sweden/Phadia AB, Uppsala, Sweden.
    Irander, Kristina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    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 in Linköping.
    Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life1997In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 52, no 7, p. 770-774Article in journal (Refereed)
    Abstract [en]

    The relationship between the appearance of nasal metachromatic cells (basophils and mast cells) during the first 18 months of life and the development of respiratory and other allergic diseases up to 6 years of age was studied prospectively in 67 children. Follow-up was done at 3, 6, 9, and 18 months and 6 years. Of the 31 children who had detectable metachromatic cells in the nasal mucosa during infancy, 18 had atopic manifestations at 6 years (58%), two were probably atopic (6%), and 11 (36%) were nonatopic. The corresponding numbers for the 33 children without detectable metachromatic cells during infancy were 10 atopic (30%), two probably atopic (6%), and 21 nonatopic (64%) at 6 years (P<0.05). Children having detectable nasal metachromatic cells at every examination were more often allergic than children with no detectable cells at any time during the 6-year follow-up period (P<0.05). In contrast, nasal metachromatic cells were equally commonly demonstrated at 6 years in children with and without current atopic manifestations. We conclude that metachromatic cells appear at an earlier age in the nasal mucosa of atopic than nonatopic infants. The observation further supports the existence of a primary immunologic abnormality in atopic patients as related to allergic inflammatory responses. The diagnostic efficacy of this marker was too low, however, to be clinically useful as a predictor of allergy.

  • 47.
    Borssén, Magnus
    et al.
    Umeå University, Sweden.
    Palmqvist, Lars
    Sahlgrenska University Hospital, University of Gothenburg, Sweden.
    Karrman, Kristina
    Skåne University Hospital, Lund University, Sweden.
    Abrahamsson, Jonas
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Behrendtz, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Heldrup, Jesper
    Skåne University Hospital, Sweden.
    Forestier, Erik
    Umeå University, Sweden .
    Roos, Göran
    Umeå University, Sweden.
    Degerman, Sofie
    Umeå University, Sweden.
    Promoter DNA Methylation Pattern Identifies Prognostic Subgroups in Childhood T-Cell Acute Lymphoblastic Leukemia2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6Article in journal (Refereed)
    Abstract [en]

    Background

    Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided.

    Design and Methods

    Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32).

    Results

    Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP− (low methylation). CIMP− T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes.

    Conclusions

    We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

  • 48.
    Braback, Lennart
    et al.
    Sundsvall Hospital.
    Vogt, Hartmut
    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.
    Hjern, A.
    National Board for Health and Welfare, Stockholm.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 49.
    Brekke, Hilde K
    et al.
    University of Gothenburg.
    Ludvigsson, Johnny
    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.
    Daily vegetable intake during pregnancy negatively associated to islet autoimmunity in the offspring-The ABIS study2010In: PEDIATRIC DIABETES, ISSN 1399-543X, Vol. 11, no 4, p. 244-250Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate if maternal diet during pregnancy is associated with occurrence of islet autoimmunity (IA) in the offspring. Methods: Of 21 700 infants invited to the All Babies in South-east Sweden (ABIS) study, 16 004 screening questionnaires, including a 22-item food frequency questionnaire (FFQ) regarding the mothers diet during pregnancy, were completed after delivery. Follow-up of the children (questionnaires and blood sampling) was performed at 1, 2.5 and 5 yr of age. IA was defined as being positive (above the 95th percentile for healthy children) in two or more measurements of autoantibodies [glutamic acid decarboxylase (GADA); tyrosine phosphatase (IA-2A), insulin autoantibodies (IAA)] analysed at the three time points or being diagnosed with type 1 diabetes during the 5-yr follow-up period. The 5 724 children in whom we carried out two to three possible blood samplings were included in the study. Logistic regression analysis was used to identify variables predicting IA. Results: Of 5 724 children,191 (3.3%) were considered positive for IA. In a univariate analysis, less than daily consumption of vegetables (3-5 times/week) in the mothers diet was associated with increased risk of IA (OR 1.71, 95% CI:1.24-2.35, p = 0.001) compared to daily consumption (p for trend = 0.004). The association was strengthened when adjusting for known IA-risk factors (p for trend andlt; 0.001). Conclusions: Daily consumption of vegetables in the mothers diet during pregnancy was associated with a decreased risk of IA in the offspring.

  • 50.
    Brodszki, N B
    et al.
    Lund University Hospital.
    Matsols, H
    Falu Lasarett.
    Fasth, A
    Drottning Silvias Barnoch Ungdomssjukhus.
    Friman, V
    Sahlgrens University Hospital.
    Lofdahl, K
    Sahlgrens University Hospital.
    Oskarsdottir, S
    Drottning Silvias Barnoch Ungdomssjukhus.
    Marthinsen, L
    Lanssjukhuset, Halmstad.
    Olinder-Nielsen, A M
    Lanssjukhuset Ryhov.
    Wagstrom, P
    Lanssjukhuset Ryhov.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Jonsson, G
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Aurivillius, M
    University Sjukhuset, Malmö.
    Lanbeck, P
    University Sjukhuset, Malmö.
    Granert, C
    Karolinska University Sjukhuset.
    Gustafson, R
    Karolinska University Sjukhuset.
    Hammarstrom, L
    Karolinska University Sjukhuset.
    Ahlin, A
    Sachsska Barnsjukhuset.
    West, C
    Norrlands University Sjukhus.
    Gunther, G
    Uppsala University.
    Pauksen, K
    Uppsala University.
    Arneborn, P
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Björkqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bjorkander, J
    Lanssjukhuset Ryhov.
    Swedish guidelines for the assessment, diagnosis and management of 6 primary immunodeficiency states: CVID, IgG subclass deficiency, IgA deficiency, XLA, SCID and CGD2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 140-141Conference paper (Refereed)
1234567 1 - 50 of 495
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format