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  • 151. Bucardo, F
    et al.
    Karlsson, B
    Nordgren, J
    Paniagua, M
    Gonzalez, A
    Amador, JJ
    Espinoza, F
    Svensson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Mutated G4P[8] rotavirus associated with a nationwide outbreak of gastroenteritis in Nicaragua in 20052007In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, no 3, p. 990-997Article in journal (Refereed)
    Abstract [en]

    During February and March 2005, one of the largest national recorded outbreaks of severe acute gastroenteritis occurred in Nicaragua, affecting ≥64,000 individuals and causing ≥56 deaths, predominantly in children under 5 years of age. Through a nationwide laboratory-based study, stool samples were collected and investigated for rotavirus. Of 108 stool samples examined, 72 (67%) were positive for rotavirus. While 69% (50/72) of the positive samples were found in children less than 2 years of age, 50% (6/12) of the adult samples were positive. A mutated G4P[8] strain was the most commonly recognized strain (85%), followed by mixed G strains (8%) and G9P[8] (7%) strains. Phylogenetic analysis of the VP7 gene revealed that the G4 strains belonged to the emerging lineage Ic and was distantly related to the ST3 and VA70 G4 strains. Secondary structure predictions of the VP7 G4 protein revealed an insert of an asparagine residue in position 76, which, combined with additional mutations, surprisingly modified two downstream β-sheets at amino acid positions 80 to 85 and 115 to 119. The 2005 G4P[8] strain compared to a G4P[8] strain from 2002 had a substitution of an asparagine residue for threonine (Asn→Thr) at position 96 within antigenic region A, thus eliminating a potential glycosylation site. The mutated G4 virus was introduced in Nicaragua after 2002 and probably emerged from Brazil, Argentina, or Uruguay. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

  • 152.
    Buonaguro, L
    et al.
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    Devito, C
    Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Tornesello, ML
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    Schröder, U
    Eurocine Vaccines AB, Sweden.
    Wahren, B
    Karolinska Institute, Sweden.
    Hinkula, Jorma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Buonaguro, FM
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity2007In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 25, no 32, p. 5968-5977Article in journal (Refereed)
    Abstract [en]

    The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. © 2007 Elsevier Ltd. All rights reserved.

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  • 153. Buzio, L
    et al.
    De Palma, G
    Mozzoni, p
    Tondel, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Buzio, C
    Franchini, I
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Mutti, A
    Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals2003In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 60, no 10, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC). Methods: One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR, occupational history was collected by a structured questionnaire. Results: Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals (OR 2.73, 95% CI 0.91 to 8.22 v 1.14, 95% CI 0.46 to 2.82) or pesticides (OR 3.46, 95% CI 1.12 to 10.74 v 1.59, 95% CI 0.48 to 5.34). The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null. Conclusions: Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.

  • 154. Buzio, L
    et al.
    Tondel, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    De Palma, G
    Buzio, C
    Franchini, I
    Mutti, A
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Occupational risk factors for renal cell cancer. An Italian case-control study2002In: Medicina del Lavoro, ISSN 0025-7818, Vol. 93, no 4, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Aim: To examine possible associations between occupational and environmental risk factors and renal cell cancer (RCC), a tumour with unclear aetiology and increasing incidence. Methods: A questionnaire-based case-control study of 100 histologically verified cases of RCC and 200 controls was conducted at Parma University Hospital. The control group was enrolled from patients attending different outpatient departments and represented the same residential area as the cases. For all exposure variables under study, two levels of duration were defined: "short" and "prolonged" for less than 10 years or more, respectively. Results: The highest risk estimates for RCC were found for "prolonged" exposure to organic solvents with an odds ratio (OR) of 2.2 (95% confidence interval, CI: 1.0-4,8). "Prolonged" exposures to pesticides and copper sulphate were also associated with increased risk, OR 2.0 (95% CI: 0.8-4.7) and OR 2.7 (95% CI: 1.3-5.5), respectively. Conclusions: Our data suggests an association between RCC and exposure to organic solvents, pesticides and copper sulphate. A risk gradient as a function of exposure duration was found for organic solvents (p= 0.044) and copper sulphate (p= 0.036), but not for pesticides.

  • 155.
    Bäckman, Jenny
    et al.
    Linköping University, Department of Physics, Chemistry and Biology.
    Kasimir Klemedtsson, Åsa
    Klemedtsson, Leif
    Lindgren, Per-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Clear-cutting affects the ammonia-oxidising community differently in limed and non-limed coniferous forest soils2004In: Biology and Fertility of Soils, ISSN 0178-2762, E-ISSN 1432-0789, Vol. 40, no 4, p. 260-267Article in journal (Refereed)
    Abstract [en]

    The effects of clear-cutting on the ammonia-oxidising bacterial community were studied in the soil of limed and non-limed spruce forest plots located in the central part of southern Sweden. The communities were studied using denaturing gradient gel electrophoresis (DGGE) profiling after polymerase chain reaction (PCR) amplification from total DNA with primers reported to be specific for β-subgroup ammonia-oxidising bacteria. The bands on the DGGE were sequenced and each unique sequence was interpreted as representing one ammonia-oxidising population. The relative abundance of each population was determined by measuring the fluorescence of the respective DGGE bands. In both limed and non-limed soil, the same two Nitrosospira populations were found, one belonging to cluster 2 (NScl2) and one to cluster 4 (NScl4). However, while NScl4 first appeared a year after the clear-cutting in the non-limed plot, it was present both before and after the cutting in the limed plot. Irrespective of previous liming, clear-cutting caused a shift in the ammonia-oxidiser community, from dominance by the NScl2 population to a community with approximately equal relative abundance of NScl2 and NScl4. In both plots the total size of the community increased after clear-cutting (based on increased DGGE band intensity), most likely due to increased NH4+ availability, but the growth response was faster in the limed plot. Hence, the prior liming increased the responsiveness of the ammonia-oxidisers to the changes caused by cutting. This is the first study to report the effects of clear-cutting on the ammonia-oxidising community, and the results show a clear correlation between increased potential nitrification and a shift in the ammonia-oxidiser community.

  • 156.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Bjurström, Jenny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mai, Xiaomei
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 5, p. 345-350Article in journal (Refereed)
    Abstract [en]

    Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.

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  • 157.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fredriksson, Jenny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hellquist, Anna
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 1, p. 27-34Article in journal (Refereed)
    Abstract [en]

    Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-γ and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-γ production was to some extent caused by TGF-β, as the effect was modified when an anti-TGF-β antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-γ production, which was partly due to the high levels of TGF-β, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-β in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

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  • 158.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Häggström, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Björksten, Bengt
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Total and allergen-specific immunoglobulin a levels in saliva in relation to the development of allergy in infants up to 2 years of age2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 9, p. 1293-1298Article in journal (Refereed)
    Abstract [en]

    Background: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. Objective: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. Methods: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and ▀-lactoglobulin specific IgA levels were analysed with ELISA. Results: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to ▀-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. Conclusion: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.

  • 159.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Breastfeeding and the development of atopic disease during childhood2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 2, p. 159-161Article in journal (Refereed)
  • 160.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Center for Allergy Research and Institute of Environmental Medicine, Karolinska Institute, Karolinska, Sweden.
    Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 1, p. 35-41Article in journal (Refereed)
    Abstract [en]

    The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.

  • 161.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Garofalo, R
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy2000In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, no 1, p. 29-39Article in journal (Refereed)
    Abstract [en]

    The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and ▀-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6 : total n-3 and the arachidonic acid, C20:4 n-6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA:EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low a-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

  • 162.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Garofalo, Roberto P.
    Department of Pediatrics, Division of Immunology/Allergy/Rheumatology, University of Texas Medical Branch, Galveston, USA.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cytokines in breast milk from allergic and nonallergic mothers2000In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, no 1, p. 157-162Article in journal (Refereed)
    Abstract [en]

    The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

  • 163.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Norin, EK
    Sandin, A
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Microflora associated characteristics in faeces from allergic and non-allergic infants.2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, p. 1591-1597Article in journal (Refereed)
  • 164.
    Cardell, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Normann, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise1999In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 31, no 2, p. 197-200Article in journal (Refereed)
    Abstract [en]

    Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

  • 165. Carel, RH
    et al.
    Boffetta, P-A
    Kauppinen, TN
    Teschke, K
    Andersen, A
    Jäppinen, P
    Pearce, N
    Andreassen Rix, B
    Bergeret, A
    Coggon, D
    Persson, Bodil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Szadkowska-Stanczyk, I
    Kielkowski, D
    Henneberger, P
    Kishi, R
    Facchini, LA
    Sala, M
    Colin, D
    Krogevinas, M
    Exposure to asbestos and lung and pleural cancer mortality among pulp and paper industry workers2002In: Journal of Occupational and Environmental Medicine, ISSN 1076-2752, E-ISSN 1536-5948, Vol. 44, no 6, p. 579-584Article in journal (Refereed)
    Abstract [en]

    We studied the mortality from lung and pleural cancers in a cohort of 62, 937 male workers employed for at least 1 year in the pulp and paper industry in 13 countries during 1945 to 1996. Mill departments were classified according to probability and level of exposure to asbestos on the basis of available dust measurements and mill-specific information on exposure circumstances. Thirty-six percent of workers were classified as ever exposed to asbestos. Standardized mortality ratios of lung cancer were 0.99 (95 % confidence interval [CI], 0.90 to 1.08) among unexposed and 1.00 (95 % CI, 0.90 to 1.11) among ever exposed workers. The number of pleural cancer deaths among unexposed workers was 10, that among exposed workers was 14, most of which occurred among maintenance workers. In internal analyses, a trend in mortality from either neoplasm was suggested for estimated cumulative exposure to asbestos, weighted for the individual probability of exposure within the department and for duration of exposure (relative risk for lung cancer for 0.78+ f/cc-years, as compared with = 0.01 f/cc-years: 1.44, 95 % CI, 0.85 to 2.45, corresponding relative risk for pleural cancer: 2.43, 95% CI, 0.43 to 13.63). Despite a possible nondifferential misclassification of exposure and outcome, this study suggests that the carcinogenic effect of asbestos can be detected among workers employed in industries such as the pulp and paper industry, in which it is not considered to be a major hazard.

  • 166. Carstensen, U
    et al.
    Hou, S
    Alexandrie, A-K
    Högstedt, B
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Warholm, M
    Rannung, A
    Lambert, B
    Axmon, A
    Hagmar, L
    Influence of genetic polymorphisms of biotransformation enzymes on gene mutations, strand breaks of deoxyribonucleic acid, and micronuclei in mononuclear blood cells and urinary 8-hydroxydeoxyguanosine in potroom workers exposed to polyaromatic hydrocarbons.1999In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 25, p. 351-360Article in journal (Refereed)
  • 167.
    Casas, Rosaura
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Transfer of humoral immunity from the mother to her off-spring2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. It has been established that T cell responses of foetal origin to inhalant allergens are present in most cord blood samples. These immune responses could possibly be explained by transplacental passage of peptides, either as free antigens or in complexes with IgG, providing the foetus with a trigger for the priming of the T cell system already in utero. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is unknown. IgA antibodies to inhalant allergens have not been previously detected in human milk.

    Objective. The aim of this thesis was to explore whether inhaled allergens in serum and IgA antibodies in breast milk could contribute to the allergic immune responses to allergens in the children.

    Methods. The presence of cat allergen Fel d 1 was analysed by ELISA in serum samples from cat allergic asthmatic children. To detect IgG immune complexes (IC), affmity chromatography purification and Western blotting were performed. Iri:nnune complexes with Fel d 1-IgE were detected by a modification of MagicLite, and their specificity was assessed by different approaches. Serum samples from allergic and non-allergic mothers, and cord blood from their infants, were measured for the presence of Fel d 1-IgG immune complexes by an amplified ELISA. Cord blood mononuclear cells (CBMC) of babies from allergic and non-allergic mothers were stimulated with cat allergen and the production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA and the levels related to the presence of IC. Furthermore, IgG1 and IgG4 antibodies to cat were measured by ELISA. Colostrum and samples of mature milk from allergic and non-allergic mothers were analysed for IgA antibodies to cat, P-lactoblobulin (BLG) and ovalbumin (OVA) by an amplified ELISA.

    Results. The cat allergen Fel d I was detected in 70% of sera from cat allergic chilch'en, but not in any of the controls. The allergen was present in complexes with IgE and IgG antibodies as corroborated by different approaches. Immune complexes with IgG were detected in sera from allergic and non-allergic mothers, as well as in the cord blood from their babies, but neither the prevalence nor the levels of complexes were related to maternal allergy. This was also the case for IgG antibodies to cat. The production of IL-5, IL-10, IL-13 and IFN-γ by CBMC was not influenced by maternal atopy. Interferon-y secretion by CBMC after stimulation with cat allergen, however, was less conunonly detected in samples with immune complexes. Secretory IgA to cat and OVA allergens were frequently detected in colostrum and mature milk, while antibodies to BLG were less common. The antibody levels to cat and BLG were similar in allergic and non-allergic mothers.

    Conclusion. The presence of IC with allergens may contribute to maintaining immune responsiveness and sensitivity in allergic individuals. Low levels of transplacentally transferred IC can conceivable provide the foetus with the signal for priming ofT cell responses to inhalant allergens. This seems to be a nonnal mechanism, as the immune responses are not related to maternal allergy. Low level exposure of the maternal mucosa, e.g. by inhalant allergens, can induce IgA antibody secretion in breast milk, but this mechanism is not related with any protective effect against allergy.

    List of papers
    1. Circulating cat allergen and immune complexes in cat- allergic children
    Open this publication in new window or tab >>Circulating cat allergen and immune complexes in cat- allergic children
    Show others...
    1998 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, p. 1258-1263Article in journal (Refereed) Published
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80093 (URN)10.1046/j.1365-2222.1998.00384.x (DOI)
    Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2017-12-07Bibliographically approved
    2. Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
    Open this publication in new window or tab >>Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

    Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

    Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

    Keywords
    Allergen, Fel d 1, cat serum albumin, IgE, IgG, IgG4, immune complex
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80113 (URN)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
    3. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, p. 59-64Article in journal (Refereed) Published
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, p. 59-64Article in journal (Refereed) Published
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
    Open this publication in new window or tab >>Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
    2004 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, p. 591-596Article in journal (Refereed) Published
    Abstract [en]

    Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.

    Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.

    Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.

    Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.

    Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.

    Keywords
    allergen, cord blood, cytokine, Fel d 1, IgG, immune complex
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22341 (URN)10.1111/j.1365-2222.2004.1924.x (DOI)1542 (Local ID)1542 (Archive number)1542 (OAI)
    Note
    On the day of the defence day the status of this article was submitted.Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 168.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Cat-specific IgA antibodies in breast milk from atopic and non-atopic mothers: detection of Fel D 1->IgG immune complexes in cord blood and sera.1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 118, p. 317-318Article in journal (Refereed)
  • 169.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, p. 59-64Article in journal (Refereed)
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

  • 170.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individualsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

    Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

    Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

  • 171.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Böttcher, Malin
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Duchén, Karel
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 6 part 1, p. 1236-1240Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.

    Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.

    Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.

    Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).

    Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)

  • 172.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Djerf, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Häggström, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ferrándiz, R.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björksten, B.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Circulating cat allergen and immune complexes in cat- allergic children1998In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, p. 1258-1263Article in journal (Refereed)
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

  • 173.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ferrándiz, RA
    Wihl, j-Å
    Fernández, B
    Dreborg, S
    Biologic activity of Dermatophagoides siboney and Blomia tropicalis allergens in exposed and unexposed mite-allergic individuals. Effect of patient selection on the biologic standardization of mite extracts.  1999In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 54, p. 392-396Article in journal (Refereed)
  • 174.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood2004In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, p. 591-596Article in journal (Refereed)
    Abstract [en]

    Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.

    Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.

    Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.

    Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.

    Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.

  • 175.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Skarsvik, Susanne
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Östergötlands Läns Landsting, Centre for Medicine, Allergy Centre UHL. Linköping University, Faculty of Health Sciences.
    Duchén, Karel
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 5, p. 591-598Article in journal (Refereed)
    Abstract [en]

    Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1β were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-α was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.

  • 176.
    Cederbrant, K
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Gunnarsson, L G
    Marcusson, J
    Mercury intolerance and lymphocyte transformation test with nickel sulfate, palladium chloride, mercuric chloride, and gold sodium thiosulfate.2000In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 84, p. 140-144Article in journal (Refereed)
  • 177.
    Cederbrant, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Anderson, C
    Andersson, T
    Marcusson-Ståhl, M
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Cytokine production, lymphocyte proliferation and T-cell receptor Vbeta expression in primary peripheral blood mononuclear cell cultures from nickel-allergic individuals2003In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 132, no 4, p. 373-379Article in journal (Refereed)
    Abstract [en]

    Background: Clinical history and patch test constitute the two cornerstones in the diagnosis of nickel (Ni) allergy. Due to technical and interpretative limits of the patch test, the in vitro lymphocyte transformation test (LTT) has been developed for confirming contact allergy, however, most studies show an overlap in lymphocyte proliferation between Ni-allergic and nonallergic subjects using the LTT. The aim of this study was to see if the secretion of cytokines, especially interleukin (IL)-10 and IL-17, or the use of T-cell receptor (TCR) V▀ families in Ni-stimulated primary peripheral blood mononuclear cell (PBMC) cultures might be more useful for discriminating between allergic and nonallergic subjects. Methods: Ni2+-stimulated primary PBMC cultures derived from female subjects diagnosed as Ni-allergic (n = 5) or nonallergic (n = 5) on the basis of a positive or negative patch test were assessed for cell proliferation by tritiated thymidine incorporation and for production of interferon-?, IL-4, IL-10 and IL-17 in the culture supernatant by ELISA. The immunophenotype and TCR-V▀ family affiliation of the Ni2+-induced lymphoblasts were determined by flow cytometry. Results: Lymphocytes from Ni-allergic individuals challenged with a high and a low concentration of Ni showed significantly higher cell proliferation than lymphocytes from nonallergic individuals, but all subjects showed a positive LTT result (stimulation index>2). We found a significantly higher release of IL-10 in Ni2+-treated cultures from Ni-allergic compared with nonallergic subjects that provided better separation between individuals in the two groups than did lymphocyte proliferation. The proliferating lymphoblasts were predominantly CD4+, and in 2 of the 5 Ni-allergic subjects, but in none of the 5 nonallergic subjects, the CD4+ lymphoblasts showed a dominance of TCR-V▀17. Conclusions: Determination of IL-10 production in primary PBMC cultures is a potentially promising in vitro method for discrimination of Ni allergy in females, as compared with cell proliferation. Copyright ⌐ 2003 S. Karger AG, Basel.

  • 178.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Gunnarsson, L-G
    Department of Neurology and Neurophysiology and Centre for Environmental Sensitivity, Örebro Medical Centre Hospital, Örebro, Sweden.
    Hultman, Per
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Norda, R.
    Department of Transfusion Medicine and Immunohaemotherapy, Örebro Medical Centre Hospital, Örebro, Sweden.
    Tibbling-Grahn, L.
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    In vitro Lymphoproliferative Assays with HgCl2 Cannot Identify Patients with Systemic Symptoms Attributed to Dental Amalgam1999In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 78, no 8, p. 1450-1458Article in journal (Refereed)
    Abstract [en]

    Dental amalgam is suspected, by some exposed individuals, to cause various systemic psychological, sensory, and neurological symptoms. Since not all amalgam-bearers experience such reactions, an individual characteristic—for example, a susceptible immune system—might explain these conditions. In vitro lymphocyte proliferation is a valuable tool in the diagnosis of allergy. With HgCl2 as the antigen, however, the test is hampered, because Hg2+ can cause unspecific lymphocyte proliferation, optimal at 1.4 to 9.5 μg HgCl2/mL. Recently, the use of suboptimal HgCl2 concentrations (≤ 0.5 μg/mL) has been suggested to circumvent these problems. The main aim of this study was to investigate whether patients with systemic symptoms alleged to result from the presence of dental amalgam differ from healthy controls, with reference to in vitro lymphoproliferative responses to HgCl2 ≤ 0.5 μg/mL. Three different test protocols—lymphocyte transformation test (LTT) in micro- and macro-cultures, and the memory lymphocyte immunostimulation assay (MELISA®)—were used. Other immune parameters—such as a standard patch test for dental materials, the number of T- and B-lymphocytes, monocytes, granulocytes, and NK cells in peripheral blood, allergic symptoms, and predisposition-were also investigated. Twenty-three amalgam patients, 30 healthy blood donors with amalgam, ten healthy subjects without amalgam, and nine patients with oral lichen planus (OLP) adjacent to dental amalgam and a positive patch test to Hg0 were tested. None of the investigated immune parameters revealed any significant differences between amalgam patients and controls. The sensitivity of in vitro lymphocyte proliferation ranged from 33 to 67%, with the OLP patients as a positive control group, and the specificity from 0 to 70% for healthy controls with a negative patch test to Hg°. Thus, despite the use of HgCl2 ≤ 0.5 μg/mL, a high frequency of positive results was obtained among healthy subjects with or without dental amalgam. Consequently, in vitro lymphocyte proliferation with HgCl2 cannot be used as an objective marker for mercury allergy in dental amalgam-bearers.

  • 179.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Characterization of mercuric mercury (Hg2+)-induced lymphoblasts from patients with mercury allergy and from healthy subjects2000In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 121, no 1, p. 23-30Article in journal (Refereed)
    Abstract [en]

    Hg2+ induces lymphocyte proliferation when added to cell cultures from both healthy and mercury-allergic subjects. Consequently, when measuring DNA synthesis a possible Hg2+-specific response, resulting from proliferating memory cells, cannot be discriminated from a non-allergic response. The mechanism behind this non-allergic response is unknown but a superantigenic effect of Hg2+ has been suggested. In this study, five mercury-allergic patients, with oral lichen planus (OLP) lesions adjacent to dental amalgam and a positive patch test to Hg0, and five healthy subjects without amalgam were examined. The immunophenotype and the T cell receptor Vβ (TCR Vβ) repertoire of Hg2+-induced lymphoblasts as well as the expression of the lymphocyte activation markers CD23 and CD134 were analysed for possible differences between healthy and allergic subjects. The mechanism of Hg2+-induced proliferation was examined by comparing the TCR Vβ expression of Hg- and staphylococcal enterotoxin B (SEB)-activated lymphoblasts, the latter used as a positive superantigen control. It was not possible to discriminate between mercury-allergic and healthy subjects using the immunophenotype or the TCR Vβ profile of the Hg2+-induced lymphoblasts or the expression of CD23 and CD134. However, Hg2+-induced CD4+ lymphoblasts showed a skewing towards Vβ2. This relative increase in Vβ2 was only detected in the CD4+ but not in the CD8+ lymphoblast population. In conclusion, Hg2+ induced a proliferation-dependent skewing towards CD4+ but not CD8+ lymphocytes expressing Vβ2. In this respect Hg2+ differs from the classical bacterial superantigen SEB, which also stimulates unique TCR Vβ families among CD8+ cells.

  • 180.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson-Ståhl, M.
    AstraZeneca R & D Södertälje, Safety Assessment, Department of Molecular Toxicology and Immunotoxicology, Södertälje, Sweden.
    Hultman, Per
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, no 10, p. 1450-1459Article in journal (Refereed)
    Abstract [en]

    Background

    Antigen-specific cell lines or clones are often used as models of drug-specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.

    Objective

    Using bacampicillin-allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.

    Methods

    A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vβ repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.

    Results

    LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test-positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR-Vβ profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vβ2, Vβ3, Vβ5.1 and/or Vβ14. An increased expression of IFNγ was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL-5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.

    Conclusion

    LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNγ is the most suitable cytokine to discriminate between type I and type IV allergy. IL-5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T-cell lines or clones for the study of drug induced allergy.

  • 181.
    Cedergren, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Effects of gestational weight gain and body mass index on obstetric outcome in Sweden2006In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 93, no 3, p. 269-274Article in journal (Other academic)
    Abstract [en]

    Objective: The objective of this study was to estimate the effects of low and high gestational weight gain, in different maternal Body Mass Index (BMI) classes, on obstetric and neonatal outcomes. Method: A prospective population-based cohort study of 245,526 singleton term pregnancies. Women were grouped in five categories of BMI and in three gestational weight gain categories, < 8 kg (low weight gain), 8-16 kg and > 16 kg (high weight gain). Obstetric and neonatal outcomes were evaluated after adjustments for maternal age, parity, smoking, year of birth. Result: Obese women with low gestational weight gain had a decreased risk for the following outcomes (adjusted odds ratio, 95% confidence interval): preeclampsia (0.52, 0.42-0.62), cesarean section (0.81, 0.73-0.90), instrumental delivery (0.75, 0.63-0.88), and LGA births (0.66, 0.59-0.75). There was a 2-fold increased risk for preeclampsia and LGA infants among average and overweight women with excessive weight gain. High gestational weight gain increased the risk for cesarean delivery in all maternal BMI classes. Conclusion: The effects of high or low gestational weight gain differ depending on maternal BMI and the outcome variable studied. Obese women may benefit from a low weight gain during pregnancy.

  • 182.
    Cedergren, Marie
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Epidemiological studies of congenital heart defects in the Southeast region of Sweden2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the most recent analysis of Swedish data on congenital malformations, it appeared that in the county of Östergötland, the prevalence of infants with a diagnosed congenital malformation was higher than in the rest of the country. This observation initiated an effort to make a more complete identification of all infants born with a congenital malformation in that county and to compare it with the other two counties in the Southeast region of Sweden (Jönköping and Kalmar), utilising all the relevant Swedish medical health registers available. A total of 10,171 infants with a congenital malformation of any type were identified in the region: 4,698 infants in Östergötland county (6.2%), and 5,473 in the reference counties (5.4%). A 15% excess malformation risk in Östergötland compared with the two reference counties. Various validations of the register data were undertaken and different types of error were detected. Limb reduction defects seemed to occur more often in Östergötland county and there was an increased risk of cardiovascular malformations in Östergötland county (22%).

    The next step comprised an exploration of putative risk factors for cardiac defects in the area. Maternal body mass index (BMI) >29 was found to be a significant risk factor for cardiac defects. Maternal diabetes mellitus and maternal use of antiepileptics were associated with an increased risk of cardiac defects in the offspring.

    To explore if the pregnant women in Östergötland county differed from the women in the reference counties, a comparative analysis of potential risk factors was performed. The only single putative risk factor that could contribute to the excess risk of cardiac defects in Östergötland county was matemal residency in a rural district. Notably, nearly all the potential risk factors studied i.e. spontaneous abortions, involuntary childlessness, maternal disease, high maternal body mass index, matemal medical during use and alcohol use in early pregnancy, parental employment and paternal age were stronger in Östergötland county compared to the reference area. A conceivable explantation is that one or more unidentified factors could activate prevalent and weak teratogenic risk factors for cardiac defects.

    Drinking water could be such a factor. By using a geographical infmmation system (GIS) it was possible to obtain individual data on drinking water characteristics. An increased tisk of a congenital cardiac defect seemed to be associated with the chlorination procedure, in particular the use of chlorine dioxide, and with increasing total trihalomethane concentration.

    List of papers
    1. Congenital malformations in the southeast of Sweden: a registry study with validation
    Open this publication in new window or tab >>Congenital malformations in the southeast of Sweden: a registry study with validation
    2000 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 10, p. 1238-1243Article in journal (Refereed) Published
    Abstract [en]

    A study was made of the occurrence of congenital malformations in the southeast region of Sweden, utilizing all available relevant health registries. Östergötland county had been pinpointed in a routine surveillance as having an increased malformation risk. Various validations of the register data were undertaken and different types of errors were detected. An increased risk was seen, in Östergötland county compared to the reference counties, for specific types of malformations: preauricular appendices, pylorostenosis, uterine/vaginal malformations, foot deformities, limb reduction defects and cardiovascular malformations. Variable classification or registration artefacts explained the excess among the first four conditions. Limb reduction defects were also mis-coded, but the increased risk in Östergötland county may persist.

    Conclusion: There is an increased risk of major cardiovascular malformations in Östergötland county compared to the reference counties that also shows an uneven distribution within the county.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25854 (URN)10.1111/j.1651-2227.2000.tb00742.x (DOI)10291 (Local ID)10291 (Archive number)10291 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Risk factors for cardiovascular malformation: a study based on prospectively collected data
    Open this publication in new window or tab >>Risk factors for cardiovascular malformation: a study based on prospectively collected data
    2002 (English)In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 28, no 1, p. 12-17Article in journal (Refereed) Published
    Abstract [en]

    Objectives The aim of this study was to identify risk factors for cardiovascular malformation.

    Methods In a case-referent study prospectively collected data were obtained from original medical records. The study included 277 woman who had infants with a severe cardiac defect, and for each case two referents (medical records study) were included. Data on parental age, maternal reproductive history, disease in early pregnancy, reported maternal use of drugs and alcohol, smoking habits, parental occupation, and maternal body mass index (BMI) were extracted. When data were available from Swedish medical health registers, a comparison was made (register study) between all infants with cardiovascular defects (2208) and all infants born (175 768).

    Results Maternal diabetes mellitus was associated with an increased risk for cardiovascular malformation [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.36-4.15], as was a high BMI (>29) (OR 1.46, 95%CI 1.12-1.90). A tendency towards an increased risk was found for involuntary childlessness, spontaneous abortion, thyroid drugs, and nonsteroid anti-inflammatory drugs.

    Conclusions Some known risk factors for cardiac defects (eg, maternal diabetes mellitus and the use of antiepileptics) could be identified. Other postulated risk factors could not be verified, for example, paternal age and parental occupation. The use of medicinal drugs seems not to be a major factor in the etiology of cardiac defects. It is possible, however, that there is an association with the use of nonsteroid anti-inflammatory drugs or drugs for thyroid disease. The relationship between a high BMI and cardiovascular malformation observed in this study may be explained by impaired maternal glucose tolerance.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26405 (URN)10.5271/sjweh.641 (DOI)10945 (Local ID)10945 (Archive number)10945 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Geographic variations in possible risk factors for severe cardiac malformations
    Open this publication in new window or tab >>Geographic variations in possible risk factors for severe cardiac malformations
    2002 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 91, no 2, p. 222-228Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01).

    Conclusion: The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26404 (URN)10.1111/j.1651-2227.2002.tb01699.x (DOI)10944 (Local ID)10944 (Archive number)10944 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Chlorination Byproducts and Nitrate in Drinking Water and Risk for Congenital Cardiac Defects
    Open this publication in new window or tab >>Chlorination Byproducts and Nitrate in Drinking Water and Risk for Congenital Cardiac Defects
    2002 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 89, no 2, p. 124-130Article in journal (Refereed) Published
    Abstract [en]

    Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00–2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26406 (URN)10.1006/enrs.2001.4362 (DOI)10946 (Local ID)10946 (Archive number)10946 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
  • 183.
    Cedergren, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Optimal gestational weight gain for body mass index categories2007In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 110, no 4, p. 759-764Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To establish optimal gestational weight gain for each maternal body mass index (BMI) category based on significant risk estimates of adverse maternal and fetal outcome. METHODS: The study population consisted of 298,648 singleton pregnancies delivered in Sweden between January 1, 1994, and December 31, 2004. The number of individuals in each weight gain class was compared with the number of individuals in all other weight gain classes in the same BMI group with regard to adverse maternal and fetal outcome. Odds ratios were calculated after suitable adjustments. RESULTS: The optimal gestational weight gain in women by prepregnancy BMI was 9-22 lb (4-10 kg) for BMI less than 20, 5-22 lb (2-10 kg) for BMI 20-24.9, less than 20 lb (less than 9 kg) for BMI 25-29.9, and less than 13 lb (less than 6 kg) for BMI of 30 or more. CONCLUSION: The gestational weight gain limits for BMI categories determined in this large population-based cohort study from Swedish Medical Registers showed that a decreased risk of adverse obstetric and neonatal outcomes was associated with lower gestational weight gain limits than was earlier recommended, especially among obese women. © 2007 The American College of Obstetricians and Gynecologists.

  • 184.
    Cedergren, Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Källén, Bengt
    Maternal obesity and the risk for orofacial clefts in the offspring2005In: The Cleft Palate-Craniofacial Journal, ISSN 1055-6656, E-ISSN 1545-1569, Vol. 42, no 4, p. 367-371Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate whether obese women have an increased risk of orofacial clefts in their offspring, compared with average-weight women. Design and Participants: The study was based on information on maternal body mass index (BMI) collected in early pregnancy and on the existence of orofacial clefts in the offspring, ascertained from multiple sources. The study included 1686 women who had infants with an orofacial cleft and as controls all delivered women (n = 988,171) during the study period, 1992 through 2001. Infants with chromosome anomalies were excluded. The women were divided into underweight (BMI <19.8), average weight (reference group, BMI 19.8 to 26), overweight (BMI 26.1 to 29), and obese (BMI >29). Adjustments were made for year of birth, maternal age, parity, and maternal smoking. Results: Obese (BMI >29) mothers had an overall increased risk for having an infant with orofacial clefts: odds ratio 1.30 (95% confidence interval 1.11 to 1.53). This increased risk was higher when the cleft was associated with other major malformations than when it was isolated. There was no statistically significant difference between the risk estimates for cleft lip and cleft palate. Conclusions: In this large sample, a positive association appears between maternal obesity in early pregnancy and orofacial clefts in the offspring. The explanation for this association is not known, but a relationship with undetected type 2 diabetes is one possibility.

  • 185.
    Cedergren, Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Källén, Bengt AJ
    Maternal obesity and infant heart defects2003In: Obesity Research, ISSN 1071-7323, E-ISSN 1550-8528, Vol. 11, no 9, p. 1065-1071Article in journal (Refereed)
    Abstract [en]

    Objective: This study determined whether obese women have an increased risk of cardiovascular defects in their offspring compared with average weight women. Research Methods and Procedures: In a case-control study, prospectively collected information was obtained from Swedish medical health registers. The study included 6801 women who had infants with a cardiovascular defect and, as controls, all delivered women (N = 812,457) during the study period (1992 to 2001). Infants with chromosomal anomalies or whose mothers had pre-existing diabetes were excluded. Obesity was defined as BMI >29 kg/m2, and morbid obesity was defined as BMI >35 kg/m2. Comparisons were made with average weight women (BMI = 19.8 to 26 kg/m2). Results: In the group of obese mothers, there was an increased risk for cardiovascular defects compared with the average weight mothers [adjusted odds ratio (OR) = 1.18, 95% CI, 1.09 to 1.27], which was slightly more pronounced for the severe types of cardiovascular defects (adjusted OR = 1.23, 95% CI, 1.05 to 1.44). With morbid obesity, the OR for cardiovascular defects was 1.40 (95% CI, 1.22 to 1.64), and for severe cardiovascular defects, the OR was 1.69 (95% CI, 1.27 to 2.26). There was an increased risk for all specific defects studied among the obese women, but only ventricular septal defects and atrial septal defects reached statistical significance. Discussion: In this sample, a positive association was found between maternal obesity in early pregnancy and congenital heart defects in the offspring. A suggested explanation is undetected type 2 diabetes in early pregnancy, but other explanations may exist.

  • 186.
    Cedergren, Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Källén, Bengt AJ
    Lund .
    Obstetric outcome of 6346 pregnancies with infants affected by congenital heart defects2006In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 125, no 2, p. 211-216Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate whether pregnancies with infants affected by congenital heart defects are associated with adverse obstetric and perinatal outcome. Study design: In a prospective population-based cohort study from Sweden (1992-2001), 6346 singleton pregnancies with infants affected by congenital heart defects were, after suitable adjustments, compared to all delivered women. Results: The prevalence of cardiovascular defects was 9.1 per 1000 births. Among them, mothers of 6346 infants (71%) had information on maternal smoking habits and maternal height and weight in early pregnancy that enabled the calculation of BMI. All cases with known chromosomal abnormalities and/or maternal pre-existing diabetes were excluded. Eighty-four percent (n = 5338) had an isolated cardiovascular defect. Severe types occurred in 21.7% (n = 1378). In the group of pregnancies with infants affected by congenital heart defects as compared to all delivered women, there was an increased risk of the following outcomes (adjusted OR (95%CI)): pre-eclampsia (1.21 (1.06-1.37)), cesarean section (1.91 (1.79-2.03)), instrumental delivery (1.21 (1.10-1.34)), pre-term delivery (2.58 (2.39-2.79)), small-for gestational age (1.96 (1.77-2.16)), meconium aspiration (1.51 (1.28-1.77)), and fetal distress (1.38 (1.17-1.63)). Conclusions: Pregnancies with infants affected by congenital heart defects are associated with several obstetric and neonatal complications. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 187.
    Cedergren, Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Selbing, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Detection of fetal structural abnormalities by an 11-14-week ultrasound dating scan in an unselected Swedish population2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 8, p. 912-915Article in journal (Refereed)
    Abstract [en]

    Background. To determine the detection rate of fetal structural abnormalities by a routine 11-14-week ultrasound scan for dating in an unselected pregnant population. Methods. A prospective observational cohort study of 2,708 unselected pregnant women attending an abdominal ultrasound examination at 11-14 weeks gestation. The number of major fetal structural abnormalities diagnosed after birth was obtained from a computerized database at the same unit. Results. Out of 2,708 pregnant women, 89 (3.3%) were found to have a missed abortion at the time of the ultrasound scan and 33 (1.2%) were diagnosed as twins. Thirteen major structural abnormalities were detected, three cases of anencephaly (one case also had a spina bifida), one case with hydranencephaly, one fetus with Dandy-Walker syndrome, two cases with gastroschisis, one case with a bilateral hydronephrosis, one case with a generalized hydrops, one fetus with multiple malformations, and three cystic hygromas. An additional 19 major structural defects were detected at birth. Four cases of neural tube defects and nine fetuses with congenital heart defects were diagnosed. The antenatal ultrasound detection rate was 40.6% (13/32). Nine patients had a nuchal translucency greater than 3.0 mm (excluding cystic hygromas), two of them had chromosomal abnormalities (trisomy 21 and trisomy 18). Conclusions. Fetal structural abnormalities were detected in 41% (95%CI = 24-59) of the cases in an unselected pregnant population at a routine 11-14-week ultrasound scan for dating purpose. Two out of nine fetuses with a nuchal translucency greater than 3.0 mm had a chromosomal abnormality. © 2006 Taylor & Francis.

  • 188.
    Cedergren, Marie
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Källén, B.
    Tornblad Institute, University of Lund, Lund, Sweden.
    Geographic variations in possible risk factors for severe cardiac malformations2002In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 91, no 2, p. 222-228Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01).

    Conclusion: The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.

  • 189.
    Cedergren, Marie
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Källén, Bengt AJ
    Tornblad Institute, University of Lund, Lund, Sweden.
    Risk factors for cardiovascular malformation: a study based on prospectively collected data2002In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 28, no 1, p. 12-17Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to identify risk factors for cardiovascular malformation.

    Methods In a case-referent study prospectively collected data were obtained from original medical records. The study included 277 woman who had infants with a severe cardiac defect, and for each case two referents (medical records study) were included. Data on parental age, maternal reproductive history, disease in early pregnancy, reported maternal use of drugs and alcohol, smoking habits, parental occupation, and maternal body mass index (BMI) were extracted. When data were available from Swedish medical health registers, a comparison was made (register study) between all infants with cardiovascular defects (2208) and all infants born (175 768).

    Results Maternal diabetes mellitus was associated with an increased risk for cardiovascular malformation [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.36-4.15], as was a high BMI (>29) (OR 1.46, 95%CI 1.12-1.90). A tendency towards an increased risk was found for involuntary childlessness, spontaneous abortion, thyroid drugs, and nonsteroid anti-inflammatory drugs.

    Conclusions Some known risk factors for cardiac defects (eg, maternal diabetes mellitus and the use of antiepileptics) could be identified. Other postulated risk factors could not be verified, for example, paternal age and parental occupation. The use of medicinal drugs seems not to be a major factor in the etiology of cardiac defects. It is possible, however, that there is an association with the use of nonsteroid anti-inflammatory drugs or drugs for thyroid disease. The relationship between a high BMI and cardiovascular malformation observed in this study may be explained by impaired maternal glucose tolerance.

  • 190.
    Cedergren, Marie
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Löfman, Owe
    Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences. Linköping University, Faculty of Health Sciences.
    Källen, Bengt A. J.
    Tornblad Institute, University of Lund, Lund, Sweden.
    Chlorination Byproducts and Nitrate in Drinking Water and Risk for Congenital Cardiac Defects2002In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 89, no 2, p. 124-130Article in journal (Refereed)
    Abstract [en]

    Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00–2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

  • 191.
    Chowdhury, Shamsul
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Haug, Peter
    Utah University USA.
    Babic, Ankica
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Methods for knowledge extraction from clinical database on liver diseases1991In: Computers and biomedical research, ISSN 0010-4809, E-ISSN 1090-2368, Vol. 24, p. 530-548Article in journal (Refereed)
  • 192.
    Chowdhury, Shamsul
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Mathiesen, Ulrik
    Oskarshamns sjukhus .
    Krusinska, Ewa
    Technical University of Wroclaw, Poland .
    Franzén, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Design and delivery of information resources and knowledge bases for the diagnosis and managementof liver disorders1994In: ANZIIS-94,1994, Brisbane: IEEE , 1994Conference paper (Refereed)
  • 193.
    Christensson, Bertil
    et al.
    Lund.
    Dahlin, Lars-Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Hogevik, Harriet
    Uddevalla.
    Tegnell, Anders
    SMI, KI.
    Öhman, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Infektioner hos reservdelsmänniskan - en epidemiologisk och klinisk översikt.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 11, p. 982-988Article in journal (Other academic)
  • 194.
    Christiansen Clifford, Jenny
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Färm, Gunilla
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Eid-Forest, Ruth
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Dermatology and Venerology UHL.
    Cederbrant, Karin
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology.
    Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold2006In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 55, no 2, p. 101-112Article in journal (Refereed)
    Abstract [en]

    10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

  • 195.
    Claesson, Carina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Svensson, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Susceptibility of staphylococci and enterococci to antimicrobial agents at different ward levels in four north European countries2007In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 39, no 11-12, p. 1002-1012Article in journal (Refereed)
    Abstract [en]

    A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively.

  • 196.
    Coble, Britt-Inger
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Nordahl-Åkesson, E
    Vinnerberg, Å
    Kihlström, Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Urine-based testing for Chlamydia trachomatis using polymerase chain reaction, leucocyte esterase and urethral and cervical smears2006In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, no 4, p. 269-278Article in journal (Refereed)
    Abstract [en]

    The performance of Roche polymerase chain reaction (PCR) Amplicor to detect Chlamydia trachomatis in first-voided urine specimens from 422 males and 456 females attending two clinics for sexually transmitted infections was evaluated in comparison with cultures of urethral and cervical specimens. At the same time, the ability of leucocyte esterase (LE) in first-voided urine and the presence of leucocytes in urethral and cervical smears to identify C. trachomatis -infected individuals based on PCR and culture was determined. The prevalence of C. trachomatis infection was 10.9 % in men and 7.7 % in women. Sensitivity, specificity, positive predictive value and negative predictive value of Amplicor was 93.5 %, 99.7 %, 97.7 % and 99.2 % in males and 91.4 %, 99.5 %, 94.1 % and 99.3 % in females. All Chlamydia-infected men were identified by means of a combination of urethritis (≥4 leucocytes in the urethral smear) and/or a positive LE test in urine, although the specificity was only 42.2 %. In women, the combination of urethritis and/or cervicitis and/or a positive LE test identified 85.7 % of Chlamydia-infected patients with a specificity of 38.2 %. It is concluded that a combination of urethral and/or cervical smears and LE testing of urine can be used as a screening test to select patients, especially males, for specific C. trachomatis testing.

  • 197. Collste, L
    et al.
    Calltorp, J
    Giesecke, K
    Thor, K
    Hauptig, S
    Stjernlöf, U
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sjögren, J
    Gör administrativ medicin till läroämne för läkarkåren!1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, p. 1809-1810Article in journal (Other (popular science, discussion, etc.))
  • 198.
    Connolly, Eamonn
    et al.
    Dept of Research, BioGaia, Stockholm.
    Abrahamsson, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Björkstén, Bengt
    Centrum för Allergiforskning KI, Stockholm.
    Safety of D(-)-lactic acid producing bacteria in the human infant2005In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 41, no 4, p. 489-492Article in journal (Refereed)
  • 199. Connolly-Andersen, AM
    et al.
    Magnusson, Karl-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Mirazimi, A
    Basolateral entry and release of Crimean-Congo hemorrhagic fever virus in polarized MDCK-1 cells2007In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 81, no 5, p. 2158-2164Article in journal (Refereed)
    Abstract [en]

    Crimean-Congo hemorrhagic fever virus (CCHFV) is an etiological agent of a disease with mortality rates in patients averaging 30%. The disease is characterized by fever, myalgia, and hemorrhage. Mechanisms underlying the hemorrhage have to our knowledge not been elucidated for CCHFV. Possibly, a direct or indirect viral effect on tight junctions (TJ) could cause the hemorrhage observed in patients, as TJ play a crucial role in vascular homeostasis and can cause leakage upon deregulation. Moreover, there is no knowledge regarding the site of entry and release of CCHFV in polarized epithelial cells. Such cells represent a barrier to virus dissemination within the host, and as a site of viral entry and release, they could play a key role in further spread. For the first time, we have shown preferential basolateral entry of CCHFV in Madin-Darby canine kidney 1 (MDCK-1) epithelial cells. Furthermore, we demonstrated basolateral release of CCHFV in polarized epithelial cells. Interestingly, by measuring transepithelial electrical resistance, we found no effect of CCHFV replication on the function of TJ in this study. Neither did we observe any difference in the localization of the TJ proteins ZO-1 and occludin in CCHFV-infected cells compared to mock-infected cells. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

  • 200. Constantin, G
    et al.
    Majeed, Meytham
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Giagulli, C
    Piccio, L
    Kim, JY
    Butcher, EC
    Laudanna, C
    Chemokines trigger immediate beta2 integrin affinity and mobility changes: Differential regulation and roles in lymphocytes arrest under flow.2000In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 13, p. 759-769Article in journal (Refereed)
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