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  • 251.
    Kjölhede, Preben
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Wahlström, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Wingren, Gun
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin.
    Pelvic floor dysfunction after Burch colposuspension - A comprehensive study. Part II2005Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, nr 9, s. 902-908Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To evaluate the prevalence of pelvic floor dysfunction (PFD) concerning bowel function at long-term follow-up after Burch colposuspension (Bc) in relation to the bowel function in an age-matched sample of women in the general population. Methods and material. This is a follow-up study of a cohort of 190 patients who underwent Bc in 1980-1988 and 305 age-matched control women without urinary anti-incontinence surgery, randomly selected from the general population. The participants answered a postal questionnaire with detailed questions about the pelvic floor function in 1998. Univariate and multivariate analyses were performed. Results. The patients showed considerable signs of bowel dysfunction compared with the general population in the following aspects: they used the fingers to help emptying the bowel [odds ratio (OR) 3.25 (1.35-7.86)], had feeling of incomplete emptying of the bowel [OR 2.29 (1.11-4.73)], felt no warning before passing a motion [OR 3.04 (1.20-7.71)], had gas incontinence [OR 1.98 (1.17-3.37), had loose stool incontinence [OR 3.67 (1.43-9.42)], used protection against fecal leakage during daytime [OR 3.22 (1.30-7.95)], and experienced that the bowel function affected the general well-being adversely [OR 2.15 (1.30-3.56)]. Conclusion. The patients who have undergone colposuspension for stress urinary incontinence have more symptoms of PFD concerning the bowel function than women without urinary anti-incontinence surgery in the general population. This affects the general well-being. A comprehensive concept of multidisciplinary assessment and treatment of PFD should be encouraged. © Acta Obstet Gynecol Scand 2005.

  • 252.
    Kleberg, Agneta
    et al.
    Karolinska Inst, Dept Women & Child Hlth, Stockholm, Sweden.
    Warren, Inga
    St Marys Natl Hlth Serv Trust, Winnicott Baby Unit, London, England.
    Norman, Elisabeth
    Lund Univ, Dept Paediat, Lund, Sweden.
    Mörelius, Eva-Lotta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Berg, Ann-Cathrine
    Lund Univ, Dept Paediat, Lund, Sweden.
    Mat-Ali, Ezam
    Northwick Pk Hosp & Clin Res Ctr, London, England.
    Holm, Kristina
    Lund Univ, Dept Ophthalmol, Lund, Sweden.
    Fielder, Alistair
    City Univ London, Dept Optometry & Visual Sci, London, England.
    Nelson, Nina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Hellstrom-Westas, Lena
    Lund Univ, Dept Paediat, Lund, Sweden.
    Lower stress responses after newborn individualized developmental care and assessment program care during eye screening examinations for retinopathy of prematurity: A randomized study2008Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 121, nr 5, s. E1267-E1278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE. Screening examination for retinopathy of prematurity is distressing and painful. The aim of the present study was to investigate whether a Newborn Individualized Developmental Care and Assessment Program intervention during a retinopathy of prematurity examination results in less adverse behavioral, pain, and stress responses as compared with standard care. METHODS. The first 2 eye examinations in 36 preterm infants were evaluated. The infants were randomly assigned at the first eye examination to receive either Newborn Individualized Developmental Care and Assessment Program care or standard care. At the second examination, crossover of subject assignment was performed. The assessments included behavioral responses, recordings of heart rate, respiration, and oxygenation, pain scores (premature infant pain profile), and salivary cortisol at defined time points up to 4 hours after the eye examination. The nursing support given during the eye examinations (intervention score) were scored using predefined criteria. RESULTS. Altogether, 68 examinations were evaluated. Newborn Individualized Developmental Care and Assessment Program care was associated with better behavioral scores during the examination but there was no difference in heart rate, respiratory rate, oxygenation, or premature infant pain profile score between the 2 care strategies before or after the eye examination. Salivary cortisol increased from baseline to 30 minutes after the eye examination independent of care strategy and decreased significantly between 30 and 60 minutes when infants were subjected to Newborn Individualized Developmental Care and Assessment Program care but not after standard care. During the study period the intervention score for standard care increased and approached the score for Newborn Individualized Developmental Care and Assessment Program care at the later eye examinations. CONCLUSION. A Newborn Individualized Developmental Care and Assessment Program-based intervention during eye examination does not decrease pain responses but results in faster recovery, as measured by lower salivary cortisol 60 minutes after the examination. The differences were seen despite the influence from the Newborn Individualized Developmental Care and Assessment Program intervention on the standard care treatment that occurred during the study period.

  • 253.
    Knip, Mikael
    et al.
    Finland .
    Veijola, Riitta
    Finland .
    Virtanen, Suvi
    Finland .
    Hyöty, Heikki
    Finland .
    Vaarala, Outi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Åkerblom, Hans
    Finland .
    Environmental triggers and determinants of type 1 diabetes2005Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, nr SUPPL. 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing β-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a several-fold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen. © 2005 by the American Diabetes Association.

  • 254.
    Knobler, R.
    et al.
    Medical University of Vienna, Austria .
    Berlin, Gösta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Calzavara-Pinton, P.
    University Hospital Spedali Civili, Italy .
    Greinix, H.
    Medical University of Vienna, Austria .
    Jaksch, P.
    Medical University of Vienna, Austria .
    Laroche, L.
    Avicenne Hospital, France .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Quaglino, P.
    University of Turin, Italy .
    Reinisch, W.
    Medical University of Vienna, Austria .
    Scarisbrick, J.
    University Hospital, England .
    Schwarz, T.
    University Hospital Schleswig Holstein, Germany .
    Wolf, P.
    Medical University of Graz, Austria .
    Arenberger, P.
    Charles University of Prague, Czech Republic .
    Assaf, C.
    HELIOS Klinikum Krefeld, Germany .
    Bagot, M.
    University of Paris 07, France .
    Barr, M.
    University of So Calif, CA USA .
    Bohbot, A.
    University of Strasbourg, France .
    Bruckner-Tuderman, L.
    University of Medical Centre Freiburg, Germany .
    Dreno, B.
    Nantes University Hospital, France .
    Enk, A.
    Heidelberg University, Germany .
    French, L.
    University of Zurich Hospital, Switzerland .
    Gniadecki, R.
    Bispebjerg Hospital, Denmark .
    Gollnick, H.
    Otto Von Guericke University, Germany .
    Hertl, M.
    University Hospital Marburg, Germany .
    Jantschitsch, C.
    Medical University of Vienna, Austria .
    Jung, A.
    Dessau Medical Centre, Germany .
    Just, U.
    Medical University of Vienna, Austria .
    -D. Klemke, C.
    Heidelberg University, Germany .
    Lippert, U.
    Dessau Medical Centre, Germany .
    Luger, T.
    University of Munster, Germany .
    Papadavid, E.
    University of Athens, Greece .
    Pehamberger, H.
    Medical University of Vienna, Austria .
    Ranki, A.
    University of Helsinki, Finland University of Helsinki, Finland .
    Stadler, R.
    Johannes Wesling Medical Centre, Germany .
    Sterry, W.
    Charite, Germany .
    H. Wolf, I.
    Medical University of Graz, Austria .
    Worm, M.
    Charite, Germany .
    Zic, J.
    Vanderbilt University, TN 37212 USA .
    C. Zouboulis, C.
    Dessau Medical Centre, Germany .
    Hillen, U.
    University of Duisburg Essen, Germany .
    Guidelines on the use of extracorporeal photopheresis2014Ingår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 28, nr s1, s. 1-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundAfter the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease. Materials and methodsIn order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. Results and conclusionThese guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.

  • 255.
    Koch, Felix-Sebastian
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sepa, Anneli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Body Dissatisfaction Measured with a Figure Preference Task and Self-Esteem in 8 Year Old Children: a Study within the ABIS-Project2008Ingår i: Clinical Medicine Insights: Pediatrics, ISSN 1179-5565, Vol. 2, s. 13-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Body dissatisfaction has been related to low self-esteem and depression in adolescents. With regard to the current world wide rise in childhood obesity and common stigmatization of adults and children with obesity, easy to use and cost effective measurements of body dissatisfaction would be helpful in epidemiological research. In the current study, detailed data on body measurements with regard to perceived and ideal body size and body dissatisfaction, as measured with the figure preference task, are presented for a population based sample of 3837 children. Perceived body size correlations to weight, body mass index [BMI], and waist circumference were between 0.41 and 0.54; and to height between 0.12 and 0.21. Odds ratios for lower self-esteem increased with increase in body dissatisfaction. Gender differences in body dissatisfaction were present but not found in relation to self-esteem. It is concluded that the figure preference task yields valuable information in epidemiological studies of children as young as 7.5 years of age. It is argued, that the figure preference task is an additional measurement which theoretically relates to psychological stress in childhood.

  • 256.
    Koch, Felix-Sebastian
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sepa, Anneli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Parents’ psychological stress over time may affect children’s cortisol at age 82010Ingår i: Journal of Pediatric Psychology, ISSN 0146-8693, E-ISSN 1465-735X, Vol. 35, nr 9, s. 950-959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study possible relations between parents’ psychological stress, children’s selfesteem and children’s saliva cortisol levels with regard to a mild stressor (drawing a blood sample).

    Method: Parenting stress and serious life events at birth, age 1, age 2, age 5 and age 8, and children’s self-esteem at age 8 were assessed. 82 paired saliva samples just before and 30 minutes after a children’s blood was drawn were analyzed.

    Results: Repeated measure general linear models indicated a relation between higher parenting stress at age 1 (p=0.03) and at age 8 (p<0.01), and elevated cortisol levels. No relation was found for serious life events. Lack of self-esteem in the domain of mental well-being was related to elevated cortisol levels (p=0.02).

    Conclusion: Parenting stress related to elevated cortisol levels of their children cross-sectionally and longitudinally and may be used as an indicator for children’s psychological stress in epidemiological studies.

  • 257.
    Koch, Felix-Sebastian
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sepa, Anneli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Hälsouniversitetet.
    Psychological Stress and Obesity2008Ingår i: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 153, nr 6, s. 839-844Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine whether there is a relationship between psychological stress in the family and obesity in 5- to 6-year-old children.

    Study design: A total of 7443 Swedish families reported on psychological stress across 4 domains as part of the prospective All Babies in Southeast Sweden-project (ABIS). Domains assessed included serious life events, parenting stress, lack of social support, and parental worries. These variables were summarized in cross-sectional and longitudinal composite measures of psychological stress. Logistic regression models were used to calculate odds ratios for childhood obesity for psychological stress.

    Results: A total of 4.2% of the children were obese according to age-adjusted international standards. Children from families that reported stress in at least 2 of the 4 domains assessed had significantly higher adjusted odds ratios (OR) for obesity, both cross-sectionally (OR, 2.1; 95% CI, 1.3-3.5; P < .01.) and longitudinally (OR, 2.6; 95% CI, 1.3-5.4, P < .01).

    Conclusion: Psychological stress in the family may be a contributing factor for childhood obesity. This finding underscores how important it is to give children with obesity and their families psychological and social support in addition to recommendations about changing life style.

  • 258.
    Krogvold, Lars
    et al.
    Oslo University Hospital HF, Norway .
    Edwin, Bjorn
    Oslo University Hospital, Norway .
    Buanes, Trond
    Oslo University Hospital, Norway .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Korsgren, Olle
    Uppsala University, Sweden .
    Hyöty, Heikki
    University of Tampere, Finland .
    Frisk, Gun
    Uppsala University, Sweden .
    Hanssen, Kristian F.
    Oslo University Hospital, Norway .
    Dahl-Jörgensen, Knut
    Oslo University Hospital HF, Norway .
    Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 4, s. 841-843Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 259.
    Krogvold, Lars
    et al.
    Paediatric Dept., Oslo University Hospital, Norway.
    Edwin, Bjørn
    Intervention Centre and Dept. of Surgery, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Norway.
    Buanes, Trond
    Dept. of Surgery, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Norway.
    Frisk, Gun
    Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
    Skog, Oskar
    Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
    Anagandula, Mahesh
    Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
    Korsgren, Olle
    Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
    Undlien, Dag
    Department of Medical Genetics, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Norway.
    Eike, Morten C
    Department of Medical Genetics, Oslo University Hospital, Norway.
    Richardson, Sarah J
    Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, UK.
    Leete, Pia
    Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, UK.
    Morgan, Noel G
    Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, UK.
    Oikarinen, Sami
    Department of Virology, School of Medicine, University of Tampere, Finland.
    Oikarinen, Maarit
    Department of Virology, School of Medicine, University of Tampere, Finland.
    Laiho, Jutta E
    Department of Virology, School of Medicine, University of Tampere, Finland.
    Hyöty, Heikki
    Department of Virology, School of Medicine, University of Tampere, Finland; Fimlab laboratories, Pirkanmaa Hospital District, Tampere, Finland.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Hanssen, Kristian F
    Dept. of Endocrinology, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Norway.
    Dahl-Jørgensen, Knut
    Paediatric Dept. Oslo University Hospital, and Faculty of Medicine, University of Oslo, Norway.
    Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes.2015Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, nr 5, s. 1682-1687Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh frozen whole pancreatic tissue using PCR and sequencing. Non-diabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetes patients (2 of 9 controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (1 of 9 controls). Enterovirus specific RNA sequences were detected in 4 of 6 cases (0 of 6 controls). The results were confirmed in different laboratories. Only 1.7 % of the islets contained VP1 positive cells and the amount of enterovirus RNA was low. The results provides evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, being consistent with the possibility that a low grade enteroviral infection in the pancreatic islets contribute to disease progression in humans.

  • 260.
    Kryh, H.
    et al.
    University of Gothenburg.
    Abrahamsson, J.
    Institute for Clinical Science, Gothenburg.
    Jegeras, E.
    University of Gothenburg.
    Sjoberg, R.-M.
    University of Gothenburg.
    Devenney, Irene
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Kogner, P.
    Karolinska Institute.
    Martinsson, T.
    University of Gothenburg.
    Characterization of amplicon junction sequences in genomic regions surrounding the MYCN gene in neuroblastoma tumors; implications for clinical follow-up of high-risk patients in FEBS JOURNAL, vol 278, issue , pp 215-2152011Ingår i: FEBS JOURNAL, Blackwell Publishing Ltd , 2011, Vol. 278, s. 215-215Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 261.
    Kryh, Hanna
    et al.
    University of Gothenburg.
    Abrahamsson, Jonas
    University of Gothenburg.
    Jegeras, Elsa
    University of Gothenburg.
    Sjoberg, Rose-Marie
    University of Gothenburg.
    Devenney, Irene
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Kogner, Per
    Karolinska Institute.
    Martinsson, Tommy
    University of Gothenburg.
    MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma2011Ingår i: International Journal of Oncology, ISSN 1019-6439, Vol. 39, nr 5, s. 1063-1071Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The MYCN gene is frequently amplified in unfavorable neuroblastoma tumors. Therefore, this study aimed at characterizing the novel junctions connecting the amplified DNA segments (amplicons) and obtaining tumor-specific PCR fragments for use in detecting minimal residual disease (MRD). High-density SNP arrays were used to map the end-points of the MYCN amplicons in a subset of neuroblastoma tumors. Primers were designed to give rise to a tumor-specific PCR product and were examined for MRD in the blood and bone marrow using quantitative PCR. Tumor-specific junction fragments were detected in all cases, confirming a head-to-tail tandem orientation of the amplicons and revealing microhomology at the amplicon junctions, thus suggesting a rolling circle caused by microhomology-mediated break-induced replication (MMBIR) as a possible mechanism initiating the MYCN amplification. We also evaluated the use of these junctions as tumor-specific targets for detecting MRD and observed that tumor DNA could be readily detected and quantified in either blood or bone marrow at a sensitivity of 1/10(6) tumor/control DNA. This study provides new information on the mechanisms of oncogene amplification and envisages means of rapidly obtaining highly sensitive PCR-based tools for tumor/patient-specific monitoring of treatment response and the early detection of relapse in patients with neuroblastoma.

  • 262.
    Källen, B
    et al.
    Tornblad Institute, Lund .
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, KG
    Sofiahemmet, Stockholm .
    Olausson, Petra
    Socialstyrelsen, Stockholm .
    Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982-2001: A register study2005Ingår i: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 331, nr 7513, s. 382-383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 263.
    Källen, Bengt
    et al.
    Tornblad Institutet, Lund .
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, Karl-Gösta
    Fertilitetskliniken, Sofiahemmet, Stockholm .
    Otterblad Olausson, Petra
    Centre for Epidemiology Socialstyrelsen, Stockholm.
    In vitro fertilization (IVF) in Sweden: Risk for congenital malformations after different IVF methods2005Ingår i: Birth defects research. Clinical and molecular teratology, ISSN 1542-0752, E-ISSN 1542-0760, Vol. 73, nr 3, s. 162-169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS: Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS: Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 15% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS: An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. © 2005 Wiley-Liss, Inc.

  • 264.
    Källén, Bengt
    et al.
    Tornblad Institute Lunds Universitet.
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, Karl-Gösta
    Fertility Clinic Sophiahemmet, Stockholm.
    Otterblad Olausson, Petra
    Centre for Epidemiology Stockholm.
    In vitro fertilization in Sweden: Maternal characteristics2005Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, nr 12, s. 1185-1191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Deliveries among women who had an in vitro fertilization (IVF) are characterized by increased risks for both the mother and the infant/child. Part of these effects may be due to maternal characteristics. Methods. Using reports from all clinics performing IVF in Sweden, 12 186 women who gave birth after such procedures were identified (13 261 deliveries, 16 280 infants born). Various social and medical characteristics of the women were studied and compared with all women giving birth. Information was retrieved by interviews in early pregnancy or by linkage with various registers. Results. Women who had IVF were older than other women who gave birth and were older after standard IVF than after intracytoplasmatic sperm injection (ICSI). They were more often of first parity and smoked less than other delivered women. There were more women with high body mass index: they worked outside home less often and were more often of Swedish nationality. Women who had standard IVF had more previous miscarriages than expected, but this was not true for women who had ICSI. Their pattern of drug usage differed from that of other women who had given birth. Conclusions. Women who underwent IVF and gave birth showed marked deviations from other women who gave birth. Some of these characteristics may help to explain the increased risks associated with these procedures. Women who had ICSI were less deviating than women who had standard IVF. © Acta Obstet Gynecol Scand 2005.

  • 265.
    Källén, Bengt
    et al.
    Tornblad Institute, Lunds universitet.
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, K-G
    Fertility Clinic, Sofiahemmet, Stockholm.
    Otterblad Olausson, Petra
    Centre for Epidemiology, Stockholm.
    In vitro fertilization in Sweden: Child morbidity including cancer risk2005Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 84, nr 3, s. 605-610Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study long-term morbidity among children conceived by IVF. Design: A register study in Sweden of IVF infants compared with all infants born. Setting: National health registers. Patient(s): More than 16,000 children born after IVF (30% of them after intracytoplasmic sperm injection) were studied with national health registers. Main Outcome Measure(s): Total number of days in hospital care at different ages, hospitalization for specific diagnoses, childhood cancer. Result(s): An overuse of hospital care was found among IVF children up to 6 years of age, which was partly explained by maternal characteristics. Discharge diagnoses indicating brain damage (mental retardation, cerebral palsy, epilepsy, behavioral problems) occurred in excess and seemed to be completely explained by preterm births. In addition, other discharge diagnoses were overrepresented, some of them linked to preterm birth. There were 29 children with cancer (21 expected), 5 of them had Langerhan's histiocytosis. Conclusion(s): Long-term morbidity among children conceived by IVF is higher than among naturally conceived infants. This was partly explained by an excess of preterm and multiple births but might also mirror different parental attitudes toward medical care for their children. No general increase in cancer risk was seen, but unexpectedly many children with histiocytosis were noted. ©2005 by American Society for Reproductive Medicine.

  • 266.
    Källén, Bengt
    et al.
    Tornblad Institute Lunds Universitet.
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, K.G.
    IVF clinic Sofiahemmet, Stockholm.
    Otterblad Olausson, Petra
    Centre for Epidemiology Stockholm.
    Wennerholm, Ulla-Britt
    Avd för Obstetrik och Gynekologi Sahlgrenska sjukhuset, Göteborg.
    In vitro fertilisation in Sweden: Obstetric characteristics, maternal morbidity and mortality2005Ingår i: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 112, nr 11, s. 1529-1535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate obstetric characteristics, maternal morbidity and mortality among Swedish women giving birth after in vitro fertilisation (IVF) treatment. Design: Register study. Setting: Nationwide study in Sweden. Sample: All women known to have had IVF in Sweden 1982-2001. Methods: Using Swedish health registers, women who had given birth after IVF were identified from all Swedish IVF clinics and compared with all women who gave birth. Analysis was performed with the Mantel-Haenszel technique. Main outcome measures: Diagnoses during pregnancy, at delivery and at re-admission within 60 days after delivery and risk of cancer. Results: IVF women had an increased risk of bleeding in early pregnancy [odds ratio (OR) = 4.59, 95% confidence interval (95% CI) 4.08-5.15] and of ovarian torsion during pregnancy (OR = 10.6, 5.69-10.7). They were also more likely to encounter pre-eclampsia (OR = 1.63, 1.53-1.74), placental abruption (2.17, 1.74-2.72), placenta praevia (3.65, 3.15-4.23), bleeding in association with vaginal delivery (1.40, 1.38-1.50) and premature rupture of membranes (PROM) (2.54, 2.34-2.76). Interventions including caesarean sections (1.38, 1.32-1.43) and induction of labour (1.37, 1.29-1.46) in singleton pregnancies was more frequent. The type of IVF method had little effect on these results, but there was a tendency for women who had received intra-cytoplasmatic sperm injection (ICSI) to have slightly fewer complications than women having standard IVF. There was a significant decrease in cancer risk after IVF (0.79, 0.69-0.91) but a suggested increase in the risk of ovarian cancer both before (2.70, 1.49-4.91) and after (2.08, 1.15-3.76) IVF. No change in mortality was observed. Conclusions: Women treated with IVF had an increased obstetric morbidity. This seems to contribute little to the well-known increased risk of preterm delivery. © RCOG 2005.

  • 267.
    Källén, Bengt
    et al.
    Tornblad Institute, Lunds Universitet.
    Finnström, Orvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, K-G
    Fertility clinic Sofiahemmet, Stockholm.
    Otterblad-Olausson, Petra
    Centre for Epidemiology Stockholm.
    In vitro fertilization (IVF) in Sweden: Infant outcome after different IVF fertilization methods2005Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 84, nr 3, s. 611-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To compare infant outcome after different IVF techniques. Design: A register study in Sweden of IVF infants compared with all infants born. Setting: National health registers. Patient(s): We studied 16,280 IVF infants, 30% of whom were conceived by intracytoplasmic sperm injection (ICSI). Intervention(s): None. Main Outcome Measure(s): Multiple births, infant sex, preterm birth, low birth weight, and small for gestational age among singletons, mortality, low Apgar score, neonatal diagnoses. Result(s): Twinning was less frequent after frozen standard IVF (18.1%) and after ICSI (21.8%) than after fresh standard IVF (24.4%). The male/female ratio was significantly increased in infants conceived after standard IVF. No significant differences were seen between singleton infants conceived after different IVF methods with respect to preterm birth, low birth weight, or infant mortality, with the possible exception of frozen standard IVF, for which some of these rates were lower than after fresh standard IVF. Infants born after ICSI had an indicated lower risk of respiratory problems than infants born after standard IVF. Conclusion(s): Little difference in outcome was seen after different IVF methods. The differences observed might be due to dissimilar characteristics of the treated women (e.g., because ICSI was mainly used in connection with male infertility). ©2005 by American Society for Reproductive Medicine.

  • 268.
    Käyhty, Helena
    et al.
    Dept of Vaccines, National Public Health Institute, Helsingfors, Finland.
    Åman, Heidi
    Wyeth Finland, Vantaa, Finland .
    Eriksson, Karin
    Wyeth Lederle Nordiska AB, Solna, Stockholm .
    Sörberg, Mikael
    Infectious Diseases Unit, Dept of Medicine, Karolinska sjukhuset, Stockholm.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Immunogenicity and tolerability of a heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 12 months of age2005Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 24, nr 2, s. 108-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The recommended vaccination schedule for the pneumococcal conjugate vaccine (PCV) includes 4 immunizations, according to the national programs in the United States and some European countries. Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses. Aims: The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life (a 2+1 dose schedule) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b (Hib) vaccine. Methods: A total of 101 healthy Swedish infants were enrolled in an open, nonrandomized, multicenter study. PCV was administered concomitantly with (at separate sites) a diphtheria-tetanus toxoids-acellular pertussis vaccine, inactivated polio vaccine and Hib conjugate vaccine combination at 3, 5 and 12 months of age. IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum samples taken at 3, 6, 12 and 13 months were determined with enzyme immunoassays. Local and systemic reactions were monitored for 3 days after each immunization, and serious adverse reactions were monitored for the whole study period. Results: Two doses of PCV induced satisfactory antibody responses, with the exception of serotypes 6B and 23F. The third dose evoked strong responses for all serotypes, which suggests good immunologic priming with the primary series of 2 doses. The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children. The PCV was well tolerated. Conclusion: The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule. The results suggest that the implementation of a 2+1 dose schedule for PCV should be considered.

  • 269.
    Lahdenperä, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Hölttä, V
    National Institute for Health and Welfare, Finland.
    Ruohtula, T
    National Institute for Health and Welfare, Finland.
    Salo, H M
    National Institute for Health and Welfare, Finland.
    Orivuori, L
    National Institute for Health and Welfare, Finland.
    Westerholm-Ormio, M
    Hospital for Children and Adolescents, University of Helsinki,.
    Savilahti, E
    Hospital for Children and Adolescents, University of Helsinki,.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Högberg, Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Norrköping.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Vaarala, O
    National Institute for Health and Welfare, Finland.
    Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes2012Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 167, nr 2, s. 226-234Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P andlt; 0·005 for all IL-17 comparisons and P andlt; 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P andlt; 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.

  • 270.
    Lahdenperä, Anne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Hogberg, Lotta
    Norrkoping Hospital, Sweden .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Vaarala, Outi
    National Institute Health and Welf, Finland .
    Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease2014Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, nr 2, s. 145-156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. Material and methods. Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. Results. The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-gamma (IFN-gamma) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-gamma but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. Conclusion. Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.

  • 271.
    Lahdenperä, Anne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Ljungberg, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Korpela, Riitta
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
    Casas, Rosaura
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Vaarala, Outi
    National Institute Health and Welf, Finland .
    Probiotics and innate immune response in infants2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    We studied the effects of probiotic treatment on the innate immune system during infancy. The study included a subgroup of infants recruited to the pilot study testing the feasibility of probiotics intervention in infants with genetic risk of type 1 diabetes (T1D). A mixture of Lactobacillus rhamnosus GG (5 x 109 cfu), Lactobacillus rhamnosus LC705 (5 x 109 cfu), Bifidobacterium breve Bbi99 (2 x 108 cfu) and Propionibacterium freudenreichii ssp. Shermani JS (2 x 109 cfu) was given to the infants beginning one to three weeks after birth until the age of 6 months. Blood samples were drawn at the age of 6, 12 and 24 months for the analyses of beta-cell autoantibodies and the phenotype and stimulation response of monocytes with flow-cytometry, including surface markers on circulating CD14+ monocytes and expression of co-stimulatory markers on CD14+ monocytes as response to stimulation with lipoteichoic acid (LTA) and lipopolysaccharide (LPS). Also gene expression of toll-like receptor (TLR) signalling molecules was studied in the peripheral blood mononuclear cell (PBMC) population.

    In the children who received probiotics the number of circulating CD14+ monocytes expressing CD58 was reduced at the age of 6 months, and a tendency for a decreased induction of CCR5, CD80 and CD58 expressing monocytes as response to LTA was seen when compared to the children who received placebo. At the age of 12 months, the number of monocytes expressing CCR5 was decreased in the probiotic group, and a decreased spontaneous expression of TNFRSF1A and an increased spontaneous expression of TLR9 was observed in the PBMC from the children treated with probiotics. In the whole study group, the numbers of circulating monocytes expressing CD80 increased with age as well as the induction of CCR5, CD80 and CD58 on monocytes as response to stimulation. By the age of 24 months one child in both groups developed multiple autoantibodies.

    We demonstrated that probiotics modulated the activation stage and stimulation response of monocytes, and that prolonged effects of the treatment were seen at the age of 12 months. The findings suggest that early microbial exposure may program the function of the innate immune system for later life.

  • 272.
    Lahdenperä, Anne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Högberg, Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Norrköping.
    Vaarala, Outi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    The effect of gluten-free diet on Th1--Th2--Th3-associated intestinal immune responses in celiac disease2011Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 46, nr 5, s. 538-549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To study T-helper (Th)1--Th2--Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. Material and methods. Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1--Th2--Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). Results. The Th1 gene expression profile including interferon (IFN)-gamma gamma, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-gamma gamma transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. Conclusion. The GFD did not correct the increased activation of the IFN-gamma gamma signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure.

  • 273.
    Lahdenperä, Anne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Regnström, Karin
    Farmakologen Uppsala.
    Kinetics of asthma- and allergy-associated immune response gene expression in peripheral blood mononuclear cells from vaccinated infants after in vitro re-stimulation with vaccine antigen2008Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, nr 14, s. 1725-1730Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The global expression of immune response genes in infants after vaccination and their role in asthma and allergy is not clearly understood. Pharmacogenomics is ideally suited to study the involved cellular responses, since the expression of thousands of genes can be assessed simultaneously. Here, array technology was used to assess the expression kinetics of immune response genes with association to asthma and allergy in peripheral blood mononuclear cells (PBMC) of five healthy infants after vaccination with Infanrix-Polio + Hib. At 12 h after in vitro re-stimulation of the PBMC with pertussis toxin (PT) antigen, 14 immune response pathways, 33 allergy-related and 66 asthma-related genes were found activated. © 2008 Elsevier Ltd. All rights reserved.

  • 274.
    Laine, Antti-Pekka
    et al.
    Immunogenetics Laboratory, University of Turku, Finland.
    Holmberg, Hanna
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Anita
    Department of Endocrinology and Paediatrics, University Hospital Malmö, University of Lund, Sweden.
    Örtqvist, Eva
    Astrid Lindgren’s Children Hospital, Karolinska Hospital, Stockholm, Sweden.
    Kiviniemi, Minna
    Immunogenetics Laboratory, University of Turku, Finland.
    Vaarala, Outi
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.
    Åkerblom, Hans K
    Hospital for Children and Adolescents, University of Helsinki, Finland.
    Simell, Olli
    Department of Paediatrics, University of Turku, Turku, Finland.
    Knip, Mikael
    Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland / Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Ivarsson, Sten-A
    Department of Endocrinology and Paediatrics, University Hospital Malmö, University of Lund, Sweden.
    Larsson, Karin
    Department of Endocrinology and Paediatrics, University Hospital Malmö, University of Lund, Sweden.
    Lernmark, Åke
    Department of Endocrinology and Paediatrics, University Hospital Malmö, University of Lund, Sweden.
    Ilonen, Jorma
    Immunogenetics Laboratory, University of Turku, Finland / Department of Clinical Microbiology, University of Kuopio, Finland.
    Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations2007Ingår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 23, nr 3, s. 139-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type 1 diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence-specific hybridization and time-resolved fluorometry reading. Distribution of the genotypes at both positions differed significantly among the affected children compared to the controls. The risk genotypes (CC, AA) were significantly more common in Finland than in Sweden, both among patients and controls. The VNTR genotype homozygous for the protective class III alleles showed a significantly stronger protective effect than the heterozygote (p=0.02). Analyzing both SNPs enabled the detection of VNTR class III subclasses IIIA and IIIB. The observed significance between effects of the protective genotypes was due to the strong protective effect of the IIIA/IIIA genotype. IIIA/IIIA was the only genotype with significant discrepancy between protective effects compared to the other class III genotypes. These observations suggest that heterogeneity between the protective IDDM2 lineages could exist, and analyzing both -23HphI and -2221MspI would thus potentially enhance the sensitivity and specificity of type 1 diabetes risk estimation.

  • 275.
    Lakshman, Rajalakshmi
    et al.
    Addenbrookes Hospital, England University of Cambridge, England .
    Zhang, Jing
    Huazhong University of Science and Technology, Peoples R China .
    Zhang, Jianduan
    Huazhong University of Science and Technology, Peoples R China .
    Koch, Felix-Sebastian
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten.
    Marcus, Claude
    Karolinska Institute, Sweden .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Ong, Ken K.
    Addenbrookes Hospital, England University of Cambridge, England .
    Sobko, Tanja
    Chinese University of Hong Kong, Peoples R China .
    Higher maternal education is associated with favourable growth of young children in different countries2013Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 67, nr 7, s. 595-602Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life. Methods We compared growth data of 4-year-old to 6-year-old children born 1997-2002 in UK (n = 15 168), Sweden (n = 6749) and rural China (n = 10 327). SD scores (SDS) were calculated against the WHO Growth Standard. Obesity and overweight were defined by the International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or body mass index (BMI)less than-2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII). Results Mean SDS height, weight and BMI in the UK (-0.01, 0.42, 0.62, respectively) and Sweden (0.45, 0.59, 0.45) were higher than in China (-0.98, -0.82, -0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in the UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: -25.8% and -12.7%). Obesity prevalence in the UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in the UK (SII: -3.3%) and Sweden (-2.8%), but not in China (+0.3%). Conclusions Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in the UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimise growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings.

  • 276.
    Lannering, Birgitta
    et al.
    University of Gothenburg.
    Sandstrom, Per-Erik
    Umeå University.
    Holm, Stefan
    Karolinska Institute.
    Lundgren, Johan
    Lund University.
    Pfeifer, Susan
    Uppsala University.
    Samuelsson, Ulf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Stromberg, Bo
    Uppsala University.
    Gustafsson, Goran
    Karolinska Institute.
    Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984-20052009Ingår i: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 98, nr 10, s. 1620-1627Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry. Methods: Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population. Results: There were 1479 children (andlt; 15 years) in Sweden diagnosed with CNS tumours 1984-2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100 000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10). Conclusions: The mean annual incidence of children with CNS tumours was 4.2/100 000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.

  • 277.
    Lauria, A.
    et al.
    University of Campus Biomed, Italy.
    Barker, A.
    MRC Epidemiol Unit, England.
    Schloot, N.
    University of Dusseldorf, Germany.
    Hosszufalusi, N.
    Semmelweis Univ, Hungary.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Mathieu, C.
    Katholieke University of Leuven, Belgium.
    Mauricio, D.
    Hospital Arnau Vilanova, Spain.
    Nordwall, Maria
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Norrköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Van der Schueren, B.
    Katholieke University of Leuven, Belgium.
    Mandrup-Poulsen, T.
    University of Copenhagen, Denmark; Karolinska Institute, Sweden.
    Scherbaum, W. A.
    University of Dusseldorf, Germany.
    Weets, I.
    VUB, Belgium; VUB, Belgium; BDR, Belgium.
    Gorus, F. K.
    VUB, Belgium; VUB, Belgium; BDR, Belgium.
    Wareham, N.
    MRC Epidemiol Unit, England.
    Leslie, R. D.
    Queen Mary University of London, England.
    Pozzilli, P.
    University of Campus Biomed, Italy; Queen Mary University of London, England.
    BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children2015Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 172, nr 2, s. 107-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. Design: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. Methods: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (less than5 years, n = 126; greater than5 years less than10 years, n = 295; greater than10 years less than18 years, n = 421; greater than18 years, n = 410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. Results: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed greater than18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P = 0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (beta = 0.026, 95% CI = 0.0097, 0.042; P = 0.002). Conclusions: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes.

  • 278.
    Leijon, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Factors of importance for neurodevelopment in preterm infants2010Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, nr 5, s. 642-644Artikel i tidskrift (Övrigt vetenskapligt)
  • 279.
    Leijon, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Svenska 20-åringar med mycket låg födelsevikt mår oväntat bra: Självskattad hälsa, utbildning och livskvalitet som hos andra jämnåriga2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 11, s. 748-752Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Totalt 85 barn med mycket låg födelsevikt (≤1 500 g) och normalviktiga kontroller födda 1987–1988 i syd­öst­ra Sverige har utvärderats dels vid 15 års ålder beträffande funktionshinder och genomgångna sjukdomar, MRI-hjärna (lågviktiga), kognition och synfunktion, dels vid 20 års ålder beträffande utbildning och livskvalitet.

    I gruppen med mycket låg födelsevikt var 15 barn (18 procent) kända vid barnhabiliteringen. I denna grupp hade pojkar fler vårdtillfällen, och 23 procent av barnen utan neurologisk funktionsnedsättning hade cerebrala MRI-förändringar. Av testade hade 20 procent IQ <70. Dess­utom förekom astigmatism, strabism och syntolkningsproblem oftare i denna grupp.

    Självskattad hälsa, utbildning och livskvalitet skilde sig inte mellan grupperna vid övergången till vuxenålder.Förutom uppföljningar inom barnhälsovård/barnmedicin rekommenderas psykologbedömning före skolstart och riktad ögonläkarundersökning under skolperioden.

  • 280.
    Leslie, R D
    et al.
    University of London.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Editorial Material: The viral aetiology of diabetes: a tribute to Keith Taylor (1929-2012)2012Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, nr 4, s. 419-419Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 281.
    Lilljebjorn, H.
    et al.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Heidenblad, M.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Nilsson, B.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Lassen, C.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Horvat, A.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Heldrup, J.
    Department of Pediatrics, Lund University Hospital, Lund, Sweden.
    Behrendtz, M.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Johansson, B.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Andersson, A.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Fioretos, T.
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
    Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region2007Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 21, nr 10, s. 2137-2144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization (array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60-201,Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq), a similar overexpression was confirmed in t(12,21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12,21)-positive leukemia.

  • 282.
    Lilljebjorn, Henrik
    et al.
    Skåne University Hospital.
    Soneson, Charlotte
    Lund University.
    Andersson, Anna
    Skåne University Hospital.
    Heldrup, Jesper
    Lund University.
    Behrendtz, Mikael
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Kawamata, Norihiko
    University of California Los Angeles.
    Ogawa, Seishi
    University of Tokyo.
    Koeffler, H. Phillip
    University of California Los Angeles.
    Mitelman, Felix
    Skåne University Hospital.
    Johansson, Bertil
    Skåne University Hospital.
    Fontes, Magnus
    Lund University.
    Fioretos, Thoas
    Skåne University Hospital.
    The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias2010Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, nr 16, s. 3150-3158Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q) and +16 as possible early events in the leukemogenic process.

  • 283.
    Lilljebjörn, H.
    et al.
    Lund University, Sweden .
    Rissler, M.
    Lund University, Sweden .
    Lassen, C.
    Lund University, Sweden .
    Heldrup, J.
    Lund University, Sweden .
    Behrendtz, M.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Mitelman, F.
    Lund University, Sweden .
    Johansson, B.
    Lund University, Sweden .
    Fioretos, T.
    Lund University, Sweden .
    Whole-exome sequencing of pediatric acute lymphoblastic leukemia2012Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 26, nr 7, s. 1602-1607Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.

  • 284.
    Ljungkrantz, M
    et al.
    Dept of Pediatrics Blekingesjukhuset, Karlskrona.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Samuelsson, Ulf
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Type 1 diabetes: Increased height and weight gains in early childhood2008Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, nr 3 PART 2, s. 50-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The accelerator/beta-cell stress hypothesis regards insulin resistance as one common basis for type 1 and type 2 diabetes and weight increase as an important trigger of type 1 diabetes. To test this hypothesis, we examined children's height and weight gain from birth to the time of diagnosis of type 1 diabetes. Method: Growth charts (n=316) from children 0-16yr old up to the time of diagnosis of type 1 diabetes were compared with growth charts from age- and sex-matched controls. Results: Compared with their controls, children who developed diabetes had experienced more pronounced gain in both weight and height. In the year of diagnosis, they were taller [0.5 vs. 0.36 standard deviation score (SDS), p<0.03] and heavier (0.7 vs. 0.45 SDS, p<0.01). Children who developed diabetes aged 5yr or less gained more weight during the period between their third month and third year of life (p<0.01). Children who were diagnosed between 6 and 10yr of age had gained more in height before they were 5yr old (p<0.05). Regression analysis showed that a high weight or a high body mass index (BMI) at 5yr of age indicated, more than the other measurements, a high risk for diabetes later during childhood, while height and weight at ages less than 5yr did not add any further information on diabetes risk. Conclusions: Rapid growth before 7yr of age and increased BMI in childhood are risk factors for later type 1 diabetes. These findings support the accelerator/beta-cell stress hypothesis. © 2008 The Author Journal compilation © 2008 Blackwell Munksgaard.

  • 285.
    Ljungman, Gustaf
    et al.
    Uppsala University.
    Jakobson, Ake
    Karolinska Institute.
    Behrendtz, Mikael
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Ek, Torben
    County Hospital, Halmstad.
    Friberg, Lars-Goran
    University of Gothenburg.
    Hjalmars, Ulf
    Umea University.
    Hjorth, Lars
    Lund University.
    Lindh, Jack
    Umea University.
    Pal, Niklas
    Karolinska Institute.
    Sandstedt, Bengt
    Karolinska Institute.
    Osterlundh, Gustaf
    University Gothenburg.
    Gustafsson, Goran
    Karolinska Institute.
    Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 20072011Ingår i: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 100, nr 5, s. 750-757Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: Two thousand four hundred and eighty-seven children (andlt; 15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p andlt; 0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.

  • 286.
    Lonnerholm, G.
    et al.
    Lönnerholm, G., Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden, Department of Women's and Children's Health, University Children's Hospital, SE-751 85 Uppsala, Sweden.
    Frost, B.-M.
    Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden.
    Abrahamsson, J.
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Behrendtz, Mikael
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Castor, A.
    Department of Paediatrics, University Hospital, Lund, Sweden.
    Forestier, E.
    Department of Clinical Sciences, Paediatrics, University of Umeå, Umeå, Sweden.
    Heyman, M.
    Childhood Cancer Research Unit, Karolinska University Hospital, Stockholm, Sweden.
    Uges, D.R.A.
    Department of Pharmacy, University Hospital, Groningen, Netherlands.
    De, Graaf S.S.N.
    De Graaf, S.S.N., Department of Pediatrics, University Medical Centre St. Radboud, Nijmegen, Netherlands.
    Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia2008Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 142, nr 4, s. 616-621Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10.5 years, range 7.3-12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m2 and the area under the plasma concentration-time curve (AUC) was 4.49 and 5.40 mg/l x min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where treatment depends more heavily on vincristine than in other subgroups, the relative risk (RR) of relapse was significantly increased for patients with clearance values above median (RR 5.2, P = 0.036), or AUC values below median (RR 5.8, P = 0.025). Our data suggest a relationship between the antileukemic effect and the systemic exposure of the drug, which warrants further studies. © 2008 The Authors.

  • 287.
    Lonnerholm, Gudmar
    et al.
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Thorn, Ingrid
    Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden.
    Sundstrom, Christer
    Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden.
    Frost, Britt-Marie
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Abrahamsson, Jonas
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Behrendtz, Mikael
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Heldrup, Jesper
    Univ Lund Hosp, Dept Pediat, S-22185 Lund, Sweden.
    Jacobsson, Stefan
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden.
    Li, AiHong
    Umea Univ, Dept Biosci, S-90187 Umea, Sweden.
    Olofsson, Tor
    Lund Univ, Dept Lab Med, Div Hematol & Transfus Med, Lund, Sweden.
    Porwit, Anna
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
    Soderhall, Stefan
    Karolinska Univ Hosp, Dept Pediat Oncol, Stockholm, Sweden.
    Larsson, Rolf
    Univ Hosp, Pharmacol Sect, Dept Med Sci, Uppsala, Sweden.
    Forestier, Erik
    Umea Univ, Dept Clin Sci, S-90187 Umea, Sweden.
    In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia2009Ingår i: LEUKEMIA RESEARCH, ISSN 0145-2126, Vol. 33, nr 1, s. 46-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p < 0.001) and doxorubicin (p = 0.01 7), drugs administered during induction therapy. In patients with t(12;21) (n = 20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p = 0.031; R-2 = 0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29.

  • 288.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Adequate doses of autoantigen administered using the appropriate route may create tolerance and stop autoimmunity2009Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr 1, s. 175-176Artikel i tidskrift (Övrigt vetenskapligt)
  • 289.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Alla Barn i Sydöstra Sverige (ABIS)2007Ingår i: Diabetesvård, ISSN 1652-697X, nr 4, s. 32-33Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

      

  • 290.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Barndiabetesfonden - med forskning ska diabetes hos barn besegras!2007Ingår i: Diabetesvård, ISSN 1652-697X, nr 4, s. 36-36Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 291.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Biography: Lise G. Heding, 1936-20082009Övrigt (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 292.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Combination therapy for preservation of beta cell function in Type 1 diabetes: New attitudes and strategies are needed!2014Ingår i: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 159, nr 1-2, s. 30-35Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In several diseases where the immune system plays an important role there has been a tremendous progress in treatment efficacy during the last decades. Based on necessary basic science these improvements are results of rapid, numerous and open-minded clinical trials where pieces of positive results step by step have been added into treatment schemes. Treatment of Type 1 diabetes has certainly improved but too slowly. It has been difficult to convince the scientific community of opinions which among non-professionals have been regarded as common sense such as the value of normal blood glucose and preservation of insulin secretion. Lack of motivation to participate in clinical trials has slowed down progress, as well as too narrow views on both pathogenesis of Type 1 diabetes and how studies should be designed to test therapeutic interventions. Studies in experimental animals can create and support hypothesis for human conditions but must not delay clinical trials too long. There is already evidence enough for intervention trials where immune suppression is combined with antigen treatment, beta cell protection, anti-inflammatory treatment, and efforts to stimulate beta cell regeneration. Regimens should be elaborated and first tried in those groups of patients where response can be expected to be best, and thereafter adjusted to increase efficacy step-wise, and in broader patient categories.

  • 293.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Cow-milk-free diet during last trimester of pregnancy does not influence diabetes-related autoantibodies in nondiabetic children2003Ingår i: IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN / [ed] Sanjeevi, CB; Eisenbarth, GS, New York Academy of Sciences, 2003, Vol. 1005, s. 275-278Konferensbidrag (Refereegranskat)
    Abstract [en]

    The aim was to study whether cow-milk-free diet during the last trimester of pregnancy influences the development of diabetes-related autoantibodies in nondiabetic children. We also examined the effect of later introduction of cow milk proteins and gluten. Blood samples were taken from 205 children at 6 weeks, 6 months, 18 months, and 5 years, whose mothers had been randomized to either a cow-mllk-free diet or not during the last trimester of pregnancy. During the first 3 months of life, cow milk proteins were not fed to the children. Autoantibodies against GAD65 (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by a radioligand-binding assay. We found specific autoantibodles, although in low concentrations below the traditional cutoff for positivity in the children. The diet of the mother during pregnancy had no influence on development of autoantibodies, nor did duration of breast-feeding or time for introduction of gluten. Cow milk introduction between 3 and 6 months caused a transient increase in GADA at 6 months of age (p < 0.05). Children who developed atopic disease had significantly lower IA-2A at 6 months (p < 0.001).

  • 294.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    C-peptide an adequate endpoint in type 1 diabetes2009Ingår i: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 25, nr 8, s. 691-693Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 295.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    C-peptide in diabetes diagnosis and therapy2013Ingår i: Frontiers in Bioscience (Elite Edition), ISSN 1945-0494, E-ISSN 1945-0508, Vol. 5, s. 214-223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    C-peptide is known for several decades. It is released in equimolar amounts together with insulin from the pancreatic beta cells. Still there has been quite remarkable lack of interest in C-peptide. C-peptide is rarely used to classify type of diabetes although it seems self-evident that it is important to estimate the function of those cells which do not function good enough and therefore causes a syndrome which requires life-long treatment and leads to serious complications. Not until recent years C-peptide is accepted as a relevant outcome in trials aiming at preservation of beta cell function, although it is known for decades that some C-peptide is associated with less complications in type 1 diabetes (T1D). Preservation of beta cell function is important to make diabetes milder, and when beta cell function can be preserved before clinical manifestation of T1D, we are on our way to prevent that disease. Residual C-peptide/insulin secretion can be of value in classification of diabetes in different types. C-peptide may give valuable clinical information on why patients are more or less stable/labile in their blood glucose and more or less easy to treat. It explains why patients with T1D have different tendency to develop severe acute complications, both severe hypoglycaemia and diabetic keto-acidosis (DKA). Longstanding C-peptide may decrease risk of developing severe late complications. Finally, although still under debate, C-peptide seems to have several effects on different organs suggesting that it is an important hormone, interesting per se, and not only as a reflection of insulin secretion.

  • 296.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    CSII - a valuable tool in the treatment of diabetes in children and teenagers but not the solution to all problems!2007Ingår i: Infusystems International, Vol. 6, nr 1Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

      

  • 297.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Establishing paediatric diabetes registries in developing countries - an important step towards decreased morbidity and mortality2012Ingår i: ASPAE Newsletter, ISSN 1041-6323, Vol. 2, nr 3, s. 6-7Artikel, forskningsöversikt (Övrigt vetenskapligt)
  • 298.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Etikprövningsnämnder måste kunna granska kvalitet2015Övrigt (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Det kan vara oetiskt att inte forska, men dålig forskning är oetisk forskning. Etikprövningsnämnderna bör inte bara granska etiska aspekter utan även kvaliteten på klinisk forskning. Det skriver Johnny Ludvigson, senior professor vid Linköpings universitet, i en replik på inläggen av Hugo Lagercrantz och Nils Erik Sahlin om etiska tillstånd vid kliniska studier.

  • 299.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Farmakoterapi vid typ 1-diabetes2015Ingår i: BestPractice, ISSN 1329-1874, Vol. 5, nr 14, s. 27-31Artikel, forskningsöversikt (Övrigt vetenskapligt)
  • 300.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    For debate: Are we ready for GAD-vaccination in the treatment and/or prevention of type 1 diabetes?2008Ingår i: Pediatric Endocrinology Reviews: diabetes, nutrition, metabolism, ISSN 1565-4753, Vol. 5, nr 4, s. 871-872Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

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