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  • 1601.
    Ydrenius, Liselotte
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Majeed, Meytham
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    J Rasmusson, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Stendahl, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Särndahl, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis2000In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 67, no 4, p. 520-528Article in journal (Refereed)
    Abstract [en]

    We have investigated the role of cAMP and cAMP-dependent protein kinase (cAPK) in neutrophil phagocytosis. Inhibition of cAPK with H-89 reduced complement- and IgG-dependent phagocytosis to 83 and 46%, respectively. Fluorescence intensity measurements of phalloidin-stained actin in neutrophils showed a reduced amount of filamentous actin (F-actin) in pseudopods and around the phagosome in cells treated with H-89 or cAMP-elevating agents (forskolin and rolipram). The amount of phosphotyrosine-containing proteins was also reduced in pseudopods and around the phagosome. Taken together, the data show that cAMP/cAPK regulates F-actin reorganization during receptor-mediated phagocytosis, particularly triggered by IgG-FcR interaction. Our results support the hypothesis that active subcortical reorganization of F-actin is a prerequisite for FcR-mediated phagocytosis, but is less important during CR3-mediated ingestion.

  • 1602.
    Yu, Guo
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Polyunsaturated fatty acids in relation to childhood and maternal allergic diseases1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to study polyunsaturated fatty acid (PUPA) in relation to the appem11nce of anergic diseases in children and mothers in late pregnancy and during the lactation period and to the development of atopy in children, as well as the influence of maternal PUF A on their babies.

    The levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polyunsaturated fatty acids (LCP) were lower (p = 0.01 and< 0.05) and the ratio of total n-6 to n-3 LCP was higher (p < 0.01) in serum phospholipids (PL) in 22 allergic school children than in 23 controls. The levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to its precursor dihomo-y-linolenic acid (DHGLA, C20:3n-6) were also lower in 12 children with positive skin prick test (SPT), as compared to SPT negative children (both p < 0.05). Higher levels of C20:2n-6 and lower EPA were recorded in allergic children with serum IgE above the median level (56kU/L), as compared to those with lower IgE levels,

    The levels of DHGLA, eicosapentaenoic acid (EPA, C20:5n-3), DPA and DHA were all lower in milk total lipid (TL) obtained from atopic, as compared to non-atopic mothers after one month oflactation (all p < 0.05). Similarly, the lower levels of DHGLA, AA, EPA, DPA and DHA were also observed in serum 1L of the atopic mothers at the time of delivery (all P < 0.05), while the levels of a-linolenic acid and C20:2n-6 were higher. Several ratios of n-6 to n- 3 LCP in mature milk at 1 and 3 months were significantly higher in atopic than non-atopic mothers (all p < 0.05). An n-3 fatty acid C20:4n-3 was present in human milk, but not in the blood samples of the mothers and children.

    The levels of most of the individual PUFA con·elated well in blood of non-allergic children and in colostrum and mature milk of non-atopic mothers (r > 0.5, p < 0.01 as significant), but the correlations were largely absent in the atopic groups. Furthmore, a correlation between linoleic acid (LA, C18:2n-6) and AA levels was observed in serum samples of non-allergic (r = 0.64, p < 0.001), but not allergic mothers at delivery (r = 0.25, p > 0.05).

    There were some correlations between AA and its precursor DHGLA and metabolite C22:4n-6 and between several n-3 and n-6 LCP, i.e. DPA and C22:4n-6, DHA and DHGLA and AA in semm phospholipids from cord blood of children without a family history of allergy (FHA) and who did not develop allergic diseases during the first 6 years of life. These relationships between the LCP levels were not seen in children with a FHA and in those who developed allergic diseases in later life. Furthermore, an abnormal PUF A composition in maternal blood and breast milk was related to the appearance of allergy in their children.

    The LA levels correlated in 22 non-allergic mothers and their babies at the time of delivery (r = 0.53, p = 0.01). Furthermore, the serum levels of maternal DHGLA correlated with some LCP levels in cord serum of their babies, i.e. AA, C22:4 and DHA (all r= 0.65, p = 0.001). None of these relationships were observed in 25 allergic mothers and their babies.

    The findings confirmed an abnormal PUF A composition in allergic children, in allergic mothers at the time of delivery and early lactation period and in newborn infants who developed allergic diseases during the first 6 years of life. The latter finding indicates that an abnormality of PUF A composition may be primary in allergic diseases. An impaired 0-6-desaturase activity in allergic diseases could not be confirmed, The presence of n-3 series fatty acid C20:4n-3 in human milk but not blood samples may contribute to the anti-inflammatory effect of human milk,

  • 1603.
    Zalavary, Stefan
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Adenosine Regulation of Neutrophil Function1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The neutrophil granulocyte is an essential component of the human immune system. When rrricrobes invade the body, the highly motile neutrophils quickly leave the vascular compartment and approach, engulf and kill the intruders by releasing a battery of antimicrobial substances. Adenosine is an endogenous purine nucleoside that is supposed to regulate the inflammatory response, for example, by modulating the activity of neutrophils through occupation of A1 and Az receptors. The aim of the present work was to characterize the effects of adenosine on neutrophil functions, particularly phagocytosis and the production of reactive oxygen species (ROS).

    Adenosine modulated IgG~mediated phagocytosis in neutrophils in a Ca2+dependent way via stimulatory At and inhibitory Az receptors. The Az receptor~mediated inhibition was associated with an elevation of cAMP, which probably activated protein kinase A (PKA) and thereby interfered with actin dynarrrics and expression of BZ integrins. Production of ROS induced by the chemotactic peptide N~formyl-methionylleucyl~ phenylalanine (fMLP) or IgG~opsonized yeast particles was not affected by occupancy of the At receptor, but was, via a cAMP~dependent mechanism, inhibited by engagement of the A2 receptor. Adenosine also reduced L-selectin-induced production of ROS. The inhibition of ROS production by adenosine was more pronounced during fMLP stimulation than during L~selectin~ and IgG~mediated activation, probably because the latter entailed removal of extracellular adenosine through increased activity of adenosine dearrrinase (ADA).

    Platelets participate in inflammatory reactions, for instance, by affecting neutrophil actiyity. In the present work, platelets inhibited !MLP~stimulated extracellular generation of ROS by inducing the neutrophils to release adenosine and to form a peripheral actin barrier. In contrast, platelets potentiated IgG~mediated phagocytosis and generation of ROS in neutrophils. This involved engagement of neutrophil Pz receptors by plateletderived ATP and enhanced formation of cortical actin filaments. Expanded ADA activity associated with !gO-stimulation counteracted the inhibitory effects of adenosine accumulated during neutrophil-platelet interaction.

    In conclusion, this work accentuates the importance of adenosine, both exogenously applied and endogenously formed, as an inflammatory agent modulating the activity of the neutrophil granulocyte.

  • 1604. Zar, M
    et al.
    Wijma, Klaas
    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.
    Wijma, Barbro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Pre- and postpartum fear of childbirth in nulliparous and parous women.2001In: Scandinavian Journal of Behaviour Therapy, ISSN 0284-5717, Vol. 30, p. 75-84Article in journal (Refereed)
  • 1605. Zar, M
    et al.
    Wijma, Klaas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology.
    Wijma, Barbro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Relations between anxiety disorders and fear of childbirth during late pregnancy2002In: Clinical Psychology and Psychotherapy, ISSN 1063-3995, E-ISSN 1099-0879, Vol. 9, no 2, p. 122-130Article in journal (Refereed)
    Abstract [en]

    In a group of late pregnant women we investigated the prevalence of extreme fear of childbirth and anxiety disorders, both assessed by means of diagnostic interviews. We also explored the relation between anxiety disorders and extreme fear of childbirth on the one hand and fear of childbirth, as measured by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), on the other hand. A subgroup of women (2.4%) fulfilled the criteria for a phobia-like fear of childbirth. Anxiety disorders were related to fear of childbirth, as measured by the W-DEQ. The group of women with extreme fear of childbirth (with or without anxiety disorders) had obviously the highest W-DEQ scores. But also in the group of women with anxiety disorders only the W-DEQ scores were high. Clinical assessment of anxiety disorders among pregnant women should be considered, above all in women who report fear of the anticipated delivery. Copyright ⌐ 2002 John Wiley & Sons, Ltd.

  • 1606.
    Zdolsek, Helena
    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.
    Reduced levels of soluble CD14 in atopic children2004In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, p. 532-539Article in journal (Refereed)
    Abstract [en]

    Background A reduced microbial stimulation has been reported as a reason for the increasing prevalence of atopic diseases in industrialized countries. Antigen-presenting cells (APC), responding to microbial signals by pattern recognition receptors such as CD14, have an important role in the development of the Th1/Th2 balance.

    Objective We hypothesized that atopic children have a lower expression of CD14 on monocytes and lower soluble CD14 levels (sCD14).

    Methods Seventy-six children were followed prospectively from birth and signs of atopic disease were evaluated. The expression of CD14 on monocytes was analysed with flow cytometry at 0, 3, 6, 12 and 18 months. Circulating levels of sCD14 were analysed by ELISA and total IgE was analysed by fluoroenzymo immunoassay at these ages, and in a subgroup, followed up at 7 years.

    Results Levels of sCD14 were reduced at 7 years both in children with a current or a cumulative history of atopy compared to non-atopic children with P=0.002 and 0.001, respectively. Sensitized children with atopic symptoms had lower sCD14 at 3 and 18 months and at 7 years of age than non-atopic non-sensitized children with P=0.023, 0.039 and 0.008, respectively.

    Conclusion The lower levels of sCD14 observed in atopic children may be a consequence of an atopic family heredity and/or atopic disease, but it may also reflect a reduced capacity to respond to microbial signals.

  • 1607.
    Zetterström, Olle
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Östergötlands Läns Landsting, Centre for Medicine, Allergy Centre UHL.
    Buhl, R
    Mellem, H
    Andersson, F
    The whole story: treatment outcomes with Symbicort?2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no Supplement A, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort(R) (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort(R) were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physician education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort(R) is more cost-effective than treatment with budesonide alone.

  • 1608.
    Zheng, Limin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology .
    Forsberg, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Stendahl, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology .
    Invasive Salmonella typhimurium induces apoptosis in human U937 cells by activating Rho GTPases2000In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 11, p. 1527-Conference paper (Other academic)
  • 1609.
    Zimmerli, Stefan
    et al.
    Division of Infectious Diseases and The Rosalind Russell Arthritis Research Laboratory, San Francisco General Hospital, University of California at San Francisco, San Francisco, California, USA.
    Majeed, Meytham
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mikael
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sanan, David A.
    Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
    Ernst, Joel D.
    Division of Infectious Diseases and The Rosalind Russell Arthritis Research Laboratory, San Francisco General Hospital, University of California at San Francisco, San Francisco, California, USA.
    Phagosome-Lysosome Fusion Is a Calcium-independent Event in Macrophages1996In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 132, no 1-2, p. 49-61Article in journal (Refereed)
    Abstract [en]

    Phagosome-lysosome membrane fusion is a highly regulated event that is essential for intracellular killing of microorganisms, Functionally, it represents a form of polarized regulated secretion, which is classically dependent on increases in intracellular ionized calcium ([Ca2+](i)). Indeed, increases in [Ca2+](i) are essential for phagosome-granule (lysosome) fusion in neutrophils and for lysosomal fusion events that mediate host cell invasion by Trypanosoma cruzi trypomastigotes, Since several intracellular pathogens survive in macrophage phagosomes that do not fuse with lysosomes, we examined the regulation of phagosome-lysosome fusion in macrophages. Macrophages (MO) were treated with 12.5 mu M bis-(2-amino-S-methylphenoxy) ethane-N,N,N',N',-tetraacetic acid tetraacetoxymethyl ester (MAPT/AM), a cell-permeant calcium chelator which reduced resting cytoplasmic [Ca2+]; from 80 nM to less than or equal to 20 nM and completely blocked increases in [Ca2+](i) in response to multiple stimuli, even in the presence of extracellular calcium, Subsequently, MO phagocytosed serum-opsonized zymosan, staphylococci, or Mycobacterium bovis, Microbes were enumerated by 4',6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining, and phagosome-lysosome fusion was scored using both lysosome-associated membrane protein (LAMP-1) as a membrane marker and rhodamine dextran as a content marker for lysosomes, Confirmation of phagosomelysosome fusion by electron microscopy validated the fluorescence microscopy findings, We found that phagosome-lysosome fusion in MO occurs normally at very low [Ca2+](i) (less than or equal to 20 nM), Kinetic analysis showed that in MO none of the steps leading from particle binding to eventual phagosome-lysosome fusion are regulated by [Ca2+](i) in a rate-limiting way. Furthermore, confocal microscopy revealed no difference in the intensity of LAMP-1 immunofluorescence in phagolysosome membranes in calcium-buffered vs, control macrophages, We conclude that neither membrane recognition nor fusion events in the phagosomal pathway in macrophages are dependent on or regulated by calcium.

  • 1610. Zouali, H
    et al.
    Chamaillard, M
    Lesage, S
    Cezard, JP
    Colombel, JF
    Belaiche, J
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Tysk, C
    Montague, S
    Gassull, M
    Christensen, S
    Finkel, Y
    Gower-Rousseau, C
    Modigliani, R
    Macry, J
    Selinger-Leneman, H
    Thomas, G
    Hugot, JP
    Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease2001In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 9, no 10, p. 731-742Article in journal (Refereed)
    Abstract [en]

    Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37 ╫ 10-4) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.

  • 1611. Zouali, H
    et al.
    Lesage, S
    Merlin, F
    Cezard, JP
    Colombel, JF
    Belaiche, J
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-magtarm.
    Tysk, C
    O'Morain, C
    Gassull, M
    Christensen, S
    Finkel, Y
    Modigliani, R
    Gower-Rousseau, C
    Macry, J
    Chamaillard, M
    Thomas, G
    Hugot, JP
    CARD4/NOD1 is not involved in inflammatory bowel disease2003In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 52, no 1, p. 71-74Article in journal (Refereed)
    Abstract [en]

    Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic Factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

  • 1612. Zwaan, Christian M
    et al.
    Reinhardt, Dirk
    Corbacioglu, Selim
    van Wering, Elisabeth R
    Bökkerink, Jos PM
    Tissing, Wím JE
    Samuelsson, Ulf
    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.
    Feingold, Jay
    Creutzig, Ursula
    Kaspers, Gertjan
    Gemtuzumab ozomagicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated onc ompassionate use basis.2003In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, p. 3868-3871Article in journal (Refereed)
  • 1613.
    Åkerblom, Hans
    et al.
    Biomedicum, Helsinki, Finland.
    Virtanen, SM
    Tampere Schoolf of Public Health, Tampere, Finland.
    Ilonen, Jorma
    Dept of Virology, Univeristy of Turku, Finland.
    Savilathi, Errki
    Biomedicum, Helsinki, Finland.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Reunanen, A
    Dept of Health and Functional Capacity, Helsinki, Finland.
    Teramo, K
    Dept of Obstetics and Gynecology, Helsinki, Finland.
    Hämäläinen, A M
    Dept of Pediatrics, University of Oulu, Finland.
    Paronen, J
    Biomedicum, Helsinki, Finland.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: A pilot study2005In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 48, no 5, p. 829-837Article in journal (Refereed)
    Abstract [en]

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

  • 1614.
    Öberg, Åke
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Assessment of cartilage thickness utilising reflectance spectroscopy2004In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 42, no 1Article in journal (Refereed)
    Abstract [en]

    A new principle for cartilage layer thickness assessments in joints is presented. It is based on the differences between the absorption spectra of cartilage and subchondral bone (containing blood). High-resolution ultrasound measurements of cartilage thickness were compared with reflection spectroscopy data from the same area of bovine hip joint condyles. A simple mathematical model allowed calculation of thickness and comparison with ultrasound data. The cartilage thickness was changed by being ground in short episodes. For thicker cartilage layers, a high degree of reflection in the 400-600nm wavelength interval was seen. For thinner cartilage layers, the characteristics of the spectra of blood and bone dominated those of cartilage. The mean (±SD) thickness of intact cartilage was 1.21± 0.30 mm (n = 30). In an exponential regression model, spectroscopic estimation of cartilage thickness showed a correlation coefficient of r= 0.69 (n = 182). For thinner cartilage layers (d<0.5mm), the mean model error was 0.19±0.17mm. Results from a bi-layer Monte Carlo simulation supported the assumption of an exponential relationship between spectroscopy data and reference ultrasound data. The conclusion is that optical reflection spectroscopy can be used for cartilage layer thickness assessment.

  • 1615.
    Öberg, Åke
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Sundberg, Mikael
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Characterisation of the cartilage/bone interface utilising reflectance spectroscopy2001In: 23rd Annual International Conference IEEE EMBS,2001, IEEE , 2001, Vol. 3, p. 3002-3004Conference paper (Refereed)
    Abstract [en]

    Optical reflection spectra of the cartilage/bone interface from hip joints of cows were studied. When comparing to ultrasonic measurement, it was found that cartilage thickness could be extracted using optical reflectance spectroscopy. For thicker cartilage layers, a high reflection for the wavelengths 400-600 nm was seen, and for thinner cartilage layers, the characteristic spectra of blood and bone dominated. The optical reflectance spectra may be used to characterise cartilage, and specifically cartilage thickness, in connection with in situ diagnosis or autologous chondrocyte implantation (ACI).

  • 1616.
    Örtegren Kugelberg, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Yin, Lan
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 14, p. 3381-3392Article in journal (Refereed)
    Abstract [en]

    Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

  • 1617.
    Örtqvist, Eva
    et al.
    Astrid Lindgrens Barnsjukhus Stockholm.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Åman, Jan
    Barnkliniken Universitetssjukhuset, Örebro.
    Johansson, Calle
    Barnkliniken Ryhovs sjukhus, Jönköping.
    Karlsson, Anders
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Forsander, Gun
    Barnkliniken Lasarettet, Falun.
    Lindgren, Fredrik
    Sachsska Barnsjukhuset Stockholm.
    Persson, Bengt
    Astrid Lindgrens Barnsjukhus Stockholm.
    Berglund, Lars
    Clinical Research Centre Uppsala Universitet.
    Berne, Christian
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Bengtsson, Mats
    Klinisk Immunologi Uppsala Universitet.
    Björk, Elisabeth
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Wallensteen, Måna
    Astrid Lindgrens Barnsjukhus Stockholm.
    Temporary preservation of β-cell function by diazoxide treatment in childhood type 1 diabetes2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 9, p. 2191-2197Article in journal (Refereed)
    Abstract [en]

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

  • 1618.
    Örtqvist, Å.
    et al.
    Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.
    Valtonen, M.
    University Central Hospital, Helsinki, Finland.
    Cars, O.
    Uppsala University, Sweden.
    Wahl, M.
    Östra Hospital, Göteborg University, Sweden.
    Saikku, P.
    University of Oulu and National Public Health Institute, Finland.
    Jean, C.
    Rhone DPC Europe, Paris, France.
    Augustinsson (Nilsdotter-Augustinsson), Åsa
    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.
    Oral empiric treatment of community-acquired pneumonia: A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group1996In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 110, no 6, p. 1499-1506Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVE:

    Comparison of efficacy and safety of sparfloxacin (Spfx) vs roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP).

    DESIGN:

    Multicenter, double-blind, randomized study.

    SETTING:

    Twenty-three university and community hospitals in Scandinavia.

    PATIENTS:

    Three hundred four adults (> or = 18 years of age) with CAP treated as outpatients (25%) or inpatients (75%).

    INTERVENTIONS:

    Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses in intention-to-treat (ITT) and evaluable populations.

    RESULTS:

    Three hundred three of 304 patients were included in the ITT and safety analyses and 260 (86%) were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40 (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT population, and 94% and 79%, respectively, in the evaluable population. The odds ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the evaluable population. Both drugs were, overall, equally safe. GI symptoms were the most common adverse experiences in both groups. Prolongation of QTc, without clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients, and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group.

    CONCLUSIONS:

    Oral treatment with Spfx was superior to ROXI for the treatment of moderately severe CAP. Spfx was effective for all isolated pathogens, including S pneumoniae, and may be an alternative for empiric treatment of CAP, especially in areas with a high incidence of beta-lactam-resistant pneumococci.

  • 1619.
    Östling, Ann
    et al.
    Landstinget Västmanland.
    Weitz, Per
    Landstinget Västmanland.
    Bäckman, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Department of Molecular and Clinical Medicine.
    Garpenby, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics.
    Öppna prioriteringar i Landstinget Västmanland2010Report (Other academic)
    Abstract [sv]

    Landstinget Västmanland genomförde under 2009 en öppen prioriteringsprocess. I landstinget hade en medvetenhet vuxit fram bland politiker, högre tjänstemän och medarbetare om att de traditionella metoderna ‒ såsom att förändra strukturer, effektivisera och rationalisera ‒ inte räckte som verktyg för en bra resursfördelning.

    Motivet för landstinget att påbörja detta arbete var främst de stora utmaningar som väntade i form av ökade medicinska möjligheter som gör att fler människor kan bli föremål för insatser från hälso- och sjukvården. Ett medel för landstinget att möta detta var öppna prioriteringar – såväl vertikalt (inom verksamheter och specialiteter) som horisontellt (mellan verksamheter och specialiteter). Samtliga partier inom såväl majoritet som opposition ställde sig bakom processen. Syftet med prioriteringsprocessen var att den skulle bidra till en mer rättvis öppen fördelning av landstingets tillgängliga resurser. Arbetet med "Öppna prioriteringar", som processen kom att kallas, ingick också som en del av en större förändringsprocess inom landstinget – som gick under namnet HOPP (Helhet Och PatientPerspektiv.

    I denna rapport presenteras planeringen och genomförandet av prioriteringsprocessen i Landstinget Västmanland 2009/2010. Beskrivningen bygger till största delen på erfarenheter sammanställda av landstingets två projektledare. I Appendix presenteras även delar av den uppföljning av arbetet som Prioriteringscentrum gjorde genom enkäter till olika aktörer i prioriteringsarbetet.

    Ett viktigt inslag i förberedelsearbetet var att genomföra ett antal studiebesök i landsting som tidigare genomfört prioriteringsarbeten, såsom Västerbottens läns landsting, Landstinget Kronoberg och Jämtlands läns landsting. Avsikten var att ta fasta på deras erfarenheter och överväga dessa inför byggandet av den egna prioriteringsprocessen. Det som kom att utmärka Västmanlands prioriteringsprocess var ansträngningarna att skapa en process där intern öppenhet och interaktion mellan många olika parter stod i fokus; verksamhetsföreträdare, politiker och koncernledningen. Förutsättningar för insyn och dialog skapades genom att de tillsammans arbetade med förslagen fram till slutresultatet.

    Den 15 januari 2010 fattade Landstingsstyrelsen i Västmanland slutligen det formella beslutet om vilka objekt som skulle ingå i listan över öppna prioriteringar som arbetats fram. Beslutsunderlaget omfattade såväl effektiviseringsobjekt som prioriteringsobjekt, motsvarande 2,4 procent av nettobudgeten, i siffror 106 miljoner kronor.

     

    Den lista över prioriteringsobjekt som slutligen presenterades för verksamheterna och för allmänheten innehöll ca 160 objekt fördelade under fyra olika rubriker:

    1.  Objekt för bortprioritering

    2.  Objekt med lägre ambitionsnivå alternativt högre indikationsnivå

    3.  Objekt som underlag för dialog med framför allt kommunerna

    4.  Objekt som rörde avgifter och bidrag.

    Download full text (pdf)
    Öppna prioriteringar i Landstinget Västmanland
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