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  • 1.
    Nordeman, Patrik
    et al.
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
    Johansson, Leif B. G.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Estrada, Sergio
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden..
    Hall, Håkan
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden..
    Sjölander, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Westermark, Gunilla T.
    Department of Medicinal Cell Biology, Uppsala University, Uppsala, Sweden.
    Westermark, Per
    Department of Immunology, Genetics and Pathology, Uppsala University, UppsalaSweden.
    Nilsson, Lars
    Department of Pharmacology, University of Oslo, Oslo, Norway.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, K. Peter R.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Antoni, Gunnar
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
    11C and 18FRadiolabeling of Tetra- and Pentathiophenes as PET-ligands for Amyloid Protein Aggregates2016In: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, no 4, 368-373 p.Article in journal (Refereed)
    Abstract [en]

    Three oligothiophenes were evaluated as PET tracers for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver and spleen. To verify the specificity of the oligothiophenes towards amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, in vivo rat and monkey PET-CT studies showed very low uptake in the brain, pancreas and heart of the healthy animals indicating low non-specific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.

  • 2.
    Holmbom, Martin
    et al.
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Giske, Christian G.
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden..
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    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.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoffmann, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    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.
    14-Year Survey in a Swedish County Reveals a Pronounced Increase in Bloodstream Infections (BSI). Comorbidity: An Independent Risk Factor for Both BSI and Mortality2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11Article in journal (Refereed)
    Abstract [en]

    Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county.

    Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI).

    Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04).

    Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics.

  • 3.
    Browaldh, Nanna
    et al.
    Karolinska University Hospital.
    Friberg, Danielle
    Karolinska University Hospital.
    Svanborg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurophysiology UHL.
    Nerfeldt, Pia
    Karolinska University Hospital.
    15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data2011In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 131, no 12, 1303-1310 p.Article in journal (Refereed)
    Abstract [en]

    Conclusions: This follow-up showed a stable and significant decrease in median oxygen desaturation index 4% (ODI(4)) values over the years. Approximately two-thirds of the patients fulfilled the success criteria (ODI4 reduction of 50% and andlt;20) after 15 years. A majority had improved/cured excessive daytime sleepiness (EDS) and were satisfied. No increased mortality rate was seen. Objectives: To evaluate sleep apnoea recordings and symptoms in patients with obstructive sleep apnoea syndrome 15 years after uvulopalatopharyngoplasty (UPPP) compared to baseline and previous follow-ups. Methods: This was a non-randomized, prospective intervention study on 50 patients who underwent UPPP during 1985-88. Their initial median age was 49 years (range 38-71) and ODI4 was 26.5 (4-82). Results: In all, 13 patients had died; 26 patients underwent sleep apnoea recordings. Median ODI4 had decreased from 26.5 (range 4-82) to 8.5 (0-60), p andlt; 0.01, a mean reduction of 52%; 65% of patients achieved the success criteria. One-third was objectively categorized as non-snorers. Median body mass index was unchanged. The questionnaires were answered by 32 of 37 patients; 88% reported improved or cured EDS and 78% were satisfied. Pharyngeal disturbances ratings were low. The standardized mortality rate did not differ from the general Swedish population.

  • 4.
    Kallstrom, Ann-Christine
    et al.
    Helsingborg Hospital.
    Salme, Rebecka
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ryden, Lisa
    Lund University.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jonsson, Per-Ebbe
    Helsingborg Hospital.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    17 beta-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer2010In: EUROPEAN JOURNAL OF CANCER, ISSN 0959-8049, Vol. 46, no 5, 892-900 p.Article in journal (Refereed)
    Abstract [en]

    17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with hormone-receptor positive tumours, with low levels (-/+/++) of 17HSD1, had a 43% reduced risk of recurrence, when treated with tamoxifen (Hazard Ratio (HR) = 0.57; 95% confidence interval (CI), 0.37-0.86; p = 0.0086). On the other hand high expression (+++) of 17HSD1 was associated with no significant difference between the two treatment arms (HR = 0.91; 95% CI, 0.43-1.95; p = 0.82). The interaction between 17HSD1 and tamoxifen was significant during the first 5 years of follow-up (p = 0.023). In the cohort of systemically untreated patients no prognostic importance was observed for 17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of 17HSD1 in a cohort of premenopausal women with breast cancer randomised to tamoxifen. Our data suggest that 17HSD1 might be a predictive factor in this group of patients.

  • 5.
    Jansson , Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    17Beta-hydroxysteroid dehydrogenase enzymes and breast cancer2009In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, ISSN 0960-0760 , Vol. 114, no 1-2, 64-67 p.Article in journal (Refereed)
    Abstract [en]

    Sex steroids play an important role in the development and differentiation in several tissues. Biologically active hormones that are locally converted in endocrine organs in the tissue where they exert their effects without release into extracellular space is a field of endocrinology that has been called intracrinology. In pre-menopausal women the ovary is the main source of estrogens, but in post-menopausal women the estrogen production as main site of synthesis moves to peripheral tissues and almost all of the sex steroids are synthesised from precursors of adrenal origin. In breast cancer 60-80% of the tumors express high levels of oestrogen receptor (ER) alpha which gives estrogen a proliferative effect. Breast tumors tend to have a higher intratumoral estrogen concentration than normal breast tissue and plasma, and in situ synthesis and the metabolism of estrogens is believed to be of great importance for the development and progression of the disease. The activity of estrogen metabolizing enzymes in breast are mainly aromatase, estrone sulfatases and 17HSD enzymes. 17HSD1 and 17HSD2 are the family members known to be of main importance in breast cancer. High expression of 17HSD1 has been associated to poor prognosis in breast cancer and late relapse among patients with ER-positive tumors. One of the mechanisms behind high 17HSD1 expression is gene amplification. Low or absent expression of 17HSD2 is associated to decreased survival in ER-positive breast cancer. 17HSD14 is one of the latest discovered 17HSD enzymes, transfection of 17HSD14 in human breast cancer cells significantly decreased the levels of estradiol in the culture medium. Low expression of 17HSD14 mRNA expression in breast cancer was correlated to decreased survival.

    The understanding of intratumoral synthesis of sex steroids in breast cancer is crucial to understand the disease both in pre- and post-menopausal women. Further studies are desirable to state the direct role of these enzymes in breast cancer and which patients that may benefit from new therapeutic strategies targeting 17HSD enzymes. The new inhibitors targeting 17HSD1 have shown promising results in preclinical studies to have clinical potential in the future.

  • 6.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Cohen, Maja
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sivik, Tove
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    17β-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer2006In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 66, no 23, 11471-11477 p.Article in journal (Refereed)
    Abstract [en]

    Estrogens have an important role in the progression of breast cancer. The 17β-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormone-dependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrence-free survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)-positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancer-specific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression levels of the enzyme. ©2006 American Association for Cancer Research.

  • 7.
    Sivik, Tove
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Medical Genetics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Fornander, Tommy
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Skoog, Lambert
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    17β-hydroxysteroid dehydrogenase type 14 is a predictive marker for tamoxifen response in oestrogen receptor positive breast cancer2012In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 7, e40568- p.Article in journal (Refereed)
    Abstract [en]

    Introduction: 17β-hydroxysteroid dehydrogenases (17βHSDs) are important enzymes regulating the pool of bioactive steroids in the breast. The current study was undertaken in order to evaluate implications of 17βHSD14 in breast cancer, measuring 17βHSD14 protein expression in breast tumours.

    Methods: An antibody targeting the 17βHSD14 antigen was generated and validated using HSD17B14-transfected cells and a peptide-neutralising assay. Tissue microarrays with tumours from 912 post-menopausal women diagnosed with lymph node-negative breast cancer, and randomised to adjuvant tamoxifen or no endocrine treatment, were analysed for 17βHSD14 protein expression with immunohistochemistry.

    Results: Results were obtained from 847 tumours. Patients with oestrogen positive tumours with high 17βHSD14 expression had fewer local recurrences when treated with tamoxifen (HR 0.38; 95% C.I. 0.19–0.77, p = 0.007) compared to patients with lower tumoural 17βHSD14 expression, for whom tamoxifen did not reduce the number of local recurrences (HR 1.19; 95% C.I. 0.54–2.59; p = 0.66). No prognostic importance of 17βHSD14 was seen for systemically untreated patients.

    Conclusions: Using a highly specific validated antibody for immunohistochemical analysis of a large number of breast tumours, we have shown that tumoural expression levels of 17βHSD14 can predict the outcome of adjuvant tamoxifen treatment in terms of local recurrence-free survival in patients with lymph node-negative ER+ breast cancer. The results need be verified to confirm any clinical relevance.

  • 8.
    Gunnarsson, Cecilia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Hellqvist, Eva
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    17β-hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer2005In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 92, no 3, 547-552 p.Article in journal (Refereed)
    Abstract [en]

    The 17β-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P = 0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P = 0.0047), ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P = 0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.

  • 9.
    Lundberg, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Department of Biochemistry, University of Sydney, Australia.
    Dudman, Nicholas P.
    Department of Cardiovascular Medicine, Prince Henry Hospital, University of New South Wales, Australia.
    Kuchel, Philip W.
    Department of Biochemistry, University of Sydney, Australia.
    Wilcken, David E. L.
    Present address: Department of Physical Chemistry, University of Umeå, Umeå, Sweden.
    1H NMR determination of urinary betaine in patients with premature vascular disease and mild homocysteinemia1995In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 41, no 2, 275-283 p.Article in journal (Refereed)
    Abstract [en]

    Urinary N,N,N-trimethylglycine (betaine) and N,N-dimethylglycine (DMG) have been identified and quantified for clinical purposes by proton nuclear magnetic resonance (1H NMR) measurement in previous studies. We have assessed these procedures by using both one-dimensional (1-D) and 2-D NMR spectroscopy, together with pH titration of urinary extracts to help assign 1H NMR spectral peaks. The betaine calibration curve linearity was excellent (r = 0.997, P = 0.0001) over the concentration range 0.2-1.2 mmol/L, and CVs for replicate betaine analyses ranged from 7% (n = 10) at the lowest concentration to 1% (n = 9) at the highest. The detection limit for betaine was < 15 mumol/L. Urinary DMG concentrations were substantially lower than those of betaine. Urinary betaine and DMG concentrations measured by 1H NMR spectroscopy from 13 patients with premature vascular disease and 17 normal controls provided clinically pertinent data. We conclude that 1H NMR provides unique advantages as a research tool for determination of urinary betaine and DMG concentrations.

  • 10.
    Hallert, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    28-joint count disease activity score at 3 months after diagnosis of early rheumatoid arthritis is strongly associated with direct and indirect costs over the following 4 years: the Swedish TIRA project2011In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, no 7, 1259-1267 p.Article in journal (Refereed)
    Abstract [en]

    Methods. Three-hundred and twenty patients with early (1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. Results. Three months after diagnosis, a DAS-28 level of epsilon 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 epsilon 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 less than 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. Conclusions. Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.

  • 11.
    Hamrin, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    30th anniversary commentary on Hamrin E. (1982) attitudes of nursing staff in general medical wards towards activation of stroke patients. Journal of Advanced Nursing 7, 33-422006In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 53, no 1, 43-44 p.43-44 p.Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 12.
    Saraste, Helena
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Abbott, Allan
    Katashev, A
    Murans, G
    3D analysis of spine and chest wall form and mobility. Application of a new method to evaluate treatment outcome in pediatric spine deformities2012Conference paper (Other academic)
    Abstract [en]

    Summary

    A new optical scanning method is applyed for a static and dynamic analysis of thorax and spine deformities in brace and surgically treated scoliosis patients to capture intervention dependent changes over time. The costs and additional information captured by the method is analysed.

    Introduction

    To evaluate the intervention dependent changes in spine and chest wall deformities, such as mobility of thorax, volume, symmetry of growth, and possible growth distorting factors are poorly known and should be studied. In patients with neuropathic spine deformities, the seat loading is of importance to enhance balanced sitting and preventing pressure problems. Quantitative methods to be used for over time comparisons need to be further developed.

    In adolescents the decision to treat a spine deformity is mainly based on radiographic findings, whereas many patients are more interested in how their body configuration deviates from the normality. There is a need to implement and evaluate a method for this purpose. In brace treated children and adolescents, a non-radiation producing examination is to prefer for repeated follow-up controls.

    Methods

    A consequtive series of children with spine deformity, who are enrolled in the treatment protocol, are invited to take part in the tests. In surgery group, tests are performed before and 3 months after surgery aimed to correct the spine and/or thorax deformity. In brace treatment and follow-up groups tests are made at the same time points as x-rays. The static and dynamic recordings are performed by and optic scanenr Artec 3D (Artec Group, San Diego, CA), and the sitting load distribution measurements with a sensor mat (Clin-seat Type 5315 by Tekscan, Boston, Massachusetts, USA). 60 children/year in brace treatment, 40 in surgery, and 50 in the follow-up group are estimated to be included. These methods´ costs and benefits as well as their added value for the clinical decision making will be evaluated after 2-3 years.

    Results

    A feasibility test shows that clinically small enough differences can be recorded and numerically expressed and analysed. An application on a consecutive, clinical patient group will be carried on.

    Conclusion

    The optical scanning method by Artec, allows a static and dynamic capturing of respiratoryassociated thorax movements and the changes of a spine deformity over time. The new method will be applied in a consecutive series of patients.

  • 13.
    Ong, Jeb A.
    et al.
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    Auvinet, Edouard
    University of Montreal, Canada.
    Forget, Karolyn J.
    Maisonneuve Rosemt Hospital, Canada.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Maisonneuve Rosemt Hospital, Canada.
    Meunier, Jean
    University of Montreal, Canada; University of Montreal, Canada.
    Brunette, Isabelle
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 6, 2355-2365 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS. Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linkoping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS. The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS. Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

  • 14. Imura, M
    et al.
    Kuroda, T
    Oshiro, O
    Chihara, K
    Brandberg, Joakim
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    3-D flow visualization for construction of the model of the blood flow in the heart2000In: Japanese Journal of Applied Physics, ISSN 0021-4922, Vol. 39, no 5 B, 3246-3251 p.Article in journal (Refereed)
    Abstract [en]

    The authors have been developing a model of blood flow in the heart. The flow model of the heart enables us to estimate the entire blood flow of the heart from a couple of 2-D color Doppler images. Therefore, the load on patients is expected to be reduced. To develop the model of the heart, precise observation and an understanding of the blood flow are indispensable, because the flow is strongly related to the diagnosis of heart diseases. The visualization method must have the following features: (1) 3-D (2) objectivity (3) interactivity and (4) multi-aspect. The authors have developed visualization methods to meet the above-mentioned requirements and evaluated the proposed methods with the in-vitro flow data set. The results clearly reveal that the proposed system enables the researchers of the modeling group to obtain the state of entire flow, such as the occurrence of turbulence.

  • 15.
    Cahill, N
    et al.
    Uppsala University, Sweden.
    Bergh, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kanduri, M
    Uppsala University, Sweden.
    Göransson-Kultima, H
    Uppsala University, Sweden.
    Mansouri, L
    Uppsala University, Sweden.
    Isaksson, A
    Sahlgrenska University Hospital, Sweden.
    Ryan, F
    Institute of Technology, Dublin, Ireland.
    Smedby, K E
    Karolinska Institutet, Stockholm, Sweden.
    Juliusson, G
    Institute of Technology, Dublin, Ireland.
    Sundström, C
    Uppsala University, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rosenquist, R
    Uppsala University, Sweden.
    450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments2013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 1, 150-158 p.Article in journal (Refereed)
    Abstract [en]

    In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K-arrays, we provide the most comprehensive DNA methylation study of CLL to date, analysing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (e.g. CLLU1, LPL, ZAP70, NOTCH1), epigenetic regulator (e.g. HDAC9, HDAC4, DNMT3B), B-cell signaling (e.g. IBTK) and numerous TGF-ß and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.Leukemia accepted article preview online, 27 August 2012; doi:10.1038/leu.2012.245.

  • 16.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, 558-565 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

    MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

    RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

    CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

  • 17.
    Baron, Ralf
    et al.
    University Klinikum Schleswig Holstein.
    Mayoral, Victor
    Hospital Llobregat.
    Leijon, Göran
    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.
    Binder, Andreas
    University Klinikum Schleswig Holstein.
    Steigerwald, Ilona
    Grunenthal GmbH.
    Serpell, Michael
    University of Glasgow.
    5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study2009In: CURRENT MEDICAL RESEARCH AND OPINION, ISSN 0300-7995, Vol. 25, no 7, 1663-1676 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). Study design and methods: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of greater than= 2 points or an absolute value of less than= 4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs). Results: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (cor-responding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. Conclusion: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

  • 18.
    Sundbom, Per
    et al.
    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 Cardiology in Linköping.
    Ahn, Henrik
    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.
    Kornhall, B
    Skane University Hospital, Lund.
    Loebe, M
    Division of Transplant and Assist Devices at Methodist DeBakey Heart & Vascular Centre, Houston, Texas, USA.
    Granfeldt, Hans
    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.
    (556) – Change in Acoustic Fingerprints at Increased Pump Speed During Echocardiographic Ramp Test2014Conference paper (Refereed)
    Abstract [en]

    Purpose

    The continuous flow mechanical circulatory support HeartMate II (Thoratec Corporation, Inc. Pleasanton, USA) (HMII), generates an auditory signal (acoustic fingerprint) that can be registered by routine auscultation. A temporary or permanent change in sound indicates a change in pump function. Previous mock loop studies have shown that changes in acoustic fingerprint are due to changes in speed, so the aim of this study was to see if the acoustic fingerprint changed during an echocardiographic ramp test.

    Methods

    Four stable, event-free patients included in the SoundMate study performed an echocardiographic ramp test. The speed was increased stepwise by 400 rpm between 8 000 and 12 000 rpm, and the left ventricular end diastolic diameter, flow, power consumption and blood pressure were measured. Sounds from HMII were recorded using an iPhone™ (Apple Inc. Cupertino, CA, USA) with the stethoscope application iStethPro™ (Dr. Peter J Bentley, UK) and the frequency map analyzed using the Audacity™ program (Unicode, Ash, Chinen and Crook, USA). The acoustic fingerprint is divided into regions (R1: 1 000-6 500, R2: 8 500-14 000, R3: 15 000-21 000 Hz) and peaks (P1: 0-1 000, P2: 6 500-8 500, P4: 21 000-23 000 Hz) in order to facilitate calculations and clarify changes in frequency.

    Results

    There were significant (p<005) changes in the acoustic fingerprint when increasing the pump speed between 8 000 and 12 000 rpm. In 2/4 patients there were no significant changes in P1, otherwise there were significant changes in all regions and peaks. During the ramp test the power increased in mean 7 W, flow 3,1 L/min and the blood pressure measured with Doppler increased by ~15 mmHg. The left ventricular size decreased with ~2 cm.

    Conclusion

    The acoustic fingerprint changes with pump speed. This implies that when using sound check for detection of pump dysfunction, a new baseline should be set after every adjustment of speed.

  • 19.
    Hemdan, Tammer
    et al.
    University Hospital Uppsala, Sweden.
    Johansson, Robert
    Umeå University Hospital, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hellström, Pekka
    University Central Hospital, Oulu, Finland.
    Tasdemir, Ilker
    Central Hospital of Rogaland, Stavanger, Norway.
    Malmström, Per-Uno
    University Hospital Uppsala, Sweden.
    5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guerin with Epirubicin and Interferon-alpha 2b in Patients with T1 Bladder Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, 1244-1249 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha 2b in the treatment of patients with T1 bladder cancer. Materials and Methods: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. Results: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. Conclusions: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy.

  • 20.
    Lagerqvist, Bo
    et al.
    Uppsala.
    Husted, Steen
    Århus,Danmark.
    Koontny, Fredrik
    Oslo, Norge.
    Ståhle, Elisabeth
    Uppsala.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, Lars
    Uppsala.
    5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study2006In: The Lancet, ISSN 0140-6736, Vol. 368, no 9540, 998-1004 p.Article in journal (Refereed)
    Abstract [en]

    Background: The FRISC-II invasive trial compared an early invasive with a non-invasive strategy in terms of death and myocardial infarction in non-ST-elevation acute coronary syndrome. We present 5-year follow-up results, overall and in subgroups based on recommended risk stratification criteria. Methods: In the FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were randomised to early invasive strategy (coronary angiography and, if appropriate, revascularisation, within 7 days from admission) or non-invasive primarily medical strategy. Risk stratification was done on the basis of risk indicators at randomisation: age older than 65 years, male sex, diabetes mellitus, previous myocardial infarction, ST-segment depression, raised troponin concentration (>0·03 μg/L), and raised C-reactive protein or interleukin 6. Information on events after 24 months was taken from national registries. Analyses were done on an intention-to-treat basis. Findings: At 5 years the groups differed in terms of the primary composite endpoint of death, myocardial infarction, or both (invasive 217, 19·9 %, noninvasive 270, 24·5 %, risk ratio 0·81, 95% CI 0·69-0·95, p=0·009). 5-year mortality was 117 (9·7%) in the invasive group compared with 124 (10·1%) in the noninvasive group (0·95, 0·75 -1·21, p=0·693). Rates of myocardial infarction were 141 (12·9 %) in the invasive and 195 (17.7%) in the non-invasive group (0·73, 0·60-0·89, p=0·002). The benefit of the invasive strategy was confined to male patients, non-smokers, and patients with two or more risk indicators. Interpretation: The 5-year outcome of this trial indicates sustained benefit of an early invasive strategy in patients with non-ST-elevation acute coronary syndrome at moderate to high risk. © 2006 Elsevier Ltd. All rights reserved.

  • 21.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Topooco, Naira
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Havik, Odd
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Nordgreen, Tine
    University of Bergen, Norway; Haukeland Hospital, Norway.
    6 Internet-supported versus face-to-face cognitive behavior therapy for depression2016In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 16, no 1, 55-60 p.Article, review/survey (Refereed)
    Abstract [en]

    Major depression and depressive symptoms are highly prevalent and there is a need for different forms of psychological treatments that can be delivered from a distance at a low cost. In the present review the authors contrast face-to-face and Internet-delivered cognitive behavior therapy (ICBT) for depression. A total of five studies are reviewed in which guided ICBT was directly compared against face-to-face CBT. Meta-analytic summary statistics were calculated for the five studies involving a total of 429 participants. The average effect size difference was Hedges g=0.12 (95% CI: -0.06-0.30) in the direction of favoring guided ICBT. The small difference in effect has no implication for clinical practice. The overall empirical status of clinician-guided ICBT for depression is commented on and future challenges are highlighted. Among these are developing treatments for patients with more severe and long-standing depression and for children, adolescents and the elderly. Also, there is a need to investigate mechanisms of change.

  • 22.
    Broström, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Nursing Science.
    Johansson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Albers, Jan
    City Hospital Ryhov.
    Wiberg, Jan
    City Hospital Ryhov.
    Svanborg, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurophysiology UHL.
    Fridlund, Bengt
    Vaxjö University.
    6-month CPAP-treatment in a young male patient with severe obstructive sleep apnoea syndrome - A case study from the couples perspective2008In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, Vol. 7, no 2, 103-112 p.Article in journal (Refereed)
    Abstract [en]

    Background: Obstructive sleep apnoea syndrome (OSAS) is independently associated with an increased risk for hypertension and cardiovascular disease. Continuous positive airway pressure (CPAP) can reduce mortality and morbidity, but low compliance rates are seen. Aim: To explore and describe the experiences of CPAP-treatment in a young male patient with severe OSAS during a 6-month period from the couples perspective.

    Methods and the case: A single case study with a phenomenographic approach was employed. Diagnostic procedures of OSAS and initiation of treatment with Auto-CPAP, humidifier and a nasal mask were performed during 4 visits. Conceptions were collected at 4 different occasions during the 6-month period (before, and 2 weeks, 3 months, and 6 months after treatment initiation) by means of interviews with a 33-year old male patient and his female partner.

    Findings: Totally 17 different structural aspects were found to fluctuate during the 6-month period in relation to; influence of stressors, social reactions and adaptation to increase compliance.

    Conclusion: An increased knowledge about the influence of stressors, the social reactions, and the adaptation can help healthcare personnel to identify and better understand concerns of other patients and spouses during different time phases of the initial 6-month period of CPAP-treatment.

  • 23.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hindorf , U
    Lund University.
    6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients2009In: Digestive and Liver Disease, ISSN 1590-8658, Vol. 41, no 3, 194-200 p.Article in journal (Refereed)
    Abstract [en]

    Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety.

    Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times.

    Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80.

    Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.

  • 24. de Boer, NKH
    et al.
    Reinisch, W
    Teml, A
    van Bodegraven, AA
    Schwab, M
    Lukas, M
    Ochsenkuhn, T
    Petritsch, W
    Knoflach, P
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    van der Merwe, SW
    Herrlinger, KR
    Seiderer, J
    Vogelsang, H
    Mulder, CJJ
    6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party2006In: Digestion, ISSN 0012-2823, Vol. 73, no 1, 25-31 p.Article in journal (Refereed)
    Abstract [en]

    Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel.

  • 25.
    Li, Wei
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Johnson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    7beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 11, 1072-1079 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 26.
    Li, Wei
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Johnson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    7ß-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009In: Free radical research, ISSN 1071-5762, Vol. 43, no 11, 1072-1079 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 27. Kälkner, Karl Mikael
    et al.
    Westlin, Jan-Erik
    Strang, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin. Östergötlands Läns Landsting, ViN, LAH Linnea.
    89Strontium in the management of painful sceletal metastases2000In: Anticancer Research, ISSN 0250-7005, Vol. 20, no 2 B, 1109-1114 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To make a review of the literature of 89strontium-chloride and a retrospective study of time to palliative intended external irradiation number of portals and overall-survival after 89strontium-chloride therapy. Results: In total 93 patients were treated 116 times with 89strontium. The patients with prostatic carcinoma received 91% of all 89strontium therapies. Median over-all survival was 10 months after injection. In those cases when 89strontium was given before palliative radiotherapy, the average of total number of local fields was significantly lower (1.1 versus 4.1) compared to those cases where local fields preceded 89strontium therapy. However, time to 89new external irradiation after 89strontium injection was equal between these groups (3.8 versus 2.9 months). Conclusion:A review of literature conclude that 89strontium is effective for the reduction of pain originating from osteoblastic metastases. It also reduce the need for external radiotherapy and therefore is cost-effective. However, 89strontium is more effective in an early phase of the metastatic disease and preferably as an adjuvance to external radiotherapy.

  • 28.
    Wedajo, W.
    et al.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia; Department of Biology, Jimma UniversityJimma, Ethiopia.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Department of Infectious Diseases and Microbiology, Kalmar County HospitalKalmar, Sweden.
    Bedru, A.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia.
    Kiros, T.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia.
    Hailu, E.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Mebrahtu, T.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Yamuah, L.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Angeby, K.
    Department of Clinical Microbiology MTC, Karolinska Hospital, Karolinska University HospitalStockholm, Sweden.
    Werngren, J.
    Department of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control (SMI)Solna, Sweden.
    Onyebujoh, P.
    World Health Organization, Regional Office for Africa, Inter-country Support Team for East0/Southern AfricaHarare, Zimbabwe.
    Dagne, K.
    Addis Ababa University, Faculty of Life SciencesAddis Ababa, Ethiopia.
    Aseffa, A.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    A 24-well plate assay for simultaneous testing of first and second line drugs against Mycobacterium tuberculosis in a high endemic setting2014In: BMC Research Notes, ISSN 1756-0500, Vol. 7, no 1, 512- p.Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of drug resistance is one of the priorities of tuberculosis (TB) control programs as drug resistance is increasing. New molecular assays are only accessible for a minority of the second line drugs and their availability in high endemic settings is also hampered by high cost and logistic challenges. Therefore, we evaluated a previously developed method for drug susceptibility testing (DST) including both first- and second line anti-TB drugs for use in high endemic areas. Results: Baseline mycobacterial isolates from 78 consecutive pulmonary TB patients from Addis Ababa, Ethiopia who were culture positive for Mycobacterium tuberculosis at the end of a two-month directly observed treatment short course (DOTS) were included. The isolates were simultaneously tested for isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide and para-aminosalicylic acid susceptibility using the indirect proportion method adopted for 24-well agar plates containing Middlebrook 7H10 medium. Applying the 24-well plate assay, 43 (55.1%) isolates were resistant to one or more of the first line drugs tested (isoniazid, rifampicin and ethambutol). MDR-TB was identified in 20.5% of this selected group and there was a perfect correlation for rifampicin resistance with the results from the genotype MTBDRplus assay. All isolates were susceptible to aminoglycosides and fluoroquinolones in agreement with the genotype MTBDRsl assay. The only tested second line drug associated to resistance was ethionamide (14.1% resistant). The method was reproducible with stable results for internal controls (one multi-drug resistant (MDR) and one pan-susceptible strain (H37Rv) and DST results could be reported at two weeks. Conclusions: The 24-well plate method for simultaneous DST for first- and second line drugs was found to be reproducible and correlated well to molecular drug susceptibility tests. It is likely to be useful in high-endemic areas for surveillance as well as for the detection of second line drug resistance in targeted groups such as in those who fail empirical MDR treatment.

  • 29.
    Ziemssen, Tjalf
    et al.
    Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    de Sa, Joao C.
    Hospital Santa Mari, Belgium.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Hop Tenon, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Lander Delgado, Rafael H.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin City University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no 11, 2101-2111 p.Article in journal (Refereed)
    Abstract [en]

    Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p less than 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p less than 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

  • 30.
    Lindgren, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Oral Surgery UHL.
    Mordenfeld, Arne
    Department of Oral and Maxillofacial Surgery, Gävle, County Hospital, Sweden/Dept of Biomaterials, Institute of Clinical Sciences, Göteborg University, Sweden.
    Johansson, CB
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hallman, Mats
    Department of Oral and Maxillofacial Surgery, Gävle, County Hospital, Sweden/Department of Oral & Maxillofacial Surgery, Umeå University, Umeå Sweden and Center for Research and Development, Uppsala University/Gävleborg County Council, Sweden.
    A 3-year clinical follow-up of implants placed in 2 differentbiomaterials used for sinus augmentationManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: The aims of the present study were to compare a novel biphasic calcium phosphate (BCP) with deproteinized bovine bone (DBB) used for maxillary sinus floor augmentation (MSFA) in a split mouth design, and to perform a clinical follow-up of placed dental implants.

    Material and Methods: Nine completely edentulous patients and two partially edentulous patients with a mean age of 67 years requiring bilateral sinus augmentation were included in the study. The patients were randomized for augmentation with BCP (test) and DBB (control) in the contralateral side. After 8 months of graft healing, 62 implants with an SLActive® surface (Strauman®, Basel, Switzerland) were placed. After 3 years of graft healing core biopsies were obtained from the grafted areas for histological and histomorphometrical analysis. After 3 years of functional implant loading, implant survival/success rate, clinical indexes, radiographical examination and resonance frequency analysis (RFA) wereperformed.

    Results: The mean values of the area of newly formed bone in the biopsies was 29% ±14.3% and 32% ± 18.0% for BCP and DBB respectively and graft particles in contact with bone in the BCP group was 38% ± 10.9% compared to 44% ± 12.1% for the DBB group, showing no significant differences between the groups. The mean values of the area of BCP particles and DBB particles were 20% ± 7.5% and 24% ± 13.5% respectively (non-significant).

    Irrespective of particles used, one dental implant was lost from each group, giving an overall implant survival rate of 96.8% after 3-years of loading. Conclusion: The results of this prospective 3-year clinical and histological follow up demonstrated a similar amount of newly formed bone irrespectively of the used biomaterial. The choice of biomaterial does not seem to influence the survival rates of the implants.

  • 31.
    Lindgren, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Oral Surgery UHL.
    Mordenfeld, Arne
    Gävle County Hospital, Sweden Gothenburg University, Sweden .
    Johansson, Carina B
    University of Örebro, Sweden .
    Hallman, Mats
    Gävle County Hospital, Sweden Umeå University, Sweden Uppsala University, Sweden .
    A 3-Year Clinical Follow-up of Implants Placed in Two Different Biomaterials Used for Sinus Augmentation2012In: International Journal of Oral & Maxillofacial Implants, ISSN 0882-2786, Vol. 27, no 5, 1151-1162 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The aims of the present study were to compare a novel biphasic calcium phosphate (BCP) with deproteinized bovine bone (DBB) for maxillary sinus floor augmentation in a split-mouth design and to perform a clinical follow-up of dental implants placed in the augmented sinuses. Materials and Methods: Partially or completely edentulous patients requiring bilateral sinus augmentation were included in the study. The patients were randomized for augmentation with BCP (test) and DBB (control) in the contralateral side. Eight months after grafting, dental implants were placed. After 3 years of graft healing, core biopsy specimens were obtained from the grafted areas for histologic and histomorphometric analyses. After 3 years of functional implant loading, implant survival/success rates and clinical indices were assessed and radiographic examination and resonance frequency analysis were performed. Results: Nine completely edentulous patients and two partially edentulous patients (mean age, 67 years) who required bilateral sinus augmentation were included in the study, and 62 implants were placed. The mean values for the area of newly formed bone in the retrieved specimens were 29% +/- 14.3% and 32% +/- 18.0% for BCP and DBB, respectively; the percentage of graft particles in contact with bone was 38% +/- 10.9% in the BCP group and 44% +/- 12.1% in the DBB group (no statistical significant differences between groups). The mean values for the area of BCP particles and DBB particles were 20% +/- 7.5% and 24% +/- 13.5%, respectively (difference not significant). One dental implant was lost from each group, resulting in an overall implant survival rate of 96.8% after 3 years of loading. Conclusion: After 3 years, a similar amount of newly formed bone was present regardless of the biomaterial used. The choice of biomaterial did not seem to influence implant survival rates.

  • 32. Hultcrantz, R
    et al.
    Olsson, R
    Danielsson, Å
    Järnerot, G
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Lööf, L
    Rydén, BO
    Wahren, B
    Broomé, U
    A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. 1999In: Journal of Hepatology, ISSN 0168-8278, Vol. 30, 669-673 p.Article in journal (Refereed)
  • 33.
    Olsson, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Eriksson, M
    Johnson, O
    Kjellström, T
    Lanke, J
    Lytken Larsen, M
    Pedersen, T
    Tikkanen, MJ
    Wiklund, O
    A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The Treat-to-Target (3T) Study2003In: Clinical Therapeutics, ISSN 0149-2918, Vol. 25, no 1, 119-138 p.Article in journal (Refereed)
    Abstract [en]

    Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C =2.6 mmol/L, TG =1.5 mmol/L, and both LDL-C =2.6 mmol/L and TG =1.5 mmol/L. Methods: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration =4.0 mmol/L (=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. Results: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation of the drugs' effects on YG. Patient demographic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001, 52 weeks: -49% vs -44%, P < 0.001) and in YG (8 weeks: -23% vs -14%, P < 0.001, 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%, P < 0.001). Fewer atorvastatin patients needed to have their dose doubled, nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%, P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. Conclusions: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d m reducing LDL-C and YG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statins were well tolerated.

  • 34. Amin, AI
    et al.
    Hallböök, Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Lee, AJ
    Sexton, R
    Moran, BJ
    Heald, RJ
    A 5-cm colonic J pouch colo-anal reconstruction following anterior resection for low rectal cancer results in acceptable evacuation and continence in the long term2003In: Colorectal Disease, ISSN 1462-8910, Vol. 5, no 1, 33-37 p.Article in journal (Refereed)
    Abstract [en]

    Background. Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. Methods. In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces, and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. Results. The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, post-operative leak and length of follow-up had no demonstrable effect on either score. Conclusion. Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.

  • 35.
    Engquist, Markus
    et al.
    Ryhov Hospital, Sweden.
    Löfgren, Håkan
    Ryhov Hospital, Sweden.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Holtz, Anders
    University of Uppsala Hospital, Sweden.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Söderlund, Anne
    Mälardalen University, Sweden.
    Vavruch, Ludek
    Ryhov Hospital, Sweden.
    Lind, Bengt
    University of Gothenburg, Sweden; Spine Centre Göteborg, Sweden.
    A 5-to 8-year randomized study on the treatment of cervical radiculopathy: anterior cervical decompression and fusion plus physiotherapy versus physiotherapy alone2017In: JOURNAL OF NEUROSURGERY-SPINE, ISSN 1547-5654, Vol. 26, no 1, 19-27 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The aim of this study was to evaluate the 5- to 8-year outcome of anterior cervical decompression and fusion (ACDF) combined with a structured physiotherapy program as compared with that following the same physiotherapy program alone in patients with cervical radiculopathy. No previous prospective randomized studies with a follow-up of more than 2 years have compared outcomes of surgical versus nonsurgical intervention for cervical radiculopathy. METHODS Fifty-nine patients were randomized to ACDF surgery with postoperative physiotherapy (30 patients) or to structured physiotherapy alone (29 patients). The physiotherapy program included general and specific exercises as well as pain coping strategies. Outcome measures included neck disability (Neck Disability Index [NDI]), neck and arm pain intensity (visual analog scale [VAS]), health state (EQ-5D questionnaire), and a patient global assessment. Patients were followed up for 5-8 years. RESULTS After 5-8 years, the NDI was reduced by a mean score% of 21 (95% CI 14-28) in the surgical group and 11% (95% CI 4%-18%) in the nonsurgical group (p = 0.03). Neck pain was reduced by a mean score of 39 mm (95% CI 26-53 mm) compared with 19 mm (95% CI 7-30 mm; p = 0.01), and arm pain was reduced by a mean score of 33 mm (95% CI 18-49 mm) compared with 19 mm (95% CI 7-32 mm; p = 0.1), respectively. The EQ-5D had a mean respective increase of 0.29 (95% CI 0.13-0.45) compared with 0.14 (95% CI 0.01-0.27; p = 0.12). Ninety-three percent of patients in the surgical group rated their symptoms as "better" or "much better" compared with 62% in the nonsurgical group (p = 0.005). Both treatment groups experienced significant improvement over baseline for all outcome measures. CONCLUSIONS In this prospective randomized study of 5- to 8-year outcomes of surgical versus nonsurgical treatment in patients with cervical radiculopathy, ACDF combined with physiotherapy reduced neck disability and neck pain more effectively than physiotherapy alone. Self-rating by patients as regards treatment outcome was also superior in the surgery group. No significant differences were seen between the 2 patient groups as regards arm pain and health outcome.

  • 36. Dieperink, Willem
    et al.
    van der Horst, Iwan C C
    Nannenberg-Koops, Jaqueline W
    Brouwer, Henk W
    Jaarsma, T
    Nieuwland, Wybe
    Zijlstra, Felix
    Nijsten, Maarten W N
    A 64-year old man who sustained many episodes of acute cardiogenic pulmonary edema successfully treated with Boussignac continuous positive airway pressure: a case report.2007In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 119, no 2, 268-70 p.Article in journal (Refereed)
    Abstract [en]

    Continuous positive airway pressure (CPAP) is standard treatment for patients with acute cardiogenic pulmonary edema. We describe a patient who had 21 episodes of acute cardiogenic pulmonary edema due to very poor patient compliance. This 64-year old man had end-stage congestive heart failure based on systolic left ventricular dysfunction following two myocardial infarctions. In addition to routine medical treatment 15 episodes of pulmonary edema were successfully treated with Boussignac continuous positive airway pressure (BCPAP). The BCPAP system is a simple, disposable, FDA-approved device that delivers positive pressure without a ventilator. This extraordinary case underscores the utility of the BCPAP system to avoid repeated intubation and mechanical ventilation in patients with cardiogenic pulmonary edema.

  • 37. Balldin, J
    et al.
    Berglund, M
    Borg, S
    Mansson, M
    Bendtsen, Preben
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Beroendekliniken IHS. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Dependency.
    Franck, J
    Gustafsson, L
    Halldin, J
    Nilsson, LH
    Stolt, G
    Willander, A
    A 6-month controlled naltrexone study: Combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence2003In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, Vol. 27, no 7, 1142-1149 p.Article in journal (Refereed)
    Abstract [en]

    Background: In several studies, patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo. An interaction between the naltrexone effect and the type of psychological therapy has been observed. Methods: A 6-month, double-blind, placebo-controlled, parallel-group study was performed at 10 different investigation sites. After a placebo run-in period of 1 week, 118 patients were randomized into 4 treatment groups - 50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy (CBT) or supportive therapy. The CBT was performed over nine sessions according to the manual of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). The supportive therapy was defined as "the treatment as usual." Alcohol consumption, craving, carbohydrate-deficient transferrin, medication compliance by tablet count, and adverse clinical events were assessed at all visits. Other liver enzymes and psychiatric symptoms were also determined. Results: Ninety-one (77%) patients completed the study, and 92 (78%) were 80% compliant with the medication regimen. A lower percentage of heavy-drinking days was shown in the naltrexone group (p = 0.045) compared with the placebo group, as was a lower craving score (p = 0.029). These results are supported by the lower levels of liver enzyme activities (p < 0.010 for aspartate aminotransferase, alanine aminotransferase, and ?-glutamyltransferase), but not by the carbohydrate-deficient transferrin levels, in the naltrexone group. The mean time period before the first day of heavy drinking was longer for the group treated with CBT (p = 0.010), especially in combination with naltrexone (p = 0.007). Naltrexone was well tolerated, and no patients discontinued the study due to side effects. Conclusions: This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected.

  • 38.
    Waller, Niels
    et al.
    Department of Psychology, University of Minnesota, N657 Elliott Hall, 75 East River Road, Minneapolis, MN, 55455, USA.
    John, Mike T.
    Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
    Feuerstahler, Leah
    Department of Psychology, University of Minnesota, N657 Elliott Hall, 75 East River Road, Minneapolis, MN, 55455, USA.
    Baba, Kazuyoshi
    Department of Prosthodontics, Showa University, Tokyo, Japan.
    Larsson, Pernilla
    Region Östergötland, Public Dental Health Care.
    Peršić, Sanja
    Department of Prosthodontics, School of Dentistry, University of Zagreb, Zagreb, Croatia.
    Kende, Dóra
    Department of Prosthodontics, University of Pécs, Pécs, Hungary.
    Reißmann, Daniel R.
    Department of Prosthetic Dentistry, Center for Dental and Oral Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany..
    Rener-Sitar, Ksenija
    Department of Prosthodontics, Dental Division, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Prosthodontics, University Dental Clinics, University Medical Center of Ljubljan, Ljubljan, Slovenia.
    A 7-day recall period for a clinical application of the oral health impact profile questionnaire.2016In: Clinical Oral Investigations, ISSN 1432-6981, E-ISSN 1436-3771, Vol. 20, no 1, 91-99 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Aims were to investigate and compare the validity and reliability of Oral Health Impact Profile (OHIP) scores referencing 7-day and 1-month recall periods in international prosthodontic patients.

    MATERIAL AND METHODS: A sample of 267 patients (mean age = 54.0 years, SD = 17.2 years, 58 % women) with stable oral health-related quality of life was recruited from prosthodontic treatment centers in Croatia, Germany, Hungary, Japan, Slovenia, and Sweden. These patients completed the OHIP on two occasions using a new 7-day recall period and the traditional 1-month recall period. OHIP score validity and reliability were investigated with structural equation models (SEMs) that included OHIP(past 7 days) and OHIP(1 month) latent factors and single indicator measures of global oral health status. The SEMs assessed measurement invariance and the relative validities of the two OHIP latent factors (representing the two recall periods).

    RESULTS: The SEMs provided cogent evidence for recall period measurement invariance for the two OHIP forms and equal validities (r = .48) with external measures of global oral health status.

    CONCLUSION: When assessed in international prosthodontic patients, OHIP scores using the new 7-day recall period were as reliable and valid as the scores using the 1-month recall period.

    CLINICAL RELEVANCE: Conceptual advantages make a 7-day recall period a preferred frame of reference in clinical applications of the OHIP questionnaire.

  • 39.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil S
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Jackson, W Bruce
    University of Ottawa Eye Institute.
    Munger, Rejean
    University of Ottawa Eye Institute.
    Liu, Yuwen
    CooperVision Inc, Pleasanton, USA .
    Polarek, James W
    FibroGen Inc, San Francisco.
    Söderqvist, Monica
    Synsam Opticians, Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study2010In: Science translational medicine, ISSN 1946-6234, Vol. 2, no 46, 46-61 p.Article in journal (Refereed)
    Abstract [en]

    Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.

  • 40.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Tengvall, Pentti
    Gothenburg University.
    Aspenberg, Per
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 5, 1148-1151 p.Article in journal (Refereed)
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

  • 41.
    Stenfelt, Stefan
    et al.
    Chalmers University Technology.
    Håkansson, B
    Chalmers University of Technology.
    Jönsson, R
    Chalmers University of Technology.
    Granström, G
    Chalmers University of Technology.
    A bone-anchored hearing aid for patients with pure sensorineural hearing impairment: A pilot study2000In: Scandinavian Audiology, ISSN 0105-0397, Vol. 29, no 3, 175-185 p.Article in journal (Refereed)
    Abstract [en]

    This pilot study assesses the potential benefits of an optimized bone-anchored hearing aid (BAHA) for patients with a mild to moderate purl sensorineural high frequency hearing impairment. The evaluation was conducted with eight first-time hearing aid users by means of psyche-acoustic sound field measurements and a questionnaire on subjective experience; all of the patients benefited from the BAHA. On average, the eight patients showed improvement in PTA threshold of 3.4 dB and in speech intelligibility in noise of 14%. Seven of the subjects, also fitted with present standard air conduction hearing aids (ACHA) found the ACHA thresholds to be improved more than the BAHA ones. In speech tests, the ACHA was only slightly better; these patients chose between their different hearing aids according to the sound environment. Although the BAHA was preferred for wearing and sound comfort, it cannot be used as the sole aid for patients with pure sensorineural impairment.

  • 42.
    Persson, Ulf
    et al.
    Lund University, Sweden Lundby Hospital, Sweden .
    Gullstrand, Birgitta
    Lund University, Sweden .
    Pettersson, Asa
    Lund University, Sweden .
    Sturfelt, Gunnar
    Lund University, Sweden .
    Truedsson, Lennart
    Lund University, Sweden .
    Segelmark, Mårten
    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.
    A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fc gamma-RIIa Genes2013In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 37, no 6, 641-648 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fc gamma-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegeners granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fc gamma-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.

  • 43.
    Palfi, Miodrag
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Hildén, Jan-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Matthiesen, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Selbing, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A case of severe Rh (D) alloimmunization treated by intensive plasma exchange and high-dose intravenous immunoglobulin2006In: Transfusion and apheresis science, ISSN 1473-0502, Vol. 35, no 2, 131-136 p.Article in journal (Refereed)
    Abstract [en]

    Background: In extremely severe Rh (D) alloimmunization, during pregnancy, early diagnosis and treatment is essential to avoid hydrops fetalis. Intrauterine transfusion (IUT) is of utmost importance in the prevention of fetal anemia but it is usually feasible only after 20 weeks of pregnancy. Therefore, additional treatment options in early pregnancy are needed. Study design and methods: A 27-year-old severely D + C immunized woman was admitted at 8 weeks of gestation in her fifth pregnancy with an extremely high concentration of anti-D. Her first pregnancy was uneventful but resulted in D + C alloimmunization. The next two pregnancies were unsuccessful, because of hydrops fetalis resulting in fetal death in pregnancy week 20 and 24, respectively, despite treatment with high-dose intravenous immunoglobulin (IVIG) and IUT treatment. A fourth pregnancy was terminated with legal abortion. The patient was eager and persistent to accomplish a successful pregnancy. Therefore, a combination of treatments consisting of plasma exchange (PE) three times/week and IVIG 100 g/week was started in pregnancy week 12. PE was performed 53 times and totally 159 L of plasma was exchanged. Results: The anti-D concentration was 12 μg/mL (IAT titer 2000) before start of treatment by PE and IVIG in pregnancy week 12. The concentration of anti-D was gradually reduced to approximately 3 μg/mL after only two weeks of treatment and was maintained at that level until pregnancy week 22. In pregnancy week 26 and 27, signs of hydrops were detected by ultrasonography and IUT were performed at each occasion. Sectio was inevitable at pregnancy week 28 + 1 and a male baby was born: Hb 58 g/L (cord sample) and 68 g/L (venous sample), weight 1385 g, Apgar score = 4-5-7, Bilirubin 56-150 mmol/L (4 h). Exchange transfusion was performed on day two and day five. Phototherapy was also implemented for eight days. The newborn's recovery thereafter was uneventful and complete. Conclusion: A combination of PE and IVIG may be an efficient treatment possible to start in early pregnancy in patients with extremely severe Rh (D) alloimmunization, with a history of hydrops fetalis in previous pregnancies. © 2006 Elsevier Ltd. All rights reserved.

  • 44.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Hosoya, Yumiko
    University of Tokyo, Japan .
    Takahashi, Masao
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    A case with recovery of response to tolvaptan associated with remission of acute kidney injury and increased urine osmolality2013In: International Heart Journal, ISSN 1349-2365, Vol. 54, no 2, 115-118 p.Article in journal (Refereed)
    Abstract [en]

    Tolvaptan (TLV), a vasopressin type 2 receptor antagonist, has been demonstrated to be effective in patients with decompensated heart failure (HF) refractory to incremental doses of diuretics, but the responsiveness has not always been predictable. We have recently proposed that urine osmolality (U-OSM) is a valuable parameter for the prediction of responses to TLV, because U-OSM reflects the activity of the collecting ducts, where TLV plays its unique role. Acute kidney injury (AKI) is often associated with severe tubular dysfunction, including the collecting ducts, and in such cases a response to TLV may not be expected. We here experienced a patient with HF and AKI in whom TLV was not effective during AKI. We also observed recovery of responsiveness to TLV along with remission of AKI as well as increased U-OSM later on. We believe that this is the first report on the reversibility of the TLV response in relation to U-OSM.

  • 45. Faresjö, Åshild
    et al.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Timpka, Toomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Åkerlind, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, National Centre for Work and Rehabilitation. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    A case-control study of irritable bowel syndrome in primary care - female patients are seriously affected by psychosocial problems in their every day life2006In: EUPHA 14th annual conference,2006, 2006Conference paper (Other academic)
  • 46.
    Bäckman, Carl G
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Orwelius, Lotti
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Walther, Sten M
    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.
    A case-control study of the influence of the ICU-diary concept on mastery and hopelessness six months after critical illnessManuscript (preprint) (Other academic)
    Abstract [en]

    The ICU-diary concept is associated with less post-traumatic stress syndrome and improved perceived health-related quality-of-life (HRQoL) after critical illness, but little is known about its effect on the coping- mastery process, or whether it reduces hopelessness.

    Objective: To see if the ICU-diary concept improves the patient’s ability to master his/her situation after critical illness, and if it reduces the feeling of hopelessness.

    Design: Case control study (subgroup analysis of a multi-centre study on health-related quality-of-life (HRQoL).

    Setting: Non-academic 8-bed general ICU.

    Patients: Adults admitted between March 2002 and June 2004.

    Measurements: Mastery and hopelessness were determined using validated questionnaires (the Mastery-Coping scale and a consolidated 2–item hopelessness questionnaire) which were sent home to patients 6 months after critical illness. Responses were compared between patients that received (Cases: n=38) or did not receive an ICU-diary (Controls: n=76) . Diaries were used when a long and complicated stay on the ICU was expected. Controls were matched with diary patients by gender and age. The effect of the ICU-diary was also examined using a multiple regression model.

    Results: The ICU-diary concept group scored significantly higher than the No-diary group in mastery (22.1 vs. 20.4, P<0.05) and lower in hopelessness scores (1.3 vs. 1.6, P<0.05). The positive influence of the ICU-diary disappeared after adjustment for confounding factors in a multiple regression model.

    Conclusion: We were unable to verify any positive influence of the ICU-diary concept on mastery and hopelessness 6 months after critical illness.

  • 47.
    Jung, Michaela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, 839- p.Article in journal (Refereed)
    Abstract [en]

    Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery.

  • 48.
    Olafsdottir, Arndis F.
    et al.
    NU Hospital Grp, Sweden; University of Gothenburg, Sweden.
    Attvall, Stig
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Sandgren, Ulrika
    Sahlgrens University Hospital, Sweden.
    Dahlqvist, Sofia
    NU Hospital Group, Uddevalla, Sweden.
    Pivodic, Aldina
    Statistiska Konsultgruppen, Sweden.
    Skrtic, Stanko
    University of Gothenburg, Sweden; AstraZeneca Rand D, Sweden.
    Theodorsson, Elvar
    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 Chemistry.
    Lind, Marcus
    NU Hospital Grp, Sweden; University of Gothenburg, Sweden.
    A Clinical Trial of the Accuracy and Treatment Experience of the Flash Glucose Monitor FreeStyle Libre in Adults with Type 1 Diabetes2017In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 19, no 3, 164-172 p.Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, FreeStyle Libre a flash glucose monitoring system came onto the market in 2014 as a complement to self-monitoring of blood glucose. The aim of this study was to evaluate the accuracy and treatment experience of the FreeStyle Libre system. Methods: Fifty-eight adults with type 1 diabetes used FreeStyle Libre for 10-14 days and measured capillary blood glucose levels with the HemoCue blood glucose measurement system at least six times a day simultaneously. Results: For the entire study period, the mean absolute relative difference (MARD) was 13.2% (95% confidence interval [CI] 12.0%-14.4%). MARD was 13.6% (95% CI 12.1%-15.4%) during week 1 and 12.7% (95% CI 11.5%-13.9%) during week 2. The mean absolute difference (MAD) for the whole study period was 19.8mg/dL (1.1mmol/L) (95% CI 17.8-21.8 mg/dL), including 20.5 mg/dL (1.14 mmol/L) during week 1 and 19.0 mg/dL (1.05 mmol/L) during week 2. The overall correlation coefficient was 0.96. For glucose values amp;lt; 72, 72-180, and amp;gt; 180mg/dL (amp;lt; 4, 4-10, and amp;gt; 10 mmol/L), the MARD was 20.3% (95% CI 17.7%-23.1%), 14.7% (95% CI 13.4%-16%), and 9.6% (95% CI 8.5%-10.8%), respectively, and respective MAD values were 12.3, 17.8, and 23.6 mg/dL (0.69, 0.99, and 1.31mmol/L). Using the 10-item visual analog scale, patients rated their experience with FreeStyle Libre as generally positive, with mean values ranging from 8.22 to 9.8. Conclusions: FreeStyle Libre had a similar overall MARD as continuous blood glucose monitoring systems in earlier studies when studied in similar at-home conditions. The overall patient satisfaction was high.

  • 49.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Janzon, Magnus
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    A clinician’s experience of using the Cardiac Reader NT-proBNP point-of-care assay in a clinical setting2008In: European Journal of Heart Failure, ISSN 1388-9842, Vol. 10, no 3, 260-266 p.Article in journal (Refereed)
    Abstract [en]

    The evaluation of natriuretic peptides has become increasingly valuable in a clinical setting, where information is often needed promptly.

    Objectives: To compare the usefulness of the recently released Roche Cardiac Reader ® NT-proBNP assay against the Roche Elecsys® NT-proBNP laboratory system in a clinical setting.

    Design and Results: Blood samples from 440 patients admitted for acute coronary syndromes, worsening of heart failure, or as policlinic heart failure patients were evaluated. The relation between the assays was analysed and the diagnostic concordance calculated. A good correlation was found between the assays (r=0.96, 95% CI: 0.94-0.97) with a diagnostic concordance of 0.93. A separate analysis was performed in the range where most clinical decisions are made (60-3000 ng/L), with a diagnostic concordance of 88%. The usefulness in a clinical setting where time is important was high.

    Conclusion: The Roche Cardiac Reader® NT-proBNP assay has been evaluated in a clinical setting. The point-of-care method shows good results, although with a restricted analytical range compared with the reference.

  • 50.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Samuelsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county2009In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 41, no 5, 324-333 p.Article in journal (Refereed)
    Abstract [en]

    In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

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