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  • 101.
    Strålin, Kristoffer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Diagnostic methods for bacterial etiology in adult community-acquired pneumonia2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The etiologic agent is often unidentified in patients with community-acquired pneumonia (CAP). Development of new diagnostic methods has been encouraged. We aimed to develop a multiplex PCR (mPCR) assay for common bacterial pathogens and evaluate the diagnostic usefulness of this assay and of respiratory culture in CAP.

    An mPCR was constructed for simultaneous identification of Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Applied to 257 bacterial strains, the analytic sensitivity was 100% and the analytic specificity 99%.

    In order to create appropriate reference standards, an indirect immunofluorescence test for H. influenzae was developed and two rapid urinary antigen tests for S. pneumoniae were evaluated. The indirect immunofluorescence test measured antibodies in paired sera against a H. influenzae strain isolated from the patient. A significant antibody rise was noted in 5/6 patients with lower respiratory tract infection (LRTI) and in 0/2 controls. The Binax NOW test and a serotype-specific latex agglutination test for 23 pneumococcal serotypes applied to urine samples, were positive in 24% and 7.4%, respectively, of 215 CAP patients tested. The Binax NOW test was false positive in 2/108 adult controls.

    In a prospective study, 235 adult CAP patients and 113 controls were enroled. S. pneumoniae, H. influenzae, M. pneumoniae, and C. pneumoniae were considered definite etiologic agents in 17%, 11%, 5.5%, and 1.3% of the patients, respectively. When applied to sputum, nasopharyngeal aspirate (NpA), and/or nasopharyngeal swab (NpS), culture identified S. pneumoniae in 34% and H. influenzae in 23%, while mPCR identified S. pneumoniae in 48%, H. influenzae in 28%, M. pneumoniae in 12%, and C. pneumoniae in 1.3%. NpA and sputum yielded similar sensitivities and specificities and were generally more sensitive than NpS. In samples collected during antibiotic treatment, S. pneumoniae was identified by culture in 4.3% and by mPCR in 14% (P=0.004). Among the controls, NpS and/or NpA identified S. pneumoniae in 4.4% with culture and 8.0% with mPCR, H. influenzae in 2.7% with culture and 4.4% with mPCR, and M. pneumoniae in 0.88% with mPCR.

    mPCR was also tested on bronchoalveolar lavage (BAL) samples from 156 adult patients with LRTI and 36 controls. BAL mPCR showed sensitivities of 86% for S. pneumoniae, 88% for H. influenzae, and 100% for M. pneumoniae, and specificities of 81% for S. pneumoniae, 64% for H. influenzae, 100% for M. pneumoniae, and 99% for C. pneumoniae. Among the controls, BAL mPCR identified S. pneumoniae in 11% and H. influenzae in 39%.

    In conclusion, an mPCR for detection off our bacteria was developed. Both culture and mPCR applied to sputum, NpA, and NpS were useful for detection of etiologic agents in CAP patients. mPCR appears particularly useful in patients treated with antibiotics. It can also be useful in BAL samples. The urinary antigen tests can reliably establish pneumococcal pneumonia.

    Delarbeid
    1. Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae to be used on sputum samples
    Åpne denne publikasjonen i ny fane eller vindu >>Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae to be used on sputum samples
    Vise andre…
    2005 (engelsk)Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 113, nr 2, s. 99-111Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A multiplex PCR (mPCR) was developed for simultaneous detection of specific genes for Streptococcus pneumoniae (lytA), Mycoplasma pneumoniae (P1), Chlamydophila pneumoniae (ompA), and Haemophilus influenzae (16S rRNA, with verification PCR for P6). When the protocol was tested on 257 bacterial strains belonging to 37 different species, no false negatives and only one false positive were noted. One Streptococcus mitis out of thirty was positive for lytA. In a pilot application study of 81 sputum samples from different patients with suspected lower respiratory tract infection (LRTI), mPCR identified S. pneumoniae in 25 samples, H. influenzae in 29, M. pneumoniae in 3, and C. pneumoniae in 1. All samples culture positive for S. pneumoniae (n=15) and H. influenzae (n=15) were mPCR positive for the same bacteria. In a pilot control study with nasopharyngeal swabs and aspirates from 10 healthy adults, both culture and mPCR were negative. No PCR inhibition was found in any of the mPCR-negative sputum or nasopharyngeal samples. Whether all samples identified as positive by mPCR are truly positive in an aetiological perspective regarding LRTI remains to be evaluated in a well-defined patient material. In conclusion, the mPCR appears to be a promising tool in the aetiological diagnostics of LRTI.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-33469 (URN)10.1111/j.1600-0463.2005.apm1130203.x (DOI)19491 (Lokal ID)19491 (Arkivnummer)19491 (OAI)
    Tilgjengelig fra: 2009-10-09 Laget: 2009-10-09 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Antibody response to the patient's own Haemophilus influenzae isolate can support the aetiology in lower respiratory tract infections
    Åpne denne publikasjonen i ny fane eller vindu >>Antibody response to the patient's own Haemophilus influenzae isolate can support the aetiology in lower respiratory tract infections
    2004 (engelsk)Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, nr 4-5, s. 299-303Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In order to understand the clinical importance of Haemophilus influenzae isolated from sputum samples, an indirect immunofluorescence (IF) assay was developed, using the patient's own isolate as the antigen. The method was tested on samples from six patients with lower respiratory tract infection (LRTI) and H. influenzae isolated from blood (n=2), sputum (n=3) or both (n=1), and on two healthy adults with H. influenzae isolated from the nasopharynx. Between acute and convalescent sera, a four-fold IgG antibody increase was achieved in five of six LRTI patients, including the three blood culture-positive patients. One LRTI patient and the two asymptomatic carriers showed stable antibody levels against their own isolate. Although small, the study indicates that indirect IF can be a promising tool for determining whether a H. influenzae strain represents the probable cause of infection or just a strain colonising the airways. More extensive studies should be performed in order to establish the usefulness of the assay.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-24245 (URN)10.1111/j.1600-0463.2004.apm11204-0511.x (DOI)3846 (Lokal ID)3846 (Arkivnummer)3846 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia
    Åpne denne publikasjonen i ny fane eller vindu >>Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia
    Vise andre…
    2004 (engelsk)Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 42, nr 8, s. 3620-3625Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Binax NOW immunochromatographic test (ICT) detecting the pneumococcal C polysaccharide and a serotype-specific latex agglutination (LA) test detecting 23 pneumococcal capsular antigens were evaluated for establishing pneumococcal etiology in community-acquired pneumonia (CAP) by use of nonconcentrated urine. ICT was considered to be strongly positive for result lines at least as intense as the control line and weakly positive for less intense result lines. When 215 adult CAP patients were tested, strong ICT, weak ICT, and LA positivity were found in 28, 24, and 16 patients, respectively; of these patients, 13 (46%), 6 (25%), and 13 (81%), respectively, had pneumococcal bacteremia and 27 (96%), 17 (71%), and 15 (94%), respectively, had Streptococcus pneumoniae isolated from blood, sputum, and/or nasopharynx. Among 108 controls tested, 2 (1.9%) were weakly ICT positive. When weak positivity was considered negative, the sensitivity of ICT decreased from 79% (19 of 24) to 54% (13 of 24), while the specificity increased from 83% (158 of 191) to 92% (176 of 191); no controls were false positive. The sensitivity and specificity of LA were 54% (13 of 24) and 98% (188 of 191), respectively. Eight of nine LA serotypes corresponded to culture serotypes. In conclusion, using nonconcentrated urine and dividing ICT-positive results into strongly and weakly positive results is a suitable way of performing ICT. While weak ICT positivity should be interpreted with caution, strong ICT positivity and LA positivity should be considered supportive of pneumococcal etiology in adult CAP. As such, these assays might have implications for antibiotic use in CAP. LA has promising potential for pneumococcal serotyping, although further evaluation is required.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-24246 (URN)10.1128/​JCM.42.8.3620-3625.2004 (DOI)3847 (Lokal ID)3847 (Arkivnummer)3847 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples
    Åpne denne publikasjonen i ny fane eller vindu >>Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples
    Vise andre…
    2006 (engelsk)Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 44, nr 2, s. 643-645Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Respiratory culture and multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae were applied to sputum, nasopharyngeal swabs, and nasopharyngeal aspirates from 235 adult patients with community-acquired pneumonia and 113 controls. Both culture and multiplex PCR performed well with the different samples and appear to be useful as diagnostic tools.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-37337 (URN)10.1128/JCM.44.2.643-645.2006 (DOI)34678 (Lokal ID)34678 (Arkivnummer)34678 (OAI)
    Tilgjengelig fra: 2009-10-10 Laget: 2009-10-10 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Multiplex PCR fir bacteruak etiology using branchoalveolar lavage in adults with lower respiratory tract infection
    Åpne denne publikasjonen i ny fane eller vindu >>Multiplex PCR fir bacteruak etiology using branchoalveolar lavage in adults with lower respiratory tract infection
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Study objective: To study the usefulness of a diagnostic multiplex PCR (mPCR) for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae applied to bronchoalveolar lavage (BAL) in lower respiratmy tract infection (LRTI).

    Design: Prospective diagnostic study.

    Setting: Silkeborg County Hospital, Silkeborg, Denmark.

    Patients and participants: Hospitalized adult LRTI patients (n=I56) and adult controls investigated on suspicion of malignancy (n=36).

    Interventions: After fiberoptic bronchoscopy (FOB) BAL fluid was analysed with bacterial culture and mPCR. S. pneumoniae and H. influenzae etiologies were established by cultures from blood, BAL and sputum, and urinary antigen test for S. pneumoniae. M. pneumoniae etiology was established by singleplex PCR on BAL and throat swab, and C. pneumoniae etiology by singleplex PCR and culture on BAL and throat swab.

    Measurements and Results: S. pneumoniae, H. influenzae, M. pneumoniae, and C. pneumoniae were etiologies in 14%, 21%, 3.2%, and 0, of the LRTI patients, respectively. These pathogens were identified by BAL mPCR in 28%, 47%, 3.2%, and 0.6%, respectively. The sensitivities of BAL mPCR were 0.86 for S. pneumoniae, 0.88 for H. influenzae, 1.0 for M. pneumoniae, and 0/0 for C. pneumoniae. The specificities were 0.81 for S. pneumoniae, 0.64 for H. influenzae, 1.0 for M. pneumoniae, and 0.99 for C. pneumoniae. In 103 patients with antibiotics taken prior to FOB, BAL culture and BAL mPCR identified S. pneumoniae in 2.9% and 31%, respectively, and H. influenzae in 20% and 50%, respectively. Among the controls, BAL culture and mPCR identified S. pneumoniae in 8.3% and 11%, respectively, and H. influenzae in 11% and 39%, respectively. No M. pneumoniae or C. pneumoniae was identified among the controls.

    Conclusions: In LRTI patients, BAL mPCR can be useful for identification of S. pneumoniae, M. pneumoniae, and C. pneumoniae. The method appears particularly useful in patients treated with antibiotics.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-81953 (URN)
    Tilgjengelig fra: 2012-09-26 Laget: 2012-09-26 Sist oppdatert: 2012-09-26bibliografisk kontrollert
  • 102.
    Strålin, Kristoffer
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Eliasson, H
    Bäck, E
    An outbreak of primary pneumonic tularemia.2002Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 346, s. 1027-1029Artikkel i tidsskrift (Fagfellevurdert)
  • 103.
    Strålin, Kristoffer
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Fredlund, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö.
    Olcén, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö.
    Labsystems enzyme immunoassay for Chlamydia pneumoniae also detects chlamydia psittaci infections.2001Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, s. 3425-3426Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 104.
    Strålin, Kristoffer
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Holmberg, H
    Causes of death for patients with community-acquired pneumonia.2002Inngår i: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 162, s. 2491-2492Artikkel i tidsskrift (Fagfellevurdert)
  • 105.
    Svensson, E
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi.
    Hanberger, Håkan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Nilsson, Maud
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö.
    Pharmacodynamic effects of amikacin, ciprofloxacin and imipenem on growing and non-growing Escherichia coli and Pseudomonas aeruginosa. 1999Inngår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 5, s. 140-148Artikkel i tidsskrift (Fagfellevurdert)
  • 106. Sörensen, OE
    et al.
    Follin, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Johnsen, AH
    Calafat, J
    Tjabringa, GS
    Hiemstra, PS
    Borregaard, N
    Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 32001Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 97, nr 12, s. 3951-3959Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species.

  • 107.
    Tegnell, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    The epidemiology and consequences of wound infections caused by coagulase negative staphylococci after thoracic surgery2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background

    Nosocomial infections in general and postoperative infections in pmticular are important aspects of modern health care. They are important factors to be taken into account when planning and organizing any kind of surgery. Thoracic surgery has become a common and important form of surgery involving significant amounts of patients and resources. Different kinds of infectious complications are not uncommon and cause considerable problems. Many microbes have been implicated in post-operative infections, but one of the most important ones in activities such as thoracic surgety is Coagulase Negative Staphylococci (CoNS). They exist in our environment and produce infections that are difficult to diagnose and complicated to treat. The source of the infections and the transmission routes remain to a great extent unclear.

    Aims

    To describe the basic epidemiology of sterna! infections after cardiac surgery and to find early indications of infections.To investigate the epidemiology of Coagulase Negative Staphylococci causing sternal infections and to describe the development of antibiotic resistance.

    Methods and results

    To describe and evaluate the impact of infections after thoracic surgety in our hospital we followed different patient populations. When examining the patients being infected we could show that risk factors mostly involved surgery and hospital related variables. The diagnosis of the infections was often late and the treatment is difficult and consuming major resomces. The late diagnosis could be explained by the discrete symptoms and that a marker for infection like CRP are difficult to evaluate in the post-operative patient. With increased surveillance of the wounds an earlier diagnosis would be possible. Following the development of the management of the infections in our hospital during the 90's we could also show that the time to diagnosis and the treatment periods became shorter.

    CoNS caused the majority of the infections in our patients with little change during the 10-year petiod. Preliminary results indicate that the source of the CoNS is the hospital environment in a majority of the serious infections. The place and route of transmission is unclear but the operating theatre remains a possible place of transmissions. Even if the resistance patterns of the CoNS are quite diverse they are often multi resistant and to a substantial degree vancomycin remains the only antibiotic that can be used for the treatment.

    Conclusions

    Wound infections after cardiac surgery are an important cause of morbidity and mortality, and CoNS play a major role in these infections. Risk factors that contribute to the infections are often associated with complicated surgery. Symptoms of the infections are often discrete and the diagnosis and treatment of the infections often stmt late. Intensified surveillance of the wounds could improve management of infections. We found a clone of CoNS causing a majority of the infections indicating that the source of the bacteria is often the hospital environment. CoNS as a major pathogen makes antibiotic treatment difficult, and there is a high risk of extensive antibiotic resistance.

    Delarbeid
    1. Coagulase-negative staphylococci and sternal infections after cardiac operation
    Åpne denne publikasjonen i ny fane eller vindu >>Coagulase-negative staphylococci and sternal infections after cardiac operation
    2000 (engelsk)Inngår i: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 69, nr 4, s. 1104-1119Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background. Coagulase negative staphylococci (CoNS) have been recognized as important pathogens in nosocomial infections, especially in connection with implanted foreign materials. In cardiac operation they are among the most common pathogens isolated from infected sternal wounds. The definition of the infection is very important. In this study we focus on deep postoperative chest infections.

    Methods. By studying 33 infected patients retrospectively and comparing them to 33 matched uninfected controls, we studied the characteristics and costs of the infections.

    Results. Typical for these infections is the late and insidious onset, and that the infections initially give only minor symptoms such as pain, redness, and serous secretion. We found the following risk factors for infection: number of preoperative days in a hospital, the total length of the operation, and if the patient had undergone an early reoperation due to causes other than infection. This kind of infection more than doubled the hospital costs for the patients affected.

    Conclusions. Coagulase negative staphylococci are the most important pathogens in deep postoperative infections in this material. They cause infections that are difficult to recognize since they give only discrete symptoms and start well after the patients leave the hospital. The risk factors for patients with CoNS infections are mostly associated with a long exposure to the hospital environment. The treatment is often difficult and costly because of multiresistant bacteria and frequent need for repeated surgical revisions.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26120 (URN)10.1016/S0003-4975(99)01563-5 (DOI)10579 (Lokal ID)10579 (Arkivnummer)10579 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Wound infections after cardiac surgery: a Wound Scoring System may Improve Early Detection
    Åpne denne publikasjonen i ny fane eller vindu >>Wound infections after cardiac surgery: a Wound Scoring System may Improve Early Detection
    2002 (engelsk)Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 36, nr 1, s. 60-64Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective - This study was aimed at describing the early development of wound infections after cardiac surgery to identify markers for upcoming infections.

    Design - We followed a cohort of 200 patients for 3 months after cardiac surgery to establish the incidence of all types of postoperative infections. Wound healing and C-reactive protein (CRP) were followed for the first 2 weeks.

    Results - A total of 175 patients out of 200 could be followed up. Using a broad definition of wound infection a total of 30% of the patients had some kind of wound infection. The diagnosis of most infections occurred after the patients had left the cardiac surgery unit (median 12 d after surgery). Our wound scoring method shows significant differences at an early stage between infected and non-infected wounds. At the time of diagnoses CRP was elevated in patients with deep sternal infection.

    Conclusion - A long follow-up period is needed to establish the true incidence of infection. Wound scoring can give an early indication of wound infections and CRP can help in the diagnoses of deep infections.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26593 (URN)10.1080/140174302317282401 (DOI)11158 (Lokal ID)11158 (Arkivnummer)11158 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Changes in the appearance and treatment of deep sternal infections
    Åpne denne publikasjonen i ny fane eller vindu >>Changes in the appearance and treatment of deep sternal infections
    2002 (engelsk)Inngår i: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 50, nr 4, s. 298-303Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Department of Thoracic Surgery at the University Hospital, Linköping, Sweden, has actively followed up infectious complications of cardiac surgery since 1989. The aim of this study was to investigate whether changes occurred during the 1990s in the appearance and the management of deep infections. This was done by studying patients undergoing surgical revision of infected wounds. We studied 42 patients during 1990–94 and 49 during 1997–98 (total number of operations in these periods, 3075 and 1646, respectively). Pre-operative and intra-operative variables were recorded for the two patient populations. The proportion of cardiac surgery procedures followed by a surgical revision for an infection in the sternal wound increased between the two periods (1.4% vs. 3.0%). Variables associated with the surgical procedures preceding the infection remained unchanged. In the later period, treatment was started earlier (64 vs. 24 days), and the length of antibiotic treatment was decreased (115 vs. 72 days). The incidence of osteomyelitis of the sternal bone was lower (61% vs. 27%). It appears that as the proportion of patients undergoing surgical revision increased, management of the infections became more effective, with aggressive surgical and antibiotic treatment policies and shorter treatment periods. This indicates that in order to evaluate the overall impact of measures designed to reduce infections after cardiac surgery, not only the incidence of infection needs to be followed up but other factors also need to be taken into account.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26497 (URN)10.1053/jhin.2002.1178 (DOI)11053 (Lokal ID)11053 (Arkivnummer)11053 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. A clone of coagulase-negative staphylococci among patients with post-cardiac surgery infections
    Åpne denne publikasjonen i ny fane eller vindu >>A clone of coagulase-negative staphylococci among patients with post-cardiac surgery infections
    Vise andre…
    2002 (engelsk)Inngår i: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 52, nr 1, s. 37-42Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Coagulase-negative staphylococci (CoNS) are important causes of hospital-acquired infections such as infections after cardiac surgery. Efforts to reduce these infections are hampered by the lack of knowledge concerning the epidemiology of CoNS in this setting. Forty strains of CoNS collected during the surgical revision of 27 patients operated on between 1997 and 2000 were analysed. Strains were also collected from the ambient air in the operating suite. Their pulsed-field gel electrophoresis (PFGE) characteristics and antibiotic resistance were analysed. Using PFGE 19 of 40 strains from 15 of 27 patients were shown to belong to one clone, and strains from this clone were also isolated from the ambient air. This clone had caused infections throughout the period. Antibiotic resistance did not correlate with PFGE patterns. Using PFGE one clone could be identified that caused 56% of the CoNS infections during this period. A strain from this clone was also found in the air of the operating suite suggesting the origin of the CoNS causing infections was the hospital environment.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26496 (URN)10.1053/jhin.2002.1267 (DOI)11052 (Lokal ID)11052 (Arkivnummer)11052 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Study of developed resistance due to antibiotic treatment of coagulase-negative staphylococci
    Åpne denne publikasjonen i ny fane eller vindu >>Study of developed resistance due to antibiotic treatment of coagulase-negative staphylococci
    Vise andre…
    2003 (engelsk)Inngår i: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 9, nr 1, s. 1-6Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Coagulase-negative Staphylococci (CoNS) are a major cause of postoperative infections. These infections are often associated with foreign material implants and/or a compromised immune system in the patient. Multiresistant strains are increasingly common in the hospital environment and there is concern that the infections will become difficult or impossible to treat. This report is based on a study of 75 patients, with postoperative infections caused by CoNS after thoracic surgery. All patients were treated with surgical revision and antibiotic therapy. One or more bacterial cultures were made in each case, and the resistance pattern of the CoNS found was determined. The goal of the study was to evaluate possible relationships between antibiotic therapy and the appearance of resistance to antibiotics in CoNS found. To describe this relationship, three models were constructed and analyzed by multiple logistic regression. The results indicate an increased resistance to β-lactam antibiotics and clindamycin after the use of cephalosporins. Also, the use of vancomycin or vancomycin combination with rifampicin or fusidic acid increases the risk for development of resistance to β-lactam antibiotics, ciprofloxacin, fusidic acid, clindamycin, netilmycin, and rifampicin. The hypothesis that a combination of antibiotics will curtail the development of resistance was not supported in this study.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-48659 (URN)10.1089/107662903764736283 (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-12bibliografisk kontrollert
  • 108.
    Tegnell, Anders
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ahrén, Claes
    Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet.
    Öhman, Lena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Wound infections after cardiac surgery: a Wound Scoring System may Improve Early Detection2002Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 36, nr 1, s. 60-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective - This study was aimed at describing the early development of wound infections after cardiac surgery to identify markers for upcoming infections.

    Design - We followed a cohort of 200 patients for 3 months after cardiac surgery to establish the incidence of all types of postoperative infections. Wound healing and C-reactive protein (CRP) were followed for the first 2 weeks.

    Results - A total of 175 patients out of 200 could be followed up. Using a broad definition of wound infection a total of 30% of the patients had some kind of wound infection. The diagnosis of most infections occurred after the patients had left the cardiac surgery unit (median 12 d after surgery). Our wound scoring method shows significant differences at an early stage between infected and non-infected wounds. At the time of diagnoses CRP was elevated in patients with deep sternal infection.

    Conclusion - A long follow-up period is needed to establish the true incidence of infection. Wound scoring can give an early indication of wound infections and CRP can help in the diagnoses of deep infections.

  • 109.
    Tegnell, Anders
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Arén, Claes
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Öhman, Lena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Coagulase-negative staphylococci and sternal infections after cardiac operation2000Inngår i: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 69, nr 4, s. 1104-1119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Coagulase negative staphylococci (CoNS) have been recognized as important pathogens in nosocomial infections, especially in connection with implanted foreign materials. In cardiac operation they are among the most common pathogens isolated from infected sternal wounds. The definition of the infection is very important. In this study we focus on deep postoperative chest infections.

    Methods. By studying 33 infected patients retrospectively and comparing them to 33 matched uninfected controls, we studied the characteristics and costs of the infections.

    Results. Typical for these infections is the late and insidious onset, and that the infections initially give only minor symptoms such as pain, redness, and serous secretion. We found the following risk factors for infection: number of preoperative days in a hospital, the total length of the operation, and if the patient had undergone an early reoperation due to causes other than infection. This kind of infection more than doubled the hospital costs for the patients affected.

    Conclusions. Coagulase negative staphylococci are the most important pathogens in deep postoperative infections in this material. They cause infections that are difficult to recognize since they give only discrete symptoms and start well after the patients leave the hospital. The risk factors for patients with CoNS infections are mostly associated with a long exposure to the hospital environment. The treatment is often difficult and costly because of multiresistant bacteria and frequent need for repeated surgical revisions.

  • 110.
    Tegnell, Anders
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Dannetun, E
    Andersson, M
    Elgh, F
    Krim-Kongoblödarfeber i Kosovo2001Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, s. 5670-5671Artikkel i tidsskrift (Annet vitenskapelig)
  • 111.
    Tegnell, Anders
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Barbro
    Linköpings universitet, Hälsouniversitetet.
    Granfeldt, Hans
    Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet.
    Öhman, Lena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Changes in the appearance and treatment of deep sternal infections2002Inngår i: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 50, nr 4, s. 298-303Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Department of Thoracic Surgery at the University Hospital, Linköping, Sweden, has actively followed up infectious complications of cardiac surgery since 1989. The aim of this study was to investigate whether changes occurred during the 1990s in the appearance and the management of deep infections. This was done by studying patients undergoing surgical revision of infected wounds. We studied 42 patients during 1990–94 and 49 during 1997–98 (total number of operations in these periods, 3075 and 1646, respectively). Pre-operative and intra-operative variables were recorded for the two patient populations. The proportion of cardiac surgery procedures followed by a surgical revision for an infection in the sternal wound increased between the two periods (1.4% vs. 3.0%). Variables associated with the surgical procedures preceding the infection remained unchanged. In the later period, treatment was started earlier (64 vs. 24 days), and the length of antibiotic treatment was decreased (115 vs. 72 days). The incidence of osteomyelitis of the sternal bone was lower (61% vs. 27%). It appears that as the proportion of patients undergoing surgical revision increased, management of the infections became more effective, with aggressive surgical and antibiotic treatment policies and shorter treatment periods. This indicates that in order to evaluate the overall impact of measures designed to reduce infections after cardiac surgery, not only the incidence of infection needs to be followed up but other factors also need to be taken into account.

  • 112.
    Tegnell, Anders
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Saeedi, Baharak
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Barbro
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Granfeldt, Hans
    Linköpings universitet, Institutionen för medicin och vård, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet.
    Öhman, Lena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    A clone of coagulase-negative staphylococci among patients with post-cardiac surgery infections2002Inngår i: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 52, nr 1, s. 37-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Coagulase-negative staphylococci (CoNS) are important causes of hospital-acquired infections such as infections after cardiac surgery. Efforts to reduce these infections are hampered by the lack of knowledge concerning the epidemiology of CoNS in this setting. Forty strains of CoNS collected during the surgical revision of 27 patients operated on between 1997 and 2000 were analysed. Strains were also collected from the ambient air in the operating suite. Their pulsed-field gel electrophoresis (PFGE) characteristics and antibiotic resistance were analysed. Using PFGE 19 of 40 strains from 15 of 27 patients were shown to belong to one clone, and strains from this clone were also isolated from the ambient air. This clone had caused infections throughout the period. Antibiotic resistance did not correlate with PFGE patterns. Using PFGE one clone could be identified that caused 56% of the CoNS infections during this period. A strain from this clone was also found in the air of the operating suite suggesting the origin of the CoNS causing infections was the hospital environment.

  • 113.
    Tegnell, Anders
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Wahren, B
    Elgh, F
    Smallpox-eradicated, but a growing terror threat.2002Inngår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 8, s. 504-509Artikkel i tidsskrift (Fagfellevurdert)
  • 114.
    Tegnell, Anders
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Wahren, B
    Elgh, F
    Smallpox-eradicated disease and a potential terrorist weapon.2002Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, s. 2145-2149Artikkel i tidsskrift (Annet vitenskapelig)
  • 115.
    Theilgaard-Mönch, Kim
    et al.
    Danmark.
    Knudsen, Steen
    Danmark.
    Follin, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Borregaard, Niels
    Danmark.
    The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing2004Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 172, nr 12, s. 7684-7693Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing.

  • 116.
    Vrethem, Magnus
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Hellblom, L
    Widlund, M
    Ahl, M
    Danielsson, O
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Forsberg, Pia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Chronic symptoms are common in patients with neuroborreliosis - A questionnaire follow-up study2002Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 106, nr 4, s. 205-208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives - The existence of chronic neuroborreliosis is controversial. The aim of our study was to investigate the existence and kind of persistent symptoms in patients previously treated because of neurological symptoms as a result of neuroborreliosis. Material and methods - A total of 106 patients with neuroborreliosis, according to established criteria, and a control group of 123 patients with Borrelia induced erythema migrans diagnosed in a general practitioner office were studied. A questionnaire was sent to patients and controls concerning their health situation. Time from onset of neurological symptoms to the questionnaire sendout was 32 months (mean) for the patients with neuroborreliosis and 33 months (mean) for the controls. Results - Fifty per cent of the individuals in the patient group compared with 16% of the individuals in the control group showed persistent complaints after their Borrelia infection (P < 0.0001). The most significant differences between the groups were the presence of neuropsychiatric symptoms such as headache, attention problems, memory difficulties and depression. Paresthesia, pain and persistent facial palsy was also significantly more common in patients treated because of neuroborreliosis. Conclusion - Our study shows that persisting neurological symptoms are common after a neuroborreliosis infection. The pathological mechanisms that lay behind the development of chronic symptoms, however, are still uncertain.

  • 117.
    Walther, Sten
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Agvald-Öhman, Christina
    Blomqvist, Hans
    Monnet, Dominique
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi.
    Hanberger, Håkan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Multiresistenta bakterier kan bli allt större hot på svenska IVA.2006Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, nr 49, s. 3930-3933Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

      

  • 118. Weiland, O
    et al.
    Braconier, JH
    Frydén, Aril
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Norkrans, G
    Reichard, O
    Uhnoo, I
    Influence of pre-treatment factors on outcome of interferon-alpha treatment of patients with chronic hepatitis C.  1999Inngår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 31, s. 115-118Artikkel i tidsskrift (Fagfellevurdert)
  • 119.
    Widhe, Mona
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Immune responses in human lyme borreliosis: cytokines and IgG subclasses in relation to clinical outcome2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Lyme borreliosis is a tick-borne infectious disease caused by the spirochete Borrelia burgdorferi sensu lato. The disease is characterised by several disease stages, where multiple organ systems might be affected, e.g. the skin, nervous system, heart or joints. The disease might lead to chronic symptoms of e.g. the nervous system, so called chronic neuroborreliosis (NB). The clinical features are often less severe in children, as compared to adults. The mechanisms responsible for the development of chronic symptoms are not fully established, but several factors might be involved. Probably the type of immune response elicited against the Borrelia spirochete during infection has implications on the clinical outcome, including development of chronic symptoms. Pro-inflammatory and type 1 responses are known to be efficient for elimination of pathogens, but may also be disease generating, whereas anti-inflammatory and type 2 responses are believed to regulate inflammation and possible tissue-harm, and have been reported in relation to resolution of symptoms in inflammatory diseases. In human Lyme borreliosis, mostly pro-inflammatory and type 1 responses have been reported previously.

    Aim: To examine selected aspects of the immune response- i.e. type 1/type 2 responses and pro-/anti-inflammatory responses - during the course of human Lyme borreliosis in patients with chronic and non-chronic manifestations, and in children vs. adults with NB, and to relate the type of immune response to the clinical outcome.

    Material and methods: Adult patients with the non-chronic manifestations erythema migrans and non-chronic NB or the chronic manifestations chronic NB and acrodermatitis chronica atrophicans (ACA), and children with NB were included in the study. Some of the adult patients were followed during the course of the disease. The Borrelia-specific cytokine production of interferon (IFN)-γ and interleukin (IL)-4 and the Borrelia-specific IgG subclass distribution were analysed as a measure of type 1 and type 2 responses, and the cytokinelevels of tumour necrosis factor (TNF)-α, IL-6 and transforming growth factor (TGF)-ß1 were analysed as a measure of the pro- and anti-inflammatory responses. IFN-γ and IL-4 were measured as number of cytokine secreting cells, using the sensitive method ELISPOT. Mononuclear cells were separated from blood and cerebrospinal fluid (CSF) and stimulated with a Borrelia antigen containing outer surface protein (Osp)A and OspB. Borrelia-specific IgG subclasses were measured in serum and CSF by ELISA using a flagellin-containing antigen. Levels of TNF-α, IL-6 and total TGF-ß1 were measured in serum and CSF by ELISA.

    Results: Adult patients with non-chronic NB showed a strong initial TNF-α and IFN-γ response in the CSF with production of the complement-activating and opsonizing IgG1 and IgG3. Subsequently, this inflammatory response seemed to be down-regulated by an upregulation of IL-4. TGF-ß1 was expressed during the entire follow-up period. Patients with EM showed the same pattern, with an early IFN-γ response, elevated levels of TGF-ß1 and a late up-regulation of IL-4. In addition, the children with early stage NB had elevated production of both IFN-γ and IL-4. The chronic NB patients, however, lacked early TNF-α in CSF and the subsequent up-regulation of IL-4, but showed persistent expression of IFN-γ. Furthermore, they did not show IgG3 or early TGF-ß1 in serum. Furthermore, ACA patients showed elevated IFN-γ late in disease.

    Conclusions: Altogether, the results suggest that good prognosis of human Lyme borreliosis is associated with a strong initial pro-inflammatory type 1 response, effective for elimination of Borrelia spirochetes, which is subsequently down-regulated by up-regulation of a type-2 response, and whose possible harmful effects might also be limited by TGF-ß1. Chronic manifestations, on the contrary, seem to be associated with lack of early pro-inflammatory responses, plausibly limiting their ability to eradicate the pathogen, followed by persistent inflammatory type 1 response, which might be self-destructive and disease-generating. In addition, the relative absence of type-2 responses in chronic manifestations may reduce the ability to limit the possibly harmful effects generated by long-standing IFN-γ. The results may have implications on future development of immuomodulatory treatments of chronic Lyme neuroborreliosis.

    Delarbeid
    1. IgG subclasses in Lyme borreliosis: a study of specific IgG subclass distribution in an interferon-γ-predominated disease
    Åpne denne publikasjonen i ny fane eller vindu >>IgG subclasses in Lyme borreliosis: a study of specific IgG subclass distribution in an interferon-γ-predominated disease
    Vise andre…
    1998 (engelsk)Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 47, nr 6, s. 575-581Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Lyme borreliosis has shown a T helper type 1 (Th1)-like immune response with high production of interferon-gamma. Since the cytokine environment seems to be important in the regulation of immunoglobulin production and in the switch between different isotypes and subclasses, and since the subclasses of IgG have different functions, we wanted to examine the IgG subclass distribution in Lyme borreliosis. We have developed an ELISA measuring flagellin-specific antibodies of the different IgG subclasses in serum and cerebrospinal fluid (CSF). Thirty-five seropositive patients with varying manifestations of Lyme borreliosis were included in the study. According to the results, the predominating subclasses in both serum and CSF were IgG1 and IgG3. In samples taken early in disease this pattern was more pronounced in patients with a subacute disease, defined as recovery within 3 months, compared to patients that later on developed chronic borreliosis. The levels of IgG2 were generally low and IgG4 was below detection level. Thus, in the IFN-gamma-predominated immune response seen in Lyme borreliosis, mainly IgG1 and IgG3 were found, i.e. the subclasses that are complement activating as well as opsonizing in humans. Increased levels of these two subclasses early in disease might contribute to recovery and counteract the development of chronicity. The absence of IgG4 is in accordance with the presumed Th1-like situation of Lyme borreliosis.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84546 (URN)9652826 (PubMedID)
    Tilgjengelig fra: 2012-10-12 Laget: 2012-10-12 Sist oppdatert: 2020-01-16bibliografisk kontrollert
    2. Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-α and transforming growth factor-β1 responses are associated with chronic neuroborreliosis
    Åpne denne publikasjonen i ny fane eller vindu >>Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-α and transforming growth factor-β1 responses are associated with chronic neuroborreliosis
    Vise andre…
    2002 (engelsk)Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 107, nr 1, s. 46-55Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-α were found in non-chronic patients than in chronic patients (P<0·05). Moreover, TGF-β1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0·01). Elevated serum levels of TGF-β1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0·05). The high TNF-α levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-β1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-46895 (URN)10.1046/j.1365-2567.2002.01500.x (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2020-01-16bibliografisk kontrollert
    3. Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome
    Åpne denne publikasjonen i ny fane eller vindu >>Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome
    Vise andre…
    2004 (engelsk)Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 189, nr 10, s. 1881-1891Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Borrelia-specific interferon (IFN)-γ and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN-γ (P < .05) and subsequent up-regulation of IL-4 ( P < .05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN-γ responses were observed in the CSF cells of patients with chronic NB ( P < .05). In patients with erythema migrans, increased IFN-γ (P < .001 ) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 ( P < .05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN-γ (P < .001 ), but not IL-4, detected in blood samples. The present data suggest that an initial IFN-γ response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN-γ response may lead to chronic Lyme borreliosis.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13800 (URN)10.1086/382893 (DOI)
    Tilgjengelig fra: 2006-03-22 Laget: 2006-03-22 Sist oppdatert: 2020-01-16
    4. A multicenter study on children with Lyme Neuroborreliosis: Up-regulation of Borrelia-specific IL-4 and IFN-γ secreting cells in cerebrospinal fluid and blood
    Åpne denne publikasjonen i ny fane eller vindu >>A multicenter study on children with Lyme Neuroborreliosis: Up-regulation of Borrelia-specific IL-4 and IFN-γ secreting cells in cerebrospinal fluid and blood
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. As suggested by animal models the interleukin (IL)-4 and interferon (IFN)-γ responses seem to play a role in Lyme borreliosis. In adults with neuroborreliosis (NB), a type 1 like response with high production of Borrelia-specific IFN-γ, but no IL-4, in the cerebrospinal fluid (CSF) and blood has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 like responses in children with NB. CSF and blood were collected from children during the acute stage of 'confirmed NB' (n=34), 'possible NB' (n=30) and 'non-NB' (n=10). The number of Borrelia-speciflc IL-4 and IFN-γ producing cells was measured by ELISPOT. Borrelia-specific secretion of both IL-4 and IFN-γ was increased in CSF in confirmed (p<0.05) and possible (p<0,01) NB, compared with non-NB. Furthermore, children with NB had significantly higher Borrelia-speciflc IL-4 secretion in cerebrospinal fluid than an adult reference material with NB (p<0,05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly hannful. effects of prolonged IFN-γ responses, the observed prominent IL-4 response in the CNS-compartment might contribute to the more benign disease course seen in children with Lyme NB.

    Emneord
    Lyme neuroborreliosis, children, cerebrospinal fluid, cytokines, interleukin-4, interferon-y
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84552 (URN)
    Tilgjengelig fra: 2012-10-12 Laget: 2012-10-12 Sist oppdatert: 2020-01-16bibliografisk kontrollert
  • 120.
    Widhe, Mona
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland, Transfusionsmedicin och klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Pia
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Bergström, S.
    Department of Microbiology, University of Umeå, Umeå, Sweden.
    Ernerudh, Jan
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland, Transfusionsmedicin och klinisk immunologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    IgG subclasses in Lyme borreliosis: a study of specific IgG subclass distribution in an interferon-γ-predominated disease1998Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 47, nr 6, s. 575-581Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lyme borreliosis has shown a T helper type 1 (Th1)-like immune response with high production of interferon-gamma. Since the cytokine environment seems to be important in the regulation of immunoglobulin production and in the switch between different isotypes and subclasses, and since the subclasses of IgG have different functions, we wanted to examine the IgG subclass distribution in Lyme borreliosis. We have developed an ELISA measuring flagellin-specific antibodies of the different IgG subclasses in serum and cerebrospinal fluid (CSF). Thirty-five seropositive patients with varying manifestations of Lyme borreliosis were included in the study. According to the results, the predominating subclasses in both serum and CSF were IgG1 and IgG3. In samples taken early in disease this pattern was more pronounced in patients with a subacute disease, defined as recovery within 3 months, compared to patients that later on developed chronic borreliosis. The levels of IgG2 were generally low and IgG4 was below detection level. Thus, in the IFN-gamma-predominated immune response seen in Lyme borreliosis, mainly IgG1 and IgG3 were found, i.e. the subclasses that are complement activating as well as opsonizing in humans. Increased levels of these two subclasses early in disease might contribute to recovery and counteract the development of chronicity. The absence of IgG4 is in accordance with the presumed Th1-like situation of Lyme borreliosis.

  • 121.
    Widhe, Mona
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Grusell, Mattias
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurofysiologi. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-α and transforming growth factor-β1 responses are associated with chronic neuroborreliosis2002Inngår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 107, nr 1, s. 46-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-α were found in non-chronic patients than in chronic patients (P<0·05). Moreover, TGF-β1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0·01). Elevated serum levels of TGF-β1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0·05). The high TNF-α levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-β1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.

  • 122.
    Widhe, Mona
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Hedin Skogman, Barbro
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jarefors, Sara
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Eknefelt, Mattias
    Jönköping, Sweden.
    Eneström, Gunilla
    Västervik, Sweden.
    Nordwall, Maria
    Norrköping, Sweden.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Croner, Stefan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Pia
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    A multicenter study on children with Lyme Neuroborreliosis: Up-regulation of Borrelia-specific IL-4 and IFN-γ secreting cells in cerebrospinal fluid and bloodManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. As suggested by animal models the interleukin (IL)-4 and interferon (IFN)-γ responses seem to play a role in Lyme borreliosis. In adults with neuroborreliosis (NB), a type 1 like response with high production of Borrelia-specific IFN-γ, but no IL-4, in the cerebrospinal fluid (CSF) and blood has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 like responses in children with NB. CSF and blood were collected from children during the acute stage of 'confirmed NB' (n=34), 'possible NB' (n=30) and 'non-NB' (n=10). The number of Borrelia-speciflc IL-4 and IFN-γ producing cells was measured by ELISPOT. Borrelia-specific secretion of both IL-4 and IFN-γ was increased in CSF in confirmed (p<0.05) and possible (p<0,01) NB, compared with non-NB. Furthermore, children with NB had significantly higher Borrelia-speciflc IL-4 secretion in cerebrospinal fluid than an adult reference material with NB (p<0,05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly hannful. effects of prolonged IFN-γ responses, the observed prominent IL-4 response in the CNS-compartment might contribute to the more benign disease course seen in children with Lyme NB.

  • 123.
    Widhe, Mona
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Jarefors, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurofysiologi. Linköpings universitet, Hälsouniversitetet.
    Bergström, Sven
    Department of Molecular Biology, University of Umeå, Umeå, Sweden.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet.
    Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome2004Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 189, nr 10, s. 1881-1891Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Borrelia-specific interferon (IFN)-γ and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN-γ (P < .05) and subsequent up-regulation of IL-4 ( P < .05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN-γ responses were observed in the CSF cells of patients with chronic NB ( P < .05). In patients with erythema migrans, increased IFN-γ (P < .001 ) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 ( P < .05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN-γ (P < .001 ), but not IL-4, detected in blood samples. The present data suggest that an initial IFN-γ response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN-γ response may lead to chronic Lyme borreliosis.

  • 124. Wikby, A
    et al.
    Johansson, B
    Olsson, J
    Löfgren, S
    Nilsson, B-O
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin.
    Ferguson, F
    Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study.2002Inngår i: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 37, s. 445-453Artikkel i tidsskrift (Fagfellevurdert)
  • 125. Xu, Junyang
    et al.
    Jiang, Fengxia
    Nayeri, Fariba
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Zetterström, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Allergicentrum. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Allergicentrum US.
    Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin2007Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, nr 7, s. 1447-1454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. Methods: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. Results: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P < 0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r = - 0.85 and -0.79, P < 0.01 and P < 0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r = - 0.85, P < 0.01), or stable asthma (r = - 0.69, P < 0.05). Additional positive corrlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r = 0.93, P < 0.01) or stable asthma (r = 0.82, P < 0.05) were observed. Conclusions: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation. © 2007 Elsevier Ltd. All rights reserved.

  • 126.
    Örtqvist, Å.
    et al.
    Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.
    Valtonen, M.
    University Central Hospital, Helsinki, Finland.
    Cars, O.
    Uppsala University, Sweden.
    Wahl, M.
    Östra Hospital, Göteborg University, Sweden.
    Saikku, P.
    University of Oulu and National Public Health Institute, Finland.
    Jean, C.
    Rhone DPC Europe, Paris, France.
    Augustinsson (Nilsdotter-Augustinsson), Åsa
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Oral empiric treatment of community-acquired pneumonia: A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group1996Inngår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 110, nr 6, s. 1499-1506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    STUDY OBJECTIVE:

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

    DESIGN:

    Multicenter, double-blind, randomized study.

    SETTING:

    Twenty-three university and community hospitals in Scandinavia.

    PATIENTS:

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

    INTERVENTIONS:

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

    RESULTS:

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

    CONCLUSIONS:

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

123 101 - 126 of 126
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