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  • 1.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Lindell, Å
    Åselius, H
    Sörén, Lars
    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.
    Svensson, L
    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.
    Eribe, ERK
    Olsen, I
    Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families2005In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 110, no 3, p. 217-231Article in journal (Refereed)
    Abstract [en]

    We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A, Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

  • 2.
    Aspevall, Olle
    et al.
    Karolinska Inst Stockholm.
    Forsum, Urban
    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.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Preiminary report: Concepts and terms used to describe urinary tract infection in primary health care and in the clinical microbiology laboratory1999In: Medical Informatics Europe99,1999, Amsterdam: IOS Press , 1999, p. 899-Conference paper (Refereed)
  • 3.
    Aspevall, Olle
    et al.
    Karolinska institutet Stockholm.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Forsum, Urban
    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.
    Building a concept system to structure the contents of a decision support system - a grounded theory study of concepts in the knowledge domain of urinary tract infection2001In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 26, no 2, p. 115-129Article in journal (Refereed)
  • 4.
    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.

  • 5.
    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.

  • 6.
    Dahle, Charlotte
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Åberg, A K
    Örebro.
    Jalal, A
    Örebro.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Methods of choice for diagnostic antinuclear antibody (ANA) screening: Benefit of adding antigen-specific assays to immunofluorescence microscopy2004In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 22, no 3, p. 241-248Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate and compare the performances of three enzyme-immunoassays (EIAs) and a double radial immunodiffusion (DRID) test in addition to immunofluorescence (IF) microscopy for routine laboratory screening of patient sera sent for antinuclear antibody (ANA) analysis. Methods. 3079 consecutive patient sera sent for routine testing of ANA were analysed by IF microscopy on HEp-2 cells (IF-ANA), three different ANA-EIAs, and a DRID test for antibodies against extractable nuclear antigens. The IF-ANA and DRID tests were regarded as reference methods. Results. By IF-ANA and/or DRID, 375 sera (12%) turned out ANA-positive. A further 171 sera (6%) were positive by EIA, but could not be confirmed either by IF microscopy or DRID. 32 of the 375 ANA-positive (9%) sera were negative by IF microscopy, but had precipitating antibodies against Ro/SS-A (52 and/or 60 kD). Conclusions. Different assays for ANA analysis give overlapping results to a certain extent, but are by no means interchangeable. Thus, different ANA tests reflect different aspects of these autoantibodies. The diagnostic utility of ANA testing still mainly refers to IF-microscopy and precipitin tests. IF-ANA should not be abandoned as the golden standard in clinical routine, until diagnostic and classification criteria for systemic lupus erythematosus and other systemic inflammatory autoimmune diseases have been revised. However, in addition we strongly advocate that a specific test for anti-Ro/SS-A antibodies is always included.

  • 7.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    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.
    Jönsson, Anna-Lena
    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.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ärlehag, L
    Forsum, Urban
    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.
    Lyme borreliosis in Sweden - Diagnostic performance of five commercial Borrelia serology kits using sera from well-defined patient groups2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 1, p. 74-78Article in journal (Refereed)
    Abstract [en]

    Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.

  • 8.
    Eriksson, K
    et al.
    Department of Obstetrics and Gynecology, Ålands Centralsjukhus, Finland.
    Forsum, Urban
    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.
    Björnerem, A
    Dept. of Obstetrics and Gynecology, Regionssjukhuset, Tromsö, Norway.
    Platz-Christensen, JJ
    Dept. of Obstetrics and Gynecology, University Hospital of Malmö.
    Larsson, Per-Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine.
    Validation of the use of Pap-stained vaginal smears for diagnosis of bacterial vaginosis2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 7, p. 809-813Article in journal (Refereed)
    Abstract [en]

    Papanicolaou-stained cervicovaginal smears (Pap smears) are used to screen for cervical cancer. Since there is a lack of consensus in published reports respecting the efficacy of Pap-stained smears in BV diagnostics, there is a need to validate their use for diagnosis of BV. Slides from the international BV00 workshop were Pap stained and independently analyzed by four investigators under a phase-contrast microscope. All workshop slides - whether Pap-stained, Gram-stained or rehydrated air-dried smears - were scored according to the same Nugent classification. The diagnostic accuracy of Pap smears for diagnosis of BV had a sensitivity of 0.85 and a specificity of 0.92, with a positive and negative predictive value of 0.84 and 0.93, respectively. The interobserver weighted kappa index was 0.86 for Pap-stained smears compared to 0.81 for Gram-stained smears, and 0.70 for rehydrated air-dried smears using the mean Nugent score as the criterion standard. Provided that the samples are taken from equivalent locations (the vaginal fornix) and analyzed according to the same scoring criteria, there is no discernable difference in the diagnostic accuracy of the three smear-staining methods. The Pap-stained vaginal smears can be used as a wholly adequate alternative to Gram-stained smears for BV diagnosis. © Apmis 2007.

  • 9.
    Eriksson, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Carlsson, Bodil
    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.
    Forsum, Urban
    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.
    Larsson, P-G
    Department of Obstetrics and Gynecology, Central Hospital of Sko¨vde, Sweden.
    A double-blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules2005In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 85, no 1, p. 42-46Article in journal (Refereed)
    Abstract [en]

    The expected 4-week cure rate after conventional treatment of bacterial vaginosis are only 65-70%. In an attempt to improve the cure rate by adding probiotic lactobacilli we performed a double-blind placebo-controlled study of adjuvant lactobacilli treatment after an open treatment with vaginal clindamycin ovules. Women with bacterial vaginosis as defined by Amsel's criteria were treated with clindamycin ovules. Vaginal smears were collected and analysed according to Nugent's criteria. During the following menstruation period the women used, as an adjuvant treatment, either lactobacilli-prepared tampons or placebo tampons. The lactobacilli tampons were loaded with a mixture of freeze-dried L. fermentum, L. casei var. rhamnosus and L. gasseri. The cure rate was recorded after the second menstruation period. There was no improvement in the cure rate after treatment with lactobacilli-containing tampons compared to placebo tampons, the cure rates as defined by Amsel's criteria were 56% and 62%, respectively, and 55% and 63%, as defined by Nugent's criteria. This is the first study to report cure rates for women with 'intermediate' wet smear ratings according to Nugent's classification and this group had an overall cure rate of 44%. The cure rate of treatment of bacterial vaginosis was not improved by using lactobacilli-prepared tampons for one menstruation.

  • 10.
    Forsberg, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Signal transduction in human phagocytic cells during phagocytosis, oxidative activation and apoptosis2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neutrophils and macrophages are professional phagocytic cells that play a crucial role in host defense against invading microorganisms. They bind to, internalize, and subsequently kill microbes with an arsenal of reactive oxygen metabolites and microbicidal agents. The microbes are recognized by cell surface receptors, mainly by the phagocytic receptors FcγR and complement receptor 3 (CR3) that recognize IgG and complement fragments C3b/C3bi, respectively. Microbial pathogens such as Salmonella typhimurium have developed sophisticated mechanisms to avoid the host defense system and enter the cells by invasion, mediated by a type III secretion system.

    The objective of this thesis was to investigate the signaling pathways during receptor-mediated phagocytosis by FcγRIIa, FcγRIIIb and complement receptor 3 (CR3), or during invasion by Salmonella typhimurium in human phagocytic cells. We have focused on the intracellular signaling pathways controlling phagocytosis, production of reactive oxygen metabolites, and apoptosis. Paper I-III focus on signal transduction events triggered after ligation of CR3, FcγRIIa, and FcγRIIIb in human neutrophils. Both activation of CR3 and FcγR induced production of reactive oxygen metabolites (ROM), where CR3 induced the most prominent response. The ROM production was dependent on intracellular Ca2+, tyrosine kinase activation, and phospholipase D (PLD) activity. FcγRIIa induced a strong phosphorylation Syk, which was less pronounced following FcγRIIIb ligation, and absent after CR3 activation. Our data indicate that CR3 and FcγR activate different signaling pathways. By exposing neutrophils to TNF-α prior to ligation of CR3, the oxidative response was strongly enhanced, whereas the response to FcγR-ligation was unaffected. This increase was in part due to a p38 MAPK-dependent upregulation of CR3 on the cell surface, but also due to modulation of intracellular signaling pathways since Syk was activated by CR3 as well as FcγR in TNF-α treated cells. In contrast to macrophages where only FcγR activates Rac, Cdc42, and the subsequent ROM production, we show that CR3 as well as FcγR activate the GTPases Rac2 and Cdc42 in human neutrophils. Their downstream target p21 activated kinase was also activated, and Rac2 translocated to the membrane fraction. Correct function of these small GTP-binding proteins was necessary for generating a proper signal for ROM production in these cells.

    One survival strategy exploited by microbial pathogens might be to induce apoptosis of tbe host. Invasive Salmonella typhimurium efficiently entered U937 cells and induced a pronounced degree of apoptosis in contrast to its opsonized mutants, which were internalized by receptor-mediated phagocytosis but failed to induce apoptosis. Invasion by Salmonella typhimurium activated Rac1 and Cdc42 independently of PI3 K and tyrosine kinase activation. Inhibition of Racl and Cdc42 inhibited both invasion and the induction of apoptosis. Receptor-mediated phagocytosis activated the survival signals Akt/PKB which protected the cells from apoptosis. Thus, control of apoptosis is a fine tuned balance between pro- and anti-apoptotic signaling proteins.

    List of papers
    1. CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
    Open this publication in new window or tab >>CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
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    1999 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1452, no 1, p. 46-59Article in journal (Refereed) Published
    Abstract [en]

    Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcγRIIA and FcγRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcγRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcγRIIA Pansorbins induced an even weaker signal. However, FcγRIIA induced strong phosphorylation of p72syk whereas FcγRIIIB induced only a very weak p72syk phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72syk was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72syk that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72syk phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcγRIIA and FcγRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72syk is an early signal in the cascade induced by FcγRIIA but not by CR3.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25448 (URN)10.1016/S0167-4889(99)00112-3 (DOI)9894 (Local ID)9894 (Archive number)9894 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Tumour necrosis factor-α potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils
    Open this publication in new window or tab >>Tumour necrosis factor-α potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils
    2001 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 103, no 4, p. 465-472Article in journal (Refereed) Published
    Abstract [en]

    CR3 and FcγRs are the main receptors involved in the phagocytic process leading to engulfment and killing of microbes by production of reactive oxygen intermediates (ROI) and degranulation. Various inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS), are known to prime neutrophils leading to increased bactericidal responses, but the underlying mechanism of priming has only been partially elucidated. The purpose of this study was to investigate how TNF-α primes neutrophils for subsequent stimuli via either CR3 or FcγR. The receptors were specifically activated with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3, anti-FcγRIIa, or anti-FcγRIIIb monoclonal antibody. Activation of neutrophils with these particles resulted in ROI production as measured by chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production in neutrophils. TNF-α potentiated the CR3-mediated respiratory burst but had little effect on that mediated by FcγRs. The priming effect of TNF-α on CR3-mediated ROI production is associated with an increased activation of p38 MAPK as well as tyrosine phosphorylation of p72syk. Pretreatment of neutrophils with the inhibitors for p38 MAPK and p72syk markedly suppressed the respiratory burst induced by CR3. Furthermore, TNF-α induced about a three-fold increase in the expression of CR3 in neutrophils, an effect which is blocked by the p38 MAPK inhibitor. Taken together, these results showed that TNF-α potentiates the CR3-mediated respiratory burst in neutrophils not only by triggering a p38 MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling pathways.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25910 (URN)10.1046/j.1365-2567.2001.01270.x (DOI)10352 (Local ID)10352 (Archive number)10352 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils
    Open this publication in new window or tab >>Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils
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    2003 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 611-619Article in journal (Refereed) Published
    Abstract [en]

    Phagocytosis is a complex process engaging a concerted action of signal-transduction cascades that leads to ingestion, subsequent phagolysosome fusion, and oxidative activation. We have previously shown that in human neutrophils, C3bi-mediated phagocytosis elicits a significant oxidative response, suggesting that activation of the small GTPase Rac is involved in this process. This is contradictory to macrophages, where only Fc receptor for immunoglobulin G (FcγR)-mediated activation is Rac-dependent. The present study shows that engagement of the complement receptor 3 (CR3) and FcγR and CR3- and FcγR-mediated phagocytosis activates Rac, as well as Cdc42. Furthermore, following receptor-engagement of the CR3 or FcγRs, a downstream target of these small GTPases, p21-activated kinase, becomes phosphorylated, and Rac2 is translocated to the membrane fraction. Using the methyltransferase inhibitors N-acetyl-S-farnesyl-L-cysteine and N-acetyl-S-geranylgeranyl-L-cysteine, we found that the phagocytic uptake of bacteria was not Rac2- or Cdc42-dependent, whereas the oxidative activation was decreased. In conclusion, our results indicate that in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24991 (URN)10.1189/jlb.1102525 (DOI)9411 (Local ID)9411 (Archive number)9411 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages: potential role of Rho–GTPases and Akt
    Open this publication in new window or tab >>Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages: potential role of Rho–GTPases and Akt
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    2003 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 620-629Article in journal (Refereed) Published
    Abstract [en]

    In addition to direct activation of caspase-1 and induction of apoptosis by SipB, invasive Salmonella stimulates multiple signaling pathways that are key regulators of host cell survival. Nevertheless, little is known about the relative contributions of these pathways to Salmonella-mediated death of macrophages. We studied human monocytic U937 cells and found that apoptosis was induced by invading wild-type Salmonella typhimurium but not by phagocytosed, serum-opsonized, noninvasive Salmonella mutants. Pretreating U937 cells with inhibitors of tyrosine kinases or phosphatidylinositol-3 kinase (PI-3K) completely blocked phagocytosis of opsonized Salmonella mutants but did not affect invasion by wild-type Salmonella or the apoptosis caused by invasion. However, pretreatment with GGTI-298, a geranylgeranyltransferase-1 inhibitor that prevents prenylation of Cdc42 and Rac1, suppressed Salmonella-induced apoptosis by ∼70%. Transduction of Tat fusion constructs containing dominant-negative Cdc42 or Rac1 significantly inhibited Salmonella-induced cell death, indicating that the cytotoxicity of Salmonella requires activation of Cdc42 and Rac. In contrast to phagocytosis of opsonized bacteria, invasion by S. typhimurium stimulated Cdc42 and Rac1, regardless of the activities of tyrosine- or PI-3K. Moreover, Salmonella infection activated Akt protein in a tyrosine-kinase or PI-3K-dependent manner, and a reduced expression of Akt by antisense transfection rendered the cells more sensitive to apoptosis induced by opsonized Salmonella. These results indicate that direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells, whereas the simultaneous activation of Akt by tyrosine kinase and PI-3K during receptor-mediated phagocytosis protects cells from apoptosis.

    Keywords
    macrophages, bacterial apoptosis, signal transduction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14003 (URN)10.1189/jlb.1202586 (DOI)
    Available from: 2006-09-27 Created: 2006-09-27 Last updated: 2017-12-13Bibliographically approved
  • 11.
    Forsum, Urban
    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.
    The Swedish Society for Medical Microbiology, activities and scientific success during the first 100 years.2007Collection (editor) (Refereed)
  • 12.
    Forsum, Urban
    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.
    Varning för Ellen!2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 17, p. 1544-1544Article in journal (Other (popular science, discussion, etc.))
  • 13.
    Forsum, Urban
    et al.
    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.
    Danielsson, Dan
    Uppsala.
    Developments in the recent past - Immunology2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 5, p. 406-408Article in journal (Other academic)
  • 14.
    Forsum, Urban
    et al.
    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.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Annorlunda kurslitteratur. Skönlitteratur en del av läkarutbildningen i Linköping.2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 35, p. 2483-2484Article in journal (Other academic)
  • 15.
    Forsum, Urban
    et al.
    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.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Literary fiction in the medical programme2006In: Celebrating the past by expanding the future.: the Faculty of Health Sciences, Linköping University 1986-2006 / [ed] Mats Hammar, Björn Bergdahl, Lena Öhman, Lecture Notes in Computer Science , 2006, p. 38-40Chapter in book (Other academic)
    Abstract [en]

    During the fall of 2006, the Faculty of Health Sciences (FHS) celebrates its 20th birthday. Linköping has a long tradition of health education; our nursing programme started already in 1895 and occupational therapy began in 1965. From the late 1960’s, medical students from Uppsala spent their last seven semesters in Linköping, mainly for clinical studies. After some years, academic and teachers from the young faculty, together with the county council, realized the enormous potential benefits of a complete undergraduate medical programme at Linköping University. Inspired by apparent innovations from McMaster University in Canada, Maastricht in Holland, Ben Gurion in Israel and Tromsø in Norway, these ideas and ideals were gradually turned into reality. In a complicated process, concerning the life or death of the medical faculty, a close co-operation between the University and the County Council of Östergötland was extremely fruitful. A proposal regarding a complete medical programme, and study periods integrated between the other health education programmes, was forwarded to the Swedish government in December 1982 and approved in 1984.

  • 16.
    Forsum, Urban
    et al.
    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.
    Hallander, Hans O.
    Swedish Institute for Infectious Disease Control Stockholm.
    Kallner, Anders
    Dept of Clinical Chemistry Karolinska Univesity Hospital.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    The impact of qualitative analysis in laboratory medicine2005In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 24, no 6, p. 546-555Article in journal (Refereed)
    Abstract [en]

    Laboratory medicine is a challenge for the metrologically and terminologically inclined scientist. One main reason is the need for a sound theory that can be applied in a systematic way to cover all aspects of examinations, i.e., those procedures whose results are reported on an ordinal scale and those reported on more primitive scales (e.g., classifications and narratives). Validation of procedures for examinations involving properties on a nominal scale is especially difficult to achieve because it is hard to find gold standards, in the conventional sense, against which to validate and which combine performance characteristics and clinically relevant specificity and sensitivity. We present a systematic, unambiguously defined terminology (the C-NPU coding scheme) for metrologically derived terms for expressing properties, and present some examples of how to attain diagnostic goals. If the analytic process in the laboratory can be subsumed into medical contexts in a systematic way, many pitfalls in reporting results can be avoided. © 2005 Elsevier Ltd. All rights reserved.

  • 17.
    Forsum, Urban
    et al.
    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.
    Holst, E
    Larsson, Per-Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Vasquesz, A
    Jakobsson, Tell
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Mattsby-Baltzer, I
    Bacterial vaginosis - A microbiological and immunological enigma2005In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 113, no 2, p. 81-90Article in journal (Refereed)
    Abstract [en]

    The development of bacterial vaginosis (BV) among women of childbearing age and the resulting quantitative and qualitative shift from normally occurring lactobacilli in the vagina to a mixture of mainly anaerobic bacteria is a microbiological and immunological enigma that so far has precluded the formulation of a unifying generally accepted theory on the aetiology and clinical course of BV. This critical review highlights some of the more important aspects of BV research that could help in formulating new basic ideas respecting the biology of BV, not least the importance of the interleukin mediators of local inflammatory responses and the bacterial shift from the normally occurring lactobacilli species: L. crispatus, L. gasseri, L. jensenii, and L. iners to a mixed flora dominated by anaerobic bacteria. Copyright © APMIS 2005.

  • 18.
    Forsum, Urban
    et al.
    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.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Begrepp och termer inom hälso- och sjukvård1999In: Socialmedicinsk tidskrift, ISSN 0037-833X, no 6, p. 540-547Article in journal (Refereed)
  • 19.
    Forsum, Urban
    et al.
    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.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Terminology, categories and representation of examinations in laboratory medicine [2]2005In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 43, no 3, p. 344-345Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 20.
    Forsum, Urban
    et al.
    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.
    Larsson, P-G
    Bakteriell vaginos2004Book (Other academic)
  • 21.
    Forsum, Urban
    et al.
    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.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Skurnik, Mikael
    Diagnostic clinical bacteriology - Recent developments in the application of molecular biology tools2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 11-12, p. 709-712Article in journal (Refereed)
  • 22.
    Forsum, Urban
    et al.
    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.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Skurnik, Mikael
    Methods in molecular biology2004Book (Other academic)
    Abstract [en]

    An accessible introduction to how genomics has and will provide novel methods for bacterial investigation and advance our understanding and knowledge of bacterial pathogenicity. The authors critically evaluate the applications of genomics to diagnostic bacteriology, highlighting both current and likely future uses, describing real-time PCR methods, and outlining the promise of microarrays in clinical bacteriology. Their discussion examines in detail genomic approaches to antibacterial discovery, the nature of pathogenicity, the discovery of new pathogens, the exploration of the concept of clonality in bacteria, and bacterial taxonomics.

  • 23.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide2004In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1699, no 1-2, p. 57-63Article in journal (Refereed)
    Abstract [en]

    Here, we demonstrate the presence of multiple isoforms of palate lung nasal epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.

  • 24.
    Grodzinsky, Ewa
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases.
    Serological markers in subclinical and clinical gluten enteropathy1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An enzyme-linked immunosorbent assay (ELISA) has been developed for the measurement of anti-gliadin antibodies (AGA), thereby providing a practical and cheap assay for use in the diagnosis of coeliac disease (CD). Since gliadin is a common food antigen for most people, a large group of apparently healthy blood donors (n=l866) was analysed, as well as children and adults with symptoms more or less suggesting CD. The effects of various cut-offvalues on the sensitivity, specificity and predictive value (PV) of the test were calculated, both alone and together with anti-endomysium antibodies (EMA). A high prevalence value, of at least 1/256 (7!1866), for gluten enteropathy (GE) was found in the blood donor population. Moreover, a high frequency of CD among fanners with diffuse symptoms, conceivably due to a high exposure to gluten by inhalation, was also observed. It was impossible to combine high sensitivity with high specificity for both IgA- and IgG AGA, and vice versa, in adults. A significant increase in the mean lgA AGA level with age was seen when the blood donors were divided into age groups. A positive PV of 18-25% was found for IgA-AGA, depending on how-the cut-off value was defined. For IgG-AGA the positive PV was 0% (0/35) among asymptomatic subjects. IgA-EMA yielded both high specificity and a high positive PV, but a lower sensitivity than IgA-AGA, especially in children younger than 2 years, with signs of CD. When screening for GE in a population with expected low prevalence, measurement of IgA-AGA is suggested as a primary test because of fairly good sensitivity, technical simplicity, and low cost. Sera found to be positive are then re tested with IgA-EMA, which gives a positive PV close to 100%. For populations with a moderate or high expected prevalence for CD, our results indicate that different tests should be used depending on the age of the population studied. In younger children ( < 2 years old) lgA-AGA yielded a high sensitivity (lOO%) and a high specificity (86%). fu older children (> 2 years old) and adults the use of IgA-EMA seems more suitable, because of the high specificity (99-100%) and positive PV (95-100% ). Since, however, the negative PV was not 100%, a negative test result does not exclude CD.

  • 25.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Pharmacodynamic effects of antibiotics: studies on bacterial morphology, initial killing, postantibiotic effect and effecitive regrowth time1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pharmacodynamics of antibiotics deals with time course of drug activity and mechanisms of action of drugs on bacteria. In this thesis pharmacodynamic parameters have been studied after brief exposure of gram-positive bacteria to daptomycin, imipenem or vancomycin and after short exposure of gram-negative bacteria to amikacin, ampicillin, aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, imipenem, mecillinal,11, or piperacillin.The studies have been focused on morphological alterations, initial killing, postantibiotic effect (PAE) and effective regrowth time (ERT) and a method, based on bioluminescence assay of intracellular A TP has been used. The basic principle behind this technique is that A TP in living cells is present in a relatively constant amount, and hence affords a measure of the number of microbial cells. The PAE describes the delayed regrowth of bacteria after brief exposure to antibiotics. The number of cells measured after this antibiotic exposure describes the initialkilling and is also the start value for calculating the PAE. PAEs of 2-3 h were obtained by bioluminescence for gram-positive bacteria exposed to imipenern or v ancomycin. This is in agreement with results obtained by viable count and is probably due to similiar weak initialdecrease in cell density when assayed by both methods. Long (> 3 h) concentration dependent PAEs and moderate (::;; 1 1ogw) initial decrease in intracellular ATP were in general seen for gram-positive bacteria exposed to daptomycin and for gram-negative bacteria exposed to imipenem or amikacin when assayed by bioluminescence. These very long P AEs and rather weak initial killing have to be compared with the shorter PAEs and stronger initial killing reported by us and others using viable count. Furthermore, this study showed that there was a relatively good concordance between microscopy and bioluminescence, which are direct methods, in determining the initial killing and PAE of imipenem on Escherichia coli. The ERT, defined as the time for bacterial density to increase 1 logw from the pre-exposure inoculum, was independent of the method used for measuring regrowth of E. coli after brief exposure to imipenem. The combination of mecillinam with ampicillin, aztreonam, ceftazidime or piperacillin and the combination of amikacin with ceftazidirne, ceftriaxone or piperacillin induced longer PAEs on gram-negative bacteria than the sum of PAEs of the individual antibiotics. A strong initial killing in combination with a long PAE cause a long ERT and may allow the antibiotic concentration to stay below MIC during long periods of time without any regrowth. This may, in clinical practice, have implications for long dosing intervals .

  • 26.
    Hanberger, Håkan
    et al.
    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.
    Burman, LG
    Cars, O
    Erlandsson, Marcus
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordlinder, D
    Walther, Sten
    Linköping University, Department of Medicine and Care, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Low antibiotic resistance rates in Staphylococcus aureus, Escherichia coli and Klebsiella spp but not in Enterobacter spp and Pseudomonas aeruginosa: A prospective observational study in 14 Swedish ICUs over a 5-year period2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 7, p. 937-941Article in journal (Refereed)
    Abstract [en]

    Background: Intensive care units (ICUs) are hot zones for emergence and spread of antibiotic resistance because of frequent invasive procedures, antibiotic usage and transmission of bacteria. We report prospective data on antibiotic use and bacterial resistance from 14 academic and non-academic ICUs, participating in the ICU-STRAMA programme 1999-2003. Methods: The quantity of antibiotics delivered to each ICU was calculated as defined daily doses per 1000 occupied bed days (DDD1000). Specimens for culture were taken on clinical indications and only initial isolates were considered. Species-related breakpoints according to the Swedish Reference Group for Antibiotics were used. Antibiotic resistance was defined as the sum of intermediate and resistant strains. Results: Mean antibiotic use increased from 1245 DDD1000 in 1999 to 1510 DDD1000 in 2003 (P = 0.11 for trend). Of Staphylococcus aureus, 0-1.8% were methicillin resistant (MRSA). A presumptive extended spectrum beta-lactamase (ESBL) phenotype was found in <2.4% of Escherichia coli, based on cefotaxime susceptibility, except a peak in 2002 (4.6%). Cefotaxime resistance was found in 2.6-4.9% of Klebsiella spp. Rates of resistance among Enterobacter spp. to cefotaxime (20-33%) and among Pseudomonas aeruginosa to imipenem (22-33%) and ciprofloxacin (5-21%) showed no time trend. Conclusion: MRSA and cefotaxime-resistant E. coli and Klebsiella spp strains were few despite high total antibiotic consumption. This may be the result of a slow introduction of resistant strains into the ICUs, and good infection control. The cause of imipenem and ciprofloxacin resistance in P. aeruginosa could reflect the increased consumption of these agents plus spread of resistant clones. © 2007 The Authors.

  • 27.
    Hanberger, Håkan
    et al.
    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.
    Monnet, Dominique L
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Intensive care unit2005In: Antibiotic policies.: Theory and practice. / [ed] Ian M. Gould and Jos W.M. van der Meer, New York: Springer , 2005, p. 261-279Chapter in book (Other academic)
    Abstract [en]

    For 50 years, antibiotics have been dispensed like sweets. This must not be allowed to continue. This unique book assembles contributions from experts around the world concerned with responsible use of antibiotics and the consequences of overuse. For the first time, it provides up to the minute texts on both the theoretical aspects of antibiotic stewardship and the practical aspects of its implementation, with consideration of the key differences between developed and developing countries. All concerned with teaching, practice and administration of clinical medicine, surgery, pharmacy, public health, clinical pharmacology, microbiology, infectious diseases and clinical therapeutics will find Antibiotic Policies: Theory and Practice essential reading. Antibiotic use and resistance is not just the responsibility of specialists in the field but the responsibility of all doctors, pharmacists, nurses, healthcare administrators, patients and the general public.

  • 28.
    Hydén, Dag
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Åkerlind, Britt
    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.
    Peebo, Markus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Inner ear and facial nerve complications of acute otitis media with focus on bacteriology and virology2006In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 126, no 5, p. 460-466Article in journal (Refereed)
    Abstract [en]

    Conclusion. Among 20 patients with inner ear complications and/or peripheral facial palsy secondary to acute otitis media (AOM) a proven or probable bacteriological cause was found in 13 (65%). In seven patients (35%), a proven or probable viral cause was found. Only two of the patients (10%), with a proven bacterial AOM and a clinical picture of a purulent labyrinthitis in both, together with a facial palsy in one, had a substantial degree of dysfunction. Although the number of patients in this study is relatively low our findings show that inner ear complications and facial palsy due to AOM can be of both bacterial and viral origin. Severe sequelae were found only where a bacterial origin was proven. Objectives. Inner ear complications and/or peripheral facial palsy secondary to AOM are rare. The general understanding is that they are due to bacterial infections. However, in some of these patients there are no clinical or laboratory signs of bacterial infections and they have negative bacterial cultures. During recent years different viruses have been isolated from the middle ear or serologically proven in AOM patients and are thought to play a pathogenetic role. We suggest that in some cases of AOM complications from the inner ear and the facial nerve can be caused by viruses. The purpose of our study was to analyze infectious agents present in patients with inner ear complications and/or facial palsy arising from AOM. Patients and methods. The medical records of 20 patients who had inner ear complications and/or facial palsy following AOM (unilateral in 18, bilateral in 2) between January 1989 and March 2003 were evaluated. Bacterial cultures were carried out for all patients. Sera from 12 of the patients were stored and tested for a battery of specific viral antibodies. In three patients, investigated between November 2002 and March 2003, viral cultures were also performed on samples from the middle ear and nasopharynx. Results. Nineteen patients had inner ear symptoms. Eight of them had a unilateral sensorineural hearing loss and vertigo, three had vertigo as an isolated symptom and one, with bilateral AOM, had bilateral sensorineural hearing loss. Seven patients had a combination of facial palsy and inner ear symptoms (unilateral sensorineural hearing loss in three, unilateral sensorineural hearing loss and vertigo in two, bilateral sensorineural hearing loss and vertigo in one, with bilateral AOM, and vertigo alone in one). One patient had an isolated facial palsy. Healing was complete in 11 of the 20 patients. In seven patients a minor defect remained at follow-up (a sensorineural hearing loss at higher frequencies in all). Only two patients had obvious defects (a pronounced hearing loss in combination with a moderate to severe facial palsy (House-Brackman grade 4) in one, distinct vestibular symptoms and a total caloric loss in combination with a high-frequency loss in the other. Eight patients had positive bacteriological cultures from middle ear contents: Streptococcus pneumoniae in two, beta-hemolytic Streptococcus group A in two, beta-hemolytic Streptococcus group A together with Staphylococcus aureus in one, Staph. aureus alone in one and coagulase-negative staphylococci (interpreted as pathogens) in two. In the 12 patients with negative cultures, there was a probable bacteriological cause due to the outcome in SR/CRP and leukocyte count in five. In four patients serological testing showed a concomitant viral infection that was interpreted to be the cause (varicella zoster virus in two, herpes simplex virus in one and adenovirus in one.) In three there was a probable viral cause despite negative viral antibody test due to normal outcome in SR/CRP, normal leukocyte count, serous fluid at myringotomy and a relatively short pre-complication antibiotic treatment period. © 2006 Taylor & Francis.

  • 29.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Enterococci in Swedish intensive care units: studies on epidemiology, mechanisms of antibiotic resistance and virulence factors2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of this thesis was to study enterococci in Sweden, their resistance to antibiotics in general and high-level gentamicin resistance (HLGR) in particular, with a special focus on the ICU setting. Dynamics of rectal colonisation during prolonged intensive care unit (ICU) stay was assessed. In addition, enterococcal virulence factors and the ability to adhere to abiotic surfaces such as urinary catheters were studied.

    We found that among prolonged-stay patients admitted to ICUs, the rectal flora was altered, with a decrease in Gram-negative rods in favour of Gram-positive bacteria, mainly Coagulase negative staphylococci and enterococci.

    Among clinical enterococcal isolates from patients admitted to Swedish ICUs, although vancomycin resistant enterococci (VRE) were only sporadically found, multidrug resistance was common. This was most apparent in Enterococcus faecium, where the majority of isolates were ampicillin- and quinolone resistant. Enterococcus faecalis was still the most frequently isolated enterococcal species in clinical specimens. Among patients admitted to Swedish ICUs 1996-1998, E. faecalis with HLGR was found in higher frequency (20%) than previously reported. The majority (89%) of these isolates belonged to two dominating clusters of genetically related E. faecalis. Cluster I (69%), which was predominantly found in the eastern and central parts of southern Sweden and Cluster II (20%) in south-western Sweden.

    In the County of Östergötland, the first E. faecalis with HLGR isolated from blood cultures was found in 1996. The yearly incidence of isolates with HLGR in E. faecalis bacteraemia was studied from 1996-2001, and varied between 9-22%. The majority of these isolates were genetically related and belonged to Cluster I, also found in the previous study. The first blood isolate of E. faecium with HLGR in the County of Östergötland was found in 1999. A clone of E. faecium, with HLGR and ampicillin resistance, was found to colonise 6/10 and 2/11 prolonged-stay patients admitted from November 2001 through January 2002 to the general ICU and cardio-thoracic ICU, respectively, at the University Hospital of Linköping.

    All studied isolates with HLGR carried the gene aac(6')-Ie-aph(2'')-Ia encoding the bifunctional aminoglycoside modifying enzyme Aac(6')Ie-Aph(2'')Ia, which conveys resistance to all commercially available amino-glycosides except streptomycin. The location of the gene, aac(6')Ie-aph(2'')-Ia, was studied in 45 E. faecalis isolates and the gene was carried on a Tn5281-like transposon in all isolates except one. The 30 µg disc diffusion test, as recommended by the SRGA, had 100% sensitivity and specificity when compared to PCR detection of aac(6')-Ie-aph(2'')-Ia.

    E. faecalis isolates with HLGR belonging to widely disseminated clusters of genetically related isolates were more likely to carry both the gene encoding enterococcal surface protein (esp) and the gene encoding aggregation substance (asa1) compared to unique isolates. Esp was the only virulence factor found among E. faecium isolates, where it was common. E. faecalis isolates adhered with higher bacterial densities to urinary tract catheters compared to E. faecium isolates. In vitro adherence to urinary tract catheters was not affected by esp.

    List of papers
    1. Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems
    Open this publication in new window or tab >>Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems
    Show others...
    2001 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 48, no 1, p. 53-62Article in journal (Refereed) Published
    Abstract [en]

    Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25743 (URN)10.1093/jac/48.1.53 (DOI)10175 (Local ID)10175 (Archive number)10175 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units
    Open this publication in new window or tab >>Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units
    Show others...
    2003 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 52, no 2, p. 162-167Article in journal (Refereed) Published
    Abstract [en]

    We studied 45 isolates of Enterococcus faecalis with high-level gentamicin resistance (HLGR), all but one concomitantly resistant to ciprofloxacin, and 25 ciprofloxacin-resistant isolates without HLGR for genetic relatedness using pulsed-field gel electrophoresis (PFGE). E. faecalis were isolated from patients admitted to intensive care units at eight hospitals in southern Sweden from December 1996 through December 1998. Genomic analysis by PFGE resulted in three clusters of genetically related isolates (designated clusters I, II and III) and 23 unique clones. Cluster I was found predominantly in the eastern and central parts of southern Sweden and clusters II and III in south-western Sweden. Among the 45 isolates with HLGR, 69% belonged to cluster I, 20% to cluster II, and 11% had unique PFGE patterns, which suggests that the majority of isolates with HLGR are closely related. Among the 25 ciprofloxacin-resistant isolates without HLGR, 68% had unique PFGE patterns, 12% belonged to cluster I and 20% to cluster III, which suggests the ciprofloxacin-resistant isolates are not related. All isolates with HLGR contained the aac(6)Ie-aph(2)Ia gene, which was carried on a Tn5281-like transposon in all isolates except one. We conclude that HLGR in E. faecalis was mainly due to dissemination of genetically related clones during the time studied, and that HLGR in these isolates was due to the presence of the aac(6)Ie-aph(2)Ia gene.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26483 (URN)10.1093/jac/dkg315 (DOI)11035 (Local ID)11035 (Archive number)11035 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Genetic relatedness of Enterococcus faecalis isolates with high-level gentamicin resistance from patients with bacteraemia in the south east of Sweden 1994-2001
    Open this publication in new window or tab >>Genetic relatedness of Enterococcus faecalis isolates with high-level gentamicin resistance from patients with bacteraemia in the south east of Sweden 1994-2001
    Show others...
    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 36, no 6-7, p. 405-409Article in journal (Refereed) Published
    Abstract [en]

    High-level gentamicin resistant (HLGR) enterococci (Enterococcus faecalis and Enterococcus faecium) have become a substantial nosocomial problem in many countries. In this study, we investigated the prevalence of HLGR enterococci and their genetic relatedness in blood culture isolates from patients with bacteraemia admitted to the 3 hospitals in Östergötland, a county in the south east of Sweden, during 1994–2001. 36 of 250 E. faecalis (14%) and 4 of 106 E. faecium isolates (4%) were shown by PCR to carry the aac(6′)-Ie-aph(2″)-Ia aminoglycoside modifying gene and these isolates were also classified as HLGR enterococci by the gentamicin antibiotic disk diffusion method. A majority of HLGR E. faecalis isolates (83%) belonged to the same cluster of genetically related isolates, according to the pulsed-field gel electrophoresis (PFGE) patterns, whereas all 4 HLGR E. faecium isolates had unique PFGE patterns. In conclusion, our study showed that in contrast to studies from many other countries, the presence of HLGR enterococci was more common in E. faecalis than in E. faecium and appeared the first time in 1996 and 1999, respectively. Bacteraemia with HLGR enterococci in Östergötland was mainly due to the spread of a cluster related of E. faecalis strains.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24621 (URN)10.1080/00365540410020622 (DOI)6802 (Local ID)6802 (Archive number)6802 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Rectal colonization and frequency of enterococcal cross-transmission among prolonged-stay patients in two Swedish intensive care units
    Open this publication in new window or tab >>Rectal colonization and frequency of enterococcal cross-transmission among prolonged-stay patients in two Swedish intensive care units
    Show others...
    2005 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 37, no 8, p. 561-571Article in journal (Refereed) Published
    Abstract [en]

    The aims of this study were to gain insight into the dynamics of the rectal flora during prolonged ICU stay, with a particular focus on colonization and cross-transmission with resistant pathogens, and to evaluate methods for the rapid isolation of relevant bacteria from rectal swabs. Patients admitted to a general intensive care unit (GICU) or a cardiothoracic ICU (TICU) at the University Hospital of Linköping, Sweden, between 1 November 2001 and January 2002 with a length of stay > 5 d were included (n = 20). Chromogenic UTI agar medium was used for discrimination of different species, and appropriate antibiotics were added to detect resistance. Direct plating was compared to enrichment broth for a subset of specimens. The study showed an early alteration in rectal flora, with a dramatic decrease in Gram-negative rods in favour of Gram-positive bacteria. An ampicillin- and high-level gentamicin resistant clone of Enterococcus faecium was found in 6 of 10 patients in the GICU and 2 of 11 patients in the TICU. Enrichment broth did not enhance the detection of Gram-negative bacteria compared to direct plating on Chromogenic UTI medium, but enrichment broths were needed for optimal detection of resistant Gram-positive bacteria.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-30071 (URN)10.1080/00365540510038947 (DOI)15533 (Local ID)15533 (Archive number)15533 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
    5. Frequency of aggregation substance, cytolysin and enterococcal surface protein in vitro adhesion to urinary catheters of E. faecalis and E. faecium of clinical origin
    Open this publication in new window or tab >>Frequency of aggregation substance, cytolysin and enterococcal surface protein in vitro adhesion to urinary catheters of E. faecalis and E. faecium of clinical origin
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [sv]

    Enterococcal isolates, 21 E. faecium and 94 E. faecalis, isolated from blood cultures, rectal specimens and various other clinical samples were examined for the presence of the virulence factors hemolysin/cytolysin, aggregation substance (asa1) and enterococcal surface protein (esp). The isolates were previously characterized by pulsed-field gel electrophoresis (PFGE). Adhesion to siliconized latex urinary catheters was analysed in 14 clinical isolates and 3 control strains. Densities of adhering bacteria were determined by a bioluminescence assay of bacterial ATP. The only virulence factor found in E. faecium, esp, was found in 71% of the 21 E. faceium isolates. Cytolysin production, asa1 and esp were found in 13%, 79% and 73%, respectively, of the 94 E. faecalis isolates. Isolates belonging to a cluster of genetically related isolates differed significantly with respect to carriage of esp and asa1 compared to unique isolates, with the virulence factors more commonly found among clustered isolates (p<0.01). No difference was found with respect to cytolysio production (p = 0.76). E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared (p = 0.38 and 0.64).

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-82081 (URN)
    Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2012-09-28Bibliographically approved
  • 30.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Abednazari, Hossein
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ekdahl, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Samuelsson, Annika
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems2001In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 48, no 1, p. 53-62Article in journal (Refereed)
    Abstract [en]

    Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.

  • 31.
    Hällgren, Anita
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Burman, L
    Olsson-Liljequist, B
    Isaksson, Barbro
    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.
    Saedi, B
    Walther, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nilsson, Lennart
    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.
    Hanberger, Håkan
    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.
    Hög frekvens an korskolonisering med resistenta enterokocker hos "långliggare" på IVA2004In: Hygiea,2004, 2004, p. 57-57Conference paper (Other academic)
  • 32.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Claesson, Carina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Frequency of aggregation substance, cytolysin and enterococcal surface protein in vitro adhesion to urinary catheters of E. faecalis and E. faecium of clinical originManuscript (preprint) (Other academic)
    Abstract [sv]

    Enterococcal isolates, 21 E. faecium and 94 E. faecalis, isolated from blood cultures, rectal specimens and various other clinical samples were examined for the presence of the virulence factors hemolysin/cytolysin, aggregation substance (asa1) and enterococcal surface protein (esp). The isolates were previously characterized by pulsed-field gel electrophoresis (PFGE). Adhesion to siliconized latex urinary catheters was analysed in 14 clinical isolates and 3 control strains. Densities of adhering bacteria were determined by a bioluminescence assay of bacterial ATP. The only virulence factor found in E. faecium, esp, was found in 71% of the 21 E. faceium isolates. Cytolysin production, asa1 and esp were found in 13%, 79% and 73%, respectively, of the 94 E. faecalis isolates. Isolates belonging to a cluster of genetically related isolates differed significantly with respect to carriage of esp and asa1 compared to unique isolates, with the virulence factors more commonly found among clustered isolates (p<0.01). No difference was found with respect to cytolysio production (p = 0.76). E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared (p = 0.38 and 0.64).

  • 33.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    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.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units2003In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 52, no 2, p. 162-167Article in journal (Refereed)
    Abstract [en]

    We studied 45 isolates of Enterococcus faecalis with high-level gentamicin resistance (HLGR), all but one concomitantly resistant to ciprofloxacin, and 25 ciprofloxacin-resistant isolates without HLGR for genetic relatedness using pulsed-field gel electrophoresis (PFGE). E. faecalis were isolated from patients admitted to intensive care units at eight hospitals in southern Sweden from December 1996 through December 1998. Genomic analysis by PFGE resulted in three clusters of genetically related isolates (designated clusters I, II and III) and 23 unique clones. Cluster I was found predominantly in the eastern and central parts of southern Sweden and clusters II and III in south-western Sweden. Among the 45 isolates with HLGR, 69% belonged to cluster I, 20% to cluster II, and 11% had unique PFGE patterns, which suggests that the majority of isolates with HLGR are closely related. Among the 25 ciprofloxacin-resistant isolates without HLGR, 68% had unique PFGE patterns, 12% belonged to cluster I and 20% to cluster III, which suggests the ciprofloxacin-resistant isolates are not related. All isolates with HLGR contained the aac(6)Ie-aph(2)Ia gene, which was carried on a Tn5281-like transposon in all isolates except one. We conclude that HLGR in E. faecalis was mainly due to dissemination of genetically related clones during the time studied, and that HLGR in these isolates was due to the presence of the aac(6)Ie-aph(2)Ia gene.

  • 34. Innings, Åsa
    et al.
    Ullberg, Måns
    Johansson, Anders
    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.
    Rubin, Carl Johan
    Noreus, Niklas
    Isaksson, Magnus
    Herrman, Björn
    Multiplex real-time PCR targeting the RNase P RNA gene for detection and identification of Candida species in blood2007In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, no 3, p. 874-880Article in journal (Refereed)
    Abstract [en]

    We have developed a single-tube multiplex real-time PCR method for the detection of the eight most common Candida species causing septicemia: Candida albicans, C. dubliniensis, C. famata, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, and C. tropicalis. The method developed targets the RNase P RNA gene RPR1. Sequences of this geiie were determined for seven of the Candida species and showed surprisiRgly large sequence variation. C. glabrata was found to have a gene that was five times longer gene than those of the other species, and the nucleotide sequence similarity between C. krusei and C. albicans was as low as 55%. The multiplex PCR contained three probes that enabled the specific detection of C. albicans, C. glabrata, and C. krusei and a fourth probe that allowed the general detection of the remaining species. The method was able to detect 1 to 10 genome copies when the detection limit was tested repeatedly for the four species C. albicans, C. glabrata, C. krusei, and C. guilliermondii. No significant difference in the detection limit was seen when the multiplex format was compared with single-species PCR, i.e., two primers and one probe. The method detected eight clinically relevant Candida species and did not react with other tested non-Candida species or human DNA. The assay was applied to 20 blood samples from nine patients and showed a sensitivity similar to that of culture. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

  • 35.
    Isacsson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Pharmacokinetics and pharmacodynamics of aminoglycosides1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pharmacokinetics of amikacin in humans and the pharmacodynamic effects, i.e. initial killing and postantibiotic effect (P AE), of the aminoglycosides were studied in this thesis. For1y-five elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin given once or twice daily. The administration of a single dose of 15 mg!kg of amikacin yielded a higher peak concentration (55 mg/1) in comparison to the peak concentration (33 mg!l) when the same total dose was given twice daily. The area under the curve (AUC) was the same regardless of the mode of administration. The kinetics of amikacin, 11 mg/kg and 15 mg/kg were studied during a 24 h interval. Using a hiexponential equation the average serum half-lives were quite long, 4.4 - 5.2 h. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. When given to our elderly patients the peak concentration of 11 mg/kg of arnikacin ( 42 mg!l) seems to be sufficiently high in relation to the MICs of important isolated pathogens, i.e. ,2>10 x MIC. Thus this dose may be sufficient for elderly patients when given once daily. The in vitro postantibiotic effects (P AE) of amikacin, gentamicin, netilmicin and tobramycin onGram-negative bacteria and on staphylococci were studied by a bioluminescent assay of bacterial ATP. This method simplified the P AE studies and made such studies possible at high aminoglycoside concentrations. The length of the P AE was concentration-dependent for all the aminoglycosides studied. The mean P AE values of the Gram-negative strains and of the Staphylococcus aureus strains ranged between 3 to 7 h at the aminoglycoside concentrations normally reached in serum during standard dosing. The P AE of arnikacin alone, and in combination with ceftazidime, ceftriaxone or piperacillin, on Gram-negative bacteria and on enterococci was also studied. The combination of 13-lactam antibiotics with amikacin induced longer P AEs than the sum of P AEs of the individual drugs. This synergistic P AE was seen especially when the 13-lactam antibiotics were combined with amikacin concentrations close to MIC. Amikacin alone induced no P AEon the Enterococcus .faecalis strains. APAE of 1.6 h at the most resulted from exposure to piperacillin. In combination, amikacin and piperacillin increased the P AE to 5.5 h. In conclusion, with regard to the pharmacokinetics and the pharmacodynamics there is strong support for the once daily dosing regimens of aminoglycosides. The results of this study could also haveimpact on dosing regimens of antimicrobial combinations and might lead to administration of lower doses of potentially toxic drugs without loss of efficacy.

  • 36.
    Jakobsson, Tell
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Lactobacilli dominating the normal vaginal flora2003Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The microbiology of the ecological niche of the vagina is dynamic. There are numerous inhabitants, mainly anaerobic bacteria. During the fertile years the vaginal mucosa is normally dominated by lactobacilli, a fact that has been known for over a century. Lactobacilli are a phenotypically heterogeneous group of bacteria that first became possible to identify to the species level with some precision using recently developed nucleic acid based techniques. In this study vaginal fluid was cultured from women scheduled for their regular PAP smear. Two hundred and two isolates from 23 women with normal vaginal fluid were typed by randomly amplified polymorphic DNA (RAPD) PCR analysis and identified to the species level by temporal temperature gradient gel electrophoresis (TTGE), and 16S rDNA sequencing. Four hundred and four isolates from 23 women were typed with broad range PCR of 16S rRNA gene region V I and V3 by pyrosequencing. Most women harboured one single species, a few had two different species, and only one woman harboured more than two different species of lactobacilli. The species that were found, which were similar in the two studies, were: Lactobacillus crispalus, L. gasseri, L. jensenii and L. iners. L. iners has never been reported before as a member of the dominant normal vaginal lactobacillary flora. Under some conditions, which have not been determined with certainty, the lactobacilli are overgrown by large amounts of Gardnerella vaginalis and anaerobic bacteria, mainly Bacleroides spp and Mobiluncus, causing the syndrome of Bacterial Vaginosis (BV). BV is associated with several severe reproductive and genitourinary complications in women. A major issue in studying normal Lactobacilli in vaginal fluid samples from women of reproductive age is to differentiate the normal flora from that of BV. To sharpen the diagnostic tools (i.e. Nugent scoring of Gram stained slides) for separation of normal flora from that of BV, a workshop was set up. The major results showed discrepancies in diagnosis when there were very few lactobacilli. There was disagreement on where to delimit small lactobacilli from G. vaginalis and Bacteroides. The use of scoring to delimit normal flora, as was done in the workshop, is proposed as a prerequisite for further studies of normal vaginal flora

    List of papers
    1. Vaginal Lactobacillus flora of healthy Swedish women
    Open this publication in new window or tab >>Vaginal Lactobacillus flora of healthy Swedish women
    Show others...
    2002 (English)In: Journal of clinical microbiology, ISSN 0095-1137, Vol. 40, no 8, p. 2746-2749Article in journal (Refereed) Published
    Abstract [en]

    Species of the Lactobacillus acidophilus complex are generally considered to constitute most of the vaginal Lactobacillus flora, but the flora varies between studies. However, this may be due to difficulties in identifying the closely related species within the L. acidophilus complex by using traditional methods and to variations in the vaginal status of the participants. Two hundred two isolates from the vaginal fluids of 23 Swedish women without bacterial vaginosis, as defined by the criteria of Nugent et al. (R. P. Nugent, M. A. Krohn, and S. L. Hillier, J. Clin. Microbiol. 29:297-301, 1991), were typed by randomly amplified polymorphic DNA (RAPD) analysis and identified to the species level by temporal temperature gradient gel electrophoresis, multiplex PCR, and 16S ribosomal DNA sequencing. The vaginal flora of most participants was dominated by a single RAPD type, but five of them harbored two RAPD types representing two different species or strains. The most frequently occurring species were Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. L. iners has not previously been reported as one of the predominant Lactobacillus species in the vagina.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13051 (URN)10.1128/JCM.40.8.2746-2749.2002 (DOI)
    Available from: 2008-03-19 Created: 2008-03-19 Last updated: 2018-02-02
    2. Identification of randomly selected colonies of Lactobacilli from normal vaginal fluid by pyrosequencing of the 16S rDNA Variable V1 and V3 Regions
    Open this publication in new window or tab >>Identification of randomly selected colonies of Lactobacilli from normal vaginal fluid by pyrosequencing of the 16S rDNA Variable V1 and V3 Regions
    2002 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 110, no 11, p. 802-810Article in journal (Refereed) Published
    Abstract [en]

    The present study aimed to characterize lactobacilli in vaginal fluid from 23 adult healthy women by using high-throughput DNA sequencing for identification of a large number of randomly selected colonies appearing on Rogosa and blood agar. The typing method was based on broad-range PCR of 16S rRNA gene variable regions V1 and V3, pyrosequencing, and classification of the fragments by alignment with NCBI-catalogued sequences and type strain sequences. Four major groups of sequences were found among the 402 isolates clearly corresponding to Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners and Lactobacillus jensenii when compared to the sequences obtained for type strains. Our results indicate that pyrosequencing of 16S rRNA gene fragments as used here is a fast and reliable method well suited for identification to the species level, even within the Lactobacillus acidophilus complex.

    Keywords
    Lactobacillus, vaginal fluid, 16S rRNA genes, pyrosequencing
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13052 (URN)10.1034/j.1600-0463.2002.1101106.x (DOI)
    Available from: 2008-03-19 Created: 2008-03-19 Last updated: 2017-12-13Bibliographically approved
    3. An international study of the inter-observer variation between the interpretations of vaginal smear criteria of Bacterial Vaginosis
    Open this publication in new window or tab >>An international study of the inter-observer variation between the interpretations of vaginal smear criteria of Bacterial Vaginosis
    Show others...
    2002 (English)In: APMIS, ISSN 1600-0463, Vol. 110, no 11, p. 811-818Article in journal (Refereed) Published
    Abstract [en]

    An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

    Keywords
    Bacterial vaginosis, diagnosis, criteria
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13050 (URN)10.1034/j.1600-0463.2002.1101107.x (DOI)
    Available from: 2008-03-19 Created: 2008-03-19 Last updated: 2013-09-12
  • 37.
    Jakobsson, Tell
    et al.
    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.
    Forsum, Urban
    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.
    Vaginala laktobaciller som normalflora2004In: Bakteriell Vaginos / [ed] Larsson, P-G,Bergström, Mats och Forsum, Urban, Växjö: Grafiska Punkten , 2004, p. 31-35Chapter in book (Other academic)
  • 38.
    Karlsson, Daniel
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, The Institute of Technology.
    Aspects of the use of medical decision-support systems: the role of context in decision support2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is a great need today for distribution of medical information. The amount of information is growing quickly, and information that could potentially influence clinical practice fails to reach health care professionals. The supply of information to health care has from the start been the main goal of medical informatics. However, with very few exceptions, the systems developed to support the formalization and distribution of medical knowledge, i.e. decision-support or expert systems, have not attained clinical use. Thus, since there is an unsatisfied need for information and the methods developed so far have been successful to only a limited extent, it is important to gain insight into both how decision-support systems are used and which of their properties may influence the usability.

    This thesis describes aspects of the use of medical decision-support systems by looking at two prototype implementations of such systems. The prototypes concerned bacterial endocarditis and urinary tract infections respectively. The first prototype system was evaluated and a theory of the use of the system was developed, thereby leading to further theorization and the development of a new system design. The goal of the system designs was to facilitate the interpretation and assessment of generated advice. This kind of support was realized by applying an expertext system model, a model that supports triangulation of decision-support methods and information sources. To organize the information in an expertext environment, a common terminological domain model was used in the second system design. In the theorization, a special focus was on contextual aspects of system use. Differences between knowledge provider and end-user contexts concerning the use of decision-support systems were analyzed. The importance of support for multi-perspective interpretation of system output such as is present in our system designs was confirmed.

    List of papers
    1. Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
    Open this publication in new window or tab >>Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
    Show others...
    1997 (English)In: Methods of Information in Medicine, ISSN 0026-1270, Vol. 36, no 2, p. 108-114Article in journal (Refereed) Published
    Abstract [en]

    There is an obvious need for geographic distribution of expert knowledge among several health care units without increasing the cost of on-site expertise in locations where health care is provided. This paper describes the design of a knowledge-based decision-support system for extended consultation in clinical medicine. The system is based on Arden Syntax for Medical Logic Modules and hypertext using World Wide Web technology. It provides advice and explanations regarding the given advice. The explanations are presented in a hypertext format allowing the user to browse related information and to verify the relevance of the given advice. The system is intended to be used in a closed local network. With special precautions regarding issues of safety and patient security, the system can be used over wider areas such as in rural medicine. A prototype has been developed in the field of clinical microbiology and infectious diseases regarding infective endocarditis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13333 (URN)9242006 (PubMedID)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-13
    2. A study of the usage of a decision-support system for infective endocarditis
    Open this publication in new window or tab >>A study of the usage of a decision-support system for infective endocarditis
    2000 (English)In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 25, no 1, p. 1-18Article in journal (Refereed) Published
    Abstract [en]

    The objective of this study was to examine a design for a World Wide Web-based decision-support system in use by clinically active physicians. A prototype implementation of the design concerned management of infective endocarditis patient cases. The design was based on an integration of hypertext and rule-based knowledge. In the study sessions, physicians in the field of internal medicine worked on managing authentic patient cases in a laboratory setting. Data was collected from interviews with the physicians using video recordings and stimulated recall technique. The qualitative data was analysed according to the constant comparative method in order to develop a model of the physicians' usage of the system. The resulting model describes perceived contributions and criteria for usefulness of the system. The ways the physicians used the system showed that it was able to provide patient-specific support for confirming clinical decisions, for higher-level patient management, and for preparing for and initiating expert consultations. Users also stated that new medical knowledge could be gained as a side effect of using the system.

    Keywords
    Decision-support System, Endocarditis, Qualitative Methodology, Evaluation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13334 (URN)10.1080/146392300298229 (DOI)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-13
    3. A study of the concept of urinary tract infections in different domains of medicine using the MEDLINE® database
    Open this publication in new window or tab >>A study of the concept of urinary tract infections in different domains of medicine using the MEDLINE® database
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    In the construction of decision-support systems, differences between expert and end-user domains may pose a problem. As a way of studying differences between medical domains regarding management of urinary tract infections, we investigated the MEDLINE® for differences in indexing patterns. Further, our intention was to assess the MEDLINE® database as a source for studying medical domains. We examined the use of main headings, subheadings and the level of main headings in six medical domains that manage urinary tract infections. Many intuitive but also some counterintuitive results were found. We conclude that it is difficult to use the MEDLINE® database for studying medical domains mainJy due to unclear semantics both in the headings and the indexing process, which results in variability in indexing. This variability probably hides significant results. We also conclude that the differences found indicate that in addition to differences between domains, there are also large variations within domains.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-88955 (URN)
    Available from: 2013-02-19 Created: 2013-02-19 Last updated: 2013-02-19
    4. Medical decision-support systems and the concept of context
    Open this publication in new window or tab >>Medical decision-support systems and the concept of context
    2004 (English)In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 29, no 2, p. 109-118Article in journal (Refereed) Published
    Abstract [en]

    Medical decision-support systems are of necessity multi-contextual in nature. There are always at least two contexts involved in the use of such systems: the expert knowledge-provider context and the end-user context. To show this, we present examples of context-dependent aspects significant to the use of decision-support systems. The existence of discrepancies between the contexts threatens to disrupt the rationale for using decision-support systems: for the system to transfer knowledge from the expert to the end-user. Both theoretical and empirical studies show that such discrepancies exist and that they may be detrimental to the use of decision-support systems. Systems must thus give support in interpreting the output produced by the system in the context of the end-user. © 2004 Taylor and Francis Ltd.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-28810 (URN)10.1080/14639230410001684404 (DOI)13998 (Local ID)13998 (Archive number)13998 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
    5. A design and prototype for a decision-support system in the field of urinary tract infections: application of openGALEN techniques for indexing medical information
    Open this publication in new window or tab >>A design and prototype for a decision-support system in the field of urinary tract infections: application of openGALEN techniques for indexing medical information
    2001 (English)In: Studies in Health Technology and Informatics, ISSN 0926-9630, E-ISSN 1879-8365, Vol. 84, no 1, p. 479-483Article in journal (Refereed) Published
    Abstract [en]

    Differences in expert and end-user contexts may be detrimental to the use of decision-support systems. A way to attend to this problem is to triangulate decision-support methods and information sources such as in the case of the expertext system model. To organize the information contained in the system, a common domain model is suggested as a instrument for annotating information. In this paper, a design and a prototype for a decision-support system in the field of urinary tract infections using techniques and methods developed in the GALEN projects is presented.

    Place, publisher, year, edition, pages
    Amsterdam: IOS Press, 2001
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-29003 (URN)10.3233/978-1-60750-928-8-479 (DOI)14236 (Local ID)14236 (Archive number)14236 (OAI)
    Conference
    MEDINFO 2001, 10th World Congress on Medical Informatics, London, United Kingdom
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
  • 39.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Aspevall, Olle
    Karolinska Inst, Stockholm .
    Forsum, Urban
    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.
    A desision support system for urinary tract infections1999In: AMIA99,1999, Philadelphia: Hanley & Belfuse Inc , 1999, p. 1094-Conference paper (Refereed)
  • 40.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Aspevall, Olle
    KI, Huddinge .
    Forsum, Urban
    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.
    Concepts, contexts and expert systemms1999In: Medical Informatics Europe99,1999, Amsterdam: IOS Press , 1999, p. 713-Conference paper (Refereed)
  • 41.
    Karlsson, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Aspevall, Olle
    Department of Immunology, Microbiology, pathology and Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.
    Åhlfeldt, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Forsum, Urban
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    A study of the concept of urinary tract infections in different domains of medicine using the MEDLINE® databaseManuscript (preprint) (Other academic)
    Abstract [en]

    In the construction of decision-support systems, differences between expert and end-user domains may pose a problem. As a way of studying differences between medical domains regarding management of urinary tract infections, we investigated the MEDLINE® for differences in indexing patterns. Further, our intention was to assess the MEDLINE® database as a source for studying medical domains. We examined the use of main headings, subheadings and the level of main headings in six medical domains that manage urinary tract infections. Many intuitive but also some counterintuitive results were found. We conclude that it is difficult to use the MEDLINE® database for studying medical domains mainJy due to unclear semantics both in the headings and the indexing process, which results in variability in indexing. This variability probably hides significant results. We also conclude that the differences found indicate that in addition to differences between domains, there are also large variations within domains.

  • 42.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Aspvall, Olle
    KI.
    Åhlfeldt, Hans
    Linköping University, Department of Biomedical Engineering.
    Forsum, Urban
    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.
    Using the MEDLINE® database to study the concept of urinary tract infections in different domains of medicine2004In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 109, no 2, p. 141-157Article in journal (Refereed)
    Abstract [en]

    As a way of exploring differences between medical domains regarding management of urinary tract infections, we investigated the MEDLINE® database for differences in indexing patterns. Further, our intention was to assess the MEDLINE® database as a source for studying medical domains. We examined the use of main headings, subheadings and the level of main headings in six medical domains that manage urinary tract infections. Many intuitive but also some counterintuitive results were found indicating that the MEDLINE® database is difficult to use for studying medical domains mainly due to unclear semantics both in the headings and the indexing process, which results in variability in indexing. This variability probably hides sig-nificant results. We also conclude that the differences found indicate that in addition to differences between domains, there are also large variations within domains.

  • 43.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Carlsson, Mats
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Forsum, Urban
    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.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    A design for a World Wide Web decision-support system using a controlled medical terminology1996In: AMIA1996,1996, Washington: Hanley & Belfus , 1996, p. 189-Conference paper (Refereed)
  • 44.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Ekdahl, Christer
    Linköping University, Department of Molecular and Clinical Medicine.
    Shahsavar, Nosrat
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Gill, Hans
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Forsum, Urban
    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.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    A WWW-based decision-support system using medical logic modules and hypertext1996In: Medical Informatics Europe 96,1996, Amsterdam: IOS Press , 1996, p. 93-Conference paper (Refereed)
  • 45.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Ekdahl, Christer
    Linköping University, Department of Molecular and Clinical Medicine.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Forsum, Urban
    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.
    A qualitative study of clinicians ways of using a decision-support system1997In: AMIA97,1997, Philadelpia: Hanley & Belfuse Inc , 1997, p. 268-Conference paper (Refereed)
  • 46.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Ekdahl, Christer
    Linköping University, Department of Molecular and Clinical Medicine.
    Wigertz, Ove
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Forsum, Urban
    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.
    Design and evaluation of a clinical decision and information support system1998In: MEDINFO 98,1998, Australia: IOS Press , 1998, p. 574-Conference paper (Refereed)
  • 47.
    Karlsson, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Forsum, Urban
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Medical decision-support systems and the concept of context2004In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 29, no 2, p. 109-118Article in journal (Refereed)
    Abstract [en]

    Medical decision-support systems are of necessity multi-contextual in nature. There are always at least two contexts involved in the use of such systems: the expert knowledge-provider context and the end-user context. To show this, we present examples of context-dependent aspects significant to the use of decision-support systems. The existence of discrepancies between the contexts threatens to disrupt the rationale for using decision-support systems: for the system to transfer knowledge from the expert to the end-user. Both theoretical and empirical studies show that such discrepancies exist and that they may be detrimental to the use of decision-support systems. Systems must thus give support in interpreting the output produced by the system in the context of the end-user. © 2004 Taylor and Francis Ltd.

  • 48.
    Kindberg, Elin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Åkerlind, Britt
    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.
    Johnsen, Christina
    Department of Virology, Statens Serum Institut, Copenhagen, Denmark4;.
    Knudsen, Jenny Dahl
    Department of Microbiology, Hvidovre Hospital, Hvidovre, Denmark.
    Heltberg, Ole
    Department of Microbiology, Næstved Hospital, Næstved, Denmark.
    Larson, Göran
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Böttiger, Blenda
    Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
    Svensson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark2007In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, no 8, p. 2720-2722Article in journal (Refereed)
    Abstract [en]

    A total of 61 individuals involved in five norovirus outbreaks in Denmark were genotyped at nucleotides 428 and 571 of the FUT2 gene, determining secretor status, i.e., the presence of ABH antigens in secretions and on mucosa. A strong correlation (P = 0.003) was found between the secretor phenotype and symptomatic disease, extending previous knowledge and confirming that nonsense mutations in the FUT2 gene provide protection against symptomatic norovirus (GGII.4) infections. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

  • 49.
    Klingspor, Lena
    et al.
    Huddinge.
    Törnqvist, Ewa
    Örebro.
    Johansson, Anders
    Uppsala.
    Petrini, Björn
    KS.
    Forsum, Urban
    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.
    Hedin, Göran
    Västerås.
    A prospective epidemiological survey of candidaemia in Sweden2004In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 36, no 1, p. 52-55Article in journal (Refereed)
    Abstract [en]

    A prospective epidemiological survey of candidaemia was performed in central Sweden from January 1998 to December 1999. In total, 191 episodes were reported with an overall rate of 0.32/1000 admissions. Candida albicans was identified in 128 cases (67%), followed by Candida glabrata in 30 (15.7%) and Candida parapsilosis in 14 (7.3%). Predisposing factors included surgery (31.4%), intensive care (18.8%), solid tumour or haematological malignancy (15.7%), and foetal immaturity (15.7%). Now-albicans Candida species were more prevalent among patients with haematological malignancies (56%), compared to surgical (30%) and ICU patients (19%). The crude mortality rate of candidaemia was 31%. The highest mortality rate was observed in patients with haematological malignancies (41.2%), age > 70 y (41%), surgery (38.5%) and infections with > 1 Candida species (40%) or C. glabrata (38%).

  • 50. Kronvall, Göran
    et al.
    Karlsson, Inga
    Walder, Mats
    Sörberg, Mikael
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Epidemiological MIC cut-off values for tigecycline calculated from Etest MIC values using normalized resistance interpretation2006In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 57, no 3, p. 498-505Article in journal (Refereed)
    Abstract [en]

    Objectives: To apply the normalized resistance interpretation (NRI) method to Etest MIC results which have higher precision than conventional log2 dilution MIC tests due to the inclusion of intermediate values. If successful, NRI might provide an objective tool for the definition of epidemiological MIC cut-off values. Methods: MICs of tigecycline and other antimicrobial agents were determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram-negative species or species groups using the Etest. Histograms of MIC values were constructed for each species and NRI calculations were applied to them. An upper MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was used for setting the epidemiological cut-off values. Results: Calculated cut-off values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with earlier reports on the lack of activity of tigecycline against this species. Conclusions: NRI offers an objective method for the analysis of MICs produced using Etests and the determination of epidemiological MIC cut-off values. © The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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