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  • 551.
    Vogt, Hartmut
    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.
    Lindstrom, Karolina
    Karolinska Institute.
    Braback, Lennart
    Sundsvall Hospital.
    Hjern, Anders
    Stockholm University.
    Preterm Birth and Inhaled Corticosteroid Use in 6- to 19-Year-Olds: A Swedish National Cohort Study2011In: PEDIATRICS, ISSN 0031-4005, Vol. 127, no 6, p. 1052-1059Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth.

    METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators.

    RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age.

    CONCLUSION: Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth.

  • 552.
    Voor, Tina
    et al.
    Childrens clinic of Tartu Estonia.
    Julge, Kaja
    Childrens clinic of Tartu, Estonia .
    Fagerås Böttcher, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Duchén, Karel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Björksténs, Bengt
    Institutionen för Miljömedicin KI, Stockholm.
    Atopic sensitization and atopic dermatitis in Estonian and Swedish infants2005In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 35, no 2, p. 153-159Article in journal (Refereed)
    Abstract [en]

    Background: Early life events seem to have a major impact on the development of tolerance or sensitization. Objective: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. Methods: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. Results: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%, P = 0.06 and 13% vs. 24%, P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%, P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1 - 2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. Conclusions: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor. © 2005 Blackwell Publishing Ltd.

  • 553.
    Wadsby, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nelson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ingemansson, Fredrik
    Ryhov County Hospital, Sweden.
    Samuelsson, Stefan
    Linköping University, Department of Behavioural Sciences and Learning, Education, Teaching and Learning. Linköping University, Faculty of Educational Sciences.
    Leijon, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Behaviour problems and cortisol levels in very-low-birth-weight children2014In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 68, no 8, p. 626-632Article in journal (Refereed)
    Abstract [en]

    Background. There are still diverging results concerning the behaviour of children with very-low-birth-weight (VLBW) and they have been questioned to display different levels of stress hormone than normal-birth-weight (NBW) children. Aims. This study examined behaviour and the stress hormone cortisol in children with VLBW at the ages of 7 and 9 years compared with children with NBW. Results. Fifty-one VLBW and 50 NBW children were studied with the Child Behavior Checklist. Cortisol rhythm was measured through saliva samples three times a day for 2 days. VLBW children displayed more behavioural problems than NBW children, specifically social and attention problems, although still within normal ranges. They showed lower cortisol levels both at 7 and 9 years of age. No strong association between behaviour and cortisol levels was shown. Conclusion. VLBW children display more behaviour problems compared with NBW children but both groups score are within the normal range. Down-regulation of their hypothalamic-pituitary-adrenal (HPA) function in terms of lower cortisol levels is also noted.

  • 554. Wahlberg, J.
    et al.
    Fredriksson, J.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    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.
    Vaccinations may induce diabetes-related autoantibodies in one-year-old children2003In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1005, p. 404-408Conference paper (Other academic)
    Abstract [en]

    Vaccinations have been discussed as one among many environmental candidates contributing to the immune process that later may lead to type 1 diabetes. ABIS (All Babies in Southeast Sweden) is a prospective cohort study following a nonselected birth cohort of general population. In a randomly selected sample collection from 4400 children, GADA and IA-2A have been determined at the age of 1 year. The information on vaccinations was collected from questionnaires answered by the parents and was related to ß cell autoantibodies. When studying the induction of autoantibodies using the autoantibody level of 90th percentile as cutoff level, hemophdus influenza B (HIB) vaccination appeared to be a risk factor for IA-2A [OR 5.9 (CI 1.4-24.4, p = 0.01)] and for GADA [OR 3.4 (CI 1.1-10.8, p = 0.04)] in logistic regression analyses. Furthermore, the titers of IA-2A were significantly higher (p < 0.01 in Mann-Whitney test) in those children who had got HIB vaccination. When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes, BCG vaccination was associated with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A. This might be of importance under circumstances when the ß cell-related immune response is activated by other mechanisms.

  • 555. Wahlberg, J
    et al.
    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.
    Diabetes related autoantibodies in cord blood from children of healthy mothers have disappeared when the child is one-year old.2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, p. 115-Conference paper (Other academic)
  • 556. Wahlberg, JM
    et al.
    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.
    Infections during pregnancy and neonatal period influence diabetes related autoantibody levels in one-year old children2002In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, p. 139-Conference paper (Other academic)
  • 557.
    Walldén (Fredriksson), Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ilonen, Jorma
    University of Kuopio.
    Roivainen, Merja
    National Public Health Institute, Helsinki, Finland .
    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.
    Vaarala, Outi
    National Public Health Institute, Helsinki, Finland .
    Effect of HLA genotype or CTLA-4 polymorphism on cytokine response in healthy children2008In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 68, no 3, p. 345-350Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is considered to be a T-cell-mediated autoimmune disease in which genetic predisposition is affected by HLA class II alleles and polymorphisms in cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene. We tested the hypothesis whether these T1D-related gene polymorphisms modulate cytokine response and thus contribute to the development of autoimmunity. The study includes 67 non-diabetic children, typed for HLA class II alleles and CTLA-4 polymorphisms (+49A/G, CT60A/G, CTBC217_1C/T). We measured cytokine secretion of peripheral blood mononuclear cells after stimulation with tetanus toxoid (TT), polio virus, coxsackie virus B4, pertussis toxin (PT) and phytohemagglutinin (PHA). We saw higher IL-13 response to TT in individuals with DR3–DQ2 haplotype (P = 0.002). HLA class II protective haplotype, DR2–DQ6, showed association with increased production of IFN-γ (P < 0.001) and IL-2 (P = 0.005) in response to polio virus. In children with the autoimmunity-related homozygous genotypes CTLA-4 +49G/G, CT60G/G and CTBC217_1T/T, we found enhanced PT- and PHA-induced IFN-γ production (P < 0.05). The cytokine responses to studied antigens were weakly modified by HLA class II risk haplotypes, and children with T1D-associated HLA risk haplotypes are not specifically inclined to develop an immune response in general. Higher IFN-γ and IL-2 response to enterovirus in children with HLA class II protective haplotype DR2-DQ6 could be of importance in the protection from T1D-associated enterovirus infections. All autoimmunity related CTLA-4 polymorphisms were associated with enhanced IFN-γ. This suggests impaired downregulation of cellular immunity by these CTLA-4 polymorphisms.

  • 558.
    Wang, Kai
    et al.
    University of Tennessee, Knoxville, USA.
    Phillips, Charles A
    University of Tennessee, Knoxville, USA.
    Rogers, Gary L
    National Institute for Computational Sciences, Oak Ridge, Tennessee, USA.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Langston, Michael A
    University of Tennessee, Knoxville, USA.
    Differential Shannon entropy and differential coefficient of variation: alternatives and augmentations to differential expression in the search for disease-related genes2014In: International journal of computational biology and drug design, ISSN 1756-0756, Vol. 7, no 2-3, p. 183-94Article in journal (Refereed)
    Abstract [en]

    Differential expression has been a standard tool for analysing case-control transcriptomic data since the advent of microarray technology. It has proved invaluable in characterising the molecular mechanisms of disease. Nevertheless, the expression profile of a gene across samples can be perturbed in ways that leave the expression level unaltered, while a biological effect is nonetheless present. This paper describes and analyses differential Shannon entropy and differential coefficient of variation, two alternate techniques for identifying genes of interest. Ontological analysis across 16 human disease datasets demonstrates that these alternatives are effective at identifying disease-related genes not found by mere differential expression alone. Because the two alternate techniques are based on somewhat different mathematical formulations, they tend to produce somewhat different gene lists. Moreover, each may pinpoint genes completely overlooked by the other. Thus, measures of entropy and variation can be used to replace or better yet augment standard differential expression computations.

  • 559.
    Warstedt, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    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.
    Increased linoleic acid/alpha-linolenic acid ratio in Swedish cord blood samples collected between 1985 and 20052013In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 52, no 2, p. 659-665Article in journal (Refereed)
    Abstract [en]

    Cord serum (CS) phospholipid fatty acid composition is associated with maternal diet during foetal life, and maternal intake of linoleic acid (LA, C18:2 omega-6) and alpha-linolenic acid (LNA, C18:3 omega-3) has been shown to influence the LA and LNA levels in CS. A possible connection between the increased incidence of atopic diseases and increased intake of LA and decreased intake of LNA in the Western world has been proposed. less thanbrgreater than less thanbrgreater thanThe aim of this study was to explore phospholipid fatty acid proportions and total IgE levels in CS from Swedish children, collected from 1985 to 2005, a period with increasing frequency of allergic diseases in Sweden, and reveal possible changes over time. less thanbrgreater than less thanbrgreater thanPhospholipid fatty acids and total IgE antibodies were analysed with gas chromatography and UniCAP(A (R)) technology, respectively, in 300 CS samples. less thanbrgreater than less thanbrgreater thanThe proportions of LA and LNA decreased significantly from 1985 to 2005 (p andlt; 0.001 for both). However, the LA/LNA ratio did increase (p andlt; 0.001), revealing a relatively larger decrease in LNA than in LA. No correlations were found between omega-6 and omega-3 fatty acids and total IgE antibodies in CS from newborn children. less thanbrgreater than less thanbrgreater thanThe LA/LNA ratio increased (p andlt; 0.001) in cord serum samples collected between 1985 and 2005, and no correlations between fatty acids and total IgE were found.

  • 560.
    Warstedt, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Furuhjelm, Catrin
    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.
    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.
    Fälth-Magnusson, Karin
    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.
    Fagerås Böttcher, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    The Effects of Omega-3 Fatty Acid Supplementation in Pregnancy on Maternal Eicosanoid, Cytokine, and Chemokine Secretion2009In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 66, no 2, p. 212-217Article in journal (Refereed)
    Abstract [en]

    The incidence of allergic diseases has increased, and,I relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this Study was to determine the effects of omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFA) Supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E, secretion from whole blood culture supernatants (it = 59) decreased in a majority of the omega-3-supplemented mothers (18 of 28, p = 0.002). The decreased prostaglandin E-2, production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced cytokine and chemokine secretion was not affected. Out results indicate that omega-3 LCPUFA supplementation during the last trimester may dampen certain immune responses involved in allergic inflammation.

  • 561.
    Warstedt, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Furuhjelm, Catrin
    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.
    Kroes, Hilde
    Danone Research, Centre for Specialised Nutrition, 6700 CA Wageningen, The Netherlands.
    Vos, Arjan P.
    Danone Research, Centre for Specialised Nutrition, 6700 CA Wageningen, The Netherlands.
    Garssen, Johan
    Danone Research, Centre for Specialised Nutrition, 6700 CA Wageningen, The Netherlands.
    Fälth-Magnusson, Karin
    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.
    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.
    Fagerås Böttcher, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Omega-3 long chain polyunsaturated fatty acid supplementation in pregnancy and lactation and immune components in breast milkManuscript (preprint) (Other academic)
    Abstract [en]

    Human milk transfers important immunological information from mother to child. We have previously reported lower prevalence of IgE-mediated disease at 12 months after maternal supplementation with ω-3 long chain polyunsaturated fatty acid (LCPUFA) during pregnancy and lactation. Our aim was to explore the effect of ω-3 LCPUFA on the immune composition of human milk in relation to maternal atopy and allergic disease in the offspring. Pregnant women in families with a history of allergic disease were supplemented daily with 2.7 g ω-3 LCPUFA or 2.8 g soybean oil as placebo from late pregnancy to three months of lactation. Milk samples from colostrum (n=107), at 1 mo (n=102) and at 3 mo (n=95) were analyzed for IL-1ß, IL-2, IL-4, IL-5, IL-6, CXCL-8, IL-10, IL-12p40/p70, IL-13, GM-CSF, TNF, IFN-γ, PGE2, TSLP, TGF-ß2 and SIgA with multiplex assay or ELISA. The levels of several cytokines were higher in non-atopic ω-3 supplemented mothers as compared to placebo supplemented mothers regardless of atopic status. Higher levels of TGFß2 and SIgA in 3 months milk were associated with allergic disease at one year of age both with and without detectable IgE. These results suggest that ω-3 LCPUFA supplementation during pregnancy influences cytokine levels in breast milk especially in non-atopic mothers.

  • 562.
    Welander, Adina
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University Hospital, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Jonas F.
    Örebro University Hospital, Sweden .
    Breast-feeding Duration and Gluten Introduction Among Mothers With Celiac Disease2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 59, no 1, p. 89-92Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES::

    Both breastfeeding duration and age at gluten introduction have been implicated in the pathogenesis of celiac disease (CD). We hypothesized that parental CD affects the feeding pattern of the offspring, mediated by parental health awareness increasing adherence to infant feeding guidelines.

    METHODS::

    Prospectively collected infant feeding data were obtained through the All Babies in Southeast Sweden (ABIS) study. Information regarding infant feeding was available in 9,414 children. Twenty-two mothers had a history of biopsy-verified CD before delivery of a child in the study, 9,392 mothers had no diagnosis of CD prior to birth and thus constituted the unexposed or control population. Cox regression was used to compare the risk of early weaning and gluten introduction according to parental CD status, and logistic regression to assess if mothers with CD were more likely to breastfeed their children at gluten introduction.

    RESULTS::

    Some 63% of children were breastfeed for at least 9 months. We found no association between maternal CD and early weaning (adjusted hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7), nor between paternal CD and early weaning (HR 0.5; 95% CI, 0.1-1.9). Sixty percent of children were introduced to gluten in months 5-6. Maternal CD was not associated with age at gluten introduction (adjusted HR, 0.8; 95% CI, 0.6-1.3) There was no statistically significant association between maternal CD and breastfeeding at time of gluten introduction (OR, 1.4; 95% CI, 0.4-4.7).

    CONCLUSIONS::

    Feeding patterns do not seem to vary between offspring to mothers with CD and those without.

  • 563.
    Welander, Adina
    et al.
    Karolinska University Hospital, Sweden.
    Montgomery, Scott M.
    Karolinska University Hospital, Sweden; Örebro University Hospital, Sweden; University of Örebro, Sweden; UCL, England.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Karolinska University Hospital, Sweden; Örebro University Hospital, Sweden.
    Ludvigsson, Jonas F.
    Karolinska University Hospital, Sweden; Örebro University Hospital, Sweden.
    Infectious Disease at Gluten Introduction and Risk of Childhood Diabetes Mellitus2014In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, no 2, p. 326-U160Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate the risk of future diabetes mellitus type 1 (T1D) in children who suffered from infection at time of gluten introduction. Study design Population-based prospective study. Parents filled out a diary at home. We hereby obtained data on date of gluten introduction, breastfeeding duration, and infections in 9414 children born in the southeast of Sweden from October 1, 1997, through October 1, 1999 (the All Babies in Southeast Sweden cohort). The Cox proportional hazards model was used to investigate the risk of future T1D until February 1, 2012, among children with infection at time of gluten introduction. Results Forty-six children (0.5%) developed T1D and were compared with 9368 reference children from the general population. Some 10 of 46 children with later T1D had an infection at time of gluten introduction (22%) compared with 2520 reference children (27%, P = .43). Later T1D was not associated with age at end of breastfeeding, age at any infection, or age at gluten introduction. Breastfeeding at time of gluten introduction was not protective against future T1D (hazard ratio 1.2; 95% CI, 0.5-2.7). In our final model, when we adjusted for age at gluten introduction, age at infection, and breastfeeding duration, infection at time of gluten introduction did not influence the risk of future T1D (hazard ratio 0.8; 95% CI, 0.3-1.6). Conclusion Infection at time of gluten introduction is not a major risk factor for future T1D in nonselected children.

  • 564.
    Welander, Adina
    et al.
    Karolinska Institute.
    Rockert Tjernberg, Anna
    Kalmar County Hospital.
    Montgomery, Scott M
    Karolinska Institute.
    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.
    Ludvigsson, Jonas F
    Karolinska Institute.
    Infectious Disease and Risk of Later Celiac Disease in Childhood2010In: PEDIATRICS, ISSN 0031-4005, Vol. 125, no 3, p. E530-E536Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The goal was to examine whether parent-reported infection at the time of gluten introduction increases the risk of future celiac disease (CD). METHODS: Through the population-based All Infants in Southeast Sweden study, parents recorded data on feeding and infectious disease prospectively. Complete data on gluten introduction and breastfeeding duration were available for 9408 children. Those children had 42 826 parent-reported episodes of infectious disease in the first year of life (including 4003 episodes of gastroenteritis). We identified 44 children with biopsy-verified CD diagnosed after 1 year of age, and we used Cox regression to estimate the risk of future CD for children with infection at gluten introduction. RESULTS: Eighteen children with CD (40.9%) had an infection at the time of gluten introduction, compared with 2510 reference individuals (26.8%; P = .035). Few children had gastroenteritis at the time of gluten introduction (1 child with CD [2.3%] vs 166 reference individuals [1.8%]; P = .546). With adjustment for age at gluten introduction and breastfeeding duration, we found no association between a future diagnosis of CD and either any infection (adjusted hazard ratio: 1.8 [95% confidence interval: 0.9-3.6]) or gastroenteritis (adjusted hazard ratio: 2.6 [95% confidence interval: 0.2-30.8]) at the time of gluten introduction. We found no associations between breastfeeding duration, age at gluten introduction, and future CD. CONCLUSION: These results indicate that parent-reported infection at the time of gluten introduction is not a major risk factor for CD.

  • 565.
    Wide, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Glad Mattsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Mattsson, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Independence does not come with the method - treatment of neurogenic bowel dysfunction in children with myelomeningocele2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 11, p. 1159-1164Article in journal (Refereed)
    Abstract [en]

    AimThe aim was to evaluate and compare different bowel regimes with regard to satisfaction, faecal incontinence and independence, and the relationship to quality of life among children with myelomeningocele (MMC). MethodsA questionnaire, including the health-related quality of life instrument PedsQL 4.0, was sent to all children aged seven to 16years (n=172) with MMC, treated at two centres in Sweden and one in Norway. The three centres cover a third of the population in the two countries. The response rate was 62%. ResultsParents of children (30%) using antegrade colonic enemas (ACE) reported higher satisfaction (p=0.01) than the parents of those (47%) using transanal irrigation (TAI). The children reported no significant difference. Children and parents in the ACE group reported more complete evacuation of the bowels than the TAI group. No significant difference was found in faecal incontinence or independent toileting. The children (40%) who emptied their bowels independently reported a higher quality of life. Children using TAI or ACE spent around one hour on the toilet at every bowel emptying. ConclusionTAI and ACE are effective treatments, but time-consuming and difficult to perform independently. Higher parental satisfaction is obtained with ACE. Irrespective of method the children who can use the toilet independently report a higher quality of life, which makes efforts to support independence valuable.

  • 566.
    Wide, Peter
    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.
    Glad Mattsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mattsson, Sven
    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.
    Renal preservation in children with neurogenic bladder-sphincter dysfunction followed in a national program2012In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 8, no 2, p. 187-193Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Neurogenic bladder-sphincter dysfunction (NBSD) constitutes the major reason for morbidity in children with spina bifida. The aim of this study was to identify risk factors for renal damage in children with NBSD followed according to the Swedish national guidelines. MATERIALS AND METHODS: Records and cystometries from 6 to 16 years (median 11) follow up of 41 consecutive children born 1993-2003 with NBSD were evaluated. The children were divided into a high pressure group (baseline pressure above 30 cmH(2)O at maximal clean intermittent catheterization volume in at least two cystometries) and a low pressure group. Most children (34/41) were followed from birth. RESULTS: Although renal scarring on DMSA-scintigraphy was found in 5/41 children, all but one had normal renal function. Two already had renal scars on entering the follow-up program at age 2.5 and 3 years. Renal scarring was more frequent in the high pressure group (P < 0.01). Most children with renal scars (4/5) had a combination of low compliant bladder and insufficient compliance with treatment and follow up. CONCLUSION: High baseline pressure is confirmed as a risk factor that, in combination with complex social issues, creates a demanding situation for families and professionals. A structured early follow up with treatment compliance effectively prevents renal damage.

  • 567.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hedin-Skogman, Barbro
    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.
    Peterson, E. M.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bergstrom, S.
    University of Umeå.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis2009In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, ISSN 0300-9475, Vol. 70, no 2, p. 141-148Article in journal (Refereed)
    Abstract [en]

    We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

  • 568.
    Wilhelmsson, Margaretha
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Pelling, Staffan
    Linköping University, Department of Medical and Health Sciences, Nursing Science. 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.
    Hammar, Mats
    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.
    Dahlgren, Lars-Owe
    Linköping University, Department of Behavioural Sciences and Learning, Studies in Adult, Popular and Higher Education. Linköping University, Faculty of Educational Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Twenty years experiences of interprofessional education in Linkoping--ground-breaking and sustainable.2009In: Journal of Interprofessional Care, ISSN 1356-1820, E-ISSN 1469-9567, Vol. 23, no 2, p. 121-133Article in journal (Refereed)
    Abstract [en]

    A pioneering and ground-breaking effort to organize interprofessional education (IPE) was initiated in 1986 at the Faculty of Health Sciences at Linkoping University in Sweden. The so-called "Linkoping IPE model" has now yielded practical experience and development of curricula for over 20 years. The basic idea of this model is that it is favorable for the development of students' own professional identity to meet other health and social professions already into their undergraduate studies. Interprofessional learning is a process over time that requires several integrated stages to gain interprofessional competence, i.e., the skills required to work together interprofessionally in practice. We believe that defined IPE modules early in the curriculum combined with student-training ward placement as the final module is an encouraging example of how to implement undergraduate IPE among health science students. It is strengthened by problem based learning (PBL) in small groups and student-centered learning. Based on these experiences, this paper aims to contribute to the discussion on how to implement and achieve the aims of IPE and to keep it sustainable. It is not a description of "how to do it" but rather a summarizing of our experiences for successful performance of IPE. The article presents how the Linkoping model was developed, the outcomes, experiences and some outlines for future challenges.

  • 569.
    Wilkin, Terry
    et al.
    Department of Endocrinology and Metabolism, Peninsula Medical School, Plymouth, U.K..
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Greenbaum, Carla
    Department of Diabetes, Benaroya Research Institute, Seattle, Washington, USA.
    Palmer, Jerry
    Department of Diabetes, VA Medical Center, Seattle, Washington, USA.
    Becker, Dorothy
    Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
    Bruining, Jan
    Department of Pediatrics, Sophia Children’s Hospital, Rotterdam, the Netherlands.
    Future intervention trials in type 1 diabetes2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 4, p. 996-997Article in journal (Other academic)
    Abstract [en]

    n/a

  • 570.
    Winquist, Fredrik
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Holmin, Susanne
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Krantz-Rülcher, Christina
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Wide, Peter
    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.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    A hybrid electronic tongue2000In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 406, no 2, p. 147-157Article in journal (Refereed)
    Abstract [en]

    A hybrid electronic tongue is described based on a combination of potentiometry, voltammetry and conductivity. It was used for classification of six different types of fermented milk. Using ion-selective electrodes, pH, carbon dioxide and chloride ion concentrations were measured. The voltammetric electronic tongue consisted of six working electrodes of different metals (gold, iridium, palladium, platinum, rhenium and rhodium) and an Ag/AgCl reference electrode. The measurement principle is based on pulse voltammetry in which current transients are measured due to the onset of voltage pulses at decreasing potentials. The data obtained from the measurements were treated by multivariate data processing based on principal components analysis and an artificial neural net. The hybrid tongue could separate all six samples. Also, the nature of the micro-organisms in the different fermentations was reflected in the principal component analysis. Copyright (C) 2000 Elsevier Science B.V.

  • 571.
    Wolkerstorfer, A.
    et al.
    Department of Dermato, Venereology University Hospital Rotterdam, Rotterdam, Netherlands.
    Wahn, U.
    Department of Pediatric Pneumology and Immunology, Humboldt University, Berlin, Germany.
    Kjellman, N.I.M.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Diepgen, T.L.
    Department of Social Medicine, Center of Dermato Epidemiology, Occupational and Environmental Dermatology, University Hospital Heidelberg, Germany.
    De, Longueville M.
    De Longueville, M., UCB Pharma, Brussels, Belgium.
    Oranje, A.P.
    Department of Dermato, Venereology University Hospital Rotterdam, Rotterdam, Netherlands, Department of Dermato Venereology, University Hospital Rotterdam, Dr. Molewaterplein 60, 3015 GJ Rotterdam, Netherlands.
    Natural course of sensitization to cow's milk and hen's egg in childhood atopic dermatitis: ETAC™ study group2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 1, p. 70-73Article in journal (Refereed)
    Abstract [en]

    Background: Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. Methods: The placebo intention-to-treat population of the ETAC™ (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean ± SD: 17.2 ± 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. Results: Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P = 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. Conclusion: We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.

  • 572.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Chung, Kian Fan
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK / NIHR Respiratory Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London, London, UK; Royal Brompton NHS Fdn Trust, NIHR Resp Biomed Res Unit, London, England.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Targeted omics and systems medicine: personalising care2014In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 2, no 10, p. 785-787Article in journal (Other academic)
  • 573. Zwaan, CM
    et al.
    Reinhardt, D
    Corbacioglu, S
    Jurgens, H
    Samuelsson, Ulf
    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.
    Biondi, A
    Smith, OP
    Bokkerink, JPM
    Tissing, WJE
    Creutzig, U
    Kaspers, GJL
    First clinical experiences with Gemtuzumab ozogamicin (GO, Mylotarg (c)) in CD33 positive relapsed/refractory leukemia in children2003In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 17, no 3, p. P51a-Conference paper (Other academic)
  • 574.
    Åkerblom, Hans
    et al.
    Biomedicum, Helsinki, Finland.
    Virtanen, SM
    Tampere Schoolf of Public Health, Tampere, Finland.
    Ilonen, Jorma
    Dept of Virology, Univeristy of Turku, Finland.
    Savilathi, Errki
    Biomedicum, Helsinki, Finland.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Reunanen, A
    Dept of Health and Functional Capacity, Helsinki, Finland.
    Teramo, K
    Dept of Obstetics and Gynecology, Helsinki, Finland.
    Hämäläinen, A M
    Dept of Pediatrics, University of Oulu, Finland.
    Paronen, J
    Biomedicum, Helsinki, Finland.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: A pilot study2005In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 48, no 5, p. 829-837Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen, Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). Conclusions/interpretation: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy. © Springer-Verlag 2005.

  • 575.
    Åkerman, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes2013In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 148, no 1Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) patients have numeral and functional defects in peripheral immune cells, but the pre-diabetic period is fairly uncharacterized. Our aim was to analyze expression of immunological markers in T1D high risk children and relate it to clinical/immunological parameters. Children from ABIS (All Babies in Southeast Sweden) with greater than= 2 diabetes related autoantibodies were considered at high risk. Age-matched controls and new-onset T1D patients were included. Expression of genes related to immune cell function and different arms of the immune system was assessed in peripheral blood mononuclear cells using PCR array. Risk children had lower TNF and CD45, and although there were few differences between the groups, expression of many genes differed when comparing children with regard to residual insulin secretion. Hence, expression of immune related genes seemed related not only to the autoimmune process but rather to residual beta-cell function, which was decreased already during the pre-diabetic phase.

  • 576.
    Åkesson, K
    et al.
    Ryhov City Hospital.
    Carlsson, A
    Lund University.
    Ivarsson, S A
    Lund University.
    Johansson, C
    Ryhov City Hospital.
    Weidby, B M
    Ryhov City 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.
    Gustavsson, B
    Lund University.
    Lernmark, A
    Lund University.
    Kockum, I
    Karolinska Institute.
    The non-inherited maternal HLA haplotype affects the risk for type 1 diabetes2009In: International journal of immunogenetics, ISSN 1744-3121, Vol. 36, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    The aim was to test the hypothesis that the human leucocyte antigen (HLA) haplotype that is not inherited from the mother, that is, the non-inherited maternal antigen (NIMA) affects the risk for type 1 diabetes (T1D). A total of 563 children with T1D and 286 non-diabetic control children from Sweden were genotyped for DRB1, DQA1 and DQB1 alleles. The frequency of positively (DR4-DQA1*0301-B1*0302 and DR3-DQA1*0501-B1*0201), negatively (DR15-DQ A1*0102-B1*0602) or neutrally (all other) T1D associated HLA haplotypes were compared between NIMA and non-inherited paternal antigen (NIPA). All comparisons were carried out between HLA-matched patients and controls. The frequency of positively associated NIMA was higher among both DR4/X-positive healthy individuals compared wit DR4/X-positive patients (P < 0.00003) and DR3/X-positive healthy individuals compared with DR3/X-positive patients (P < 0.009). No such difference was observed for NIPA. High-risk NIMA was increased compared to NIPA among healthy DR3/X- and DR4/X-positive children (P < 0.05). There was no difference in frequency of positively associated haplotypes between patient NIMA and NIPA. The NIMA but not the NIPA affects the risk for T1D, suggesting that not only the inherited but also non-inherited maternal HLA haplotypes, perhaps through microchimerism or other mechanisms, may influence the risk for the disease.

  • 577.
    Örtqvist, Eva
    et al.
    Astrid Lindgrens Barnsjukhus Stockholm.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Åman, Jan
    Barnkliniken Universitetssjukhuset, Örebro.
    Johansson, Calle
    Barnkliniken Ryhovs sjukhus, Jönköping.
    Karlsson, Anders
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Forsander, Gun
    Barnkliniken Lasarettet, Falun.
    Lindgren, Fredrik
    Sachsska Barnsjukhuset Stockholm.
    Persson, Bengt
    Astrid Lindgrens Barnsjukhus Stockholm.
    Berglund, Lars
    Clinical Research Centre Uppsala Universitet.
    Berne, Christian
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Bengtsson, Mats
    Klinisk Immunologi Uppsala Universitet.
    Björk, Elisabeth
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Wallensteen, Måna
    Astrid Lindgrens Barnsjukhus Stockholm.
    Temporary preservation of β-cell function by diazoxide treatment in childhood type 1 diabetes2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 9, p. 2191-2197Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We examined the effect of diazoxide, an ATP-sensitive K + channel opener and inhibitor of insulin secretion, on β-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS - A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS - Diazoxide decreased circulating C-peptide concentrations by ∼50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 ± 0.22 vs. 0.31 ± 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. Placebo-treated patients (-0.05 ± 0.24 vs. -0.18 ± 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 ± 0.20 and 0.20 ± 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS - This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of β-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.

  • 578.
    Östlund, Gunnel
    et al.
    Linköping University, Department of Social and Welfare Studies, Society, Diversity, Identity . Linköping University, Faculty of Arts and Sciences.
    Borg, Karin
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Wide, Peter
    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.
    Hensing, Gunnel
    Department of Social Medicine, Sahlgrenska Academy, University of Göteborg, Sweden.
    Alexandersson, Kristina
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Client’s perceptions of contacts with professionals within health care and social insurance offices2003In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 31, no 4, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Aims: An increasing number of people interact with professionals within healthcare and social insurance offices during periods of sick leave due to musculoskeletal disorders. Knowledge of clients' perceptions of such contact is scarce. This study analysed clients' perceptions of their contact with professionals within healthcare and social insurance offices.

    Methods: A cohort study was conducted in the municipality of Linköping, Sweden. Participants were all citizens who in 1985 were aged 25 - 34 years and had at least one new sick-leave spell due to back, neck, or shoulder diagnoses exceeding 28 days (n=213). In 1996, 11 years after inclusion, a questionnaire about perception of contact with professionals, self-perceived health, and mental health was administered. Register data on sickness absence and disability pension from 1985 - 96 were also obtained.

    Results: Factor analysis indicated the existence of three dimensions of contact with professionals: supportive treatment, distant treatment, and empowering treatment. Women perceived their contact with both social insurance officers and healthcare professionals as more supportive than did the men. Respondents with disability pensions perceived their contact with social insurance officers as more supportive and empowering than persons without disability pensions. Respondents with mental health problems perceived their contact with both types of professionals as more distant. Respondents with neck/shoulder diagnoses perceived their contact with healthcare professionals as more empowering than respondents with low back diagnoses.

    Conclusion: There was a relationship between clients' perceptions of contact with professionals and the sex, disability pension, diagnosis, and mental health of clients.

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