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  • 1.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19153 (URN)
    Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-09-15Bibliographically approved
  • 2.
    Abrahamsson, Thomas R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Böttcher, Malin Fagerås
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Oldaeus, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1174-1180Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

  • 4.
    Fagerås Böttcher, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Abrahamsson, Thomas Robert
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Fredriksson, Mats
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Jakobsson, Ted
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy2008In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, no 6, p. 497-504Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Frost, B.-M.
    et al.
    University Children's Hospital, Uppsala, Sweden.
    Eksborg, S.
    Karolinska Pharmacy, Karolinska Hospital, Stockholm, Sweden.
    Bjork, O.
    Björk, O., Department of Pediatric Oncology, Karolinska Hospital, Stockholm, Sweden.
    Abrahamsson, J.
    Department of Pediatrics, Queen Silvias Child and Adolescent Hospital, Göteborg, Sweden.
    Behrendtz, M.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Castor, A.
    Department of Pediatrics, University Hospital, Lund, Sweden.
    Forestier, E.
    Karolinska Pharmacy, Karolinska Hospital, Stockholm, Sweden.
    Lonnerholm, G.
    Lönnerholm, G., University Children's Hospital, Uppsala, Sweden, Department of Pediatrics, Umeå University Hospital, Umeå, Sweden.
    Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: Multi-institutional collaborative study2002In: Medical and Pediatric Oncology, ISSN 0098-1532, E-ISSN 1096-911X, Vol. 38, no 5, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Background. In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL). Procedure. Children, 107 in number, aged 1.3-17.3 years, were studied at Day 1 of induction therapy according to the current Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m2, and analyzed by reversed-phase liquid chromatography. Results. There was a more than 10-fold difference between patients in dose normalized plasma concentration of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations differed significantly between age groups (P= 0.003). Children aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ ml, followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older children had median values of about 50 ng/ml. Patients with white blood cell (WBC) count > 50 x 109/L at diagnosis had significantly lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 109/L, median 64.4 ng/ ml (P=0.015). There was no difference in doxorubicin concentration between boys and girls. No correlation was found between doxorubicin levels and serum aminotransferases or serum creatinine. The concentration of doxorubicinol was 13% (median value) of that of doxorubicin. Four infants, 7-9 months old, had plasma clearance between 350-431 ml/ min/m2, which is in the same range as in older children. A 3-month-old infant had a clearance of 181 ml/min/m2. Conclusions. The age groups who had the highest doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a large proportion of standard risk ALL cases with good prognosis. The correlation between doxorubicin plasma levels and clinical effect needs further study. The influence of age, body composition, and tumor burden on the pharmacokinetics of antineoplastic drugs should also be further explored, aiming at improvements in the current dosing regimen based on BSA. © 2002 Wiley-Liss, Inc.

  • 6.
    Frost, B.-M.
    et al.
    Dept. of Women's/Children's Health, University Children's Hospital, Uppsala, Sweden.
    Lonnerholm, G.
    Lönnerholm, G., Dept. of Women's/Children's Health, University Children's Hospital, Uppsala, Sweden, University Children's Hospital, SE-751 85 Uppsala, Sweden.
    Koopmans, P.
    Department of Pharmacy, University Hospital, Groningen, Netherlands.
    Abrahamsson, J.
    University Children's Hospital, Uppsala, Sweden, Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Behrendtz, M.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Castor, A.
    Department of Paediatrics, University Hospital, Lund, Sweden.
    Forestier, E.
    Department of Clinical Sciences, Paediatrics, University of Umeå, Umeå, Sweden.
    Uges, D.R.A.
    Department of Pharmacy, University Hospital, Groningen, Netherlands.
    De, Graaf S.S.N.
    De Graaf, S.S.N., University Children's Hospital, Nijmegen, Netherlands, Beatrix Children's Hospital, Groningen, Netherlands.
    Vincristine in childhood leukaemia: No pharmacokinetic rationale for dose reduction in adolescents2003In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 92, no 5, p. 551-557Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day 1 of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m2 (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m 2 (137-1241) and total body clearance 362 ml/min/m2 (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002, ?-0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area > 1 m2, which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.

  • 7.
    Muraro, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI Past President, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen Natl. Centre of Asthma, Lung Diseases in Children, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children. Part II: Evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria of allergic diseases2004In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, no 3, p. 196-205Article, review/survey (Refereed)
    Abstract [en]

    The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. In this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.

  • 8.
    Muraro, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St. Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen Natl. Ctr. of Asthma, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations2004In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, no 4, p. 291-307Article, review/survey (Refereed)
    Abstract [en]

    The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

  • 9.
    Murarol, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Kon, Carlsen K.-H.
    Kon Carlsen, K.-H., Voksentoppen Natl. Centre of Asthma, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children: Part I2004In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, no 2, p. 103-111Article, review/survey (Refereed)
    Abstract [en]

    The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

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