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  • 1.
    Abednazari, Hossin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. PEAS Institute, Linköping.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nilsson, Ingela
    Kalmar County Hospital, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor is a reliable marker for efficient anti-bacterial therapy within the first day of treatment2014In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 5, no 10, p. 823-830Article in journal (Refereed)
    Abstract [en]

    Rapid diagnosis and choice of appropriate antibiotic treatment might be life-saving in serious infectious diseases. Still the available markers that can evaluate and monitor the diagnosis and treatment are few. Hepatocyte growth factor (HGF) has been studied as a potent regenerative factor produced and released during injuries such as infectious diseases. Monitoring of HGF levels might predict therapy results better than C-reactive protein (CRP) within the first day of treatment in pneumonia. For further investigation of previous observations we aimed to study HGF as a first-day marker in over-representing infectious diseases in comparison to procalcitonin (PCT), CRP and body temperature. Fifty-one patients with community acquired infectious diseases were included consequently at admittance and the serum samples were collected before and within 18 - 24 hours of treatment. HGF levels decreased significantly in case of efficient antibiotic therapy and HGF was shown to be better than PCT, CRP and body temperature to evaluate treatment. In patients with pneumonia, monitoring of HGF was most reasonable. HGF might be used as a therapeutic marker within the first day of empiric antibiotic treatment during infection.

  • 2.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lonn, J
    University of Örebro, Sweden .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Sahlgrens University Hospital, Sweden .
    Hahn-Zoric, M
    Sahlgrens University Hospital, Sweden .
    Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin-6, High-Sensitivity C-Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 3.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lönn, J
    School of Health and Medical Sciences, Örebro, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Hahn-Zoric, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tillväxtfaktorer och inflammationsmarkörer vid kronisk njursvikt2013In: Njurmedicinskt vårmöte Jönköping 12-14 maj 2013, 2013Conference paper (Refereed)
  • 4.
    Ammerlaan, H S M
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Harbarth, S
    Geneva University Hospital and Medical Sch, Switzerland.
    Buiting, A G M
    John Radcliffe Hospital, England.
    Crook, D W
    Amphia Hospital, Netherlands.
    Fitzpatrick, F
    Beaumont Hospital, Ireland.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Herwaldt, L A
    University of Iowa, IA USA.
    van Keulen, P H J
    Amphia Hospital, Netherlands.
    Kluytmans, J A J W
    St Elizabeth Hospital, Netherlands.
    Kola, A
    Charite University of Medical Berlin, Germany.
    Kuchenbecker, R S
    University of Federal Rio Grande do Sul, Brazil.
    Lingaas, E
    University of Oslo, Norway.
    Meessen, N
    University of Medical Centre Groningen, Netherlands.
    Morris-Downes, M -m.
    Beaumont Hospital, Ireland.
    Pottinger, J M.
    University of Iowa Hospital and Clin, IA USA.
    Rohner, P
    Geneva University Hospital and Medical Sch, Switzerland.
    dos Santos, R P.
    University of Federal Rio Grande do Sul, Brazil.
    Seifert, H
    University of Cologne, Germany.
    Wisplinghoff, H
    University of Cologne, Germany.
    Ziesing, S
    Hannover Medical Sch, Germany.
    Walker, A S.
    John Radcliffe Hospital, England.
    Bonten, M J M.
    University of Medical Centre Utrecht, Netherlands.
    Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection2013In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 56, no 6, p. 798-805Article in journal (Refereed)
    Abstract [en]

    Background. It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected.

    Methods. We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007.

    Results. 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from −1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4.

    Conclusions.  Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.

  • 5.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Kalmar County hospital.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Överby, Anna K.
    Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Magnus
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden / School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e103264-Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3´ non-coding region (3´NCR). A different genomic structure was found in the 3´NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3´NCRs of additional Scandinavian TBEV strains and controls, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A)  tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 6.
    Crisci, Elisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Rondahl, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergström, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Eriksson, Kristina
    University of Gothenburg, Gothenburg, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Complement opsonization promotes HSV-2 infection of human dendritic cells2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed)
    Abstract [en]

    Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

    IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

  • 7.
    Dessau, Ram B
    et al.
    Slagelse Hospital, Slagelse, Denmark.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Nyman, Dag
    Åland University, Mariehamn, Finlad.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite2015In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, no 7, p. 823-827Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886 persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and 50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods to display the antibody response and to choose thresholds for a rise in relative antibody reactivity are shown and discussed. In conclusion, 5.4% of people with tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis.

  • 8. Fransson, G
    et al.
    Edström, M
    Nilsson, L E
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    High mortaility in bacteraemia and candidaemia in critically ill patients - report from Swedish Intensive Care Registry2012In: Proceedings of the 22nd European Congress of Clinical Microbiology and Infectious Diseases, 2012, p. P1060-Conference paper (Other academic)
    Abstract [en]

    Objective: Increasing prevalence of  bacteremia and candidemia with significant resistance to antimicrobial agents is an increasing concern among ICU patients. The objective of this report from Swedish Registry of Intensive care (SIR) was to study the frequency and cause of culture verified sepsis in critically ill patients and to analyse mortality in sepsis caused by Candida albicans, Candida non albicans and bacteria.

    Methods: Setting: Starting 10 years ago an increasing number of ICU:s in Sweden reports each episode of care (EOC) to the Swedish Intensive care Registry (SIR).  Mortality is followed weekly for all patients by link to the Swedish population registry. A specific routine for collection of microbial data directly from the laboratories connected individually to each EOC has been tested and implemented for laboratories covering 1/3 of the Swedish population. Participants: 47 ICU:s reported 1540 EOC:s during the period January 2005 to November 2011, with a diagnosis of sepsis (ICD10: A419, R572 or R651) and a positive blood culture within 14 days before admission until discharge.  For patients with more than one EOC was only the last EOC included which reduced the number of observations included in mortality calculations to 1416.

    Variables: Primary outcome was 30 day mortality calculated from admission to ICU.

    Results: 1 416 patients met inclusion criteria and were included in the analysis. The most common causes of sepsis were:  E. coli (24 %) followed by Coagulase Negative Staphylococci (CoNS) (21 %), Streptococcus spp (19 %), S. aureus (14 %), Klebsiella spp (8 %) and Candida spp (6 %) [Candida albicans 4 % and Candida non albicans 2 %]. The 30-days crude mortality was 34% for patients with sepsis caused by S. aureus. Correspondingly 30 days mortality was for  Candida non albicans 34%, Candida albicans 31%,  Klebsiella spp 26 % , CoNS 25 %, E. coli 22 %. Distribution of species in blood cultures from the 87 patients with candidemia were: C. albicans 62, C. glabrata 11, C. krusei 1, C. tropicalis 4, C. other 4, C. non specified 9.

    Conclusion: The highest (>30%) crude mortality in critically ill patients with sepsis was seen in patients with S. aureus and Candida infections. Further analysis of independent risk factors for mortality in sepsis caused by different pathogens are warranted.

  • 9.
    Hammar, Mats
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bergdahl, Björn
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center.
    Öhman, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Celebrating the Past by Expanding the Future: The Faculty of Health Science, Linköping University 1986–20062006Report (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.

    The new FHS at Linköping University was launched in 1986, and by the end of August the first students began their studies. Already at the start, FHS included several programmes for health professionals: nursing, occupational therapy, physiotherapy, medicine, social welfare and laboratory technology. Speech and language pathology was added in 2003 and the education curriculum for laboratory technicians was developed into a master’s programme in medical biology. A number of important concepts were included in the new programmes. Problem based learning (PBL) was chosen as the fundamental basis for organising studies; using small tutorial groups with supervisors as “coaches” and real patient histories as triggers for learning. Since 2001, realistic cases/scenarios are made available on the Intranet.

    PBL is highly appreciated by the majority of students and teachers. This method of learning focused in contexts, according to pedagogic research, leads to a higher retention of knowledge than in traditional teacher-centered approaches toward learning. Important PBL spin-off effects are in educating students to cooperate in groups, to communicate and argue, to listen to other students’ opinions, to evaluate their own efforts and to identify learning needs. Furthermore, the method implies that students’ learn to independently find and evaluate scientific information, thereby realizing that the truth is somewhat “relative,” since what they find may differ depending on the sources used. Perhaps the most important characteristic of PBL is that it moves the main responsibility for obtaining goals and new knowledge from the teacher to the student.

    Other important elements of the various curricula at the FHS are vertical and horizontal integration. In vertical integration, e.g. between clinical and basic science, different sections are interwoven with clear progressive shifts over phases and semesters. This has shown to stimulate profound rather than superficial learning, and probably stimulates better understanding. Horizontal integration focuses on the simultaneous learning of several subjects needed to understand and explain the scenarios used.

    In PBL, teachers are expected to cooperate over departmental borders, a process that often produces positive spin-off effects extending further to research. They take on many different roles as e.g. planners, semester coordinators, tutors, lecturers and clinical supervisors. As such, newcomers may encounter certain frustration. Continuous staff development is critical to assure pedagogical selection and excellence, and thereby the quality of the programmes.

    In PBL, teachers are expected to cooperate over departmental borders, a process that often produces positive spin-off effects extending further to research. They take on many different roles as e.g. planners, semester coordinators, tutors, lecturers and clinical supervisors. As such, newcomers may encounter certain frustration. Continuous staff development is critical to assure pedagogical selection and excellence, and thereby the quality of the programmes.

    The aim to be a medical faculty with a standing among the most progressive worldwide implies continuous evaluation and development. Our mission is to foster the very best in health care; health care extending consideration toward educating competent professionals and conducting quality research with a focus on societal needs and welfare. To fulfil this mission, we need to advance teaching models based on evidence, and continuously improve and develop our educational methods. This process requires cooperation between departments, teachers and students within the university and indeed, throughout the world. Such contacts and collaborations are as important in education as they are in research, and extend an endless source of inspiration. Communication between the different undergraduate programmes at FHS has been extremely fruitful and should further be stimulated. At the faculty level, it is important to provide teachers with credit for efforts and development toward education. To keep integration and innovation at a high level, it is very important to balance the decision power and the distribution of money between departments and programmes.

    The aim of this book is to provide a general overview, in glimpses, of some of the important developments in FHS education; to describe new ideas in progress or those already turned to reality and also, to extend some consideration of publications regarding our educational innovations. We hope these examples provide the essence of inspiration for future work, contributing to improved education and better health for all.

  • 10.
    Hammarskjold, F
    et al.
    Ryhov County Hospital, Sweden .
    Mernelius, S
    Ryhov County Hospital, Sweden .
    Andersson, R. E.
    Ryhov County Hospital, Sweden .
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lofgren, S
    Ryhov County Hospital, Sweden .
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Petzold, M
    University of Gothenburg, Sweden .
    Matussek, A
    Ryhov County Hospital, Sweden .
    Possible transmission of Candida albicans on an intensive care unit: genotype and temporal cluster analyses2013In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 85, no 1, p. 60-65Article in journal (Refereed)
    Abstract [en]

    Background: Nosocomial transmission of Candida spp. has not been fully explored and previous studies have shown conflicting results. less thanbrgreater than less thanbrgreater thanAim: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU). less thanbrgreater than less thanbrgreater thanMethods: A prospective study was conducted for a period of 19 months, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing with repetitive sequence-based polymerase chain reaction was used to define genotype relationships between the Candida albicans and Candida glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time. less thanbrgreater than less thanbrgreater thanFindings: Seventy-seven patients with 78 ICU stays, representing 12% of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and 10 of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes, was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared with the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-day interval, indicating clustering. less thanbrgreater than less thanbrgreater thanConclusion: This study indicates possible transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

  • 11.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Taxbro, Knut
    Ryhov County Hospital, Sweden .
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Jonkoping Cty Council, Futurum Acad Hlth Care, Jonkoping, Sweden.
    Sustained low incidence of central venous catheter-related infections over six years in a Swedish hospital with an active central venous catheter team2014In: American Journal of Infection Control, ISSN 0196-6553, E-ISSN 1527-3296, Vol. 42, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    Background: There are limited data on the long-term effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors over a 6-year period in a hospital with an active CVC team. Methods: We conducted a continuous prospective study aiming to include all CVCs used at our hospital during the years 2004 to 2009, evaluating colonization, CRI, CRBSI, and possible risk factors. Results: A total of 2,772 CVCs was used during the study period. Data on culture results and catheterization time were available for 2,045 CVCs used in 1,674 patients. The incidences of colonization, CRI, and CRBSI were 7.0, 2.2, and 0.6 per 1,000 CVC-days, respectively. Analysis of quarterly incidences revealed 1 occasion with increasing infection rates. Catheterization time was a risk factor for CRI but not for CRBSI. Other risk factors for CRI were hemodialysis and CVC use in the internal jugular vein compared with the subclavian vein. Hemodialysis was the only risk factor for CRBSI. Conclusion: We found that a CRI prevention program led by an active CVC team and adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time.

  • 12.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mernelius, S.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Andersson, R.
    Department of Surgery, Ryhov County Hospital, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Löfgren, S.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Malmvall, Bo-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Petzold, M.
    Centre for Applied Biostatistics, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Matussek, A.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Possible transmission of Candida albicans on an intensive care unit: intensive care unit:Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Nosocomial transmission of Candida spp. has not fully been explored and previous studies have shown conflicting results.

    Aim: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU).

    Methods: We conducted a prospective study over 19 month, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing, with rep-PCR (DiversiLab) was used to define genotype relationships between the C. albicans and C. glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU, were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time.

    Findings: Seventy-seven patients with 78 ICU stays, representing twelve per cent of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and ten of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared to the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-dayinterval, indicating clustering.

    Conclusion: This study indicates transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

  • 13.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Antonelli, Massimo
    Policlinico University of A. Gemelli, Rome, Italy.
    Holmbom, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lipman, Jeffrey
    University of Queensland, Herston, Australia.
    Pickkers, Peter
    Radboud University Medical Centre, Nijmegen, The Netherlands.
    Leone, Marc
    Aix Marseille University, France.
    Rello, Jordi
    University Autonoma of Barcelona, Spain.
    Sakr, Yasser
    Friedrich-Schiller University, Jena, Germany.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Vanhems, Philippe
    University of Lyon 1, France.
    Vincent, Jean-Louis
    University Libre Bruxelles, Belgium.
    Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels2014In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 14, no 513Article in journal (Refereed)
    Abstract [en]

    Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance. Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of greater than= 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of less than 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden). Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P less than 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P less than 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P less than 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections. Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome.

  • 14.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Edlund, Charlotta
    Medical Product Agency, Uppsala.
    Furebring, Mia
    Uppsala University.
    Giske, Christian G.
    MTC – Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Melhus, Åsa
    Uppsala University.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Petersson, Johan
    Karolinska Institutet, Stockholm.
    Sjölin, Jan
    Uppsala University.
    Ternhag, Anders
    Swedish Institute for Communicable Disease Control, Solna.
    Werner, Maria
    Södra Älvsborgs Sjukhus, Borås.
    Eliasson, Erik
    Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Rational use of aminoglycosides - Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 3, p. 161-175Article, review/survey (Refereed)
    Abstract [en]

    The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk–benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

  • 15.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases in Östergötland.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ternhag, Anders
    Swedish Institute Communicable Disease Control, Sweden .
    Giske, Christian G.
    Karolinska University Hospital, Sweden .
    Letter: Rational use of aminoglycosides - author response2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 8, p. 655-656Article in journal (Other academic)
    Abstract [en]

    n/a

  • 16.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, Christian G
    Clinical microbiology — Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Giamarellou, Helen
    Athens University Medical School, Athens, Greece.
    When and how to cover for resistant gram-negative bacilli in severe sepsis and septic shock.2011In: Current Infectious Disease Reports, ISSN 1523-3847, E-ISSN 1534-3146, Vol. 13, no 5, p. 416-425Article in journal (Refereed)
    Abstract [en]

    In the 80s and 90s, increasing antibiotic resistance was met by the introduction of new effective agents with broader antibacterial spectra for the empirical treatment of severe infections. In recent years, however, few novel antimicrobials have been developed, and this has critically weakened our strength in the fight against resistant bacteria, especially Gram-negative bacilli. It has been well proven that mortality increases if initial empirical antibiotic treatment for severe infection is inappropriate due to resistance of the pathogen. Physicians are already faced with the increasing challenge of untreatable or almost untreatable Gram-negative infections due to antibiotic resistance. Empirical treatment with broader spectra and high antibiotic pressure both in- and outside hospital is the driving force behind resistance. Since new efficient drugs against Gram-negative bacilli will not be available for some time, the best we can do to stop infections caused by multidrug-resistant bacteria is to improve infection control and choice of antibiotics, which should be based on surveillance of local antibiotic consumption and resistance. We must learn more about the revived antibacterial agents colistin and fosfomycin, and the few next generation Gram-negative antibiotics that have been developed. The aim of this review is to give an update on present therapeutic options in the fight against multidrug-resistant Gram-negative bacteria.

  • 17.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Skoog, Gunilla
    Public Health Agency Sweden, Sweden .
    Ternhag, Anders
    Public Health Agency Sweden, Sweden Karolinska Institute, Sweden .
    Giske, Christian G.
    Karolinska University Hospital, Sweden .
    Antibiotic consumption and antibiotic stewardship in Swedish hospitals2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 154-161Article, review/survey (Refereed)
    Abstract [en]

    Background. The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e. g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.

  • 18.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Leone, Marc
    Department of Anesthesiology and Intensive Care Medicine, Nord Hospital, Marseille, France.
    Barie, Philip S
    Department of Surgery, Weill Cornell Medical College, New York, USA.
    Rello, Jordi
    Critical Care Department, Vall d’Hebron University Hospital, CIBERES, VHIR, Universitat Autónoma de Barcelona, Spain.
    Lipman, Jeffrey
    Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital and Burns Trauma Critical Care Research Centre, University of Queensland, Queensland, Australia.
    Marshall, John C
    Department of Surgery, University of Toronto, St Michael's Hospital, Toronto, Ontario, Canada.
    Anzueto, Antonio
    Department of Pulmonary/Critical Care, University of Texas Health Science Center, San Antonio, TX, USA.
    Sakr, Yasser
    Department of Anesthesiology and Intensive Care, Friedrich-Schiller University, Jena, Germany.
    Pickkers, Peter
    Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Felleiter, Peter
    Intensive Care Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.
    Engoren, Milo
    Department of Anesthesiology, Mercy St Vincent Medical Center, Toledo, OH, USA.
    Vincent, Jean-Louis
    Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium.
    Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study2011In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 38, no 4, p. 331-335Article in journal (Refereed)
    Abstract [en]

    Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May 2007. Demographic, physiological, bacteriological and therapeutic data were collected for 13 796 adult patients in 1265 participating Intensive Care Units (ICUs) from 75 countries on the study day. ICU and hospital outcomes were recorded. Characteristics of patients with meticillin-sensitive S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA) infections were compared. Co-morbidities, age, Simplified Acute Physiology Score (SAPS) II, site of infection, geographical region and MRSA/MSSA were entered into a multivariate model, and adjusted odds ratios (ORs) [95% confidence interval (CI)] for ICU and hospital mortality rates were calculated. On the study day, 7087 (51%) of the 13 796 patients were classified as infected. There were 494 patients with MRSA infections and 505 patients with MSSA infections. There were no significant differences between the two groups in use of mechanical ventilation or haemofiltration/haemodialysis. Cancer and chronic renal failure were more prevalent in MRSA than in MSSA patients. ICU mortality rates were 29.1% and 20.5%, respectively (P andlt; 0.01) and corresponding hospital mortality rates were 36.4% and 27.0% (P andlt; 0.01). Multivariate analysis of hospital mortality for MRSA infection showed an adjusted OR of 1.46 (95% CI 1.03-2.06) (P = 0.03). In ICU patients, MRSA infection is therefore independently associated with an almost 50% higher likelihood of hospital death compared with MSSA infection.

  • 19.
    Hedenstierna, Magnus
    et al.
    Karolinska Institutet.
    Uhnoo, Ingrid
    Academic Hospital, Uppsala.
    Aleman, Soo
    Karolinska Institutet.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Norkrans, Gunnar P
    Sahlgrenska University Hospital.
    Eilard, Anders
    Sahlgrenska University Hospital.
    Glaumann, Hans
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Weiland, Ola
    Karolinska Institutet.
    DURABILITY OF SVR AND FIBROSIS IMPROVEMENT AFTER SOC TREATMENT FOR CHRONIC HCV-10 YEARS FOLLOW-UP in HEPATOLOGY, vol 54, issue , pp 839A-840A2011In: HEPATOLOGY vol 54, Wiley-Blackwell , 2011, Vol. 54, p. 839A-840AConference paper (Refereed)
    Abstract [en]

    n/a

  • 20.
    Hedin Skogman, Barbro
    et al.
    Center for Clinical Research, Falun, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Smittskyddsinstutet .
    Åkerlind, Britt
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Are There Undiagnosed TBE-, Herpes- or Enteroviral Infections among Children Being Evaluated for Lyme Neuroborreliosis?2014In: Open Journal of Clinical Diagnostics, ISSN 2162-5816, E-ISSN 2162-5824, Vol. 4, no 3, p. 123-129Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis (LNB) in children is a challenging diagnosis based on clinical manifestations and laboratory findings. The aim of this study was to investigate whether herpes simplex virus (HSV) 1 or 2, varicella zoster virus (VZV), enterovirus or tick-borne encephalitis virus (TBEV) could be identified in cerebrospinal fluid (CSF) or serum from children being evaluated for LNB, in order to elucidate whether such infectious diseases may be missed by the clinician. Methods: Ninety-nine pediatric patients (n = 99) were retrospectively included from a previous study on LNB in southeast of Sweden. They had been diagnosed as “Possible LNB” or “Not determined” due to negative Borrelia antibody index in CSF. Routine polymerase chain reaction (PCR) methods were used for detection of herpes viral RNA or enteroviral DNA in CSF. An ELISA assay was used for detection of anti-TBEV antibodies (IgM and IgG) in serum. Results: One patient showed elevated anti-TBEV IgM and IgG antibodies in serum, indicating a current TBE infection. No positive PCR reactions for HSV 1 or 2, VZV or enterovirus were detected in CSF from any of the patients. In conclusion, our results suggest that undiagnosed herpes- or enteroviral infections are unlikely to explain CNS symptoms in children being evaluated for LNB, whereas missed TBE infections may occur. TBEV serology should be included when evaluating children for LNB in TBE endemic areas.

  • 21.
    Hellmark, B.
    et al.
    Örebro University Hospital, Sweden.
    Berglund, C.
    Aleris MEDILAB, Täby, Sweden .
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Unemo, M
    Örebro University Hospital, Sweden.
    Söderquist, B
    Örebro University Hospital, Sweden.
    Staphylococcal cassett chromosome med (SCCmec) and arginine catabolic mobile element (ACME) in Staphylococcus epidermidis isolated from prosthetic joint infections2013In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 32, no 5, p. 691-697Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to characterise the staphylococcal cassette chromosome mec (SCCmec) in Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) and, if possible, assign them to any of the presently known SCCmec types. In addition, the isolates were examined for the presence of the arginine catabolic mobile element (ACME). Sixty-one S. epidermidis isolates obtained from PJIs and 24 commensal S. epidermidis isolates were analysed. The mecA gene was detected in 49 of the 61 (80 %) PJI isolates and in four of the 24 (17 %) commensal isolates, and the composition of the SCCmec was further analysed. SCCmec types I and IV were the most common types among the PJI isolates. However, for over half (57 %) of the isolates, it was not possible to assign an SCCmec type. ACME was detected in eight (13 %) of the PJI isolates and in 14 (58 %) of the commensal isolates. The characterisation of the SCCmec elements revealed a large heterogeneity, with a high frequency of isolates carrying more than one type of the ccr gene complex. ACME was more common among the commensal isolates and may represent a survival benefit for S. epidermidis colonising healthy individuals in the community.

  • 22.
    Hellmark, Bengt
    et al.
    Örebro University Hospital, Sweden.
    Söderquist, Bo
    Örebro University Hospital and University of Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Comparison of Staphylococcus epidermidis isolated from prosthetic joint infections and commensal isolates in regard to antibiotic susceptibility, agr type, biofilm production, and epidemiology2013In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 303, no 1, p. 32-39Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is the predominant bacterial species in the normal flora of the human skin and superficial mucosal membranes. However, it has also emerged as the most important pathogen in infections related to foreign-body materials, such as prosthetic joints and heart valves. The aims of this study were to characterise S. epidermidis isolated from prosthetic joint infections (PJI; n=61) and commensal isolates from healthy individuals (n=24) in regard to antimicrobial sensitivity, agr type, hld gene presence, biofilm production including presence of ica and aap genes involved in the biofilm formation process and epidemiology using both phenotypic (the PhenePlate-system) and genotypic [multilocus sequence typing (MLST)] methods. Among the PJI isolates, the majority (67%) were multidrug-resistant. Two major clusters of PJI isolates could be identified; 44% belonged to MLST sequence type (ST) 2, all but one were of agr type 1, and 31% were assigned ST215 and were of agr type 3. Of the commensal isolates, only one isolate was multidrug-resistant, and they were more molecular epidemiologically diverse with mainly MLST singletons and a maximum of 3 isolates assigned to the identical ST. Biofilm production was detected in 41% of the PJI isolates and 58% of the commensal isolates, with the aap gene (95%) more frequently detected than the ica genes (62%) in the biofilm-positive isolates. In conclusion, S. epidermidis isolated from PJIs and commensal isolates differed regarding antimicrobial sensitivity and molecular epidemiological typing using MLST, but not substantially in the distribution of agr types, biofilm production, or the presence of ica and aap genes.

  • 23.
    Henningsson, Anna J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Jönköping.
    Tjernberg, Ivar
    Kalmar County Hospital, Kalmar.
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study2011In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 8, no 36Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods: To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results: The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p andlt; 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p andlt; 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms andlt; 2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion: Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

  • 24.
    Johansson, M
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    M Phuong, D
    Department of Microbiology, Bach Mai Hospital, Hanoi, Vietnam.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Need for improved antimicrobial and infection control stewardship in Vietnamese intensive care units2011In: TROPICAL MEDICINE and INTERNATIONAL HEALTH, ISSN 1360-2276, Vol. 16, no 6, p. 737-743Article in journal (Refereed)
    Abstract [en]

    Pandgt;Objective Survey of antibiotic consumption, microbial resistance and hygiene precautions in the intensive care units of three hospitals in northern Vietnam. Methods Observational study. Data were collected from the microbiological laboratories. Antibiotic consumption was determined based on quantities of drugs delivered from the pharmacy. A protocol to observe the application of hygiene precautions was developed and used. Bacteria were typed and tested for drug susceptibility using the disc-diffusion method. Results The mean antibiotic consumption was 811 defined daily doses per 1000 occupied bed days. The most commonly used antibiotics were third-generation cephalosporins, followed by carbapenems, amoxicillin and ampicillin. Eighty per cent of bacterial isolates were Gram-negative. The most common pathogens found in blood cultures were Escherichia coli and Klebsiella spp., Pseudomonas spp., Acinetobacter spp., Staphylococcus aureus and Enterococcus faecalis. Acinetobacter and Pseudomonas spp. were the two most frequently isolated bacteria from the respiratory tract and all other sources together. Seventy per cent of Acinetobacter species showed reduced susceptibility to imipenem, 80% to ciprofloxacin and 89% to ceftazidime. Forty-four per cent of Pseudomonas spp. showed reduced susceptibility to imipenem, 49% to ciprofloxacin and 49% to ceftazidime. Escherichia coli was fully susceptible to imipenem, but 57% of samples were resistant to both ciprofloxacin and cefotaxime. Hygiene precautions were poor, and fewer than 50% of patient contacts incorporated appropriate hand hygiene. Conclusion Low antibiotic consumption, poor hygiene precautions and the high level of antibiotic resistance indicate that there is room for improvement regarding antibiotic use and infection control.

  • 25.
    Khassebaf, Jasmine
    et al.
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Hellmark, Bengt
    Örebro University Hospital, Sweden.
    Davidsson, Sabina
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Unemo, Magnus
    Örebro University Hospital, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Söderquist, Bo
    Örebro University, Sweden.
    Antibiotic susceptibility of Propionibacterium acnes isolated from orthopaedic implant-associated infections.2015In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 32, p. 57-62Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Prosthetic joint infections (PJIs) caused by Propionibacterium acnes account for a larger proportion of the total number of PJIs than previously assumed and thus knowledge of the antimicrobial susceptibility patterns of P. acnes is of great value in everyday clinical practice.

    MATERIALS AND METHODS: Using Etest, the present study investigated the susceptibility of 55 clinical isolates of P. acnes, obtained from orthopaedic implant-associated infections of the knee joint (n = 5), hip joint (n = 17), and shoulder joint (n = 33), to eight antimicrobial agents: benzylpenicillin, clindamycin, metronidazole, fusidic acid, doxycycline, moxifloxacin, linezolid and rifampicin. Synergy testing was also conducted, in which rifampicin was combined with each of the remaining seven antibiotics.

    RESULTS: All isolates (n = 55) were susceptible to most of the antibiotics tested, with the exception of 100% resistance to metronidazole, five (9.1%) isolates displaying decreased susceptibility to clindamycin, and one (1.8%) to moxifloxacin. None of the antimicrobial agents investigated were synergistic with each other when combined and nine isolates were antagonistic for various antimicrobial combinations. The majority of the antimicrobial combinations had an indifferent effect on the isolates of P. acnes. However, the combination of rifampicin and benzylpenicillin showed an additive effect on nearly half of the isolates.

    CONCLUSION: Almost all P. acnes, isolated from orthopaedic implant-associated infections, predominantly PJIs, were susceptible to the antibiotics tested, with the exception of complete resistance to metronidazole. Synergy test could not demonstrate any synergistic effect but additive effects were found when combining various antibiotics. Antagonistic effects were rare.

  • 26.
    Leander, Gunilla
    et al.
    Blekingesjukhuset, Karlskrona.
    Eliasson, Erik
    Institutionen för laboratoriemedicin, Karolinska institutet, Karolinska universitetssjukhuset, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, CG
    Klinisk mikrobiologi, Karolinska universitetssjukhuset, Sweden.
    Betalaktamantibiotika och frågan om dosregim vid svår infektion: Förlängd infusion teoretiskt tilltalande – Ännu saknas evidens för klinisk nytta2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 13, article id CW3PArticle in journal (Refereed)
    Abstract [sv]

    Betalaktamantibiotika är första­handsmedel vid svår sepsis/septisk chock.

    Djurstudier visar att den fria antibiotikakoncentrationen i blodet bör överstiga den koncentration som krävs för att hämma bakterietillväxt (MIC) under minst 50 procent av dygnet för maximal effekt av betalaktamantibiotika. 

    Infusion av betalaktamer under flera timmar eller kontinuerlig infusion kan teoretiskt öka tiden över MIC jämfört med dagens standardadministration av bolusdoser.

    Enligt denna litteraturgenomgång saknas evidens för säker skillnad i klinisk effekt mellan kontinuerlig infusion, förlängd infusion eller standardbolusdos av betalaktamantibiotika. Inkluderade studier är mycket heterogena avseende bl a patienturval, infektionsfokus, bakteriella agens och doseringsregimer.  

    I avvaktan på resultat från nya studier bör patienter med svår sepsis, framför allt vid septisk chock, ges höga och täta intermittenta betalaktamdoser alternativt förlängd infusion i syfte att nå fri antibiotikakoncentration i blodet, som överstiger MIC under minst halva dosintervallet.

  • 27.
    Lindblom, A.
    et al.
    Uppsala University, Sweden.
    Wallménius, K.
    Uppsala University, Sweden.
    Nordberg, M.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Eliasson, I.
    Norra Älvsborg County Hospital (NÄL), Trollhättan, Sweden .
    Påhlson, C.
    Uppsala University, Sweden.
    Nilsson, K.
    Uppsala University, Sweden and Center of Clinical Research, Falun, Sweden.
    Seroreactivity for spotted fever rickettsiae and co-infections with other tick-borne agents amond habitants in central and southern Sweden2013In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 32, no 3, p. 317-323Article in journal (Refereed)
    Abstract [en]

    Patients seeking medical care with erythema migrans or flu-like symptoms after suspected or observed tick bite in the southeast of Sweden and previously investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined for serological evidence of rickettsial infection (Study 1). Twenty of 206 patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion indicative of recent or current infection and 13 patients had titres compatible with past infection, of which five patients were judged as probable infection. Of 19 patients with medical records, 11 were positive for Borrelia spp. as well, and for Anaplasma sp., one was judged as positive. Five of the 19 patients had antibodies against all three pathogens. Erythema migrans or rash was observed at all combinations of seroreactivity, with symptoms including fever, muscle pain, headache and respiratory problems. The results were compared by screening an additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for Rickettsia spp., of which five were judged as recent or current infection. Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors without clinical symptoms, approximately 1 % were seroreactive for Rickettsia spp., interpreted as past infection. The study shows that both single and co-infections do occur, which illustrate the complexity in the clinical picture and a need for further studies to fully understand how these patients should best be treated.

  • 28.
    Lindblom, Pontus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Wilhelmsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Fryland, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Haglund, Mats
    Kalmar County hospital.
    Sjöwall, Johanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Determining factors for successful vaccination against tick-borne encephalitis virus in older individuals2014Manuscript (preprint) (Other academic)
    Abstract [en]

    We performed a cross-sectional study including 533 persons (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 14 healthrelated factors: [age, gender, number of vaccine doses (0-5), time since last vaccine dose, previous TBE disease, vaccination against other flaviviruses, ≥2 tick-bites during the previous 3 months, pet-ownership, asthma, smoking, allergy, diabetes, medication, and previous tumor]. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the person and the number of vaccine doses were the two most important factors determining successful vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same response. Participants receiving medication and participants previously vaccinated against other flaviviruses had lower TBEV antibody titers on average, while those with self-reported asthma had higher titers. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

  • 29.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    County Hospital Ryhov, Sweden .
    Haglund, Mats
    County Hospital Kalmar, Sweden .
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Public Health Agency Sweden, Stockholm.
    Nyman, Dag
    Aland Central Hospital, Finland .
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e0100860-Article in journal (Refereed)
    Abstract [en]

    We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic A land Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

  • 30.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sjowall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Haglund, Mats
    Kalmar County hospital.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Andreassen, Åshild
    Norwegian Institute of Public Health, Olso, Norway.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response.2014In: Ticks and Tick Borne Diseases, ISSN 1877-959X, Vol. 5, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    The risk of tick-borne encephalitis virus (TBEV) infection after a tick bite remains largely unknown. To address this, we investigated the presence of TBEV in ticks detached from humans in an attempt to relate viral copy number, TBEV subtype, and tick feeding time with the serological and clinical response of the tick-bitten participants. Ticks, blood samples, and questionnaires were collected from tick-bitten humans at 34 primary health care centers in Sweden and in the Aland Islands (Finland). A total of 2167 ticks was received from 1886 persons in 2008-2009. Using a multiplex quantitative real-time PCR, 5 TBEV-infected ticks were found (overall prevalence 0.23%, copy range <4 X 10(2)-7.7 X 10(6) per tick). One unvaccinated person bitten by a tick containing 7.7 x 10(6) TBEV copies experienced symptoms. Another unvaccinated person bitten by a tick containing 1.8 x 10(3) TBEV copies developed neither symptoms nor TBEV antibodies. The remaining 3 persons were protected by vaccination. In contrast, despite lack of TBEV in the detached ticks, 2 persons developed antibodies against TBEV, one of whom reported symptoms. Overall, a low risk of TBEV infection was observed, and too few persons got bitten by TBEV-infected ticks to draw certain conclusions regarding the clinical outcome in relation to the duration of the blood meal and virus copy number. However, this study indicates that an antibody response may develop without clinical symptoms, that a bite by an infected tick not always leads to an antibody response or clinical symptoms, and a possible correlation between virus load and tick feeding time. (C) 2013 Elsevier GmbH. All rights reserved.

  • 31.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Grub, C.
    Oslo University Hospital.
    Jonassen, T. Ö.
    Oslo University Hospital.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 2, p. 141-147Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in A-stergotland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type I (TM) I (TM) element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

  • 32.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wistedt, Annika
    Department of Clinical Microbiology and Infection Control, Kalmar County Hospital, Kalmar, Sweden.
    Swanberg, Jonas
    Clinical Microbiology Laboratory, Ryhov Hospital, Jönköping, Sweden.
    Skov, Robert
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Rhod Larsen, Anders
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Larsen, Jesper
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Petersen, Andreas
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.

    Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.

    Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.

    Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.

  • 33.
    Lundin, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Personne, Mark
    Giftinformationscentralen, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Botulism är en behandlingsbar, mycket sällsynt förgiftning2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 12-13, p. 551-552Article in journal (Refereed)
    Abstract [sv]

    Botulism är en sällsynt förgiftning orsakad av botulinumtoxin från bakterien Clostridium botulinum.

    Bakterien tillväxer under anaeroba förhållanden och återfinns på våra breddgrader oftast i bristfälligt tillagad fisk.

    Botulism ska misstänkas vid snabbt progredierande symmetrisk nedåtstigande muskelparalys och autonoma symtom – framför allt vid pupillpåverkan (mydriasis). Behandlingen består i tillförsel av antitoxin för att förhindra symtomprogress samt symtomatiskt omhändertagande, speciellt med avseende på andningsunderstöd.Långvarig intensivvårdsbehandling kan bli aktuell, men på sikt är prognosen relativt god.

  • 34.
    Lönn, J.
    et al.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Kälvegren, Hanna
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Särndahl, E.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bengtsson, T.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition2012In: Results in Immunology, ISSN 2211-2839, Vol. 2, p. 7-12Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

  • 35.
    Lönn, J.
    et al.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Sridhar, Sravya
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bengtsson, T.
    PEAS Institute, Linköping, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    High concentrations of hepatocyte growth factor but low biological activity in patients with periodontitisManuscript (preprint) (Other academic)
    Abstract [en]

    Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, has been associated to inflammatory diseases including periodontitis. To induce cellular responses, biologic active HGF requires binding to its receptor c-Met and the co-receptor heparan sulphate proteoglycan (HSPG) on cell membranes and extracellular matrix. The aim of this study was to investigate the concentration and the biological activity of HGF and the relationship with subgingival microbiota in medically healthy subject with / without periodontitis.

    Methods: Saliva, gingival crevicular fluid (GCF) and blood samples from thirty patients with severe periodontitis and thirty periodontally healthy controls were analysed for the concentration of HGF and the binding affinity to HSPG and c-Met, using ELISA and surface plasmon resonance (SPR). Subgingival plaque were analysed for the presence of 18 bacterial species.

    Results: Compared to controls, patients with periodontitis showed higher concentrations of HGF in all three locations (P<0.001), however the binding affinity to HSPG and c-Met were markedly reduced in GCF and in saliva (P<0.002). The patients had higher prevalence of periodontal related bacterial species.

    Conclusion: The increased concentration of HGF in GCF and saliva in patients with severe periodontitis was also reflected in the circulation indicating a systemic effect by periodontitis. However, the biological activity of HGF at local sites of inflammation was reduced. A loss of function of healing factors such as HGF may be one important mechanism in the dominant degenerative processes in periodontally susceptible subjects.

  • 36.
    Lönn, Johanna
    et al.
    PEAS Institute, Linköping, Sweden.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    An antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in depp ulcer infections2012In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 60, no 2, p. 478-486Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Widely studied for the past 20 years, hepatocyte growth factor (HGF) has been identified as a regenerative marker and an important factor in the development and healing of injuries. Antithrombin III (AT III) is a protein in the blood stream with anti-thrombotic and anti-inflammatory properties and has been used as an adjuvant treatment along with antibiotics in severe sepsis.

    OBJECTIVE:

    To study the content and properties of HGF in plasma-derived AT III products, and the regenerative effect in severe deep ulcer infections.

    METHODS:

    Commercial AT III products were analyzed for the presence and biological activity of HGF. One AT III product containing biologically active HGF was used to treat 18 cases of critical, deep ulcer infections scheduled for major invasive intervention. The patients were followed up for 6-60 months.

    RESULTS:

    The AT III products contained HGF with different biological activity. No adverse reactions were observed after local administration of AT III during the study or follow-up period. In 16 of 18 cases no surgical intervention was needed within the first 6 month of inclusion.

    CONCLUSION:

    AT III products containing biologically active HGF may contribute to regeneration and healing in severe deep ulcer infections which do not respond adequately to different combinations of antibiotics alone.

  • 37.
    Lönn, Johanna
    et al.
    PEAS Institut AB, Linköping, Sweden.
    Shahzad, Faisal
    PEAS Institut AB, Linköping, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure2012In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 3, no 4, p. 516-523Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a renotropic, an- tifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS- PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for de- velopment of CRF we aimed to assess the amounts and affinity of HGF in this patient group. ELISA, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased af- finity to HSPG (P < 0.0001). Addition of protease in-hibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks af-finity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight un-derlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

     

     

  • 38.
    Lönn, Johanna
    et al.
    PEAS Institut, Linköping, Sweden.
    Sravya, Nakka
    PEAS Institut, Linköping, Sweden.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology. Karolinska Institutet, Stockholm, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping.
    Differences in the expression of hepatocyte growth factor in acute and chronic bowel inflammation - Implications for diagnosis?2013In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 4, no 8A2, p. 33-42Article in journal (Refereed)
    Abstract [en]

    Background: Hepatocyte growth factor (HGF) acts as an acute phase protein with regenerative properties. HGF is produced systemically and locally during inflammation but exhibits decreased binding affinity to heparan sulphate proteoglycan (HSPG)/glycosaminoglycan during chronic inflammation. We previously observed a high faecal concentration and binding affinity of HGF to HSPG during acute gastroenteritis. High faecal concentrations of calprotectin and HGF have been reported in chronic inflammatory bowel disease (IBD).

    Methods: Stool samples from patients with ulcerative colitis in remission (n = 11) or exacerbation (n = 5), microscopic colitis (n = 11), colon cancer (n = 6), or acute gastroenteritis caused by Clostridium difficile (n = 20), as well as healthy controls (n = 7), were analysed for the presence of HGF by ELISA, surface plasmon resonance, SDS-PAGE, and Western blot. Then in two patients with ulcerative colitis exacerbation and C. difficile infection, the expression of HGF and calprotectin was studied in colonic biopsies.

    Results: The faecal concentration of HGF was significantly higher in patients with ulcerative colitis compared to the other groups. The binding affinity to dextran was lower in all groups compared to acute inflammation. HGF receptor binding was similar across groups. In a patient with concomitant C. difficile infection and distal ulcerative colitis, HGF was highly expressed in the part of the bowel unaffected by ulcerative colitis, but no expression was found at the site of chronic inflammation. In the patient with total colitis the biopsies showed low expression of HGF. The areas with chronic inflammation exhibited infiltrating calprotectin-stained neutrophils.

    Conclusion: HGF is produced locally during inflammation of the bowel. The HGF produced during acute inflammation or exacerbations of chronic inflammation by the unaffected area shows binding affinity to glucosaminoglycans. Measuring HGF binding in faeces and biopsies may be a tool for differentiating between acute and chronic bowel inflammation, which should be assessed thoroughly in future studies.

  • 39.
    Lönn, Johanna
    et al.
    Univ Orebro, Sch Hlth & Med Sci, Div Clin Med, Orebro, Sweden; PEAS Institute, Linköping and Örebro University, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    Nakka, Sravya
    PEAS Institute, Linköping, Sweden.
    Palm, Elenor
    Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Inst, Inst Prot Environm Affin Surveys, Linkoping, Sweden.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis2014In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 85, no 1, p. 113-122Article in journal (Refereed)
    Abstract [en]

    Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, are associated with inflammatory diseases, including periodontitis. HGF biologic activity requires binding to its receptors, the proto-oncogene c-Met and heparan sulfate proteoglycan (HSPG). This study investigates HGF expression and its relationship to subgingival microbiota in medically healthy individuals with and without periodontitis.

    Methods: Saliva, gingival crevicular fluid (GCF), and blood samples from 30 patients with severe periodontitis and 30 healthy controls were analyzed for HGF concentration using enzyme-linked immunosorbent assay and binding affinity for HSPG and c-Met using surface plasmon resonance. The regenerative effects of saliva from three patients and controls were analyzed in an in vitro model of cell injury. Subgingival plaques were analyzed for the presence of 18 bacterial species.

    Results: Patients with periodontitis showed higher HGF concentrations in saliva, GCF, and serum (P <0.001); however, the binding affinities for HSPG and c-Met were reduced in GCF and saliva (P <0.002). In contrast to the controls, saliva from patients showed no significant regenerative effect over time on gingival epithelial cells. Compared with controls, patients had a higher prevalence of periodontally related bacteria.

    Conclusions: Higher circulatory HGF levels indicate a systemic effect of periodontitis. However, the HGF biologic activity at local inflammation sites was reduced, and this effect was associated with the amount of periodontal bacteria. Loss of function of healing factors may be an important mechanism in degenerative processes in periodontally susceptible individuals.

  • 40.
    Mernelius, Sara
    et al.
    Division of Medical Services, Jönköping, Sweden.
    Svensson, Per-Olof
    Unit for Health Care Hygiene, Jönköping, Sweden.
    Rensfeldt, Gunhild
    Unit for Health Care Hygiene, Jönköping, Sweden.
    Davidsson, Ewa
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology.
    Lofgren, Sture
    Division of Medical Services, Jönköping, Sweden.
    Matussek, Andreas
    Division of Medical Services, Jönköping, Sweden.
    Compliance with hygiene guidelines: The effect of a multimodal hygiene intervention and validation of direct observations2013In: American Journal of Infection Control, ISSN 0196-6553, E-ISSN 1527-3296, Vol. 41, no 5, p. E45-E48Article in journal (Refereed)
    Abstract [en]

    Background

    Good compliance with hygiene guidelines is essential to prevent bacterial transmission and health care-associated infections. However, the compliance is usually <50%.

    Methods

    A multimodal and multidisciplinary hygiene intervention was launched once the baseline compliance was determined through direct observations in 4 departments of obstetrics and gynecology. Detailed evaluations of the compliance rates were performed at point of stability (at 80%) and follow-up (3 years after hygiene intervention). Validation of direct observations was performed using blinded double appraisal and multiappraisal.

    Results

    At baseline, the compliance with barrier precautions and the dress code at the 4 departments were 39% to 47% and 79% to 98%, respectively. Point of stability was reached approximately 1 year after the hygiene intervention was launched. The compliance with barrier precautions was significantly higher at follow-up compared with baseline in 3 departments. In the validation by double appraisal, 471 of 483 components were judged identical between observers. In the multiappraisal, 95% to 100% of the observers correctly judged the 7 components.

    Conclusion

    It is possible to improve compliance with hygiene guidelines, but, to ensure a long-lasting effect, a continuous focus on barrier precautions is required. Observation is a valid method to monitor compliance.

  • 41.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Balkhed Östholm, Åse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Nilsson, MV
    Nilsson, M
    Dornbusch, Kathrine
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 12, p. 1400-1408Article in journal (Refereed)
    Abstract [en]

    Extended-spectrum β-lactamases (ESBLs) are often mediated by bla-SHV, blaTEM and blaCTX-M genes in Enterobacteriaceae and other Gram-negative bacteria. Numerous molecular typing methods, including PCR-based assays, have been developed for their identification. To reduce the number of PCR amplifications needed we have developed a multiplex PCR assay which detects and discriminates between bla-SHV, blaTEM and blaCTX-M PCR amplicons of 747, 445 and 593 bp, respectively. This multiplex PCR assay allowed the identification of bla-SHV, blaTEM and blaCTX-M genes in a series of clinical isolates of Enterobacteriaceae with previously characterised ESBL phenotype. The presence of blaSHV, blaTEM and blaCTX-M genes was confirmed by partial DNA sequence analysis. Apparently, the universal well-established CTX-M primer pair used here to reveal plasmid-encoded blaCTX-M genes would also amplify the chromosomally located K-1 enzyme gene in all Klebsiella oxytoca strains included in the study.

  • 42.
    Nguyen, Minh Vu Chuong
    et al.
    University of Grenoble 1, France .
    Lardy, Bernard
    University of Grenoble 1, France .
    Rousset, Francis
    University of Grenoble 1, France .
    Hazane-Puch, Florence
    University Hospital CHU Grenoble, France .
    Zhang, Leilei
    University of Grenoble 1, France .
    Trocme, Candice
    University Hospital CHU Grenoble, France .
    Serrander, Lena
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Krause, Karl-Heinz
    Medical Faculty and University Hospital, Geneva, Switzerland.
    Morel, Francoise
    University of Grenoble 1, France .
    Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox42013In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 85, no 11, p. 1644-1654Article in journal (Refereed)
    Abstract [en]

    NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers. Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity. In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ tBuBQ and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines. Our results indicate that the effect is specific toward Nox4 versus Nox2. Furthermore, we showed that NAD(P)H:quinone oxidoreductase (NQO1) may participate in this stimulation. Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4. Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.

  • 43.
    Nilsdotter-Augustinsson, Åsa
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Briheim, Gunnas
    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.
    Herder, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology.
    Ljunghusen, O.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Wahlström, Ola
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Öhman, Lena
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Inflammatory response in 85 patients with loosened hip prostheses: A prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening2007In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 5, p. 629-639Article in journal (Refereed)
    Abstract [en]

    Over the past decades, prosthetic hip joints have improved the quality oflife for many patients. The most common complications are aseptic biornechanical failures and prosthetic joint infections. For prosthetic hip joints, delayed low-grade infections are seen most often and they are also most difficult to distinguish from aseptic mechanical failures. A prospective study was conducted to campare inilammatory markers in patients diagnosed with aseptic or septic prosthetic loosenffig. The diagnostic criteria were based on the decisions of experienced orthoperlic surgeons and microbiological analys is of periprosthetic tissue samplestaken perioperatively. Coagulase-negative staphylococci were the most common pathogens in the infected patients. Pre- or perioperative results for C-reactive protein and erytlu-ocyte sedimentation rate were valuable tools for diagnosing most, hut not all, low virulence infections. White blood cell count in synavial fluid was an important marker of infection, which was not the case for lactate. Levels of the cytokines turnor necrosis factor-α, interleukin-1 ß. and interleukin-6 in synavial fluid were significantly higher in the infected group. Patterus of inilammatory cell infiltration in periprosthetic tissue differed significantly between the groups, and infiltration of polymorphonuclear cells proved to be the best marker of distinguish between septic and aseptic loosenffig. Treatment and outcome are described for the infected patients.

  • 44.
    Nilsdotter-Augustinsson, Åsa
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Koskela, A.
    Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Öhman, Lena
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Söderquist, B.
    Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Characterization of coagulase-negative staphylococci isolated from patients with infected hip prostheses: use of phenotypic and genotypic analyses, including tests for the presence of the ica operon2007In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 26, no 4, p. 255-265Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate phenotypic and/or genotypic heterogeneity in coagulase-negative staphylococci (CoNS) obtained from multiple tissue samples taken perioperatively during exchange surgery from each of 19 patients with clinically and/or microbiologically proven hip prosthesis infections. CoNS are important pathogens in prosthetic hip joint infections. Several virulence factors have been suggested for CoNS, such as phenotypic variation, yet the pathogenic processes that are involved remain unclear. The PhenePlate system (PhPlate AB, Stockholm Sweden) was used for phenotyping and pulsed-field gel electrophoresis for genotyping of polymorphisms in isolates of CoNS. Furthermore, polymerase chain reaction was used to determine the presence of the icaADB gene complex in the isolates. Some patients were infected with CoNS and other species, some were infected with multiple CoNS species, although infections with Staphylococcus epidermidis alone were most common, and some were infected with different S. epidermidis clones. Phenotypic variation was found among isolates both from the same tissue sample and from different samples from the same patient, and in some cases such variation represented the presence of different clones. One-third of the patients infected with S. epidermidis carried the icaADB genes. CoNS isolates showing phenotypic and/or genotypic heterogeneity were identified in tissue samples from half of the patients. The presence of the intercellular adhesion (ica) operon does not seem to be a prerequisite for establishing infection with CoNS.

  • 45.
    Nordberg, Marika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Berglund, Johan
    Blekinge Institute of Technology, School of Health Science, Karlskrona, Sweden.
    Bjöersdorff, Anneli
    Läckeby Animal Hospital, Läckeby, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Garpmo, Ulf
    Department of Clinical Microbiology and 7Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Nilsson, Kenneth
    Unit of Clinical Microbiology/Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Eliasson, Ingvar
    Department of Laboratory Medicine, Norra Älvsborg County Hospital, Trollhättan, Sweden.
    Aetiology of Tick-Borne Infections in an Adult Swedish Population: are Co-Infections with Multiple Agents Common?Manuscript (preprint) (Other academic)
    Abstract [en]

    In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tickborne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria; 1) patients with unspecific symptoms, i.e. fever (e38.0°C) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM). A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical coinfection with Anaplasma phagocytophilum, based on serology. Both TBE cases had coinfections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.

  • 46.
    Nordberg, Marika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Berglund, Johan
    Blekinge Institute of Technology, Karlskrona, Sweden.
    Bjöersdorff, Anneli
    Djursjukhusgruppen, Danderyd, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Garpmo, Ulf
    Kalmar County Hospital, Sweden.
    Haglund, Mats
    Kalmar County Hospital, Sweden.
    Nilsson, Kenneth
    Uppsala University, Sweden.
    Eliasson, Ingvar
    Nora Älvsborg County Hospital, Trollhättan, Sweden.
    Aetiology of Tick-Borne Infections in an Adult Swedish Population—Are Co-Infections with Multiple Agents Common?2014In: Open Journal of Clinical Diagnostics, ISSN 2162-5816, E-ISSN 2162-5824, Vol. 4, no 1, p. 31-40Article in journal (Refereed)
    Abstract [en]

    In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria; 1) patients with unspecific symptoms, i.e. fever (≥38.0℃) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.

  • 47.
    Nordberg, Marika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Nyman, Dag
    The Åland Borrelia Group, Åland, 22100 Mariehamn, Åland, Finland.
    Skogman, Barbro H.
    Center for Clinical Research (CKF) Dalarna, 791 36 Falun, Sweden.
    Nyberg, Clara
    The Åland Borrelia Group, Åland, 22100 Mariehamn, Åland, Finland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Eliasson, Ingvar
    Department of Laboratory Medicine, NÄL, 461 85 Trollhättan, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Can ELISPOT Be Applied to A Clinical Setting as A Diagnostic Utility for Neuroborreliosis?2012In: Cells, ISSN 2073-4409, Vol. 13, no 48, p. 153-167Article in journal (Refereed)
    Abstract [en]

    The aim of this prospective study was to investigate the diagnostic performance of Borrelia (Bb)-induced interferon (IFN)-γ secretion detected by ELISPOT modified to be feasible for clinical laboratories as a supplementary test to the laboratory diagnosis of Lyme neuroborreliosis (LNB) in an endemic setting. Between 2002 and 2004, patients with symptoms of suspected clinical LNB were included in a study conducted on the Åland islands in the Finnish archipelago, which is a hyper-endemic area for Lyme borreliosis (LB). Fourteen patients with confirmed LNB and 103 patients with non-LNB were included, and the numbers of spontaneous and Bb-induced IFN-γ-secreting cells were assayed by the ELISPOT test. The ELISPOT assay showed a weak diagnostic performance with a sensitivity of 36% and a specificity of 82%. The findings in this study show that this ELISPOT-assay modified to be feasible in clinical routine laboratories is not useful as a supplementary diagnostic tool in the laboratory diagnosis of patients with clinically suspected LNB.

  • 48.
    Paues, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Tuberculous meningitis with positive cell-count in lumbar puncture CSF though negative cell-count from ventricular drainage CSF2011In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 62, no 5, p. 404-405Article in journal (Other academic)
  • 49.
    Petropoulos, Evangelos Alexandros
    et al.
    Klinisk mikrobiologi, Karolinska universitetssjukhuset, Solna, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, Christian G
    Klinisk mikrobiologi, Karolinska universitetssjukhuset, Solna, Sweden.
    Nya antibiotika med aktivitet mot multiresistenta tarmbakterier: Kombinationspreparat prövas nu kliniskt2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 24, p. 1050-1051Article in journal (Refereed)
    Abstract [sv]

    I hela världen inklusive Sverige ökar förekomsten av ESBL-producerande tarmbakterier.

    Framför allt multiresistenta ESBLCARBA-producerande tarmbakterier utgör ett stort behandlingsproblem på grund av brist på effektiva antibiotika. Samma problem gäller dock även multiresistenta Pseudomonas aeruginosa och Acinetobacter-arter.

    Nya antibiotika (betalaktamashämmare i kombination med betalaktamantibiotika) som nu genomgår kliniska prövningar kan bli behandlingsalternativ inom några år.

    Utöver nya läkemedel behövs det omfattande vårdhygieniska insatser för att bekämpa resistensspridningen.

  • 50.
    Rondahl, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Gruber, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Joelsson, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sundqvist, Martin
    Örebro University, Sweden.
    Åkerlind, Britt
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindh, Magnus
    Göteborg University .
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer.2014In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 60, no 2, p. 172-173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination.

    OBJECTIVES: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting.

    STUDY DESIGN: In the present study, known HCV RNA positive (n=149) and negative (n=149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination.

    RESULTS: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low.

    CONCLUSIONS: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity.

12 1 - 50 of 79
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